{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:30:00Z","timestamp":1787131800721,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100024157","name":"Neurelis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100024157","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We assessed the timing, dosing, and effectiveness of diazepam nasal spray in a large dataset of seizures treated in the out\u2010of\u2010hospital setting, using as reference the International League Against Epilepsy criteria for tonic\u2013clonic status epilepticus (SE) and its treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed pooled data from two studies evaluating the use of diazepam nasal spray as acute treatment for seizures in the out\u2010of\u2010hospital setting, a phase 1\/2a pharmacokinetics and safety study (patients aged 2\u20135\u2009years) and a phase 3 long\u2010term safety study (patients aged 6\u201365\u2009years). For this analysis, tonic\u2013clonic SE episodes were defined as seizures lasting beyond time point\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>1<\/jats:sub>\n                      (5\u2009min). Responder analyses examined SE termination by time point\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>2<\/jats:sub>\n                      (30\u2009min after seizure start) and SE termination \u226420\u2009min after dose administration. SE recurrence at \u22641, 12, and 24\u2009h after SE termination was also assessed. Rate of SE episodes for which \u22652 doses of diazepam nasal spray were administered was a proxy for effectiveness. We also reported safety data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of episodes with sufficient data for classification, a total of 402 episodes were categorized as tonic\u2013clonic SE. The majority of tonic\u2013clonic SE episodes terminated by\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>2<\/jats:sub>\n                      (248 [61.7%]) and nearly half terminated within 20\u2009min after dose administration (200 [49.8%]). SE recurrence after SE termination was low, with &lt;5% of tonic\u2013clonic SE episodes followed by a recurrence in \u226424\u2009h. Rate of usage of \u22652 doses for tonic\u2013clonic SE episodes was low (5% [20 seizure episodes]). Serious treatment\u2010emergent events of SE occurred in 6.6% of patients with tonic\u2013clonic SE episodes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These findings support the safety and effectiveness of diazepam nasal spray for treating episodes of tonic\u2013clonic SE and strengthen the evidence of the benefits of immediate\u2010use antiseizure medication for seizure emergencies, including early SE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70423","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:22:49Z","timestamp":1787131369000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Outcomes of out\u2010of\u2010hospital treatment of impending tonic\u2013clonic status epilepticus with diazepam nasal spray: A retrospective combined cohort analysis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3549-1642","authenticated-orcid":false,"given":"John M.","family":"Stern","sequence":"first","affiliation":[{"name":"Department of Neurology, Geffen School of Medicine University of California, Los Angeles  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8184-1367","authenticated-orcid":false,"given":"Leock Y.","family":"Ngo","sequence":"additional","affiliation":[{"name":"Neurelis  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9986-6394","authenticated-orcid":false,"given":"Eric B.","family":"Segal","sequence":"additional","affiliation":[{"name":"Northeast Regional Epilepsy Group and Hackensack University Medical Center  Hackensack New Jersey USA"},{"name":"Departments of Pediatrics and Neurology Hackensack Meridian School of Medicine  Nutley New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-8055","authenticated-orcid":false,"given":"Danielle A.","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Neurology Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9373-0579","authenticated-orcid":false,"given":"Randa G.","family":"Jarrar","sequence":"additional","affiliation":[{"name":"Department of Neurology Phoenix Children's Hospital  Phoenix Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-2732","authenticated-orcid":false,"given":"Tracy A.","family":"Glauser","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Center Cincinnati Children's Hospital  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6725-2814","authenticated-orcid":false,"given":"Jurriaan M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Division of Epilepsy and Clinical Neurophysiology Boston Children's Hospital and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8703-223X","authenticated-orcid":false,"given":"Emilio","family":"Perucca","sequence":"additional","affiliation":[{"name":"Department of Medicine (Austin Health) University of Melbourne  Melbourne Victoria Australia"},{"name":"Department of Neuroscience Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8455-0231","authenticated-orcid":false,"given":"Evelyn K.","family":"Shih","sequence":"additional","affiliation":[{"name":"Formerly of Neurelis  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8788-0722","authenticated-orcid":false,"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis  San Diego California USA"},{"name":"University of Hawaii John A. Burns School of Medicine  Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1299-0606","authenticated-orcid":false,"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis  San Diego California USA"},{"name":"Center for Molecular Biology and Biotechnology, Charles E. Schmidt College of Science Florida Atlantic University  Boca Raton Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17492"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13121"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2020.100409"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535\u20107597\u201016.1.48"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2024.109987"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2008.02.002"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107836"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000177"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(24)00430\u20107"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1018"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2024.104306"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263\u2010022\u201000940\u20102"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010022\u201000664\u20103"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18216"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2023.07.022"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S481758"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120\u2010023\u201000568\u20104"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17041"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18473"},{"key":"e_1_2_14_21_1","volume-title":"VALTOCO\u00ae (diazepam nasal spray)","author":"Neurelis, Inc","year":"2025"},{"key":"e_1_2_14_22_1","volume-title":"Diastat\u00ae C\u2010IV (diazepam rectal gel)","author":"Bausch Health US, LLC","year":"2023"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738231185424"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa002141"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.021"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18227"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16825"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12028\u2010012\u20109695\u2010z"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurot.2024.e00514"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108390"},{"key":"e_1_2_14_31_1","unstructured":"Pina\u2010GarzaJE GlauserT SegalEB WhelessJW JarrarR PetersJM et\u00a0al.Prehospital treatment of impending status epilepticus with diazepam nasal spray. Presented at: American Epilepsy Society annual meeting December 5\u20139 2025; Atlanta GA."}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70423","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/epi.70423","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi.70423","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:22:51Z","timestamp":1787131371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi.70423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":30,"alternative-id":["10.1002\/epi.70423"],"URL":"https:\/\/doi.org\/10.1002\/epi.70423","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"epi.70423"}}