{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:48:01Z","timestamp":1794008881414,"version":"4.8.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T00:00:00Z","timestamp":1732752000000},"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"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Benzodiazepine rescue medications are established as therapy for acute termination of seizure clusters. A post\u2010hoc analysis of a clinical trial of seizure cluster treatment with diazepam nasal spray found a potential longer\u2010term impact over a year of treatment. In this retrospective analysis, we tested the hypothesis that benzodiazepine\u2010treated seizure clusters are associated with prolonged time to the next seizure cluster compared with untreated seizure clusters in a patient\u2010reported real\u2010world database.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed data on self\u2010reported seizures and benzodiazepine rescue medication administration in the Seizure Tracker\u2122 database between 2007 and 2022. Kaplan\u2013Meier analysis was used to compare treated vs untreated seizure clusters with respect to time to start of the next seizure cluster or immediate\u2010use medication administration. Mixed\u2010effects analysis was used to compare the number of seizures per cluster for treated and untreated seizure clusters. Robustness of findings was evaluated across three operational seizure\u2010cluster definitions: \u22652 seizures in 4\u2009hours as primary analysis and in 6 and 24\u2009hours as sensitivity analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 10\u2009889 benzodiazepine immediate\u2010use medication administrations (<jats:italic>n<\/jats:italic>\u2009=\u2009220 patients) met inclusion criteria. Benzodiazepine rescue administrations were followed by longer time to the next seizure cluster or rescue administration, compared with untreated seizure clusters, corresponding to a median of 4.9 days following treated seizure clusters and a median of 0.8 days following untreated seizure clusters. This prolongation was driven by a minority of patients (accounting for 45.9% of seizure clusters in the sample) and patients were more likely to be women. The number of seizures per cluster was lower when treatment was administered earlier in the seizure cluster.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>These retrospective real\u2010world data suggest that the effect of benzodiazepines on termination of seizure clusters may be more pronounced when administration occurs earlier after onset, and support a hypothesis of a possible longer\u2010term effect of benzodiazepines beyond immediate\u2010use acute seizure termination.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.18195","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T15:20:01Z","timestamp":1732807201000},"page":"369-378","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Benzodiazepine rescue medication administration for seizure clusters: Real\u2010world retrospective outcomes"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4548-4550","authenticated-orcid":false,"given":"Sharon","family":"Chiang","sequence":"first","affiliation":[{"name":"Department of Neurology and Weill Institute for Neurosciences University of California  San Francisco California USA"},{"name":"Departments of Physiology and Psychiatry and the Kavli Institute for Fundamental Neuroscience University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-5681","authenticated-orcid":false,"given":"Robert","family":"Moss","sequence":"additional","affiliation":[{"name":"Seizure Tracker LLC  Annandale Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7624-8825","authenticated-orcid":false,"given":"Sunita N.","family":"Misra","sequence":"additional","affiliation":[{"name":"SK Life Science, Inc.  Paramus New Jersey 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, Inc.  San Diego California USA"},{"name":"John A. Burns School of Medicine University of Hawaii  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, Inc.  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":[[2024,11,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000053748.83309.28"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0013\u20109580.2005.29004.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2020.106330"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528\u20101157.2002.26401.x"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17461"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/nrl.0000000000000140"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17346"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2005.08.018"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/wco.0000000000000177"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2013.02.018"},{"key":"e_1_2_12_13_1","unstructured":"Diazepam rectal gel [package insert]. Bausch Health US;2023.https:\/\/www.bauschhealth.com\/Portals\/25\/Pdf\/PI\/Diastat\u2010PI.pdf"},{"key":"e_1_2_12_14_1","unstructured":"VALTOCO\u00ae. (diazepam) nasal spray [package insert]. Neurelis Inc.2023.https:\/\/www.valtoco.com\/sites\/default\/files\/Prescribing_Information.pdf"},{"key":"e_1_2_12_15_1","unstructured":"Nayzilam\u00ae (midazolam) nasal spray [package insert]. UCB Inc.2023.https:\/\/www.ucb\u2010usa.com\/nayzilam\u2010prescribing\u2010information.pdf"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17385"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17341"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.5370"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.021"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535759720987546"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010022\u201000664\u20103"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18195","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T16:35:20Z","timestamp":1739550920000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.18195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,28]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1111\/epi.18195"],"URL":"https:\/\/doi.org\/10.1111\/epi.18195","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,28]]},"assertion":[{"value":"2024-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}