Ira Shoulson1,2, Lakshmi Arbatti2, Abhishek Hosamath2, Shirley W Eberly3, David Oakes3. 1. Department of Neurology, University of Rochester, Rochester, NY, USA. 2. Grey Matter Technologies, Inc., Longboat Key, FL, USA. 3. Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY, USA.
Abstract
BACKGROUND: The Parkinson's Disease Patient Report of Problems (PD-PROP) captures the problems and functional impact that patients report verbatim. Online research participation and advances in language analysis have enabled longitudinal collection and classification of symptoms as trial outcomes. OBJECTIVE: Analyze verbatim reports longitudinally to examine postural-instability symptoms as 1) precursors of subsequent falling and 2) newly occurring symptoms that could serve as outcome measures in randomized controlled trials. METHODS: Problems reported by >25,000 PD patients in their own words were collected online in the Fox Insight observational study and classified into symptoms by natural language processing, clinical curation, and machine learning. Symptoms of gait, balance, falling, and freezing and associated reports of having fallen in the last month were analyzed over three years of longitudinal observation by a Cox regression model in a cohort of 8,287 participants. New onset of gait, balance, falling, and freezing symptoms was analyzed by Kaplan-Meier survival techniques in 4,119 participants who had not previously reported these symptoms. RESULTS: Classified verbatim symptoms of postural instability were significant precursors of subsequent falling among participants who were older, female, and had longer PD duration. New onset of symptoms steadily increased and informed sample size estimates for clinical trials to reduce the onset of these symptoms. CONCLUSION: The tools to analyze symptoms reported by PD patients in their own words and capacity to enroll large numbers of research participants online support the feasibility and statistical power for conducting randomized clinical trials to detect effects of therapeutic interventions.
BACKGROUND: The Parkinson's Disease Patient Report of Problems (PD-PROP) captures the problems and functional impact that patients report verbatim. Online research participation and advances in language analysis have enabled longitudinal collection and classification of symptoms as trial outcomes. OBJECTIVE: Analyze verbatim reports longitudinally to examine postural-instability symptoms as 1) precursors of subsequent falling and 2) newly occurring symptoms that could serve as outcome measures in randomized controlled trials. METHODS: Problems reported by >25,000 PD patients in their own words were collected online in the Fox Insight observational study and classified into symptoms by natural language processing, clinical curation, and machine learning. Symptoms of gait, balance, falling, and freezing and associated reports of having fallen in the last month were analyzed over three years of longitudinal observation by a Cox regression model in a cohort of 8,287 participants. New onset of gait, balance, falling, and freezing symptoms was analyzed by Kaplan-Meier survival techniques in 4,119 participants who had not previously reported these symptoms. RESULTS: Classified verbatim symptoms of postural instability were significant precursors of subsequent falling among participants who were older, female, and had longer PD duration. New onset of symptoms steadily increased and informed sample size estimates for clinical trials to reduce the onset of these symptoms. CONCLUSION: The tools to analyze symptoms reported by PD patients in their own words and capacity to enroll large numbers of research participants online support the feasibility and statistical power for conducting randomized clinical trials to detect effects of therapeutic interventions.
Authors: Eric J Lenze; Caline Mattar; Charles F Zorumski; Angela Stevens; Julie Schweiger; Ginger E Nicol; J Philip Miller; Lei Yang; Michael Yingling; Michael S Avidan; Angela M Reiersen Journal: JAMA Date: 2020-12-08 Impact factor: 56.272
Authors: Michael A Schwarzschild; Alberto Ascherio; Cindy Casaceli; Gary C Curhan; Rebecca Fitzgerald; Cornelia Kamp; Codrin Lungu; Eric A Macklin; Kenneth Marek; Dariush Mozaffarian; David Oakes; Alice Rudolph; Ira Shoulson; Aleksandar Videnovic; Burton Scott; Lisa Gauger; Jason Aldred; Melissa Bixby; Jill Ciccarello; Steven A Gunzler; Claire Henchcliffe; Matthew Brodsky; Kellie Keith; Robert A Hauser; Christopher Goetz; Mark S LeDoux; Vanessa Hinson; Rajeev Kumar; Alberto J Espay; Joohi Jimenez-Shahed; Christine Hunter; Chadwick Christine; Aaron Daley; Maureen Leehey; J Antonelle de Marcaida; Joseph Harold Friedman; Albert Hung; Grace Bwala; Irene Litvan; David K Simon; Tanya Simuni; Cynthia Poon; Mya C Schiess; Kelvin Chou; Ariane Park; Danish Bhatti; Carolyn Peterson; Susan R Criswell; Liana Rosenthal; Jennifer Durphy; Holly A Shill; Shyamal H Mehta; Anwar Ahmed; Andres F Deik; John Y Fang; Natividad Stover; Lin Zhang; Richard B Dewey; Ashley Gerald; James T Boyd; Emily Houston; Valerie Suski; Sherri Mosovsky; Leslie Cloud; Binit B Shah; Marie Saint-Hilaire; Raymond James; Sarah Elizabeth Zauber; Stephen Reich; David Shprecher; Rajesh Pahwa; April Langhammer; Kathrin LaFaver; Peter A LeWitt; Patricia Kaminski; John Goudreau; Doozie Russell; David J Houghton; Ashley Laroche; Karen Thomas; Martha McGraw; Zoltan Mari; Carmen Serrano; Karen Blindauer; Marcie Rabin; Roger Kurlan; John C Morgan; Michael Soileau; Melissa Ainslie; Ivan Bodis-Wollner; Ruth B Schneider; Cheryl Waters; Amber Servi Ratel; Christopher A Beck; Patrick Bolger; Katherine F Callahan; Grace F Crotty; David Klements; Melissa Kostrzebski; Gearoid Michael McMahon; Lindsay Pothier; Sushrut S Waikar; Anthony Lang; Tiago Mestre Journal: JAMA Date: 2021-09-14 Impact factor: 56.272
Authors: E Ray Dorsey; Larsson Omberg; Emma Waddell; Jamie L Adams; Roy Adams; Mohammad Rafayet Ali; Katherine Amodeo; Abigail Arky; Erika F Augustine; Karthik Dinesh; Mohammed Ehsan Hoque; Alistair M Glidden; Stella Jensen-Roberts; Zachary Kabelac; Dina Katabi; Karl Kieburtz; Daniel R Kinel; Max A Little; Karlo J Lizarraga; Taylor Myers; Sara Riggare; Spencer Z Rosero; Suchi Saria; Giovanni Schifitto; Ruth B Schneider; Gaurav Sharma; Ira Shoulson; E Anna Stevenson; Christopher G Tarolli; Jiebo Luo; Michael P McDermott Journal: J Parkinsons Dis Date: 2020-05-22 Impact factor: 5.568
Authors: Sotirios A Parashos; Bastiaan R Bloem; Nina M Browner; Nir Giladi; Tanya Gurevich; Jeffrey M Hausdorff; Ying He; Kelly E Lyons; Zoltan Mari; John C Morgan; Bart Post; Peter N Schmidt; Catherine L Wielinski Journal: Neurol Clin Pract Date: 2018-06