Neuroinflammation in Preclinical Alzheimer's Disease: A Review of Current Evidence

The pathology of sporadic Alzheimer’s disease (AD) may be present at mid-life and precede the prodromal and clinical dementia syndromes associated with the disorder by decades. Few successful therapeutic treatments exist and, as a result, attention is turning to the preclinical stages of the disease for the development of future intervention strategies. The success of such strategies will rely on well-defined biomarkers of preclinical disease to identify and monitor changes earlier in the disease course. Here, we consider whether immune function changes are potentially useful markers of preclinical disease. We have selected studies spanning epidemiological, animal, clinical and imaging research pertaining to the earliest stages of AD pathogenesis, as well as studies of non-demented adults at high AD risk. We examine changes in inflammatory markers, alongside changes in established biomarkers, to highlight their suitability as disease indicators across preclinical and prodromal stages. We conclude that further work surrounding this topic is required, calling for larger prospective epidemiological studies of preclinical disease that incorporate serial assessment designs with a wider range of inflammatory mediators. We anticipate that future benefits of work in this area include improved disease detection and modification, as well as diagnostic accuracy of trial participants, leading to more cost-effective observation and intervention studies

Protocol for the effective feedback to improve primary care prescribing safety (EFIPPS) study : a cluster randomised controlled trial using ePrescribing data

High-risk prescribing in primary care is common and causes considerable harm. Feedback interventions to improve care are attractive because they are relatively cheap to widely implement. There is good evidence that feedback has small to moderate effects, but the most recent Cochrane review called for more high-quality, large trials that explicitly test different forms of feedback. The study is a three-arm cluster-randomised trial with general practices being randomised and outcomes measured at patient level. 262 practices in three Scottish Health Board areas have been randomised (94% of all possible practices). The two active arms receive different forms of prescribing safety data feedback, with rates of high-risk prescribing compared with a ‘usual care’ arm. Sample size estimation used baseline data from participating practices. With 85 practices randomised to each arm, then there is 93% power to detect a 25% difference in the percentage of high-risk prescribing (from 6.1% to 4.5%) between the usual care arm and each intervention arm. The primary outcome is a composite of six high-risk prescribing measures (antipsychotic prescribing to people aged ≥75 years; non-steroidal anti-inflammatory drug (NSAID) prescribing to people aged ≥75 without gastroprotection; NSAID prescribing to people prescribed aspirin/clopidogrel without gastroprotection; NSAID prescribing to people prescribed an ACE inhibitor/angiotensin receptor blocker and a diuretic; NSAID prescription to people prescribed an oral anticoagulant without gastroprotection; aspirin/clopidogrel prescription to people prescribed an oral anticoagulant without gastroprotection). The primary analysis will use multilevel modelling to account for repeated measurement of outcomes in patients clustered within practices. The study was reviewed and approved by the NHS Tayside Committee on Medical Research Ethics B (11/ES/0001). The study will be disseminated via a final report to the funder with a publicly available research summary, and peer reviewed publications

Award for Best Oral Presentation by a First Timer - Hunting zebra: retrieving rare disease guidelines

The EAHIL 2014 conference provided the opportunity to present a piece of work carried out by a team of informationprofessionals for RARE-Bestpractices (RBP), an international project to promote exchange of information andknowledge in rare disease. The authors work for Healthcare Improvement Scotland (HIS), a publicly fundedorganisation which uses evidence, scrutiny and improvement science to facilitate the delivery of safe, effective andpatient-centred healthcare. HIS is one of fifteen European partners contributing to RBP with our team providing thecore information professional support for the project. Work to develop a rare disease guideline search protocol waspresented in order to raise awareness of RARE-Bestpractices, and to demonstrate the engagement of informationprofessionals in multidisciplinary research projects

Patient and public attitudes to and awareness of clinical practice guidelines : a systematic review with thematic and narrative syntheses

Article Accepted Date: 15 July 2014 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 credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 258583 (DECIDE project). The Health Services Research Unit, Aberdeen University, is funded by the Chief Scientist Office of the Scottish Government Health Directorates. The authors accept full responsibility for this paper and the views expressed in it are those of the authors and do not necessarily reflect those of the Chief Scientist Office. NS receives funding through a Knowledge Translation Fellowship from the Canadian Institutes of Health Research. No funding bodies had a role in the manuscript. We would like to thank Healthcare Improvement Scotland and the University of Dundee for support, including access to literature. We would also like to thank Lorna Thompson (Healthcare Improvement Scotland), for her help with the protocol for this review.Peer reviewedPublisher PD

Women\u27s studies is a vital, useful pursuit

We write in response to George Will\u27s May 21 column, The sad state of women\u27s studies. Women\u27s studies is thriving at the University of Nebraska. On the Lincoln campus, a major in this field has been offered for 25 years. In Kearney, students have been able to earn a minor in women\u27s studies since 1989; a recent student conference there drew nearly 100 participants. Just 15 months after its approval at UNO, 11 students are pursuing the major in women\u27s studies.This discipline helps students answer questions and prepare for careers as no other field can. Among women\u27s studies majors at UNO are students planning careers where they\u27ll work to end domestic violence and sexual assault. Others will go into business, the public sector or graduate school

Improving the retrieval and dissemination of rare disease guidelines and research recommendations: a RARE-Bestpractices initiative

No abstract available

Pathogenic, Molecular, and Immunological Properties of a Virus Associated with Sea Turtle Fibropapillomatosis. Phase II : Viral Pathogenesis and Development of Diagnostic Assays

Research conducted under this RWO from July 1, 1997 through June 30, 2000 has provided important new information about the pathogenesis, virology, and immunology of marine turtle fibropapillomatosis. In particular, we have provided strong evidence for the association of a herpesvirus with fibropapillomatosis of the green turtle,Chelonia mydas, and the loggerhead turtle, Caretta caretta, in Florida. In addition we have provided new evidence for the absence of papillomaviruses from sea turtle fibropapillomas. Although unsuccessful, important new attempts were made to cultivate the FP-associated herpesvirus in vitro in collaboration with the National Wildlife Health Center. During this period of time, we completed publication of the first comprehensive description of the comparative pathology and pathogenesis of experimentally induced and spontaneous fibropapillomas of green turtles (Chelonia mydas). We initiated innovative studies on the persistence of a Chelonian herpesviruses in the marine environment demonstrating for the first time that the environmental survivability of Chelonian herpesviruses makes them real threats to marine turtle health. Finally, we explored development of a serological assay for FP using synthetic herpesvirus peptides and developed methodologies for detection of antibodies to LETV [Iung-eye-trachea virus] a disease-associated herpesvirus of the green turtle, Chelonia mydas.. This last initiative is ongoing and will further our efforts to develop specific immunological assays for the FP-associated herpesvirus and FP. (17 page document

Trauma and depressive symptomatology in middle-aged persons at high risk of dementia: the PREVENT Dementia Study

Objective: Depression and trauma are associated with changes in brain regions implicated in Alzheimer’s disease. The present study examined associations between childhood trauma, depression, adult cognitive functioning and risk of dementia. Methods: Data from 378 participants in the PREVENT Dementia Study aged 40–59 years. Linear and logistic models were used to assess associations between childhood trauma, depression, dementia risk, cognitive test scores and hippocampal volume. Results: Childhood trauma was associated with depression and reduced hippocampal volume but not current cognitive function or dementia risk. Poorer performance on a delayed face/name recall task was associated with depression. Childhood trauma was associated with lower hippocampal volume however poorer cognitive performance was mediated by depression rather than structural brain differences. Conclusion: Depressive symptomatology may be associated with dementia risk via multiple pathways, and future studies should consider subtypes of depressive symptomatology when examining its relationship to dementia