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A prehospital evidence-based guideline recommends using intranasal or intramuscular midazolam as first-line treatment for pediatric seizures. Despite attempts to implement these guidelines, one-third of children having a paramedic-witnessed seizure have ongoing seizures on emergency department (ED) arrival; this may be due to inadequate or delayed midazolam dosing. Replacing the error-prone, sequential calculations with age-based midazolam dosing may be simpler, faster, and more effective without compromising safety. The objective of this manuscript is to describe the methodology of the Pediatric Dose Optimization for Seizures in EMS (PediDOSE) study, a clinical trial designed to compare the effectiveness and safety of an EMS protocol with four age-based categories for midazolam dosing relative to the current weight-based dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We are conducting a large EMS-based stepped wedge trial in the Pediatric Emergency Care Applied Research Network (PECARN) by implementing midazolam dosing based on four age categories in seizure protocols in EMS systems in 20 cities. We believe that this implementation will stop more seizures before ED arrival without increasing respiratory failure rates. The primary aim of this study is to compare the effectiveness of age-based EMS midazolam dosing compared to the current weight-based dosing on seizure cessation upon ED arrival. The secondary aim is to determine the frequency of respiratory failure in children after the implementation of EMS midazolam dosing based on these age categories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>If this study demonstrates that an EMS patient care protocol with age-based midazolam dosing is safe and more effective than current practice, the potential impact of this study is a paradigm shift in the treatment of pediatric seizures that can be easily implemented in EMS systems across the country. Beyond seizures, the concept of age-based dosing may also be applicable to other commonly encountered pediatric prehospital conditions for which medication may be indicated.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-025-09342-3","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T01:54:44Z","timestamp":1765590884000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Methodology for the Pediatric Dose Optimization for Seizures in Emergency Medical Services (PediDOSE) study"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-8747","authenticated-orcid":false,"given":"Manish I.","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Adelgais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Chamberlain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry E.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey A.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Riviello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana R.","family":"Said","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimia F.","family":"Ghaffari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn M.","family":"Kothari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohsen","family":"Saidinejad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Lowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond L.","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine R.","family":"Counts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia R.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Studnek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy K.","family":"Glober","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb E.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Clemency","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Patrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel D.","family":"Munn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham M.","family":"Brant-Zawadzki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Martin-Gill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel K.","family":"Nishijima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neomi","family":"Sepulveda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"VanBuren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Pediatric Emergency Care Applied Research Network (PECARN) PediDOSE Study Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,13]]},"reference":[{"issue":"9","key":"9342_CR1","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1056\/NEJMoa002141","volume":"345","author":"BK Alldredge","year":"2001","unstructured":"Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich SK, et al. 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Morris receives funds from the following entities for the following reasons: UCSF-Benioff Children\u2019s Hospital Oakland for the invention of several patents that include nutritional supplements; from Emory University School of Medicine for the invention of patents\/patent applications for nutritional supplements and\/or medical foods for autism\/apraxia, coronaviruses, and pain; from Roche and CSL Behring for consultant fees; from TRILITY for service on the Scientific Advisory Board; from UpToDate for royalties as an editor for the sickle cell disease\u2013fever and sickle cell disease\u2013pain web-based references; and Food as Medicine Therapeutics, LLC, for her roles as the Founder and Executive Director. James J. Riviello\u2019s spouse receives funds from UpToDate for her role as a section editor. Henry E. Wang receives funds from the\n                      Journal of the American College of Emergency Physicians\n                      for his service as the editor in chief\n                      .\n                      The remainder of the authors (M. I. S., E. B. L., K. M. A., J. M. C., L. A. M., R. R. S., J. E. S., K. F. G., K. M. K., M. S., R. A. L., R. L. F., C. R. C., J. R. S., N. K. G., C. E. W., B. M. C., N. P., R. D. M., G. M. B. Z., C. M. G., D. K. N., K. L., N. S., J. M. V.) do not have any conflicts of interest to disclose. This information or content and conclusions are those of the authors and should not be construed as the official position or policy, nor should any endorsements be inferred by HRSA, HHS, or the US Government.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"53"}}