The cost of moderate and severe COPD exacerbations to the Canadian healthcare system

SummaryBackgroundThe cost of exacerbations in chronic obstructive pulmonary disease (COPD) has not been well studied. The aim of this study was to identify and quantify the (average) cost of moderate and severe exacerbations (ME and SE, respectively) from a Canadian perspective.MethodsResources used during ME and SE were identified in a year long prospective, observational study (Resource Utilization Study In COPD (RUSIC)). The units of analysis were ME and SE. Unit costs (2006$CAN), based on provincial, hospital and published sources, were applied to resources. The overall cost per ME and SE were calculated. The population burden of exacerbations was also calculated.ResultsAmong study participants (N=609, aged 68.6±9.4 years, 58.3$126 (N=574) and $515 (N=105), respectively. The average overall cost of a ME was$641. For SEs, the average hospital stay was 10.0 days. The overall mean costs of outpatient, ED and hospitalization services for SE were $114 (N=44),$774 (N=140) and $8669 (N=151), respectively. The average overall cost of a SE was$9557.ConclusionThe economic burden associated with MEs and especially SEs, in Canada, is considerable and likely has a substantial impact on healthcare costs. The overall burden of exacerbations has been estimated in the range of $646 million to$736 million per annum

Melarsoprol cyclodextrin inclusion complexes as promising oral candidates for the treatment of human African trypanosomiasis

Human African trypanosomiasis (HAT), or sleeping sickness, results from infection with the protozoan parasites <i>Trypanosoma brucei</i> (<i>T.b.</i>) <i>gambiense</i> or <i>T.b.rhodesiense</i> and is invariably fatal if untreated. There are 60 million people at risk from the disease throughout sub-Saharan Africa. The infection progresses from the haemolymphatic stage where parasites invade the blood, lymphatics and peripheral organs, to the late encephalitic stage where they enter the central nervous system (CNS) to cause serious neurological disease. The trivalent arsenical drug melarsoprol (Arsobal) is the only currently available treatment for CNS-stage <i>T.b.rhodesiense</i> infection. However, it must be administered intravenously due to the presence of propylene glycol solvent and is associated with numerous adverse reactions. A severe post-treatment reactive encephalopathy occurs in about 10% of treated patients, half of whom die. Thus melarsoprol kills 5% of all patients receiving it. Cyclodextrins have been used to improve the solubility and reduce the toxicity of a wide variety of drugs. We therefore investigated two melarsoprol cyclodextrin inclusion complexes; melarsoprol hydroxypropyl-͎-cyclodextrin and melarsoprol randomly-methylated-β-cyclodextrin. We found that these compounds retain trypanocidal properties <i>in vitro</i> and cure CNS-stage murine infections when delivered orally, once per day for 7-days, at a dosage of 0.05 mmol/kg. No overt signs of toxicity were detected. Parasite load within the brain was rapidly reduced following treatment onset and magnetic resonance imaging showed restoration of normal blood-brain barrier integrity on completion of chemotherapy. These findings strongly suggest that complexed melarsoprol could be employed as an oral treatment for CNS-stage HAT, delivering considerable improvements over current parenteral chemotherapy

Registration evaluation of dynamic breast MR images

The interpretation of dynamic contrast-enhanced breast MR images is predicated on the assumption of minimal voxel movement during the time course of the image acquisition. Misalignment of the dynamic image sequence as a result of movement during image acquisition can lead to potentially misleading diagnostic conclusions. In this paper a new methodology is presented for assessing the degree of in-plane (intra-slice) movement in a dynamic image sequence. The method is demonstrated on data from six subjects. The conclusion is that the method makes it possible to quantitatively qualify the accuracy of computed enhancement curves and more importantly to identify unacceptably poor registration

By design : negotiating flexible learning in the built environment discipline

The term ‘flexible education’ is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning ‘matching’ tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher’s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Sympathetic cooling of an atomic Bose-Fermi gas mixture

Sympathetic cooling of an atomic Fermi gas by a Bose gas is studied by solution of the coupled quantum Boltzmann equations for the confined gas mixture. Results for equilibrium temperatures and relaxation dynamics are presented, and some simple models developed. Our study illustrate that a combination of sympathetic and forced evaporative cooling enables the Fermi gas to be cooled to the degenerate regime where quantum statistics, and mean field effects are important. The influence of mean field effects on the equilibrium spatial distributions is discussed qualitatively.Comment: 8 pages, 9 figures, accepted for publication in Phys.Rev.Let

Reviewing Competence in Practice: Reform of Continuing Professional Development for Irish Pharmacists

There has been significant reform of the Continuing Professional Development (CPD) requirements for Irish pharmacists over the past five years. In 2015, a new system was established that includes quality assurance of practitioner engagement in CPD and quality assurance of practitioner competence. Pharmacists must now plan and document their learning activities in an electronic portfolio (ePortfolio) and they must participate in an ePortfolio Review process once every five-year period. A random sample is chosen each year to participate in a review of their practice for pharmacists in patient-facing roles. This paper provides an overview of the development and implementation of these quality assurance processes and it considers the outcomes that were observed in the first four years of implementation. By April 2019, almost 3000 pharmacists had participated in the ePortfolio Review process over the preceding three years, of which 96.2% demonstrated appropriate engagement in CPD. In the preceding two years, almost 200 pharmacists had participated in Practice Review, of which 97.5% have demonstrated the required level of competence across four competencies. All of the pharmacists who did not demonstrate the required level of competence in one or more competency area during Practice Review had previously demonstrated appropriate engagement in CPD through the ePortfolio Review process. This raises interesting questions regarding the use of engagement in continuing education (CE) or CPD as a surrogate measure for competence by professions

Characterization of Alzheimer's disease‐like neuropathology in Duchenne's muscular dystrophy using the DBA/2J mdx mouse model

Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disorder caused by a mutation in the dystrophin gene. In addition to muscle pathology, some patients with DMD will exhibit cognitive impairments with severity being linked to age and type of genetic mutation. Likewise, some studies have shown that mdx mice display impairments in spatial memory compared with wild-type (WT) controls, while others have not observed any such effect. Most studies have utilized the traditional C57BL/10 (C57) mdx mouse, which exhibits a mild disease phenotype. Recently, the DBA/2J (D2) mdx mouse has emerged as a more severe and perhaps clinically relevant DMD model; however, studies examining cognitive function in these mice are limited. Thus, in this study we examined cognitive function in age-matched C57 and D2 mdx mice along with their respective WT controls. Our findings show that 8- to 12-week-old C57 mdx mice did not display any differences in exploration time when challenged with a novel object recognition test. Conversely, age-matched D2 mdx mice spent less time exploring objects in total as a well as less time exploring the novel object, suggestive of impaired recognition memory. Biochemical analyses of the D2 mdx brain revealed higher soluble amyloid precursor protein b(APPb) and APP in the prefrontal cortex of mdx mice compared with WT, and lower soluble APPa in the hippocampus, suggestive of a shift towards amyloidogenesis and a similar pathogenesis to Alzheimer’s disease. Furthermore, our study demonstrates the utility of the D2 mdx model in studying cognitive impairment.Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canad