scholarly journals Entropy of Real-World Gait in Parkinson’s Disease Determined from Wearable Sensors as a Digital Marker of Altered Ambulatory Behavior

Sensors ◽  
2020 ◽  
Vol 20 (9) ◽  
pp. 2631
Author(s):  
Lucy Coates ◽  
Jian Shi ◽  
Lynn Rochester ◽  
Silvia Del Din ◽  
Annette Pantall

Parkinson’s disease (PD) is a common age-related neurodegenerative disease. Gait impairment is frequent in the later stages of PD contributing to reduced mobility and quality of life. Digital biomarkers such as gait velocity and step length are predictors of motor and cognitive decline in PD. Additional gait parameters may describe different aspects of gait and motor control in PD. Sample entropy (SampEnt), a measure of signal predictability, is a nonlinear approach that quantifies regularity of a signal. This study investigated SampEnt as a potential biomarker for PD and disease duration. Real-world gait data over a seven-day period were collected using an accelerometer (Axivity AX3, York, UK) placed on the low back and gait metrics extracted. SampEnt was determined for the stride time, with vector length and threshold parameters optimized. People with PD had higher stride time SampEnt compared to older adults, indicating reduced gait regularity. The range of SampEnt increased over 36 months for the PD group, although the mean value did not change. SampEnt was associated with dopaminergic medication dose but not with clinical motor scores. In conclusion, this pilot study indicates that SampEnt from real-world data may be a useful parameter reflecting clinical status although further research is needed involving larger populations.

2020 ◽  
Author(s):  
Daphna Laifenfeld ◽  
Chen Yanover ◽  
Michal Ozery-Flato ◽  
Oded Shaham ◽  
Michal Rozen-Zvi ◽  
...  

AbstractReal-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21stCentury Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease-modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N=88,867) and IBM MarketScan Research Databases (N=106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, for common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jamie L. Adams ◽  
Karthik Dinesh ◽  
Christopher W. Snyder ◽  
Mulin Xiong ◽  
Christopher G. Tarolli ◽  
...  

AbstractMost wearable sensor studies in Parkinson’s disease have been conducted in the clinic and thus may not be a true representation of everyday symptoms and symptom variation. Our goal was to measure activity, gait, and tremor using wearable sensors inside and outside the clinic. In this observational study, we assessed motor features using wearable sensors developed by MC10, Inc. Participants wore five sensors, one on each limb and on the trunk, during an in-person clinic visit and for two days thereafter. Using the accelerometer data from the sensors, activity states (lying, sitting, standing, walking) were determined and steps per day were also computed by aggregating over 2 s walking intervals. For non-walking periods, tremor durations were identified that had a characteristic frequency between 3 and 10 Hz. We analyzed data from 17 individuals with Parkinson’s disease and 17 age-matched controls over an average 45.4 h of sensor wear. Individuals with Parkinson’s walked significantly less (median [inter-quartile range]: 4980 [2835–7163] steps/day) than controls (7367 [5106–8928] steps/day; P = 0.04). Tremor was present for 1.6 [0.4–5.9] hours (median [range]) per day in most-affected hands (MDS-UPDRS 3.17a or 3.17b = 1–4) of individuals with Parkinson’s, which was significantly higher than the 0.5 [0.3–2.3] hours per day in less-affected hands (MDS-UPDRS 3.17a or 3.17b = 0). These results, which require replication in larger cohorts, advance our understanding of the manifestations of Parkinson’s in real-world settings.


BMC Neurology ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Audrey Tanguy ◽  
Linus Jönsson ◽  
Lianna Ishihara

2021 ◽  
Vol 12 ◽  
Author(s):  
Daphna Laifenfeld ◽  
Chen Yanover ◽  
Michal Ozery-Flato ◽  
Oded Shaham ◽  
Michal Rosen-Zvi ◽  
...  

Real-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21st Century Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease-modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N = 88,867) and IBM MarketScan Research Databases (N = 106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, beneficial against common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.


Author(s):  
Victoria Sidoroff ◽  
Cecilia Raccagni ◽  
Christine Kaindlstorfer ◽  
Sabine Eschlboeck ◽  
Alessandra Fanciulli ◽  
...  

Abstract Background Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. Objectives We compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson’s disease, and a control group of older adults. Methods Gait metrics were recorded in 11 multiple system atrophy, 12 Parkinson’s disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed. Results Multiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson’s patients did not. Compared with Parkinson’s disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients. Conclusion This analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson’s disease patients and controls.


2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Elisa Gomez-Inhiesto ◽  
María Teresa Acaiturri-Ayesta ◽  
Iker Ustarroz-Aguirre ◽  
Diana Camahuali ◽  
Maider Urtaran-Laresgoiti ◽  
...  

Parkinson’s disease is one of the main reasons for neurological consultation in Spain. Due to the nature of the disease, it impacts patients, families, and caregivers. Parkinson’s disease is a degenerative disease with no cure, although second-line therapies have recently improved the quality of life of patients in advanced stages. The aim of this study was to analyse the costs of the following therapies: deep brain stimulation (DBS), continuous duodenal levodopa/carbidopa infusion (CDLCI), and continuous subcutaneous apomorphine infusion (CSAI). The methodology used was based on real-world data obtained from an integrated healthcare organization in the Basque Country from 2016 to 2018. This bottom-up retrospective approach only took into account the healthcare perspective. The results revealed the annual cost over 3 years and the projected cost for an additional 2 years. The total costs for 5 years of treatment were as follows: €53,217 for DBS, €208,163 for CDLCI, and €170,591 for CSAI. These costs are in line with those found in the available literature on the subject. Additionally, the analysis provided details of the different costs incurred during intervention with the therapies and compared the costs to those reported in other studies.


2021 ◽  
Vol 84 (2) ◽  
pp. 129-131
Author(s):  
Filipa Meira-Carvalho ◽  
Jorge Diogo Da Silva ◽  
Margarida Rodrigues

2021 ◽  
Vol 54 (1) ◽  
Author(s):  
Kefeng Lv ◽  
Yuhua Liu ◽  
Yanbing Zheng ◽  
Shaowen Dai ◽  
Peifeng Yin ◽  
...  

Abstract Backgrounds Parkinson’s disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. Methods SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. Results MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. Conclusion Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.


2021 ◽  
pp. 1-15
Author(s):  
Eduardo Tolosa ◽  
Georg Ebersbach ◽  
Joaquim J. Ferreira ◽  
Olivier Rascol ◽  
Angelo Antonini ◽  
...  

Background: A greater understanding of the everyday experiences of people with Parkinson’s disease (PD) and their carers may help improve clinical practice. Objective: The Parkinson’s Real-world Impact assesSMent (PRISM) study evaluated medication use, health-related quality of life (HRQoL) and the use of healthcare resources by people with PD and their carers. Methods: PRISM is an observational cross-sectional study, in which people with PD and their carers completed an online survey using structured questionnaires, including the Parkinson’s Disease Quality of Life Questionnaire (PDQ-39), Non-Motor Symptoms Questionnaire (NMSQuest) and Zarit Burden Interview (ZBI). Results: Data were collected from 861 people with PD (mean age, 65.0 years; mean disease duration, 7.7 years) and 256 carers from six European countries. People with PD reported a large number of different co-morbidities, non-motor symptoms (mean NMSQuest score, 12.8), and impaired HRQoL (median PDQ-39 summary score, 29.1). Forty-five percent of people with PD reported at least one impulse control behaviour. Treatment patterns varied considerably between different European countries. Levodopa was taken in the last 12 months by 85.9% of participants, and as monotherapy by 21.8% . Carers, who were mostly female (64.8%) and the partner/spouse of the person with PD (82.1%), reported mild to moderate burden (mean ZBI total score, 26.6). Conclusions: The PRISM study sheds light on the lives of people with PD and those who care for them, re-emphasising the many challenges they face in everyday life. The study also provides insights into the current treatment of PD in Europe.


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