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Permanent URI for this collectionhttps://hdl.handle.net/11443/932
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Item Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease(BMC, 2021-01-01) Alderson V, Helen; Chinnadurai, Rajkumar; Ibrahim, Sara T.; Asar, Ozgur; Ritchie, James P.; Middleton, Rachel; Larsson, Anders; Diggle, Peter J.; Larsson, Tobias E.; Kalra, Philip A.Background Fibroblast growth factor23 (FGF23) is elevated in CKD and has been associated with outcomes such as death, cardiovascular (CV) events and progression to Renal Replacement therapy (RRT). The majority of studies have been unable to account for change in FGF23 over time and those which have demonstrate conflicting results. We performed a survival analysis looking at change in c-terminal FGF23 (cFGF23) over time to assess the relative contribution of cFGF23 to these outcomes. Methods We measured cFGF23 on plasma samples from 388 patients with CKD 3-5 who had serial measurements of cFGF23, with a mean of 4.2 samples per individual. We used linear regression analysis to assess the annual rate of change in cFGF23 and assessed the relationship between time-varying cFGF23 and the outcomes in a cox-regression analysis. Results Across our population, median baseline eGFR was 32.3mls/min/1.73m(2), median baseline cFGF23 was 162 relative units/ml (RU/ml) (IQR 101-244 RU/mL). Over 70 months (IQR 53-97) median follow-up, 76 (19.6\%) patients progressed to RRT, 86 (22.2\%) died, and 52 (13.4\%) suffered a major non-fatal CV event. On multivariate analysis, longitudinal change in cFGF23 was significantly associated with risk for death and progression to RRT but not non-fatal cardiovascular events. Conclusion In our study, increasing cFGF23 was significantly associated with risk for death and RRT.Item Linear mixed effects models for non-Gaussian continuous repeated measurement data(WILEY, 2020-01-01) Asar, Ozgur; Bolin, David; Diggle, Peter J.; Wallin, JonasWe consider the analysis of continuous repeated measurement outcomes that are collected longitudinally. A standard framework for analysing data of this kind is a linear Gaussian mixed effects model within which the outcome variable can be decomposed into fixed effects, time invariant and time-varying random effects, and measurement noise. We develop methodology that, for the first time, allows any combination of these stochastic components to be non-Gaussian, using multivariate normal variance-mean mixtures. To meet the computational challenges that are presented by large data sets, i.e. in the current context, data sets with many subjects and/or many repeated measurements per subject, we propose a novel implementation of maximum likelihood estimation using a computationally efficient subsampling-based stochastic gradient algorithm. We obtain standard error estimates by inverting the observed Fisher information matrix and obtain the predictive distributions for the random effects in both filtering (conditioning on past and current data) and smoothing (conditioning on all data) contexts. To implement these procedures, we introduce an R package: ngme. We reanalyse two data sets, from cystic fibrosis and nephrology research, that were previously analysed by using Gaussian linear mixed effects models.Item Assessing Feasibility and Acceptability of Web-Based Enhanced Relapse Prevention for Bipolar Disorder (ERPonline): A Randomized Controlled Trial(JMIR PUBLICATIONS, INC, 2017-01-01) Lobban, Fiona; Dodd, Alyson L.; Sawczuk, Adam P.; Asar, Ozgur; Dagnan, Dave; Diggle, Peter J.; Griffiths, Martin; Honary, Mahsa; Knowles, Dawn; Long, Rita; Morriss, Richard; Parker, Rob; Jones, StevenBackground Interventions that teach people with bipolar disorder (BD) to recognize and respond to early warning signs (EWS) of relapse are recommended but implementation in clinical practice is poor. Objectives The objective of this study was to test the feasibility and acceptability of a randomized controlled trial (RCT) to evaluate a Web-based enhanced relapse prevention intervention (ERPonline) and to report preliminary evidence of effectiveness. Methods A single-blind, parallel, primarily online RCT (n=96) over 48 weeks comparing ERPonline plus usual treatment with ``waitlist (WL) control{''} plus usual treatment for people with BD recruited through National Health Services (NHSs), voluntary organizations, and media. Randomization was independent, minimized on number of previous episodes (<8, 8-20, 21+). Primary outcomes were recruitment and retention rates, levels of intervention use, adverse events, and participant feedback. Process and clinical outcomes were assessed by telephone and Web and compared using linear models with intention-to-treat analysis. Results A total of 280 people registered interest online, from which 96 met inclusion criteria, consented, and were randomized (49 to WL, 47 to ERPonline) over 17 months, with 80\% retention in telephone and online follow-up at all time points, except at week 48 (76\%). Acceptability was high for both ERPonline and trial methods. ERPonline cost approximately 19,340 to create, and 2176 per year to host and maintain the site. Qualitative data highlighted the importance of the relationship that the users have with Web-based interventions. Differences between the group means suggested that access to ERPonline was associated with: a more positive model of BD at 24 weeks (10.70, 95\% CI 0.90 to 20.5) and 48 weeks (13.1, 95\% CI 2.44 to 23.93)Item Web-based integrated bipolar parenting intervention for parents with bipolar disorder: a randomised controlled pilot trial(WILEY, 2017-01-01) Jones, Steven H.; Jovanoska, Jelena; Calam, Rachel; Wainwright, Laura D.; Vincent, Helen; Asar, Ozgur; Diggle, Peter J.; Parker, Rob; Long, Rita; Sanders, Matthew; Lobban, FionaBackground: People with bipolar disorder (BD) experience additional parenting challenges associated with mood driven fluctuations in communication, impulse control and motivation. This paper describes a novel web-based self-management approach (Integrated Bipolar Parenting InterventionItem The influence of multiple episodes of acute kidney injury on survival and progression to end stage kidney disease in patients with chronic kidney disease(PUBLIC LIBRARY SCIENCE, 2019-01-01) Sykes, Lynne; Asar, Ozgur; Ritchie, James; Raman, Maharajan; Vassallo, Diana; Alderson, Helen V.; O'Donoghue, Donal J.; Green, Darren; Diggle, Peter J.; Kalra, Philip A.Background Acute kidney injury (AKI) and chronic kidney disease (CKD) are common syndromes associated with significant morbidity, mortality and cost. The extent to which repeated AKI episodes may cumulatively affect the rate of progression of all-cause CKD has not previously been investigated. In this study, we explored the hypothesis that repeated episodes of AKI increase the rate of renal functional deterioration loss in patients recruited to a large, all-cause CKD cohort. Methods Patients from the Salford Kidney Study (SKS) were considered. Application of KDIGO criteria to all available laboratory measurements of renal function identified episodes of AKI. A competing risks model was specified for four survival events: Stage 1 AKI