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Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM.
Methods
A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review.
Results
Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites.
Conclusions
Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.
ABSTRACT IMPACT: A better understanding of the spectrum of problematic opioid use will lead to more targeted treatments. OBJECTIVES/GOALS: It is unclear how to approach treatment of individuals with problematic opioid use who do not clearly meet criteria for opioid use disorder (OUD). We aim to characterize clinical, demographic, and medication use at time of identification of problematic opioid use across the spectrum as well as identify predictors of poor outcomes. METHODS/STUDY POPULATION: A national sample of Veterans coded as having opioid abuse or dependence were previously categorized as (1) high likelihood of OUD, (2) limited aberrant opioid use, and (3) prescribed opioid use with no evidence of aberrant use based on chart review. We will describe how individuals in these three categories differ demographically and clinically. We will then use a trained binary logistic regression model to predict whether individuals with limited aberrant opioid use more closely resemble category (1) or (3). Cox proportional hazards models will be used to predict all-cause mortality, suicide-related mortality, opioid-overdose related mortality, and hospitalization over a three-year period using the three categories as predictors and adjusting for relevant covariates. RESULTS/ANTICIPATED RESULTS: We anticipate that Veterans with a high likelihood of OUD will be more likely to experience homelessness and have more psychiatric comorbidities (especially PTSD). We hypothesize that Veterans with prescribed opioid use and no evidence of misuse will be significantly older, more likely to have disability, medical comorbidities (ie., chronic pain, cancer), more prescriptions for non-opioid analgesics, and be prescribed higher doses of opioids. Using a trained binary logistic regression model, we predict that Veterans with limited aberrant opioid use will more closely resemble Veterans with a high likelihood of OUD. We expect that all categories of problematic opioid use will have a high risk of mortality, with a high likelihood of OUD associated with the greatest risk of premature death. DISCUSSION/SIGNIFICANCE OF FINDINGS: Identifying and better characterizing individuals with limited aberrant opioid use may be an important opportunity to intervene prior to development of severe OUD. Future research will focus on targeting interventions to this population, which may have specific needs that are separate from classic OUD or simple pain-related opioid dependence.
Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Edited by
Jean Andrews, Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham,Isabel Torres, Professor of Spanish Golden Age Literature at Queen's University, Belfast
Objectives: The aim of this study was to estimate the cost-effectiveness of nebulized magnesium sulphate (MgSO4) in acute asthma in children from the perspective of the UK National Health Service and personal social services.
Methods: An economic evaluation was conducted based on evidence from a randomized placebo controlled multi-center trial of nebulized MgSO4 in severe acute asthma in children. Participants comprised 508 children aged 2–16 years presenting to an emergency department or a children's assessment unit with severe acute asthma across thirty hospitals in the United Kingdom. Children were randomly allocated to receive nebulized salbutamol and ipratropium bromide mixed with either 2.5 ml of isotonic MgSO4 or 2.5 ml of isotonic saline on three occasions at 20-min intervals. Cost-effectiveness outcomes were constructed around the Yung Asthma Severity Score (ASS) after 60 min of treatment; whilst cost-utility outcomes were constructed around the quality-adjusted life-year (QALY) metric. The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves at alternative cost-effectiveness thresholds for either: (i) a unit reduction in ASS; or (ii) an additional QALY.
Results: MgSO4 had a 75.1 percent probability of being cost-effective at a GBP 1,000 (EUR 1,148) per unit decrement in ASS threshold, an 88.0 percent probability of being more effective (in terms of reducing the ASS) and a 36.6 percent probability of being less costly. MgSO4 also had a 67.6 percent probability of being cost-effective at a GBP 20,000 (EUR 22,957) per QALY gained threshold, an 8.5 percent probability of being more effective (in terms of generating increased QALYs) and a 69.1 percent probability of being less costly. Sensitivity analyses showed that the results of the economic evaluation were particularly sensitive to the methods used for QALY estimation.
Conclusions: The probability of cost-effectiveness of nebulized isotonic MgSO4, given as an adjuvant to standard treatment of severe acute asthma in children, is less than 70 percent across accepted cost-effectiveness thresholds for an additional QALY.
The fourteen essays of this volume engage in distinct ways with the matter of motion in early modern Spanish poetics, without limiting the dialectic of stasis and movement to any single sphere or manifestation. Interrogation of the interdependence of tradition and innovation, poetry, power and politics, shifting signifiers, the intersection of topography and deviant temporalities, the movement between the secular and the sacred, tensions between centres and peripheries, issues of manuscript circulation and reception, poetic calls and echoes across continents and centuries, and between creative writing and reading subjects, all demonstrate that Helgerson's central notion of conspicuous movement is relevant beyond early sixteenth-century secular poetics, By opening it up we approximate a better understanding of poetry's flexible spatio-temporal co-ordinates in a period of extraordinary historical circumstances and conterminous radical cultural transformation. Los catorce ensayos de este volumen conectan de una manera perceptible con el tema del movimiento en la poesía española del siglo de oro, sin limitar la dialéctica de la estasis y movimiento a una sola esfera o manifestación única. Entre los multiples enfoques cabe destacar: el cuestionamiento de la interdependencia de la tradición e inovación, de la poesía, del poder y la política, de los significantes que se transforman, de los espacios que conectan y cruzan con los tiempos 'desviados'; análisis de las tensiones entre lo sagrado y lo secular, del conflicto centro-periferia y del complejo sistema de producción, circulación y recepción de los manuscritos; el diálogo con el eco poético a través de los siglos y de los continentes y la construcción creativa del sujeto escritor y/o lector. Al abrir la noción central de Helgerson del "movimiento conspicuo" más allá de la poesía nueva secular, este libro propone un entendimiento más completo de las coordinadas espacio-temporales de la poesía en un periodo de circunstancias históricas extrao. Jean Andrews is Associate Professor in the Department of Spanish, Portuguese and Latin American Studies, University of Nottingham. Isabel Torres is Professor of Spanish Golden Age Literature at Queen's University, Belfast. Contributors: Jean Andrews, Dana Bultman, Noelia Cirnigliaro, Marsha Collins, Trevor J. Dadson, Aurora Egido, Verónica Grossi, Anne Holloway, Mark J. Mascia, Terence O'Reilly, Carmen Peraita, Amanda Powell, Colin Thompson, Isabel Torres.
Geriatric Medicine is a young specialty in Canada, having been formally recognized in 1981. The early years of research chiefly involved designing and describing programs of care. As the specialty matured, so too did the nature of research into the clinical problems of older adults. This article discusses research published by Canadian geriatricians since 1998, the date of a previous review. Two prominent areas of research are frailty and dementia. Several groups have studied the natural history of frailty, and designed techniques to better measure outcomes. Interventional trials are also gaining prominence, with the Systeme de services intégrés pour personnes agees en perte d'automonie (SIPA) and Mobile Geriatric Assessment Team (MGAT) being good examples. The Canadian Study of Health and Aging (CSHA) is one of the largest studies of dementia epidemiology ever conducted, and the upcoming third wave will provide new data on the outcomes of cognitive impairment not meeting criteria for dementia. Other areas of interest include pharmacoepidemiology, difficult clinical problems, advanced directives and bioethics. Canadian research in geriatrics will continue to develop, with the establishment of the Canadian Institutes of Health Research providing exciting new opportunities.