Derivation and Initial Validation of Clinical Phenotypes of Children Presenting with Concussion Acutely in the Emergency Department: Latent Class Analysis of a Multi-Center, Prospective Cohort, Observational Study
Abstract
The identification of clinical phenotypes may help parse the substantial heterogeneity that characterizes children with concussion. This study used latent class analysis (LCA) to identify discernible phenotypes among children with acute concussion and examine the association between phenotypes and persistent post-concussive symptoms (PPCS) at 4 and 12 weeks post-injury. We conducted LCA of variables representing pre-injury history, clinical presentation, and parent symptom ratings, derived from a prospective cohort, observational study that recruited participants from August 2013 until June 2015 at nine pediatric emergency departments within the Pediatric Emergency Research Canada network. This substudy included 2323 children from the original cohort ages 8.00–17.99 years who had data for at least 80% of all variables included in each LCA. Concussion was defined according to Zurich consensus statement diagnostic criteria. The primary outcome was PPCS at 4 and 12 weeks after enrollment. Participants were 39.5% female and had a mean age of 12.8 years (standard deviation = 2.6). Follow-up was completed by 1980 (85%) at 4 weeks and 1744 (75%) at 12 weeks. LCA identified four groups with discrete pre-injury histories, four groups with discrete clinical presentations, and seven groups with discrete profiles of acute symptoms. Clinical phenotypes based on the profile of group membership across the three LCAs varied significantly in their predicted probability of PPCS at 4 and 12 weeks. The results indicate that children with concussion can be grouped into distinct clinical phenotypes, based on pre-injury history, clinical presentation, and acute symptoms, with markedly different risks of PPCS. With further validation, clinical phenotypes may provide a useful heuristic for clinical assessment and management.
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Copyright 2019, Mary Ann Liebert, Inc., publishers.
History
Published in print: June 2019
Published online: 22 May 2019
Published ahead of print: 6 March 2019
Published ahead of production: 8 January 2019
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Author Disclosure Statement
Dr. Stephen Freedman is supported by the Alberta Children's Hospital Foundation Professorship in Child Health and Wellness. Dr. Gioia is the author of the PCSI, a tool used in this manuscript; the PCSI is freely available, and he receives no financial benefit for its use. Dr. Meehan receives royalties from ABC-Clio publishing for the sale of the book: Kids, Sports, and Concussion: A Guide for Coaches and Parents and royalties from Wolters-Kluwer as an author for UpToDate®. Dr. Meehan is under contract with ABC-Clio publishing for a future book entitled: Concussions, and with Springer International publishing for a future book entitled: Head and Neck Injuries in Young Athletes. Dr. Meehan's research is also funded, in part, by a grant from the National Football League Players Association and by philanthropic support from the National Hockey League Alumni Association through the Corey C. Griffin Pro-Am Tournament. Dr. Brooks is funded by the CIHR Embedded Clinician Research program and receives royalties for the sales of the Pediatric Forensic Neuropsychology textbook (Oxford University Press, 2012) and three pediatric neuropsychological tests (Child and Adolescent Memory Profile [ChAMP; Sherman and Brooks, 2015, PAR Inc.], Memory Validity Profile [MVP; Sherman and Brooks, 2015, PAR Inc.], and Multidimensional Everyday Memory Ratings for Youth [MEMRY; Sherman and Brooks, 2017, PAR Inc.]). He has received in-kind support (free test credits) from the publisher of a computerized cognitive test (CNS Vital Signs, Chapel Hill, NC). Dr. Yeates is supported by the University of Calgary Robert and Irene Ward Chair in Pediatric Brain Injury, funded by the Alberta Children's Hospital Foundation. Dr. Zemek is supported by the University of Ottawa Brain and Mind Research Institute Clinical Research Chair in Pediatric Concussion. The other authors report no competing financial interests.
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