Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease
dc.contributor.author | Nihat, A | |
dc.contributor.author | Ranson, JM | |
dc.contributor.author | Harris, D | |
dc.contributor.author | McNiven, K | |
dc.contributor.author | Mok, T | |
dc.contributor.author | Rudge, P | |
dc.contributor.author | Collinge, J | |
dc.contributor.author | Llewellyn, DJ | |
dc.contributor.author | Mead, S | |
dc.date.accessioned | 2023-01-26T15:16:59Z | |
dc.date.issued | 2022-08-02 | |
dc.date.updated | 2023-01-26T14:28:07Z | |
dc.description.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. | en_GB |
dc.format.extent | fcac201- | |
dc.format.medium | Electronic-eCollection | |
dc.identifier.citation | Vol. 4(4), article fcac201 | en_GB |
dc.identifier.doi | https://doi.org/10.1093/braincomms/fcac201 | |
dc.identifier.uri | http://hdl.handle.net/10871/132348 | |
dc.identifier | ORCID: 0000-0001-9491-3940 (Ranson, Janice M) | |
dc.identifier | ScopusID: 57147327100 (Ranson, Janice M) | |
dc.identifier | ORCID: 0000-0002-2441-4246 (Llewellyn, David J) | |
dc.language.iso | en | en_GB |
dc.publisher | Oxford University Press (OUP) | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/35974795 | en_GB |
dc.rights | © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. | en_GB |
dc.subject | Creutzfeldt-Jakob | en_GB |
dc.subject | dementia | en_GB |
dc.subject | prion | en_GB |
dc.subject | prognosis | en_GB |
dc.subject | survival model | en_GB |
dc.title | Development of prognostic models for survival and care status in sporadic Creutzfeldt-Jakob disease | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-01-26T15:16:59Z | |
dc.identifier.issn | 2632-1297 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from Oxford University Press via the DOI in this record | en_GB |
dc.description | Data availability: Patient data from the National Prion Monitoring Cohort are owned by University College London. This patient data are not currently publicly available. For researchers interested in accessing this data, further information can be found at https://www.ucl.ac.uk/national-prion-clinic/national-prion-monitoring-cohort-npmc. | en_GB |
dc.identifier.eissn | 2632-1297 | |
dc.identifier.journal | Brain Communications | en_GB |
dc.relation.ispartof | Brain Commun, 4(4) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2022-08-01 | |
dc.rights.license | CC BY | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2022-08-02 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-01-26T15:14:46Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-01-26T15:17:06Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2022-08-02 |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's licence is described as © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.