What Huntington's Disease Patients Say About Their Illness: An Online Direct-to-Participant Pilot Study.

Background: Direct-to-participant online reporting facilitates the conduct of clinical research by increasing access and clinically meaningful patient engagement. Objective: We assessed feasibility of online data collection from adults with diagnosed Huntington's disease (HD) who directly reported their problems and impact in their own words. Methods: Data were collected online from consenting United States residents who self-identified as 1) having been diagnosed with Huntington's disease, 2) able to ambulate independently, and 3) self-sufficient for most daily needs. Data for this pilot study were collected using the Huntington Study Group myHDstory online research platform. The Huntington Disease Patient Report of Problems (HD-PROP), an open-ended questionnaire, was used to capture verbatim bothersome problems and functional impact. Natural language processing, human-in-the-loop curation of verbatim reports involving clinical and experience experts, and machine learning classified verbatim-reports into clinically meaningful symptoms. Results: All 8 questionnaires in the online pilot study were completed by 345 participants who were 60.9% men, 34.5±9.9 (mean±SD) years old, and 9.5±8.4 years since HD diagnosis. Racial self-identification was 46.4% Caucasian, 28.7% African American, 15.4% American Indian/Alaska Native, and 9.5% other. Accuracy of verbatim classification was 99%. Non-motor problems were the most frequently reported symptoms; depression and cognitive impairment were the most common. Conclusions: Online research participation was feasible for a diverse cohort of adults who self-reported an HD diagnosis and predominantly non-motor symptoms related to mood and cognition. Online research tools can help inform what bothers HD patients, identify clinically meaningful outcomes, and facilitate participation by diverse and under-represented populations.

In Their Own Words: Fears Expressed by People with Parkinson's Disease in an Online Symptom Database.

Parkinson's disease (PD) carries substantial psychosocial burden. Using a database of responses by people with PD reporting up to five "most bothersome problems," we identified 225 fear-based verbatims, which were organized using the framework method into 26 categories. Commonly-reported fears included uncertainty of progression (n = 60, 26.7%), fear of future cognitive impairment (n = 24, 10.7%) and fear of becoming a burden on others (n = 23, 10.2%). Fears in PD are wide-ranging and can constitute the most bothersome aspect of the condition. These data can be used to design interventions to lessen the psychosocial burden of PD.

Association between Subjective Cognitive Complaints and Incident Functional Impairment in Parkinson's Disease.

BACKGROUND: Early identification of subjective cognitive complaints (SCC) in Parkinson's disease (PD) may improve patient care if it predicts cognition-related functional impairment (CFI). OBJECTIVES: The aim was to determine the cross-sectional and longitudinal association between SCC and CFI in PD. METHODS: Data were obtained from Fox Insight, an online longitudinal study that collects PD patient-reported outcomes. Participants completed a PD Patient Report of Problems that asked participants for their five most bothersome disease problems. SCCs were placed into eight categories through human-in-the-loop curation and classification. CFI had a Penn Parkinson's Daily Activities Questionnaire (PDAQ-15) score ≤49. Cox proportional hazards models and Kaplan-Meier survival analyses determined if baseline SCC was associated with incident CFI. RESULTS: The PD-PROP cohort (N = 21,160) was 55.8% male, mean age was 65.9 years, and PD duration was 4.8 years. At baseline, 31.9% (N = 6750) of participants reported one or more SCCs among their five most bothersome problems, including memory (13.2%), language/word finding (12.5%), and concentration/attention (9.6%). CFI occurred in 34.7% (N = 7332) of participants. At baseline, SCC was associated with CFI (P-value <0.001). SCC at baseline was associated with incident CFI (hazard ratio [HR] = 1.58 [95% confidence interval: 1.45, 1.72], P-value <0.001), as did cognitive impairment not otherwise specified (HR = 2.31), executive abilities (HR = 1.97), memory (HR = 1.85), and cognitive slowing (HR = 1.77) (P-values <0.001). Kaplan-Meier curves showed that by year 3 an estimated 45% of participants with any SCC at baseline developed new-onset CFI. CONCLUSIONS: Self-reported bothersome cognitive complaints are associated with new-onset CFI in PD. Remote electronic assessment can facilitate widespread use of patient self-report at population scale. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Internal tremor in people with Parkinson's Disease: Demographic characteristics and comorbid symptoms.

Introduction: Internal tremor (IT) occurs in > 30 % of people with Parkinson's Disease (PwPD), but remains largely uninvestigated. Our objective was to describe demographic characteristics and associated symptoms in PwPD who reported IT. Methods: This was a matched case-control survey study. Data were from PwPD in the Fox Insight study who answered the Patient Report of Problems (PD-PROP) assessment, a series of open-ended questions that asks people to report in their own words their most bothersome PD-related problems. Cases were those who reported IT ≥ 1 times compared with PwPD controls who did not report IT and were matched 1:3 by age and disease duration. Results: 243 PwPD reported IT as a bothersome problem. Mean (SD) age of cases was 64.9 (9.4) years and disease duration was 3.8 (4.0) years. The proportion of women was greater among cases compared to controls (74 % vs 47 %, p < 0.0001). External tremor as a PD-PROP symptom was reported by 98 % cases and 48 % controls (p < 0.0001). Several non-motor symptoms were more common among cases than controls, including anxiety (35 % vs 20 %), fatigue (41 % vs 31 %), and pain (57 % vs 37 %). The odds of IT was significantly higher in women when adjusting for anxiety and motor experiences of daily living score (OR 3.07, 95 %CI 2.14-4.41, p < 0.0001). Conclusion: PwPD with IT report a range of associated symptoms, including external tremor, anxiety, and pain. Sex differences in the experience of IT may exist. Studies of IT are needed to understand its etiology and inform clinical care.

What Patients Say: Large-Scale Analyses of Replies to the Parkinson's Disease Patient Report of Problems (PD-PROP).

BACKGROUND: Free-text, verbatim replies in the words of people with Parkinson's disease (PD) have the potential to provide unvarnished information about their feelings and experiences. Challenges of processing such data on a large scale are a barrier to analyzing verbatim data collection in large cohorts. OBJECTIVE: To develop a method for curating responses from the Parkinson's Disease Patient Report of Problems (PD-PROP), open-ended questions that asks people with PD to report their most bothersome problems and associated functional consequences. METHODS: Human curation, natural language processing, and machine learning were used to develop an algorithm to convert verbatim responses to classified symptoms. Nine curators including clinicians, people with PD, and a non-clinician PD expert classified a sample of responses as reporting each symptom or not. Responses to the PD-PROP were collected within the Fox Insight cohort study. RESULTS: Approximately 3,500 PD-PROP responses were curated by a human team. Subsequently, approximately 1,500 responses were used in the validation phase; median age of respondents was 67 years, 55% were men and median years since PD diagnosis was 3 years. 168,260 verbatim responses were classified by machine. Accuracy of machine classification was 95% on a held-out test set. 65 symptoms were grouped into 14 domains. The most frequently reported symptoms at first report were tremor (by 46% of respondents), gait and balance problems (>39%), and pain/discomfort (33%). CONCLUSION: A human-in-the-loop method of curation provides both accuracy and efficiency, permitting a clinically useful analysis of large datasets of verbatim reports about the problems that bother PD patients.

Longitudinal Cohort Study of Verbatim-Reported Postural Instability Symptoms as Outcomes for Online Parkinson's Disease Trials.

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.

Predictive Value of Verbatim Parkinson's Disease Patient-Reported Symptoms of Postural Instability and Falling.

BACKGROUND: Postural instability is an intractable sign of Parkinson's disease, associated with poor disease prognosis, fall risk, and decreased quality of life. OBJECTIVE: 1) Characterize verbatim reports of postural instability and associated symptoms (gait disorder, balance, falling, freezing, and posture), 2) compare reports with responses to three pre-specified questions from Part II of the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS), and 3) examine postural instability symptoms and MDS-UPDRS responses as predictors of future falls. METHODS: Fox Insight research participants reported their problems attributed to PD in their own words using the Parkinson Disease Patient Reports of Problems (PD-PROP). Natural language processing, clinical curation, and data mining techniques were applied to classify text into problem domains and clinically-curated symptoms. Baseline postural instability symptoms were mapped to MDS-UPDRS questions 2.11-2.13. T-tests and chi-square tests were used to compare postural instability reporters and non-reporters, and Cochran-Armitage trend tests were used to evaluate associations between PD-PROP and MDS-UPDRS responses; survival methods were utilized to evaluate the predictive utility of PD-PROP and MDS-UPDRS responses in time-to-fall analyses. RESULTS: Of participants within 10 years of PD diagnosis, 9,692 (56.0%) reported postural instability symptoms referable to gait unsteadiness, balance, falling, freezing, or posture at baseline. Postural instability symptoms were significantly associated with patient-reported measures from the MDS-UPDRS questions. Balance problems reported on PD-PROP and MDS-UPDRS 2.11-2.13 measures were predictive of future falls. CONCLUSION: Verbatim-reported problems captured by the PD-PROP and categorized by natural language processing and clinical curation and MDS-UPDRS responses predicted falls. The PD-PROP output was more granular than, and as informative as, the categorical responses.