{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:14:46Z","timestamp":1790374486799,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T00:00:00Z","timestamp":1398124800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate whether vagus nerve stimulation (VNS) as adjunct to best medical practice (VNS\u00a0+\u00a0BMP) is superior to BMP\u00a0alone in improving long\u2010term health\u2010related quality of life (HRQoL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      PuLsE (Open\n                      <jats:styled-content>P<\/jats:styled-content>\n                      rospective Randomized\n                      <jats:styled-content>L<\/jats:styled-content>\n                      ong\u2010term\n                      <jats:styled-content>E<\/jats:styled-content>\n                      ffectiveness) was a prospective, randomized, parallel\u2010group, open\u2010label, and long\u2010term effectiveness study (conducted at 28\u00a0sites in Europe and Canada). Adults with pharmacoresistant focal seizures (n\u00a0=\u00a0112) received VNS\u00a0+\u00a0BMP or BMP (1:1 ratio). Medications and VNS parameters could be adjusted as clinically indicated for optimal seizure control while minimizing adverse effects. Primary endpoint was mean change from baseline HRQoL (using Quality of Life in Epilepsy Inventory\u201089 total score; QOLIE\u201089). Secondary endpoints included changes in seizure frequency, responder rate (\u226550% decrease in seizure frequency), Centre for Epidemiologic Studies Depression scale (CES\u2010D), Neurological Disorders Depression Inventory\u2010Epilepsy scale (NDDI\u2010E), Clinical Global Impression\u2010Improvement scale (CGI\u2010I), Adverse Event Profile\u00a0(AEP), and antiepileptic drug\u00a0(AED) load. The study was prematurely terminated due to recruitment difficulties prior to completing the planned enrollment of n\u00a0=\u00a0362. Results for n\u00a0=\u00a096 who had baseline and at least one follow\u2010up QOLIE\u201089 assessment (from months\u00a03\u201012) were included in this analysis. Mixed model repeated measures (MMRM) analysis of variance was performed on change from baseline for the primary and secondary endpoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Significant between\u2010group differences in favor of VNS\u00a0+\u00a0BMP were observed regarding improvement in HRQoL, seizure frequency, and CGI\u2010I score (respective p\u2010values\u00a0&lt;\u00a00.05, 0.03, and 0.01). More patients in the VNS\u00a0+\u00a0BMP group (43%) reported adverse events\u00a0(AEs) versus BMP group (21%) (p\u00a0=\u00a00.01), a difference reflecting primarily mostly transient AEs related to VNS implantation or stimulation. No significant difference between treatment groups was observed for changes in CES\u2010D, NDDI\u2010E, AEP, and AED load.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>VNS therapy as a treatment adjunct to BMP in patients with pharmacoresistant focal seizures was associated with a significant improvement in HRQoL compared with BMP alone.<\/jats:p>\n                    <jats:p>\n                      A PowerPoint slide summarizing this article is available for download in the Supporting Information section\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.12611\/supinfo\">here<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.12611","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T11:34:55Z","timestamp":1398166495000},"page":"893-900","source":"Crossref","is-referenced-by-count":176,"title":["The long\u2010term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long\u2010term Effectiveness) trial"],"prefix":"10.1111","volume":"55","author":[{"given":"Philippe","family":"Ryvlin","sequence":"first","affiliation":[{"name":"TIGER CRNL INSERM U1028 CNRS 5292 and Hospices Civils de Lyon and Claude Bernard Lyon\u20101 University Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank G.","family":"Gilliam","sequence":"additional","affiliation":[{"name":"The Pennsylvania State University Hershey Pennsylvania U.S.A"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dang K.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Neurology University Hospital Center of Montr\u00e9al (Notre\u2010Dame Hospital) Montr\u00e9al Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Colicchio","sequence":"additional","affiliation":[{"name":"Institute of Neurosurgery Catholic University of the Sacred Heart Roma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Iudice","sequence":"additional","affiliation":[{"name":"Neurological Clinic University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Tinuper","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences RCCS Institute of Neurological Sciences University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelia","family":"Zamponi","sequence":"additional","affiliation":[{"name":"Pediatric Neuropsychiatry University Hospital Center Ancona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Aguglia","sequence":"additional","affiliation":[{"name":"Regional Epilepsy Center Italy Magna Graecia University of Catanzaro United Hospitals of Reggio Calabria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Wagner","sequence":"additional","affiliation":[{"name":"Kempenhaeghe Neurology Department Oosterhout The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorella","family":"Minotti","sequence":"additional","affiliation":[{"name":"Neurology Department CHU Grenoble Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Stefan","sequence":"additional","affiliation":[{"name":"ZEE Center for Epilepsy University Clinic of Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Neurology UZ Gent Gent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Sadler","sequence":"additional","affiliation":[{"name":"QEII Health Sciences Centre Dalhousie University Halifax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Benna","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Epilepsy Center University of Torino Torino Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradheep","family":"Raman","sequence":"additional","affiliation":[{"name":"Cyberonics Inc. 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