{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T15:54:59Z","timestamp":1772553299976,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T00:00:00Z","timestamp":1746835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"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 Open"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>The Seizure Termination Project developed expert consensus recommendations for outpatient management of seizure clusters and prolonged seizures to prevent progression to a higher\u2010level emergency. The consensus recommendations described therapeutic scenarios for seizure clusters (acute cluster treatment [ACT]) to prevent further seizures in a cluster and treatment to stop ongoing seizures that were expected to be prolonged (rapid and early seizure termination [REST]). Here, we review ACT and REST as categories and explore their practical application by examining patient\u2010level data for diazepam nasal spray. ACT and REST criteria were examined using data from the long\u2010term safety study that evaluated diazepam nasal spray for seizure clusters. To explore the effectiveness and duration of treatment for ACT, the proportion of seizure clusters for which second doses were administered within 24\u2009h was used as a proxy. REST was investigated using the time from administration to seizure cluster termination; timing for the termination of prolonged seizures (5\u201315\u2009min for the purposes of this analysis) in clusters also was examined. In the long\u2010term safety study of diazepam nasal spray, a single dose demonstrated effectiveness at terminating a substantial majority of seizure clusters (3368\/3853 [87.4%]) across 24\u2009h, demonstrating its use as ACT. The majority of seizure clusters (2169\/3225 [67.3%]) were recognized and treated quickly, within 5\u2009min from onset, demonstrating its utility as REST. Notably, effectiveness was maintained in seizures treated after they had become prolonged. These findings from the large dataset of the long\u2010term safety study of diazepam nasal spray demonstrate that it is of benefit in immediate use for both termination of an acute seizure and prolonged seizures within seizure clusters, thus supporting the recent expert consensus recommendations. Early use of a single rescue treatment can meet the need for ACT and REST, simplifying patient care.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>\n                      An expert group defined 2 groups of seizure medicines for patients and caregivers to use. \u201cACT\u201d medicines are for\n                      <jats:italic>acute cluster treatment<\/jats:italic>\n                      to prevent more seizures in a cluster. \u201cREST\u201d medicines for\n                      <jats:italic>rapid and early seizure treatment<\/jats:italic>\n                      stop prolonged seizures. Diazepam nasal spray for seizure clusters was looked at to see if it could fit in both categories. Study data showed that for most seizure clusters only 1 dose of diazepam nasal spray was used over 24\u2009h (fitting ACT), and seizures were treated and ended quickly (fitting REST). One medicine for REST and ACT may make treatment simpler.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70054","type":"journal-article","created":{"date-parts":[[2025,5,10]],"date-time":"2025-05-10T11:54:28Z","timestamp":1746878068000},"page":"999-1008","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring proposed recommendations for immediate\u2010use seizure medication: Treating both cluster and prolonged seizures with diazepam nasal spray"],"prefix":"10.1002","volume":"10","author":[{"given":"Michael","family":"Chez","sequence":"first","affiliation":[{"name":"Sutter Neuroscience Institute  Sacramento California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pavel","family":"Klein","sequence":"additional","affiliation":[{"name":"Mid\u2010Atlantic Epilepsy and Sleep Center  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-8055","authenticated-orcid":false,"given":"Danielle","family":"Becker","sequence":"additional","affiliation":[{"name":"Department of Neurology Ohio State University Wexner Medical Center  Columbus Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurriaan M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Neurology Harvard Medical School and Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Carrazana","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"},{"name":"John A. Burns School of Medicine, University of Hawaii  Honolulu Hawaii USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian L.","family":"Rabinowicz","sequence":"additional","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"},{"name":"Center for Molecular Biology and Biotechnology (CMBB) in the Charles E. Schmidt College of Science at Florida Atlantic University  Boca Raton Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,10]]},"reference":[{"key":"e_1_2_13_2_1","volume-title":"VALTOCO\u00ae (diazepam nasal spray). Full prescribing information","author":"Neurelis, Inc","year":"2025"},{"key":"e_1_2_13_3_1","volume-title":"Nayzilam\u00ae (midazolam nasal spray). Full prescribing information","author":"UCB, Inc","year":"2023"},{"key":"e_1_2_13_4_1","volume-title":"Diastat\u00ae C\u2010IV (diazepam rectal gel). Full prescribing information","author":"Bausch Health US, LLC","year":"2023"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107836"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000177"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13121"},{"issue":"1","key":"e_1_2_13_8_1","first-page":"S6","article-title":"Recognizing seizure clusters in the community: the path to uniformity and individualization in nomenclature and definition","volume":"63","author":"Haut SR","year":"2022","journal-title":"Epilepsia"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2024.109987"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16847"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-023-00568-4"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.5698\/1535-7597-16.1.48"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/epd2.20243"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.021"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17041"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17911"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2022.04.011"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2022.108811"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.108013"},{"key":"e_1_2_13_20_1","unstructured":"TarquinioD DlugosD WhelessJW DesaiJ BoroA CarrazanaE et\u00a0al.Safety of Valtoco\u00ae (diazepam nasal spray) in children and adolescents with epilepsy: final subgroup results from a phase 3 long\u2010term open\u2010label repeat\u2010dose safety study [poster #236]. Presented at: 50th Annual Child Neurology Congress; September 29\u2013October 2 2021; Boston MA."},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17177"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17249"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2024.100644"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S376104"},{"issue":"1","key":"e_1_2_13_25_1","first-page":"S34","article-title":"Rescue therapies for seizure clusters: pharmacology and target of treatments","volume":"63","author":"Gidal B","year":"2022","journal-title":"Epilepsia"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40120-023-00515-3"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16704"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)66909-7"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16449"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.15159"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1982.tb06198.x"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.123"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebr.2023.100612"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.14069"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16506"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.51.5.1274"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199806253382602"}],"container-title":["Epilepsia Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/epi4.70054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T15:44:27Z","timestamp":1767109467000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/epi4.70054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,10]]},"references-count":36,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/epi4.70054"],"URL":"https:\/\/doi.org\/10.1002\/epi4.70054","archive":["Portico"],"relation":{},"ISSN":["2470-9239","2470-9239"],"issn-type":[{"value":"2470-9239","type":"print"},{"value":"2470-9239","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,10]]},"assertion":[{"value":"2024-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}