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BACKGROUND - Vascular health factors frequently co-occur with Alzheimer's disease (AD). A better understanding of how systemic vascular and cerebrovascular health intersects with clinical and pathological AD may inform prevention and treatment opportunities.
OBJECTIVE - To establish the Vanderbilt Memory & Aging Project, a case-control longitudinal study investigating vascular health and brain aging, and describe baseline methodology and participant characteristics.
METHODS - From September 2012 to November 2014, 335 participants age 60- 92 were enrolled, including 168 individuals with mild cognitive impairment (MCI, 73±8 years, 41% female) and 167 age-, sex-, and race-matched cognitively normal controls (NC, 72±7 years, 41% female). At baseline, participants completed a physical and frailty examination, fasting blood draw, neuropsychological assessment, echocardiogram, cardiac MRI, and brain MRI. A subset underwent 24-hour ambulatory blood pressure monitoring and lumbar puncture for cerebrospinal fluid (CSF) collection.
RESULTS - As designed, participant groups were comparable for age (p = 0.31), sex (p = 0.95), and race (p = 0.65). MCI participants had greater Framingham Stroke Risk Profile scores (p = 0.008), systolic blood pressure values (p = 0.008), and history of left ventricular hypertrophy (p = 0.04) than NC participants. As expected, MCI participants performed worse on all neuropsychological measures (p-values < 0.001), were more likely to be APOEɛ4 carriers (p = 0.02), and had enhanced CSF biomarkers, including lower Aβ42 (p = 0.02), higher total tau (p = 0.004), and higher p-tau (p = 0.02) compared to NC participants.
CONCLUSION - Diverse sources of baseline and longitudinal data will provide rich opportunities to investigate pathways linking vascular and cerebrovascular health, clinical and pathological AD, and neurodegeneration contributing to novel strategies to delay or prevent cognitive decline.
BACKGROUND - The objective of this article is to describe the organisation of an international, clinical registry, the Chronic Kidney Disease Observational Database (CKDOD), the processes of enrolling patients and entering data and preliminary results to date.
DESIGN - The Chronic Kidney Disease Observational Database (CKDOD) is designed to assess the association between different factors with a known influence on chronic kidney disease (CKD) progression as well as treatment strategies such as dietary modifications, blood pressure control and pharmacological interventions in Asian countries (India, China, Malaysia and Thailand). The only inclusion criterion is the presence of CKD stage 2 or higher as defined by the KDIGO guidelines. Demographic and clinical information are collected by a standardised electronic questionnaire, available in English and Chinese. The data are transferred to the CKDOD database either by e-mail or via web access. All data are checked for consistency and missing values. Collection of data started in September 2011 and by April 2015, data on 1323 individual patients had been submitted. The mean age at inclusion was 57 ± 14 years, 67 % were male and 36 % were diabetic. The baseline estimated glomerular filtration rate was 26 ml/min/1.73 m(2). Of all enrolled patients, 324 (24 %) received ketoanalogue supplementation during at least one recorded visit.
DISCUSSION - The CKDOD is a very large and comprehensive data repository, currently focused in subjects recruited from Asia. The database is expected to provide important long-term information on CKD progression, nutritional and metabolic derangements that accompany CKD progression and treatment strategies to ameliorate progression and complications of CKD.
TRIAL REGISTRATION - Clinical Trial Registry - India: CTRI/2012/06/002743 ; 25th July 2012.
Despite extensive research, no therapeutic interventions have been shown to prevent AKI, accelerate recovery of AKI, or reduce progression of AKI to CKD in patients. This failure in translation has led investigators to speculate that the animal models being used do not predict therapeutic responses in humans. Although this issue continues to be debated, an important concern that has not been addressed is whether improvements in preclinical study design can be identified that might also increase the likelihood of translating basic AKI research into clinical practice using the current models. In this review, we have taken an evidence-based approach to identify common weaknesses in study design and reporting in preclinical AKI research that may contribute to the poor translatability of the findings. We focused on use of N-acetylcysteine or sodium bicarbonate for the prevention of contrast-induced AKI and use of erythropoietin for the prevention of AKI, two therapeutic approaches that have been extensively studied in clinical trials. On the basis of our findings, we identified five areas for improvement in preclinical study design and reporting. These suggested and preliminary guidelines may help improve the quality of preclinical research for AKI drug development.
Copyright © 2015 by the American Society of Nephrology.
OBJECTIVE - This study describes the development and psychometric evaluation of HPV Clinical Trial Survey for Parents with Children Aged 9 to 15 (CTSP-HPV) using traditional instrument development methods and community engagement principles.
METHODS - An expert panel and parental input informed survey content and parents recommended study design changes (e.g., flyer wording). A convenience sample of 256 parents completed the final survey measuring parental willingness to consent to HPV clinical trial (CT) participation and other factors hypothesized to influence willingness (e.g., HPV vaccine benefits). Cronbach's a, Spearman correlations, and multiple linear regression were used to estimate internal consistency, convergent and discriminant validity, and predictively validity, respectively.
RESULTS - Internal reliability was confirmed for all scales (a ≥ 0.70.). Parental willingness was positively associated (p < 0.05) with trust in medical researchers, adolescent CT knowledge, HPV vaccine benefits, advantages of adolescent CTs (r range 0.33-0.42), supporting convergent validity. Moderate discriminant construct validity was also demonstrated. Regression results indicate reasonable predictive validity with the six scales accounting for 31% of the variance in parents' willingness.
CONCLUSIONS - This instrument can inform interventions based on factors that influence parental willingness, which may lead to the eventual increase in trial participation. Further psychometric testing is warranted.
© 2015 Wiley Periodicals, Inc.
The key idea of statistical hypothesis testing is to fix, and thereby control, the Type I error (false positive) rate across samples of any size. Multiple comparisons inflate the global (family-wise) Type I error rate and the traditional solution to maintaining control of the error rate is to increase the local (comparison-wise) Type II error (false negative) rates. However, in the analysis of human brain imaging data, the number of comparisons is so large that this solution breaks down: the local Type II error rate ends up being so large that scientifically meaningful analysis is precluded. Here we propose a novel solution to this problem: allow the Type I error rate to converge to zero along with the Type II error rate. It works because when the Type I error rate per comparison is very small, the accumulation (or global) Type I error rate is also small. This solution is achieved by employing the likelihood paradigm, which uses likelihood ratios to measure the strength of evidence on a voxel-by-voxel basis. In this paper, we provide theoretical and empirical justification for a likelihood approach to the analysis of human brain imaging data. In addition, we present extensive simulations that show the likelihood approach is viable, leading to "cleaner"-looking brain maps and operational superiority (lower average error rate). Finally, we include a case study on cognitive control related activation in the prefrontal cortex of the human brain.
Copyright © 2015 Elsevier Inc. All rights reserved.
Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.
OBJECTIVE - The study goal is to highlight strategies for promoting relevance of research capacity-building efforts targeting community organizations (CO)s.
METHODS - Two community partners, representing two COs, were invited to participate in CO research development trainings, Community Research Forums (Forum)s. Their contributions were documented via Forum document review. Forum participants, representatives from other COs, completed post-Forum surveys to identify additional training needs and rate Forum impact relative to their training expectations. A content-based analysis and descriptive statistics were used to summarize needs assessment- and impact-related survey responses, respectively.
RESULTS - Community partners were involved in eight Forum-related activities including marketing (planning), facilitation (implementation), and manuscript coauthorship (dissemination). Eighty-one individuals, representing 55 COs, attended the Forums. Needs assessment responses revealed a desire for additional assistance with existing Forum topics (e.g., defining research priorities) and a need for new ones (e.g., promoting organizational buy in for research). Ninety-one percent of participants agreed that the Forum demonstrated the value of research to COs and how to create a research agenda.
CONCLUSIONS - Including community partners in all Forum phases ensured that CO perspectives were integrated throughout. Post-Forum needs and impact assessment results will help in tailoring, where needed, future training topics and strategies, respectively.
© 2015 Wiley Periodicals, Inc.
Dynamic reflexivity is central to enabling flexible and emergent qualitatively driven inductive mixed-method and multiple methods research designs. Yet too often, such reflexivity, and how it is used at various points of a study, is absent when we write our research reports. Instead, reports of mixed-method and multiple methods research focus on what was done rather than how it came to be done. This article seeks to redress this absence of emphasis on the reflexive thinking underpinning the way that mixed- and multiple methods, qualitatively driven research approaches are thought about and subsequently used throughout a project. Using Morse's notion of an armchair walkthrough, we excavate and explore the layers of decisions we made about how, and why, to use qualitatively driven mixed-method and multiple methods research in a study of mindfulness training (MT) in schoolchildren.
© The Author(s) 2015.