{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T20:51:31Z","timestamp":1778964691666,"version":"3.51.4"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15056.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000}},{"DOI":"10.12688\/wellcomeopenres.15056.2","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000}}],"reference-count":20,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["210772"],"award-info":[{"award-number":["210772"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["104803"],"award-info":[{"award-number":["104803"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203135"],"award-info":[{"award-number":["203135"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["FC0010218"],"award-info":[{"award-number":["FC0010218"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns4:p>\n                    <ns4:bold>Background:<\/ns4:bold>\n                    Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis. Delayed diagnosis and treatment, which is a risk factor for poor outcome, is caused in part by lack of availability of diagnostic tests that are both rapid and accurate. Several attempts have been made to develop clinical scoring systems to fill this gap, but none have performed sufficiently well to be broadly implemented. We aim to identify and validate a set of clinical predictors that accurately classify TBM using individual patient data (IPD) from published studies.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Methods:<\/ns4:bold>\n                    We will perform a systematic review and obtain IPD from studies published from the year 1990 which undertook diagnostic testing for TBM in adolescents or adults using at least one of, microscopy for acid-fast bacilli, commercial nucleic acid amplification test for\n                    <ns4:italic>Mycobacterium tuberculosis<\/ns4:italic>\n                    or mycobacterial culture of cerebrospinal fluid.\u00a0 Clinical data that have previously been shown to be associated with TBM, and can inform the final diagnosis, will be requested. The data-set will be divided into training and test\/validation data-sets for model building. A predictive logistic model will be built using a training set with patients with definite TBM and no TBM. Should it be warranted, factor analysis may be employed, depending on evidence for multicollinearity or the case for including latent variables in the model.\n                  <\/ns4:p>\n                  <ns4:p>\n                    <ns4:bold>Discussion:<\/ns4:bold>\n                    We will systematically identify and extract key clinical parameters associated with TBM from published studies and use a \u2018big data\u2019 approach to develop and validate a clinical prediction model with enhanced generalisability. The final model will be made available through a smartphone application. Further work will be external validation of the model and test of efficacy in a randomised controlled trial.\n                  <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15056.3","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T11:02:06Z","timestamp":1609758126000},"page":"19","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The diagnosis of tuberculous meningitis in adults and adolescents: protocol for a systematic review and individual patient data meta-analysis to inform a multivariable prediction 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Snell, Centre for Prognosis Research, School of Medicine, Keele University, Keele, UK, 04 Feb 2021, version 3, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/4-19\/v3#referee-response-41935","order":1,"name":"referee-response-41935","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [210772; 104803; 203135; FC0010218]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}