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      Predicting the longitudinal changes of levodopa dose requirements in Parkinson’s disease using item response theory assessment of real‐world Unified Parkinson's Disease Rating Scale

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          Abstract

          Item response theory (IRT) has been recently adopted to successfully characterize the progression of Parkinson's disease using serial Unified Parkinson's Disease Rating Scale (UPDRS) measurements. However, it has yet to be applied in predicting the longitudinal changes of levodopa dose requirements in the real‐world setting. Here we use IRT to extract two latent variables that represent tremor and non‐tremor‐related symptoms from baseline assessments of UPDRS Part III scores. We show that relative magnitudes of the two latent variables are strong predictors of the progressive increase of levodopa equivalent dose (LED). Retrospectively collected item‐level UPDRS Part III scores and longitudinal records of prescribed medication doses of 128 patients with de novo PD extracted from the electronic medical records were used for model building. Supplementary analysis based on a subset of 36 patients with at least three serial assessments of UPDRS Part III scores suggested that the two latent variables progress at significantly different rates. A web application was developed to facilitate the use of our model in making individualized predictions of future LED and disease progression.

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          Most cited references23

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          Systematic review of levodopa dose equivalency reporting in Parkinson's disease.

          Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications. © 2010 Movement Disorder Society.
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            Parkinson's disease: clinical features and diagnosis.

            Parkinson's disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included "Parkinson's disease", "diagnosis" and "signs and symptoms". Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.
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              The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations.

              (2003)
              The Movement Disorder Society Task Force for Rating Scales for Parkinson's Disease prepared a critique of the Unified Parkinson's Disease Rating Scale (UPDRS). Strengths of the UPDRS include its wide utilization, its application across the clinical spectrum of PD, its nearly comprehensive coverage of motor symptoms, and its clinimetric properties, including reliability and validity. Weaknesses include several ambiguities in the written text, inadequate instructions for raters, some metric flaws, and the absence of screening questions on several important non-motor aspects of PD. The Task Force recommends that the MDS sponsor the development of a new version of the UPDRS and encourage efforts to establish its clinimetric properties, especially addressing the need to define a Minimal Clinically Relevant Difference and a Minimal Clinically Relevant Incremental Difference, as well as testing its correlation with the current UPDRS. If developed, the new scale should be culturally unbiased and be tested in different racial, gender, and age-groups. Future goals should include the definition of UPDRS scores with confidence intervals that correlate with clinically pertinent designations, "minimal," "mild," "moderate," and "severe" PD. Whereas the presence of non-motor components of PD can be identified with screening questions, a new version of the UPDRS should include an official appendix that includes other, more detailed, and optionally used scales to determine severity of these impairments. Copyright 2003 Movement Disorder Society
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                Author and article information

                Contributors
                KSPARK@yuhs.ac , PHLEE@yuhs.ac
                Journal
                CPT Pharmacometrics Syst Pharmacol
                CPT Pharmacometrics Syst Pharmacol
                10.1002/(ISSN)2163-8306
                PSP4
                CPT: Pharmacometrics & Systems Pharmacology
                John Wiley and Sons Inc. (Hoboken )
                2163-8306
                03 May 2021
                June 2021
                : 10
                : 6 ( doiID: 10.1002/psp4.v10.6 )
                : 611-621
                Affiliations
                [ 1 ] Division of Pharmacometrics Department of Pharmacology Yonsei University College of Medicine Seoul South Korea
                [ 2 ] Department of Neurology Myongji Hospital Hanyang University College of Medicine Goyang South Korea
                [ 3 ] Department of Neurology Yonsei University College of Medicine Seoul South Korea
                Author notes
                [*] [* ] Correspondence

                Kyungsoo Park, Division of Pharmacometrics, Department of Pharmacology, Yonsei University College of Medicine, Seoul, South Korea.

                Email: KSPARK@ 123456yuhs.ac

                Phil Hyu Lee, Department of Neurology, Yonsei University College of Medicine, Seoul, South Korea.

                Email: PHLEE@ 123456yuhs.ac

                Article
                PSP412632
                10.1002/psp4.12632
                8213413
                33939329
                524b908a-7694-4065-a566-06e6fee91525
                © 2021 The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 15 March 2021
                : 21 January 2021
                : 18 March 2021
                Page count
                Figures: 4, Tables: 2, Pages: 11, Words: 6271
                Funding
                Funded by: Yonsei University , open-funder-registry 10.13039/501100002573;
                Funded by: Medical College
                Award ID: 6‐2019‐0073
                Categories
                Article
                Research
                Articles
                Custom metadata
                2.0
                June 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:18.06.2021

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