Use of Real-World Data Sources for Canadian Drug Pricing and Reimbursement Decisions: Stakeholder Views and Lessons for Other Countries.

Background: Canada has a long history of the use of clinical evidence to support healthcare decision making. Given improvements in data holdings and analytic capacity in Canada and stakeholder interest, the purpose of this study is to reflect on perceptions of the value of real-world evidence in pricing and reimbursement decisions, barriers to its optimal use in pricing and reimbursement, current initiatives that may lead to its increased use, and what role the pharmaceutical industry may play in this.Methods/ResultsTo capture stakeholder perceptions, ninety-one participants identified as key stakeholders were identified according to background roles and geography and invited to participate in four round table discussions conducted under Chatham House rule.

Is radiograph glenopolar angle accurate for extraarticular scapular neck fractures?

Background: Plain radiographs still play a role in management of extraarticular scapular neck fractures. Glenopolar angle (GPA) is one of the radiograph measurements that is used to determine the necessity for surgery. Our aim was to establish reliability of GPA on plain radiograph in patients with extraarticular scapular neck fractures.

Endodontic Management of a Mandibular Central Incisor with Type IV Canal Pattern: A Case Report.

The success of endodontic treatment requires the knowledge of tooth morphology and its variations. Mandibular incisor's anatomy presents a challenge when an endodontic access is made, because of its small size and high prevalence of two canals. We are describing a Weine's Type IV root canal configuration that was detected in a mandibular central incisor, which was demonstrated by a radiographic examination.

Hemangioma: review of literature.

Hemangiomas are tumors identifed by rapid endothelial cell proliferation in early infancy, followed by involution over time. All other abnormalities are malformations resulting from anomalous development of vascular plexuses. The malformations have a normal endothelial cell growth cycle that affects the veins, the capillaries or the lymphatics and they do not involute.

Second-line therapy in patients with type 2 diabetes inadequately controlled with metformin monotherapy: a systematic review and mixed-treatment comparison meta-analysis.

Background: Although there is general agreement that metformin should be used as first-line pharmacotherapy in patients with type 2 diabetes, uncertainty remains regarding the choice of second-line therapy once metformin is no longer effective. We conducted a systematic review and meta-analysis to assess the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

Methods: MEDLINE, EMBASE, BIOSIS Previews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published in English from 1980 to October 2009.

Choline-mediated depression of hippocampal synaptic transmission.

Choline is a micronutrient essential for the structural integrity of cellular membranes, and its presence at synapses follows either depolarization-induced pre-synaptic release or degradation of acetylcholine. Previous studies using whole-cell recording have shown that choline can modulate inhibitory input to hippocampal pyramidal neurons by acting upon nicotinic acetylcholine receptors (nAChRs) found on interneurons. However, little is known about how choline affects neuronal activity at the population level; therefore, we used extracellular recordings to assess its influence upon synaptic transmission in acutely prepared hippocampal slices.

A novel silicon patch-clamp chip permits high-fidelity recording of ion channel activity from functionally defined neurons.

We report on a simple and high-yield manufacturing process for silicon planar patch-clamp chips, which allow low capacitance and series resistance from individually identified cultured neurons. Apertures are etched in a high-quality silicon nitride film on a silicon wafer; wells are opened on the backside of the wafer by wet etching and passivated by a thick deposited silicon dioxide film to reduce the capacitance of the chip and to facilitate the formation of a high-impedance cell to aperture seal. The chip surface is suitable for culture of neurons over a small orifice in the substrate with minimal leak current.

Elevated synaptic activity preconditions neurons against an in vitro model of ischemia.

Tolerance to otherwise lethal cerebral ischemia in vivo or to oxygen-glucose deprivation (OGD) in vitro can be induced by prior transient exposure to N-methyl-D-aspartic acid (NMDA): preconditioning in this manner activates extrasynaptic and synaptic NMDA receptors and can require bringing neurons to the "brink of death." We considered if this stressful requirement could be minimized by the stimulation of primarily synaptic NMDA receptors. Subjecting cultured cortical neurons to prolonged elevations in electrical activity induced tolerance to OGD.

Synaptic activity and triphenyltetrazolium chloride metabolism are correlated after oxygen-glucose deprivation in acute, but not cultured, hippocampal slices.

The importance of the hippocampus to learning and memory has attracted significant attention to how the structure responds to damage. Although many studies have used either the acute hippocampal slice preparation or organotypic hippocampal slice cultures, little work has been done to determine if the choice of model is an important variable. The present study examined whether differences exist in how each model responds to a commonly studied ischemic-like paradigm, oxygen-glucose deprivation.

Longitudinal study of the effects of a high-fat diet on glucose regulation, hippocampal function, and cerebral insulin sensitivity in C57BL/6 mice.

Although the increasing rate of obesity has stimulated interest in the effects of diet composition on peripheral systems, comparatively little work has been done to examine effects upon the brain. A diet high in fat is one of many factors that can promote obesity, and previous research has shown that such a diet can produce learning and memory impairment in rodents. In the present study, C57BL/6 mice were placed on either a high-fat (45% kcal fat) or regular (5% kcal fat) diet, and examined at different points during the subsequent year.