Affiliation:
1. MRC Prion Unit at UCL, UCL Institute of Prion Diseases , Cleveland Street, London W1W 7FF , UK
2. National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust , London WC1N 3BG , UK
3. College of Medicine and Health, University of Exeter , Exeter EX1 2HZ , UK
4. Deep Dementia Phenotyping Network , Exeter EX1 2LU , UK
5. Alan Turing Institute , London NW1 2DB , UK
Abstract
Abstract
Sporadic Creutzfeldt-Jakob disease, the most common human prion disease, typically presents as a rapidly progressive dementia and has a highly variable prognosis. Despite this heterogeneity, clinicians need to give timely advice on likely prognosis and care needs. No prognostic models have been developed that predict survival or time to increased care status from the point of diagnosis. We aimed to develop clinically useful prognostic models with data from a large prospective observational cohort study. Five hundred and thirty-seven patients were visited by mobile teams of doctors and nurses from the National Health Service National Prion Clinic within 5 days of notification of a suspected diagnosis of sporadic Creutzfeldt-Jakob disease, enrolled to the study between October 2008 and March 2020, and followed up until November 2020. Prediction of survival over 10-, 30- and 100-day periods was the main outcome. Escalation of care status over the same time periods was a secondary outcome for a subsample of 113 patients with low care status at initial assessment. Two hundred and eighty (52.1%) patients were female and the median age was 67.2 (interquartile range 10.5) years. Median survival from initial assessment was 24 days (range 0–1633); 414 patients died within 100 days (77%). Ten variables were included in the final prediction models: sex; days since symptom onset; baseline care status; PRNP codon 129 genotype; Medical Research Council Prion Disease Rating Scale, Motor and Cognitive Examination Scales; count of MRI abnormalities; Mini-Mental State Examination score and categorical disease phenotype. The strongest predictor was PRNP codon 129 genotype (odds ratio 6.65 for methionine homozygous compared with methionine-valine heterozygous; 95% confidence interval 3.02–14.68 for 30-day mortality). Of 113 patients with lower care status at initial assessment, 88 (78%) had escalated care status within 100 days, with a median of 35 days. Area under the curve for models predicting outcomes within 10, 30 and 100 days was 0.94, 0.92 and 0.91 for survival, and 0.87, 0.87 and 0.95 for care status escalation, respectively. Models without PRNP codon 129 genotype, which is not immediately available at initial assessment, were also highly accurate. We have developed a model that can accurately predict survival and care status escalation in sporadic Creutzfeldt-Jakob disease patients using clinical, imaging and genetic data routinely available in a specialist national referral service. The utility and generalizability of these models to other settings could be prospectively evaluated when recruiting to clinical trials and providing clinical care.
Funder
Creutzfeldt-Jakob Disease Support Network
Alzheimer’s Research
UK
Alan Turing Institute/Engineering and Physical Sciences Research Council
National Institute for Health Research
Applied Research Collaboration
South-West Peninsula
National Health and Medical Research Council
National Institute on Aging
National Institutes of Health
Alan Turing Institute
Engineering and Physical Sciences Research Council
Medical Research Council
National Institute for Health Research Senior Investigators
Department of Health and Social Care
National Institute for Health Research’s Biomedical Research Centre
University College London Hospitals NHS Foundation Trust
Medical Research Council Clinical Research Training Fellowship
National Institute for Health Research’s Comprehensive Local Research Network
Publisher
Oxford University Press (OUP)
Subject
General Earth and Planetary Sciences,General Environmental Science
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献