{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:08:47Z","timestamp":1787069327216,"version":"build-2736575974"},"reference-count":31,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["91215076"],"award-info":[{"award-number":["91215076"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Both patients and physicians may choose to delay initiation of dopamine replacement therapy in Parkinson's disease (PD) for various reasons. We used observational data to estimate the effect of earlier treatment in PD. Observational data offer a valuable source of evidence, complementary to controlled trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We studied the Parkinson's Progression Markers Initiative cohort of patients with de novo PD to estimate the effects of duration of PD treatment during the first 2\u2009years of follow\u2010up, exploiting natural interindividual variation in the time to start first treatment. We estimated the Movement Disorder Society\u2013Unified Parkinson's Disease Rating Scale (MDS\u2010UPDRS) Part III (primary outcome) and several functionally relevant outcomes at 2, 3, and 4\u2009years after baseline. To adjust for time\u2010varying confounding, we used marginal structural models with inverse probability of treatment weighting and the parametric g\u2010formula.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 302 patients from the Parkinson's Progression Markers Initiative cohort. There was a small improvement in MDS\u2010UPDRS Part III scores after 2\u2009years of follow\u2010up for patients who started treatment earlier, and similar, but nonstatistically significant, differences in subsequent years. We found no statistically significant differences in most secondary outcomes, including the presence of motor fluctuations, nonmotor symptoms, MDS\u2010UPDRS Part II scores, and the Schwab and England Activities of Daily Living Scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Earlier treatment initiation does not lead to worse MDS\u2010UPDRS motor scores and may offer small improvements. These findings, based on observational data, are in line with earlier findings from clinical trials. Observational data, when combined with appropriate causal methods, are a valuable source of additional evidence to support real\u2010world clinical decisions. \u00a9 2020 The Authors.\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.28339","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T06:14:54Z","timestamp":1603779294000},"page":"407-414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Estimating the Effect of Early Treatment Initiation in Parkinson's Disease Using Observational Data"],"prefix":"10.1002","volume":"36","author":[{"given":"Lieneke","family":"van den Heuvel","sequence":"first","affiliation":[{"name":"Center of Expertise for Parkinson &amp; Movement Disorders, department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8241-5087","authenticated-orcid":false,"given":"Luc J.W.","family":"Evers","sequence":"additional","affiliation":[{"name":"Center of Expertise for Parkinson &amp; Movement Disorders, department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen the Netherlands"},{"name":"Institute for Computing and Information Sciences Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6491-7035","authenticated-orcid":false,"given":"Marjan J.","family":"Meinders","sequence":"additional","affiliation":[{"name":"Scientific Center for Quality of Healthcare (IQ Healthcare), Radboud Institute for Health Sciences Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Post","sequence":"additional","affiliation":[{"name":"Center of Expertise for Parkinson &amp; Movement Disorders, department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6293-4509","authenticated-orcid":false,"given":"Anne M.","family":"Stiggelbout","sequence":"additional","affiliation":[{"name":"Department of Biomedical Data Sciences, Medical Decision Making Leiden University Medical Centre  Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3398-5235","authenticated-orcid":false,"given":"Tom M.","family":"Heskes","sequence":"additional","affiliation":[{"name":"Institute for Computing and Information Sciences Radboud University  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-3337","authenticated-orcid":false,"given":"Bastiaan R.","family":"Bloem","sequence":"additional","affiliation":[{"name":"Center of Expertise for Parkinson &amp; Movement Disorders, department of Neurology, Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Center  Nijmegen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3435-6358","authenticated-orcid":false,"given":"Jesse H.","family":"Krijthe","sequence":"additional","affiliation":[{"name":"Institute for Computing and Information Sciences Radboud University  Nijmegen the Netherlands"},{"name":"Department of Intelligent Systems Delft University of Technology  Delft the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1809983"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa033447"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26119"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318232ab4c"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.0348"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60683-8"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0809335"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380512"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70117-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191712"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871-016-0265-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2008.09.030"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k182"},{"key":"e_1_2_8_15_1","volume-title":"Causal Inference","author":"Hernan MA","year":"2019"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2011.09.005"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001648-200009000-00011"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1198\/016214501753168154"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0270-0255(86)90088-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwq472"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000160"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v081.i01"},{"key":"e_1_2_8_23_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2019"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30036-3"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30285-6"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2013.06.002"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2018.05.027"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-150570"},{"key":"e_1_2_8_29_1","unstructured":"C\u2010Path. 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