(Correcting) misdiagnoses of asthma: A cost effectiveness analysis

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The prevalence of physician-diagnosed-asthma has risen over the past three decades and misdiagnosis of asthma is potentially common. Objective: to determine whether a secondary-screening-program to establish a correct diagnosis of asthma in those who report a physician diagnosis of asthma is cost effective.Method: Randomly selected physician-diagnosed-asthmatic subjects from 8 Canadian cities were studied with an extensive diagnostic algorithm to rule-in, or rule-out, a correct diagnosis of asthma. Subjects in whom the diagnosis of asthma was excluded were followed up for 6-months and data on asthma medications and heath care utilization was obtained. Economic analysis was performed to estimate the incremental lifetime costs associated with secondary screening of previously diagnosed asthmatic subjects. Analysis was from the perspective of the Canadian healthcare system and is reported in Canadian dollars.Results: Of 540 randomly selected patients with physician diagnosed asthma 150 (28%; 95%CI 19-37%) did not have asthma when objectively studied. 71% of these misdiagnosed patients were on some asthma medications. Incorporating the incremental cost of secondary-screening for the diagnosis of asthma, we found that the average cost savings per 100 individuals screened was $35,141 (95$4,588-$69,278).Conclusion: Cost savings primarily resulted from lifetime costs of medication use averted in those who had been misdiagnosed.This work was funded by the Canadian Institute of Health Research, Canada and the University Of Ottawa Division Of Respiratory Medicine

Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies

Peer reviewedPublisher PD

Formal Subdivision of the Holocene Series/Epoch: A Summary

The Holocene Series/Epoch is the most recent series/epoch in the geological timescale, spanning the interval from 11,700 yr to the present day. Together with the subadjacent Pleistocene, it comprises the Quaternary System/Period. The Holocene record contains diverse geomorphological, biotic, climatological and archaeological evidence, within sequences that are often continuous and extremely well-preserved at decadal, annual and even seasonal resolution. As a consequence, the Holocene is perhaps the most intensively-studied series/epoch within the entire Geological Time Scale. Yet until recently little attention had been paid to a formal subdivision of the Holocene. Here we describe an initiative by the Subcommission on Quaternary Stratigraphy (SQS) of the International Commission on Stratigraphy (ICS) to develop a formal stratigraphical subdivision of the Holocene, with three new stages/ages, two underpinned by Global Boundary Stratotype Sections and Points (GSSPs) in an ice core, and a third in a speleothem. These stages/ages are defined along with their equivalent subseries/subepochs. The new stages/ages are the Greenlandian with its GSSP in the Greenland NGRIP2 ice core and dated at 11,700 yr b2k (before 2000 CE); the NorthGrippian with its GSSP in the Greenland NGRIP1 ice core and dated to 8236 yr b2k; and the Meghalayan, with its GSSP in a speleothem from Mawmluh Cave, northeastern India, with a date of 4250 yr b2k. This subdivision was formally ratified by the Executive Committee of the International Union of Geological Sciences (IUGS) on 14th June 2018.non

Simian virus 40 vectors for pulmonary gene therapy

<p>Abstract</p> <p>Background</p> <p>Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy.</p> <p>Methods</p> <p>Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/<it>luc) </it>were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by <it>in vivo </it>light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector.</p> <p>Results</p> <p>Luc expression measured by <it>in vivo </it>light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response.</p> <p>Conclusion</p> <p>In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of <it>in vivo </it>transduction of alveolar type II cells and may thus become a future therapeutic tool.</p

Antiepileptic drugs’ tolerability and safety – a systematic review and meta-analysis of adverse effects in dogs

<p>Various anti-epileptic drugs (AEDs) are used for the management of idiopathic epilepsy (IE) in dogs. Their safety profile is an important consideration for regulatory bodies, owners and prescribing clinicians. However, information on their adverse effects still remains limited with most of it derived from non-blinded non-randomized uncontrolled trials and case reports.</p><p><span>This poster won third place, which was presented at the Veterinary Evidence Today conference, Edinburgh November 1-3, 2016. </span></p><br /> <img src="https://www.veterinaryevidence.org/rcvskmod/icons/oa-icon.jpg" alt="Open Access" /

Phagocytosis and digestion of pH-sensitive fluorescent dye (Eos-FP) transfected E. coli in whole blood assays from patients with severe sepsis and septic shock

The function of phagocytic and antigen presenting cells is of crucial importance to sustain immune competence against infectious agents as well as malignancies. We here describe a reproducible procedure for the quantification of phagocytosis by leukocytes in whole blood. For this, a pH-sensitive green-fluorescent protein- (GFP) like dye (Eos-FP) is transfected into infectious microroganisms. After UV-irradiation, the transfected bacteria emit green (≈5160 nm) and red (≈581 nm) fluorescent light at 490 nm excitation. Since the red fluorescent light is sensitive to acidic pH, the phagocytosed bacteria stop emitting red fluorescent light as soon as the phagosomes fuse with lysosomes. The green fluorescence is maintained in the phagolysosome until pathogen degradation is completed. Fluorescence emission can be followed by flow cytometry with filter settings documenting fluorescence 1 (FL 1, FITC) and fluorescence 2 (FL 2, phycoerythrin, PE). Eos-FP transfected bacteria can also be traced within phagocytes using microscopical techniques. A standardized assay has been developed which is suitable for clinical studies by providing clinicians with syringes pre-filled with fixed and appropriately UV-irradiated Eos-FP E. coli (TruCulture™). After adding blood or body fluids to these containers and starting the incubation at 37°C, phagocytosis by granulocytes proceeds over time. Cultures can be terminated at a given time by lysing red blood cells followed by flow cytometry. A pilot study demonstrated that Eos-FP E. coli phagocytosis and digestion was up-regulated in the majority of patients with either severe sepsis or septic shock as compared to healthy donors (p < 0.0001 after o/n incubation). Following treatment with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in selected patients with sepsis, phagolysosome fusion appeared to be accelerated

Assessing Communities of Practice in health policy : A conceptual framework as a first step towards empirical research

Peer reviewe

Clostridium difficile infection in an endemic setting in the Netherlands

The purpose of this investigation was to study risk factors for Clostridium difficile infection (CDI) in an endemic setting. In a 34-month prospective case–control study, we compared the risk factors and clinical characteristics of all consecutively diagnosed hospitalised CDI patients (n = 93) with those of patients without diarrhoea (n = 76) and patients with non-CDI diarrhoea (n = 64). The incidence of CDI was 17.5 per 10,000 hospital admissions. C. difficile polymerase chain reaction (PCR) ribotype 014 was the most frequently found type (15.9%), followed by types 078 (12.7%) and 015 (7.9%). Independent risk factors for endemic CDI were the use of second-generation cephalosporins, previous hospital admission and previous stay at the intensive care unit (ICU). The use of third-generation cephalosporins was a risk factor for diarrhoea in general. We found no association of CDI with the use of fluoroquinolones or proton pump inhibitors (PPIs). The overall 30-day mortality among CDI patients, patients without diarrhoea and patients with non-CDI diarrhoea was 7.5%, 0% and 1.6%, respectively. In this endemic setting, risk factors for CDI differed from those in outbreak situations. Some risk factors that have been ascribed to CDI earlier were, in this study, not specific for CDI, but for diarrhoea in general. The 30-day mortality among CDI patients was relatively high

Relationship between craving and personality in treatment-seeking women with substance-related disorders

BACKGROUND: Individual differences may impact susceptibility to addiction. The impact of personality features on drug craving, however, has not been studied, particularly in women. METHODS: Ninety-five treatment-seeking women with substance dependence, abstinent for at least 5 and no more than 21 days, were investigated regarding the correlation between personality factors and craving. Personality was assessed using the Temperament and Character Inventory (TCI), the NEO Personality Inventory Revised (NEO-PI-R), and the Barratt Impulsiveness Scale version 11 (BIS-11). Cravings were assessed through the Pennsylvania Craving Scale (PCS), and the Craving Questionnaire (CQ). Anxiety and depressive symptomatology were also recorded. RESULTS: Craving scores were positively correlated with depression and negatively correlated with number of days abstinent from substance use. Also, craving scores were positively associated with the novelty-seeking factor from the TCI and the total score on the BIS-11, and negatively associated with the conscientiousness and agreeableness facets of the NEO-PI-R. CONCLUSION: Findings suggest that personality features, particularly impulsiveness, can be important predictors of craving in women, which has important implications for treatment planning