{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:36:07Z","timestamp":1790008567706,"version":"4.0.1"},"reference-count":38,"publisher":"BMJ","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002001","name":"Health Services and Delivery Research Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment Programme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ"],"accepted":{"date-parts":[[2023,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To develop and validate a prognostic model to inform risk stratified decisions on frequency of monitoring blood tests during long term methotrexate treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Electronic health records within the UK\u2019s Clinical Practice Research Datalink (CPRD) Gold and CPRD Aurum.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>Adults (\u226518 years) with a diagnosis of an immune mediated inflammatory disease who were prescribed methotrexate by their general practitioner for six months or more during 2007-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measure<\/jats:title>\n                    <jats:p>Discontinuation of methotrexate owing to abnormal monitoring blood test result. Patients were followed-up from six months after their first prescription for methotrexate in primary care to the earliest of outcome, drug discontinuation for any other reason, leaving the practice, last data collection from the practice, death, five years, or 31 December 2019. Cox regression was performed to develop the risk equation, with bootstrapping used to shrink predictor effects for optimism. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data from 13\u2009110 (854 events) and 23\u2009999 (1486 events) participants were included in the development and validation cohorts, respectively. 11 candidate predictors (17 parameters) were included. In the development dataset, the optimism adjusted R\n                      <jats:sup>2<\/jats:sup>\n                      was 0.13 and the optimism adjusted Royston D statistic was 0.79. The calibration slope and Royston D statistic in the validation dataset for the entire follow-up period was 0.94 (95% confidence interval 0.85 to 1.02) and 0.75 (95% confidence interval 0.67 to 0.83), respectively. The prognostic model performed well in predicting outcomes in clinically relevant subgroups defined by age group, type of immune mediated inflammatory disease, and methotrexate dose.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>A prognostic model was developed and validated that uses information collected during routine clinical care and may be used to risk stratify the frequency of monitoring blood test during long term methotrexate treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmj-2022-074678","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T07:15:10Z","timestamp":1685430910000},"page":"e074678","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":27,"title":["Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and validation using primary care data from the UK"],"prefix":"10.1136","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3859-7354","authenticated-orcid":false,"given":"Georgina","family":"Nakafero","sequence":"first","affiliation":[{"name":"Academic Rheumatology, University of Nottingham, Nottingham NG5 1PB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J","family":"Grainge","sequence":"additional","affiliation":[{"name":"Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hywel C","family":"Williams","sequence":"additional","affiliation":[{"name":"Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Card","sequence":"additional","affiliation":[{"name":"Lifespan and Population Health, School of Medicine, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten W","family":"Taal","sequence":"additional","affiliation":[{"name":"Centre for Kidney Research and Innovation, Translational Medical Sciences, University of Nottingham, Derby, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-4830","authenticated-orcid":false,"given":"Guruprasad P","family":"Aithal","sequence":"additional","affiliation":[{"name":"Nottingham Digestive Diseases Centre, Translational Medical Sciences, University of Nottingham, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Haematology, Nottingham University Hospital NHS Trust, Nottingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian 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