{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:52:31Z","timestamp":1789707151213,"version":"4.0.1"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Intermittent rescue therapy may be used for seizure clusters, which are clinical emergencies that may persist \u226524\u2009h and increase risk of status epilepticus, emergency room visits, and reduced quality of life for patients with epilepsy. Beyond effectiveness for aborting seizure clusters, no data exist on how intermittent rescue therapy may impact the long\u2010term natural course of seizure clusters. This novel analysis explores SEIzure interVAL (SEIVAL; time between seizure clusters) in patients from a long\u2010term safety study of diazepam nasal spray (Valtoco) to assess SEIVAL changes with intermittent rescue therapy across time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients were aged 6\u201365\u2009years. Age\u2010 and weight\u2010based doses of diazepam nasal spray were administered during a 12\u2010month treatment period with an optional follow\u2010up period. SEIVAL was evaluated in patients receiving two or more doses of diazepam nasal spray using 90\u2010day periods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 163 treated patients, 151 had one or more SEIVALs. One hundred twenty had SEIVALs in Period 1 and one or more other periods. An increase in SEIVAL was noted from Period 1 compared with all subsequent periods (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u2009.001). A consistent cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a076) had one or more SEIVALs in each of Periods 1\u20134 (360\u2009days); mean SEIVALs increased significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.01) from 12.2\u2009days (Period 1) to 25.7\u2009days (Period 4). Similar SEIVAL patterns occurred when repeat doses within a seizure cluster were eliminated and irrespective of age group, treatment duration, and change to concomitant medications. In adults, Quality of Life in Epilepsy scores were maintained with increased SEIVALs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Across 12\u2009months, increases in SEIVAL were demonstrated in patients using diazepam nasal spray for seizure cluster treatment in a phase 3 safety study. Increased time between seizure clusters may reflect a previously unrecognized beneficial effect of intermittent rescue therapy. These results generate a range of biological and behavioral hypotheses and warrant exploration of the impact of intermittent rescue therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.17385","type":"journal-article","created":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T21:54:40Z","timestamp":1659736480000},"page":"2684-2693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Significant improvements in\n                    <scp>SEIzure interVAL<\/scp>\n                    (time between seizure clusters) across time in patients treated with diazepam nasal spray as intermittent rescue therapy for seizure clusters"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7624-8825","authenticated-orcid":false,"given":"Sunita N.","family":"Misra","sequence":"first","affiliation":[{"name":"Neurelis, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0708-6006","authenticated-orcid":false,"given":"Michael R.","family":"Sperling","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6389-2638","authenticated-orcid":false,"given":"Vikram R.","family":"Rao","sequence":"additional","affiliation":[{"name":"University of California, San Francisco  San Francisco California 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":"Boston Children's Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Davis","sequence":"additional","affiliation":[{"name":"CSD Biostatistics  Oro Valley Arizona 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"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2015.04.022"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000180685.84547.7f"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-021-00827-8"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13375"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17177"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17041"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2020.107713"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13465"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.05.013"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000177"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/NRL.0000000000000140"},{"key":"e_1_2_13_13_1","unstructured":"NAYZILAM\u00ae (midazolam nasal spray). Full prescribing information. Smyrna GA: UCB; 2021."},{"key":"e_1_2_13_14_1","unstructured":"Valtoco (diazepam nasal spray). Full Prescribing Information. San Diego CA: Neurelis; 2022."},{"key":"e_1_2_13_15_1","unstructured":"US Food and Drug Administration.Clinical superiority findings[cited 2020 Jun 23]. Available from:https:\/\/www.fda.gov\/industry\/designating\u2010orphan\u2010product\u2010drugs\u2010and\u2010biological\u2010products\/clinical\u2010superiority\u2010findings"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2021.107983"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-5050(03)00004-0"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1998.tb01278.x"},{"key":"e_1_2_13_19_1","unstructured":"MisraSN FaughtE DavisC CarrazanaE RabinowiczAL.Results for the Quality of Life in Epilepsy Scale from a long\u2010term safety study of diazepam nasal spray for seizure clusters. 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