{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:05:25Z","timestamp":1786982725210,"version":"build-2736575974"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"},{"start":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T00:00:00Z","timestamp":1705363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"funder":[{"name":"Kyowa Kirin Co., Ltd., Tokyo, Japan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurol Ther"],"published-print":{"date-parts":[[2024,4]]},"DOI":"10.1007\/s40120-023-00574-6","type":"journal-article","created":{"date-parts":[[2024,1,16]],"date-time":"2024-01-16T07:02:32Z","timestamp":1705388552000},"page":"323-338","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of Istradefylline on Levodopa Dose Escalation in Parkinson\u2019s Disease: ISTRA ADJUST PD Study, a Multicenter, Open-Label, Randomized, Parallel-Group Controlled Study"],"prefix":"10.1007","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6808-0444","authenticated-orcid":false,"given":"Taku","family":"Hatano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renpei","family":"Sengoku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Nagayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotake","family":"Yanagisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Yoritaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Nishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Mukai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoichi","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihito","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morinobu","family":"Seki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miho Kawabe","family":"Matsukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroo","family":"Terashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuo","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Hirano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetomo","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideto","family":"Joki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Uchiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Shimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Ogaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiro","family":"Fukae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazushi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimasa","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Kaida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Ihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutomi","family":"Kanemaru","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"574_CR1","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1093\/brain\/awu195","volume":"137","author":"R Cilia","year":"2014","unstructured":"Cilia R, Akpalu A, Sarfo FS, et al. The modern pre-levodopa era of Parkinson\u2019s disease: insights into motor complications from sub-Saharan Africa. Brain. 2014;137:2731\u201342. https:\/\/doi.org\/10.1093\/brain\/awu195.","journal-title":"Brain"},{"key":"574_CR2","doi-asserted-by":"publisher","first-page":"44","DOI":"10.4103\/aian.AIAN_460_18","volume":"23","author":"RT Athulya","year":"2020","unstructured":"Athulya RT, Jayakrishnan S, Iype T, Rajan R, Alapatt PJ. Predictors of levo-dopa induced dyskinesias in Parkinson\u2019s disease. Ann Indian Acad Neurol. 2020;23:44\u20137. https:\/\/doi.org\/10.4103\/aian.AIAN_460_18.","journal-title":"Ann Indian Acad Neurol"},{"key":"574_CR3","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1016\/S1474-4422(21)00249-0","volume":"20","author":"O Rascol","year":"2021","unstructured":"Rascol O, Fabbri M, Poewe W. Amantadine in the treatment of Parkinson\u2019s disease and other movement disorders. Lancet Neurol. 2021;20:1048\u201356. https:\/\/doi.org\/10.1016\/S1474-4422(21)00249-0.","journal-title":"Lancet Neurol"},{"key":"574_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2021.120026","volume":"430","author":"Y Tsuboi","year":"2021","unstructured":"Tsuboi Y, Nakamura M, Maruyama H, Matsumoto Y. Zonisamide improves wearing off in Parkinson\u2019s disease without exacerbating dyskinesia: post hoc analysis of phase 2 and phase 3 clinical trials. J Neurol Sci. 2021;430: 120026. https:\/\/doi.org\/10.1016\/j.jns.2021.120026.","journal-title":"J Neurol Sci"},{"key":"574_CR5","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1124\/pharmrev.121.000445","volume":"74","author":"AP Ijzerman","year":"2022","unstructured":"Ijzerman AP, Jacobson KA, M\u00fcller CE, Cronstein BN, Cunha RA. International union of basic and clinical pharmacology. CXII: adenosine receptors: a further update. Pharmacol Rev. 2022;74:340\u201372. https:\/\/doi.org\/10.1124\/pharmrev.121.000445.","journal-title":"Pharmacol Rev."},{"issue":"Suppl 1","key":"574_CR6","doi-asserted-by":"publisher","first-page":"S28","DOI":"10.1016\/j.parkreldis.2020.09.022","volume":"80","author":"P Jenner","year":"2020","unstructured":"Jenner P, Mori A, Kanda T. Can adenosine A2A receptor antagonists be used to treat cognitive impairment, depression or excessive sleepiness in Parkinson\u2019s disease? Parkinsonism Relat Disord. 2020;80(Suppl 1):S28\u201336. https:\/\/doi.org\/10.1016\/j.parkreldis.2020.09.022.","journal-title":"Parkinsonism Relat Disord"},{"key":"574_CR7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/ene.14108","volume":"27","author":"R Balestrino","year":"2020","unstructured":"Balestrino R, Schapira AHV. Parkinson disease. Eur J Neurol. 2020;27:27\u201342. https:\/\/doi.org\/10.1111\/ene.14108.","journal-title":"Eur J Neurol"},{"key":"574_CR8","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.parkreldis.2008.12.006","volume":"15","author":"P Jenner","year":"2009","unstructured":"Jenner P, Mori A, Hauser R, Morelli M, Fredholm BB, Chen JF. Adenosine, adenosine A2A antagonists, and Parkinson\u2019s disease. Parkinsonism Relat Disord. 2009;15:406\u201313. https:\/\/doi.org\/10.1016\/j.parkreldis.2008.12.006.","journal-title":"Parkinsonism Relat Disord"},{"key":"574_CR9","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1212\/01.wnl.0000073136.00548.d4","volume":"61","author":"W Bara-Jimenez","year":"2003","unstructured":"Bara-Jimenez W, Sherzai A, Dimitrova T, et al. Adenosine A(2A) receptor antagonist treatment of Parkinson\u2019s disease. Neurology. 2003;61:293\u20136. https:\/\/doi.org\/10.1212\/01.wnl.0000073136.00548.d4.","journal-title":"Neurology"},{"key":"574_CR10","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1254\/jphs.13250fp","volume":"124","author":"S Uchida","year":"2014","unstructured":"Uchida S, Tashiro T, Kawai-Uchida M, Mori A, Jenner P, Kanda T. The adenosine A2A-receptor antagonist istradefylline enhances the motor response of L-DOPA without worsening dyskinesia in MPTP-treated common marmosets. J Pharmacol Sci. 2014;124:480\u20135. https:\/\/doi.org\/10.1254\/jphs.13250fp.","journal-title":"J Pharmacol Sci"},{"key":"574_CR11","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1097\/WNF.0000000000000249","volume":"40","author":"I Yabe","year":"2017","unstructured":"Yabe I, Kitagawa M, Takahashi I, Matsushima M, Sasaki H. The efficacy of istradefylline for treating mild wearing-off in Parkinson disease. Clin Neuropharmacol. 2017;40:261\u20133. https:\/\/doi.org\/10.1097\/WNF.0000000000000249.","journal-title":"Clin Neuropharmacol"},{"key":"574_CR12","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12883-022-02600-w","volume":"22","author":"T Hatano","year":"2022","unstructured":"Hatano T, Kano O, Sengoku R, et al. Evaluating the impact of adjunctive istradefylline on the cumulative dose of levodopa-containing medications in Parkinson\u2019s disease: study protocol for the ISTRA ADJUST PD randomized, controlled study. BMC Neurol. 2022;22:71. https:\/\/doi.org\/10.1186\/s12883-022-02600-w.","journal-title":"BMC Neurol"},{"key":"574_CR13","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","volume":"23","author":"CG Goetz","year":"2008","unstructured":"Goetz CG, Tilley BC, Shaftman SR, et al. Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23:2129\u201370. https:\/\/doi.org\/10.1002\/mds.22340.","journal-title":"Mov Disord"},{"key":"574_CR14","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/mds.22890","volume":"25","author":"RL Watts","year":"2010","unstructured":"Watts RL, Lyons KE, Pahwa R, et al. Onset of dyskinesia with adjunct ropinirole prolonged-release or additional levodopa in early Parkinson\u2019s disease. Mov Disord. 2010;25:858\u201366. https:\/\/doi.org\/10.1002\/mds.22890.","journal-title":"Mov Disord"},{"key":"574_CR15","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1016\/j.parkreldis.2015.10.006","volume":"21","author":"K Horv\u00e1th","year":"2015","unstructured":"Horv\u00e1th K, Aschermann Z, \u00c1cs P, et al. Minimal clinically important difference on the motor examination part of MDS-UPDRS. Parkinsonism Relat Disord. 2015;21:1421\u20136. https:\/\/doi.org\/10.1016\/j.parkreldis.2015.10.006.","journal-title":"Parkinsonism Relat Disord"},{"key":"574_CR16","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1185\/03007995.2015.1086994","volume":"31","author":"ZJ Li","year":"2015","unstructured":"Li ZJ, Wu Q, Yi CJ. Clinical efficacy of istradefylline versus rTMS on Parkinson\u2019s disease in a randomized clinical trial. Curr Med Res Opin. 2015;31:2055\u20138. https:\/\/doi.org\/10.1185\/03007995.2015.1086994.","journal-title":"Curr Med Res Opin"},{"key":"574_CR17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s12013-014-0162-7","volume":"71","author":"Y Tao","year":"2015","unstructured":"Tao Y, Liang G. Efficacy of adenosine A2A receptor antagonist istradefylline as augmentation for Parkinson\u2019s disease: a meta-analysis of randomized controlled trials. Cell Biochem Biophys. 2015;71:57\u201362. https:\/\/doi.org\/10.1007\/s12013-014-0162-7.","journal-title":"Cell Biochem Biophys"},{"key":"574_CR18","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1001\/jama.2021.10207","volume":"326","author":"MA Schwarzschild","year":"2021","unstructured":"Schwarzschild MA, Ascherio A, Casaceli C, et al. Effect of urate-elevating inosine on early Parkinson disease progression: the SURE-PD3 randomized clinical trial. JAMA. 2021;326:926\u201339. https:\/\/doi.org\/10.1001\/jama.2021.10207.","journal-title":"JAMA."},{"key":"574_CR19","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1001\/jamaneurol.2021.4736","volume":"79","author":"R Gray","year":"2022","unstructured":"Gray R, Patel S, Ives N, et al. Long-term effectiveness of adjuvant treatment with catechol-o-methyltransferase or monoamine oxidase B inhibitors compared with dopamine agonists among patients with Parkinson disease uncontrolled by levodopa therapy: the PD MED randomized clinical trial. JAMA Neurol. 2022;79:131\u201340. https:\/\/doi.org\/10.1001\/jamaneurol.2021.4736.","journal-title":"JAMA Neurol"},{"key":"574_CR20","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.jns.2018.11.005","volume":"396","author":"H Nagayama","year":"2019","unstructured":"Nagayama H, Kano O, Murakami H, et al. Effect of istradefylline on mood disorders in Parkinson\u2019s disease. J Neurol Sci. 2019;396:78\u201383. https:\/\/doi.org\/10.1016\/j.jns.2018.11.005.","journal-title":"J Neurol Sci"},{"key":"574_CR21","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.jns.2017.07.045","volume":"380","author":"K Suzuki","year":"2017","unstructured":"Suzuki K, Miyamoto M, Miyamoto T, et al. Istradefylline improves daytime sleepiness in patients with Parkinson\u2019s disease: an open-label, 3-month study. J Neurol Sci. 2017;380:230\u20133. https:\/\/doi.org\/10.1016\/j.jns.2017.07.045.","journal-title":"J Neurol Sci"},{"key":"574_CR22","doi-asserted-by":"publisher","first-page":"24","DOI":"10.4236\/apd.2016.52004","volume":"5","author":"K Abe","year":"2016","unstructured":"Abe K, Fujita M, Yoshikawa H. Effectiveness of istradefylline for fatigue and quality of life in Parkinson\u2019s disease patients\u2019 and of their caregivers\u2019. Adv Parkinson\u2019s Dis. 2016;5:24\u20138. https:\/\/doi.org\/10.4236\/apd.2016.52004.","journal-title":"Adv Parkinson\u2019s Dis"},{"key":"574_CR23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178896","volume":"12","author":"XJ Tu","year":"2017","unstructured":"Tu XJ, Hwang WJ, Ma HI, Chang LH, Hsu SP. Determinants of generic and specific health-related quality of life in patients with Parkinson\u2019s disease. PLoS ONE. 2017;12: e0178896. https:\/\/doi.org\/10.1371\/journal.pone.0178896.","journal-title":"PLoS ONE"},{"key":"574_CR24","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1080\/14656566.2019.1614167","volume":"20","author":"M Iijima","year":"2019","unstructured":"Iijima M, Orimo S, Terashi H, et al. Efficacy of istradefylline for gait disorders with freezing of gait in Parkinson\u2019s disease: a single-arm, open-label, prospective, multicenter study. Expert Opin Pharmacother. 2019;20:1405\u201311. https:\/\/doi.org\/10.1080\/14656566.2019.1614167.","journal-title":"Expert Opin Pharmacother"}],"container-title":["Neurology and Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-023-00574-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s40120-023-00574-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s40120-023-00574-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T11:24:41Z","timestamp":1710847481000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s40120-023-00574-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,16]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["574"],"URL":"https:\/\/doi.org\/10.1007\/s40120-023-00574-6","relation":{},"ISSN":["2193-8253","2193-6536"],"issn-type":[{"value":"2193-8253","type":"print"},{"value":"2193-6536","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,16]]},"assertion":[{"value":"17 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Taku Hatano reports receiving grants from the Setsuro Fujii Memorial, the Osaka Foundation for Promotion of Fundamental Medical Research, JSPS KAKENHI (under grant number 21K07424), Japan Agency for Medical Research and Development (grant number 20dm0107156, 21wm0425015, and 21dk0207055); speaker\u2019s honoraria from Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Novartis Pharma K.K., Sanofi K.K., Eisai Co. Ltd. and Otsuka Pharmaceutical Co., Ltd. during the conduct of the study. Taku Hatano also reports receiving grants and speaker\u2019s honoraria from Kyowa Kirin Co., Ltd. during the conduct of the study. Renpei Sengoku reports no relevant disclosures. Renpei Sengoku, Hiroshi Nagayama, Naotake Yanagisawa, Keisuke Suzuki, and Hiroo Terashi report grants and consultation fees from Kyowa Kirin Co., Ltd. during the conduct of the study. Asako Yoritaka received speaker\u2019s honoraria from Kyowa Kirin Co., Ltd. during the conduct of the study. Noriko Nishikawa, Kyoichi Nomura, Norihito Yoshida, Morinobu Seki, Miho Kawabe Matsukawa, Shigeki Hirano, Hidetomo Murakami, Hideto Joki, Tsuyoshi Uchiyama, Kotaro Ogaki, Jiro Fukae, Kazushi Takahashi, and Toshimasa Yamamoto report grants from Kyowa Kirin Co., Ltd. during the conduct of the study. Hiroshi Nagayama reports no relevant disclosures. Naotake Yanagisawa reports no relevant disclosures. Asako Yoritaka received lecture fees from Sumitomo Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Eisai Co., Ltd. and Kyowa Kirin Co., Ltd. Keisuke Suzuki reports receiving speaker honoraria from Kyowa Kirin Co. Ltd, Otsuka Pharmaceutical, Co. Ltd, Sumitomo Pharma Co. Ltd, Takeda Pharmaceuticals Co. Ltd, Eisai Co. Ltd, and Novartis Pharma K.K. Noriko Nishikawa reports no relevant disclosures. Yohei Mukai reports no relevant disclosures. Yohei Mukai reports receiving honoraria fee for lectures from Kyowa Kirin Co., Ltd. during the conduct of the study. Kyoichi Nomura reports no relevant disclosures. Norihito Yoshida reports no relevant disclosures. Morinobu Seki received a Takeda Japan Medical Affairs Funded Research Grant 2018, and grants from Kanae Foundation for the Promotion of Medical Science, outside the submitted work. Miho Kawabe Matsukawa reports no relevant disclosures. Hiroo Terashi reports no relevant disclosures. Katsuo Kimura reports personal fees from Medtronic Japan Co., Ltd., Boston Scientific Corporation, Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., AbbVie GK, Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sumitomo Pharma Co., Ltd., and grants from Novartis AG, outside the submitted work. Katsuo Kimura reports grants and lecture fees from Kyowa Kirin Co., Ltd. during the conduct of the study. Jun Tashiro reports grants and non-financial support from Kyowa Kirin Co., Ltd. during the conduct of the study. Hideki Shimura reports grants and lecture fees from Kyowa Kirin Co., Ltd. during the conduct of the study. Yoshio Tsuboi, Kenichi Kaida, Ryoko Ihara, Kazutomi Kanemaru, and Osamu Kano report no relevant disclosures during the conduct of the study. Jun Tashiro reports grants and non-financial support from CSL Behring K.K. and personal fees and non-financial support from Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., FP Pharmaceutical Corporation, Ono Pharmaceutical Co., Ltd., Eisai Co., Ltd., and AbbVie GK outside the submitted work. Shigeki Hirano reports grants from Eli Lilly Japan K.K., and grants and lecture fees from Nihon Medi-Physics Co., Ltd. outside the submitted work. Hidetomo Murakami reports no relevant disclosures. Hideto Joki reports no relevant disclosures. Tsuyoshi Uchiyama reports no relevant disclosures. Hideki Shimura reports no relevant disclosures. Kotaro Ogaki reports receiving grants from JSPS KAKENHI (under grant number 19K17047), speakers honoraria from Sumitomo Pharma Co., Ltd, Takeda Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Ono Pharmaceutical Co. Ltd., FP Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd, and Eli Lilly Japan K.K. Jiro Fukae reports no relevant disclosures. Yoshio Tsuboi received personal fees from Eisai Co., Ltd., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Sumitomo Pharma Co., Ltd., AbbVie GK, and Otsuka Pharmaceutical Co., Ltd., and Kyowa Kirin Co., Ltd., outside the submitted work; and were supported by a grant from Nipro Corporation. Kazushi Takahashi reports no relevant disclosures. Toshimasa Yamamoto reports no relevant disclosures. Kenichi Kaida reports no relevant disclosures. Ryoko Ihara reports no relevant disclosures. Kazutomi Kanemaru reports no relevant disclosures. Osamu Kano reports honoraria from AbbVie GK, Alexion Pharmaceuticals, Inc., Biogen Japan Ltd., Biogen Inc., Chugai Pharmaceutical Co., Ltd., Sumitomo Pharma Co., Ltd., Eisai Co., Ltd, Kyowa Kirin Co., Ltd., Mitsubishi Tanabe Pharma Co., Mochida Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and scholarship grants from Eisai Co., Ltd., and Otsuka Pharmaceutical Co., Ltd., and writing fees from Mitsubishi Tanabe Pharma Co., outside the submitted work, and grants for commissioned work from Alexion Pharmaceuticals, Inc., and Mitsubishi Tanabe Pharma Co.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"We carried out the present study in compliance with the Japan Clinical Trials Act and all related national and international guidelines for human trials, and with the Declaration of Helsinki. The Juntendo University Certified Review Board (J18-006) reviewed and approved the study protocol (Version 6.0, 1 November 2021) and all other study documentation (approval number CRB3180012). This trial was registered with the Japan Registry of Clinical Trials (jRCTs031180248). All patients provided written informed consent before enrollment. We anonymized all patient data so that no personal information was associated with the wearable devices. We confirm that we have read the Journal\u2019s position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}