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Development and validation of outcome prediction models for aneurysmal subarachnoid haemorrhage: the SAHIT multinational cohort study

BMJ 2018; 360 doi: https://doi.org/10.1136/bmj.j5745 (Published 18 January 2018) Cite this as: BMJ 2018;360:j5745
  1. Blessing N R Jaja, research associate1 3 4,
  2. Gustavo Saposnik, associate professor2 3 4,
  3. Hester F Lingsma, associate professor8,
  4. Erin Macdonald, research assistant3,
  5. Kevin E Thorpe, assistant professor6,
  6. Muhammed Mamdani, professor4 6,
  7. Ewout W Steyerberg, professor8 9,
  8. Andrew Molyneux, professor10,
  9. Airton Leonardo de Oliveira Manoel, critical care fellow1 3,
  10. Bawarjan Schatlo, assistant professor11,
  11. Daniel Hanggi, professor12,
  12. David Hasan, associate professor13,
  13. George K C Wong, professor14,
  14. Nima Etminan, associate professor12,
  15. Hitoshi Fukuda, assistant professor15,
  16. James Torner, professor16,
  17. Karl L Schaller, professor17,
  18. Jose I Suarez, professor18,
  19. Martin N Stienen, neurosurgery fellow19,
  20. Mervyn D I Vergouwen, assistant professor20,
  21. Gabriel J E Rinkel, professor20,
  22. Julian Spears, associate professor1 5,
  23. Michael D Cusimano, professor1 4 5,
  24. Michael Todd, professor21,
  25. Peter Le Roux, professor22,
  26. Peter Kirkpatrick, honorary consultant neurosurgeon23,
  27. John Pickard, professor23,
  28. Walter M van den Bergh, associate professor24,
  29. Gordon Murray, professor25,
  30. S Claiborne Johnston, professor26,
  31. Sen Yamagata, professor15,
  32. Stephan Mayer, professor27,
  33. Tom A Schweizer, associate professor1 3 4 5,
  34. R Loch Macdonald, professor1 3 4 5
  35. on behalf of the SAHIT collaboration
  1. 1Division of Neurosurgery, St Michael’s Hospital, Toronto, ON, Canada
  2. 2Division of Neurology, St Michael’s Hospital, Toronto, ON, Canada
  3. 3Neuroscience Research Program of the Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, ON, Canada
  4. 4Institute of Medical Science, University of Toronto, ON, Canada
  5. 5Department of Surgery, University of Toronto, ON, Canada
  6. 6Department of Health Policy, Management and Evaluation, University of Toronto, ON, Canada
  7. 7Dalla Lana School of Public Health of the University of Toronto, ON, Canada
  8. 8Department of Public Health, Erasmus MC-University Medical Centre Rotterdam, Rotterdam, Netherlands
  9. 9Department of Medical Statistics, Leiden University Medical Centre, Leiden, Netherlands
  10. 10Division of Endovascular Neurosurgery, Department of Neurosurgery, University of Oxford, Oxford, UK
  11. 11Department of Neurosurgery, University Hospital Göttingen, Germany
  12. 12Department of Neurosurgery, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg Theodor-Kutzer-Ufer 1-3, Germany
  13. 13Department of Neurosurgery, University of Iowa Carver College of Medicine, Iowa City, IA, USA
  14. 14Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
  15. 15Department of Neurosurgery, Kurashiki Central Hospital, Kurashiki-city, Okayama, Japan
  16. 16Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA
  17. 17Department of Clinical Neurosciences, Hôpitaux, Universitaire de Genève, Geneva, Switzerland
  18. 18Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21287, USA
  19. 19Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, 8091 Zürich, Switzerland
  20. 20Brain Centre Rudolf Magnus, Department of Neurology and Neurosurgery, room G03-228, University Medical Centre Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands
  21. 21Department of Anesthesia, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA
  22. 22The Brain and Spine Center, Lankenau Medical Center, Wynnewood, PA, USA
  23. 23Division of Neurosurgery, Department of Clinical Neurosciences, Addenbrooke’s Hospital, University of Cambridge, Cambridge CB2 0QQ, UK
  24. 24Department of Critical Care, University Medical Centre Groningen, University of Groningen, Groningen, Netherlands
  25. 25Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK
  26. 26Dell School of Medicine, University of Texas, Austin, TX, USA
  27. 27Division of Critical Care Neurology, Columbia University College of Physicians and Surgeons, New York, USA
  1. Correspondence to: R Loch Macdonald, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Biomedical Research Centre of the Li Ka Shing Knowledge Institute of St Michael’s Hospital, Department of Surgery, University of Toronto, 30 Bond Street, Toronto, ON, Canada, M5B 1W8 macdonaldlo{at}smh.ca
  • Accepted 24 November 2017

Abstract

Objective To develop and validate a set of practical prediction tools that reliably estimate the outcome of subarachnoid haemorrhage from ruptured intracranial aneurysms (SAH).

Design Cohort study with logistic regression analysis to combine predictors and treatment modality.

Setting Subarachnoid Haemorrhage International Trialists’ (SAHIT) data repository, including randomised clinical trials, prospective observational studies, and hospital registries.

Participants Researchers collaborated to pool datasets of prospective observational studies, hospital registries, and randomised clinical trials of SAH from multiple geographical regions to develop and validate clinical prediction models.

Main outcome measure Predicted risk of mortality or functional outcome at three months according to score on the Glasgow outcome scale.

Results Clinical prediction models were developed with individual patient data from 10 936 patients and validated with data from 3355 patients after development of the model. In the validation cohort, a core model including patient age, premorbid hypertension, and neurological grade on admission to predict risk of functional outcome had good discrimination, with an area under the receiver operator characteristics curve (AUC) of 0.80 (95% confidence interval 0.78 to 0.82). When the core model was extended to a “neuroimaging model,” with inclusion of clot volume, aneurysm size, and location, the AUC improved to 0.81 (0.79 to 0.84). A full model that extended the neuroimaging model by including treatment modality had AUC of 0.81 (0.79 to 0.83). Discrimination was lower for a similar set of models to predict risk of mortality (AUC for full model 0.76, 0.69 to 0.82). All models showed satisfactory calibration in the validation cohort.

Conclusion The prediction models reliably estimate the outcome of patients who were managed in various settings for ruptured intracranial aneurysms that caused subarachnoid haemorrhage. The predictor items are readily derived at hospital admission. The web based SAHIT prognostic calculator (http://sahitscore.com) and the related app could be adjunctive tools to support management of patients.

Footnotes

  • Contributors: RLM initiated the SAHIT Collaboration, monitored data collection for the study, supervised the study, and revised and approved the final version of the manuscript. He is guarantor. BNRJ cleaned and merged the datasets, co-designed the analysis plan, performed the statistical analysis, and drafted and revised the paper. HFL and EWS co-designed the analysis plan, contributed statistical analysis codes, and revised the draft paper. The other authors and all members of the SAHIT collaboration designed the study, contributed data, and revised the draft paper.

  • Funding: This work was supported by a grant from the Canadian Institutes for Health Research, Personnel Award from the Heart and Stroke Foundation of Canada, an early researcher award from the Ontario Ministry of Research and Innovation, and a special overseas scholarship to BNRJ from the Rivers State Government of Nigeria.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; RLM receives grant support from the Physicians Services Incorporated Foundation, Brain Aneurysm Foundation, Canadian Institutes for Health Research, and the Heart and Stroke Foundation of Canada and is chief scientific officer of Edge Therapeutics; GS is supported by the distinguished clinician scientist award from Heart and Stroke Foundation of Canada (HSFC); SM is a consultant to Actelion Pharmaceuticals; PLeR is a member of the scientific advisory board of Edge Therapeutics and Cerebrotech and provides regular consultation for Integra LifeSciences, Depuy-Synthes, Codman, and Neurologica; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: The study was approved by the research ethics board of the St Michael’s Hospital, Toronto, Canada.

  • Data sharing: Patient level data and statistical codes are available from the corresponding author. Participants consent was not obtained and the study involved de-identified data; hence, the risk of patient identification is low.

  • Transparency: The lead author (RLM) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

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