Standing Balance Conditions and Digital Sway Measures for Clinical Trials of Friedreich's Ataxia.

BACKGROUND: Progressive loss of standing balance is a feature of Friedreich's ataxia (FRDA). OBJECTIVES: This study aimed to identify standing balance conditions and digital postural sway measures that best discriminate between FRDA and healthy controls (HC). We assessed test-retest reliability and correlations between sway measures and clinical scores. METHODS: Twenty-eight subjects with FRDA and 20 HC completed six standing conditions: feet apart, feet together, and feet tandem, both with eyes opened (EO) and eyes closed. Sway was measured using a wearable sensor on the lumbar spine for 30 seconds. Test completion rate, test-retest reliability with intraclass correlation coefficients, and areas under the receiver operating characteristic curves (AUCs) for each measure were compared to identify distinguishable FRDA sway characteristics from HC. Pearson correlations were used to evaluate the relationships between discriminative measures and clinical scores. RESULTS: Three of the six standing conditions had completion rates over 70%. Of these three conditions, natural stance and feet together with EO showed the greatest completion rates. All six of the sway measures' mean values were significantly different between FRDA and HC. Four of these six measures discriminated between groups with >0.9 AUC in all three conditions. The Friedreich Ataxia Rating Scale Upright Stability and Total scores correlated with sway measures with P-values <0.05 and r-values (0.63-0.86) and (0.65-0.81), respectively. CONCLUSION: Digital postural sway measures using wearable sensors are discriminative and reliable for assessing standing balance in individuals with FRDA. Natural stance and feet together stance with EO conditions suggest use in clinical trials for FRDA. © 2024 International Parkinson and Movement Disorder Society.

Digital Measures of Postural Sway Quantify Balance Deficits in Spinocerebellar Ataxia.

BACKGROUND: Maintaining balance is crucial for independence and quality of life. Loss of balance is a hallmark of spinocerebellar ataxia (SCA). OBJECTIVE: The aim of this study was to identify which standing balance conditions and digital measures of body sway were most discriminative, reliable, and valid for quantifying balance in SCA. METHODS: Fifty-three people with SCA (13 SCA1, 13 SCA2, 14 SCA3, and 13 SCA6) and Scale for Assessment and Rating of Ataxia (SARA) scores 9.28 ± 4.36 and 31 healthy controls were recruited. Subjects stood in six test conditions (natural stance, feet together and tandem, each with eyes open [EO] and eyes closed [EC]) with an inertial sensor on their lower back for 30 seconds (×2). We compared test completion rate, test-retest reliability, and areas under the receiver operating characteristic curve (AUC) for seven digital sway measures. Pearson's correlations related sway with the SARA and the Patient-Reported Outcome Measure of Ataxia (PROM ataxia). RESULTS: Most individuals with SCA (85%-100%) could stand for 30 seconds with natural stance EO or EC, and with feet together EO. The most discriminative digital sway measures (path length, range, area, and root mean square) from the two most reliable and discriminative conditions (natural stance EC and feet together EO) showed intraclass correlation coefficients from 0.70 to 0.91 and AUCs from 0.83 to 0.93. Correlations of sway with SARA were significant (maximum r = 0.65 and 0.73). Correlations with PROM ataxia were mild to moderate (maximum r = 0.56 and 0.34). CONCLUSION: Inertial sensor measures of extent of postural sway in conditions of natural stance EC and feet together stance EO were discriminative, reliable, and valid for monitoring SCA. © 2024 International Parkinson and Movement Disorder Society.

Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.

Gait and turning characteristics from daily life increase ability to predict future falls in people with Parkinson's disease.

Objectives: To investigate if digital measures of gait (walking and turning) collected passively over a week of daily activities in people with Parkinson's disease (PD) increases the discriminative ability to predict future falls compared to fall history alone. Methods: We recruited 34 individuals with PD (17 with history of falls and 17 non-fallers), age: 68 ± 6 years, MDS-UPDRS III ON: 31 ± 9. Participants were classified as fallers (at least one fall) or non-fallers based on self-reported falls in past 6 months. Eighty digital measures of gait were derived from 3 inertial sensors (Opal® V2 System) placed on the feet and lower back for a week of passive gait monitoring. Logistic regression employing a "best subsets selection strategy" was used to find combinations of measures that discriminated future fallers from non-fallers, and the Area Under Curve (AUC). Participants were followed via email every 2 weeks over the year after the study for self-reported falls. Results: Twenty-five subjects reported falls in the follow-up year. Quantity of gait and turning measures (e.g., number of gait bouts and turns per hour) were similar in future fallers and non-fallers. The AUC to discriminate future fallers from non-fallers using fall history alone was 0.77 (95% CI: [0.50-1.00]). In contrast, the highest AUC for gait and turning digital measures with 4 combinations was 0.94 [0.84-1.00]. From the top 10 models (all AUCs>0.90) via the best subsets strategy, the most consistently selected measures were variability of toe-out angle of the foot (9 out of 10), pitch angle of the foot during mid-swing (8 out of 10), and peak turn velocity (7 out of 10). Conclusions: These findings highlight the importance of considering precise digital measures, captured via sensors strategically placed on the feet and low back, to quantify several different aspects of gait (walking and turning) during daily life to improve the classification of future fallers in PD.

Opal Actigraphy (Activity and Sleep) Measures Compared to ActiGraph: A Validation Study.

Physical activity and sleep monitoring in daily life provide vital information to track health status and physical fitness. The aim of this study was to establish concurrent validity for the new Opal Actigraphy solution in relation to the widely used ActiGraph GT9X for measuring physical activity from accelerometry epic counts (sedentary to vigorous levels) and sleep periods in daily life. Twenty participants (age 56 + 22 years) wore two wearable devices on each wrist for 7 days and nights, recording 3-D accelerations at 30 Hz. Bland-Altman plots and intraclass correlation coefficients (ICCs) assessed validity (agreement) and test-retest reliability between ActiGraph and Opal Actigraphy sleep durations and activity levels, as well as between the two different versions of the ActiGraph. ICCs showed excellent reliability for physical activity measures and moderate-to-excellent reliability for sleep measures between Opal versus Actigraph GT9X and between GT3X versus GT9X. Bland-Altman plots and mean absolute percentage error (MAPE) also show a comparable performance (within 10%) between Opal and ActiGraph and between the two ActiGraph monitors across activity and sleep measures. In conclusion, physical activity and sleep measures using Opal Actigraphy demonstrate performance comparable to that of ActiGraph, supporting concurrent validation. Opal Actigraphy can be used to quantify activity and monitor sleep patterns in research and clinical studies.

Effect of Levodopa and Environmental Setting on Gait and Turning Digital Markers Related to Falls in People with Parkinson's Disease.

Background: It is unknown whether medication status (off and on levodopa) or laboratory versus home settings plays a role in discriminating fallers and non-fallers in people with Parkinson's disease (PD). Objectives: To investigate which specific digital gait and turning measures, obtained with body-worn sensors, best discriminated fallers from non-fallers with PD in the clinic and during daily life. Methods: We recruited 34 subjects with PD (17 fallers and 17 non-fallers based on the past 6 month's falls). Subjects wore three inertial sensors attached to both feet and the lumbar region in the laboratory for a 3-minute walking task (both off and on levodopa) and during daily life activities for a week. We derived 24 digital (18 gait and 6 turn) measures from the 3-minute walk and from daily life. Results: In clinic, none of the gait and turning measures collected during on levodopa state were significantly different between fallers and non-fallers. In contrast, digital measures collected in the off levodopa state were significantly different between groups, (average turn velocity, average number of steps to complete a turn, and variability of gait speed, P < 0.03). During daily life, the variability of average turn velocity (P = 0.023) was significantly different in fallers than non-fallers. Last, the average number of steps to complete a turn was significantly correlated with the patient-reported outcomes. Conclusions: Digital measures of turning, but not gait, were different in fallers compared to non-fallers with PD, in the laboratory when off medication and during a daily life.

Feasibility of Tracking Human Kinematics with Simultaneous Localization and Mapping (SLAM).

We evaluated a new wearable technology that fuses inertial sensors and cameras for tracking human kinematics. These devices use on-board simultaneous localization and mapping (SLAM) algorithms to localize the camera within the environment. Significance of this technology is in its potential to overcome many of the limitations of the other dominant technologies. Our results demonstrate this system often attains an estimated orientation error of less than 1° and a position error of less than 4 cm as compared to a robotic arm. This demonstrates that SLAM's accuracy is adequate for many practical applications for tracking human kinematics.

Continuous Monitoring of Essential Tremor: Standards and Challenges.

Background: The value of continuous symptom monitoring in people with essential tremor is uncertain. Objectives: To determine the relationship between tremor amplitude measured with wearable inertial sensors and clinician- and patient-rated measures. Methods: For 14 days, patients (1) wore inertial sensors on both wrists, (2) self-rated their tremor using a diary, (3) drew spirals, and (4) completed an activities of daily living scale once daily. Patients were also scored using The Essential Tremor Rating Scale (TETRAS) performance in the clinic by a clinician. Results: We found strong correlations in patient-reported metrics of tremor, but weak correlations between these data and both the inertial sensor data and the in-clinic TETRAS scores. Conclusions: The patient experience of tremor during normal daily activities may differ from the transducer-based measures of tremor amplitude and rating scales of tremor severity. Future studies should consider how to record features of tremor that are important to patients.

Fall Prediction Based on Instrumented Measures of Gait and Turning in Daily Life in People with Multiple Sclerosis.

This study investigates the potential of passive monitoring of gait and turning in daily life in people with multiple sclerosis (PwMS) to identify those at future risk of falls. Seven days of passive monitoring of gait and turning were carried out in a pilot study of 26 PwMS in home settings using wearable inertial sensors. The retrospective fall history was collected at the baseline. After gait and turning data collection in daily life, PwMS were followed biweekly for a year and were classified as fallers if they experienced >1 fall. The ability of short-term passive monitoring of gait and turning, as well as retrospective fall history to predict future falls were compared using receiver operator curves and regression analysis. The history of retrospective falls was not identified as a significant predictor of future falls in this cohort (AUC = 0.62, p = 0.32). Among quantitative monitoring measures of gait and turning, the pitch at toe-off was the best predictor of falls (AUC = 0.86, p < 0.01). Fallers had a smaller pitch of their feet at toe-off, reflecting less plantarflexion during the push-off phase of walking, which can impact forward propulsion and swing initiation and can result in poor foot clearance and an increased metabolic cost of walking. In conclusion, our cohort of PwMS showed that objective monitoring of gait and turning in daily life can identify those at future risk of falls, and the pitch at toe-off was the single most influential predictor of future falls. Therefore, interventions aimed at improving the strength of plantarflexion muscles, range of motion, and increased proprioceptive input may benefit PwMS at future fall risk.

Inertial Sensor Algorithm to Estimate Walk Distance.

The "total distance walked" obtained during a standardized walking test is an integral component of physical fitness and health status tracking in a range of consumer and clinical applications. Wearable inertial sensors offer the advantages of providing accurate, objective, and reliable measures of gait while streamlining walk test administration. The aim of this study was to develop an inertial sensor-based algorithm to estimate the total distance walked using older subjects with impaired fasting glucose (Study I), and to test the generalizability of the proposed algorithm in patients with Multiple Sclerosis (Study II). All subjects wore two inertial sensors (Opals by Clario-APDM Wearable Technologies) on their feet. The walking distance algorithm was developed based on 108 older adults in Study I performing a 400 m walk test along a 20 m straight walkway. The validity of the algorithm was tested using a 6-minute walk test (6MWT) in two sub-studies of Study II with different lengths of a walkway, 15 m (Study II-A, n = 24) and 20 m (Study II-B, n = 22), respectively. The start and turn around points were marked with lines on the floor while smaller horizontal lines placed every 1 m served to calculate the manual distance walked (ground truth). The proposed algorithm calculates the forward distance traveled during each step as the change in the horizontal position from each foot-flat period to the subsequent foot-flat period. The total distance walked is then computed as the sum of walk distances for each stride, including turns. The proposed algorithm achieved an average absolute error rate of 1.92% with respect to a fixed 400 m distance for Study I. The same algorithm achieved an absolute error rate of 4.17% and 3.21% with respect to an averaged manual distance for 6MWT in Study II-A and Study II-B, respectively. These results demonstrate the potential of an inertial sensor-based algorithm to estimate a total distance walked with good accuracy with respect to the manual, clinical standard. Further work is needed to test the generalizability of the proposed algorithm with different administrators and populations, as well as larger diverse cohorts.

Gait Variability in Spinocerebellar Ataxia Assessed Using Wearable Inertial Sensors.

BACKGROUND: Quantitative assessment of severity of ataxia-specific gait impairments from wearable technology could provide sensitive performance outcome measures with high face validity to power clinical trials. OBJECTIVES: The aim of this study was to identify a set of gait measures from body-worn inertial sensors that best discriminate between people with prodromal or manifest spinocerebellar ataxia (SCA) and age-matched, healthy control subjects (HC) and determine how these measures relate to disease severity. METHODS: One hundred and sixty-three people with SCA (subtypes 1, 2, 3, and 6), 42 people with prodromal SCA, and 96 HC wore 6 inertial sensors while performing a natural pace, 2-minute walk. Areas under the receiver operating characteristic curves (AUC) were compared for 25 gait measures, including standard deviations as variability, to discriminate between ataxic and normal gait. Pearson's correlation coefficient assessed the relationships between the gait measures and severity of ataxia. RESULTS: Increased gait variability was the most discriminative gait feature of SCA; toe-out angle variability (AUC = 0.936; sensitivity = 0.871; specificity = 0.896) and double-support time variability (AUC = 0.932; sensitivity = 0.834; specificity = 0.865) were the most sensitive and specific measures. These variability measures were also significantly correlated with the scale for the assessment and rating of ataxia (SARA) and disease duration. The same gait measures discriminated gait of people with prodromal SCA from the gait of HC (AUC = 0.610, and 0.670, respectively). CONCLUSIONS: Wearable inertial sensors provide sensitive and specific measures of excessive gait variability in both manifest and prodromal SCAs that are reliable and related to the severity of the disease, suggesting they may be useful as clinical trial performance outcome measures. © 2021 International Parkinson and Movement Disorder Society.

Errata to "Quantifying Tremor in Essential Tremor Using Inertial Sensors Validation of an Algorithm".

[This corrects the article DOI: 10.1109/JTEHM.2020.3032924.].

Does gait bout definition influence the ability to discriminate gait quality between people with and without multiple sclerosis during daily life?

BACKGROUND: There is currently no consensus about standardized gait bout definitions when passively monitoring walking during normal daily life activities. It is also not known how different definitions of a gait bout in daily life monitoring affects the ability to distinguish pathological gait quality. Specifically, how many seconds of a pause with no walking indicates an end to one gait bout and the start of another bout? In this study, we investigated the effect of 3 gait bout definitions on the discriminative ability to distinguish quality of walking in people with multiple sclerosis (MS) from healthy control subjects (HC) during a week of daily living. METHODS: 15 subjects with MS and 16 HC wore instrumented socks on each foot and one Opal sensor over the lower lumbar area for a week of daily activities for at least 8 h/day. Three gait bout definitions were based on the length of the pause between the end of one gait bout and start of another bout (1.25 s, 2.50 s, and 5.0 s pause). Area under the curve (AUC) was used to compare gait quality measures in MS versus HC. RESULTS: Total number of gait bouts over the week were statistically significantly different across bout definitions, as expected. However, AUCs of gait quality measures (such as gait speed, stride length, stride time) discriminating people with MS from HC were not different despite the 3 bout definitions. SIGNIFICANCE: Quality of gait measures that discriminate MS from HC during daily life are not influenced by the length of a gait bout, despite large differences in quantity of gait across bout definitions. Thus, gait quality measures in people with MS versus controls can be compared across studies using different gait bout definitions with pause lengths ≤5 s.

Quantifying Tremor in Essential Tremor Using Inertial Sensors-Validation of an Algorithm.

Background Assessment of essential tremor is often done by a trained clinician who observes the limbs during different postures and actions and subsequently rates the tremor. While this method has been shown to be reliable, the inter- and intra-rater reliability and need for training can make the use of this method for symptom progression difficult. Many limitations of clinical rating scales can potentially be overcome by using inertial sensors, but to date many algorithms designed to quantify tremor have key limitations. Methods We propose a novel algorithm to characterize tremor using inertial sensors. It uses a two-stage approach that 1) estimates the tremor frequency of a subject and only quantifies tremor near that range; 2) estimates the tremor amplitude as the portion of signal power above baseline activity during recording, allowing tremor estimation even in the presence of other activity; and 3) estimates tremor amplitude in physical units of translation (cm) and rotation (°), consistent with current tremor rating scales. We validated the algorithm technically using a robotic arm and clinically by comparing algorithm output with data reported by a trained clinician administering a tremor rating scale to a cohort of essential tremor patients. Results Technical validation demonstrated rotational amplitude accuracy better than ±0.2 degrees and position amplitude accuracy better than ±0.1 cm. Clinical validation revealed that both rotation and position components were significantly correlated with tremor rating scale scores. Conclusion We demonstrate that our algorithm can quantify tremor accurately even in the presence of other activities, perhaps providing a step forward for at-home monitoring.

Inertial Sensor Algorithms to Characterize Turning in Neurological Patients With Turn Hesitations.

BACKGROUND: One difficulty in turning algorithm design for inertial sensors is detecting two discrete turns in the same direction, close in time. A second difficulty is under-estimation of turn angle due to short-duration hesitations by people with neurological disorders. We aimed to validate and determine the generalizability of a: I. Discrete Turn Algorithm for variable and sequential turns close in time and II: Merged Turn Algorithm for a single turn angle in the presence of hesitations. METHODS: We validated the Discrete Turn Algorithm with motion capture in healthy controls (HC, n = 10) performing a spectrum of turn angles. Subsequently, the generalizability of the Discrete Turn Algorithm and associated, Merged Turn Algorithm were tested in people with Parkinson's disease (PD, n = 124), spinocerebellar ataxia (SCA, n = 51), and HC (n = 125). RESULTS: The Discrete Turn Algorithm shows improved agreement with optical motion capture and with known turn angles, compared to our previous algorithm by El-Gohary et al. The Merged Turn algorithm that merges consecutive turns in the same direction with short hesitations resulted in turn angle estimates closer to a fixed 180-degree turn angle in the PD, SCA, and HC subjects compared to our previous turn algorithm. Additional metrics were proposed to capture turn hesitations in PD and SCA. CONCLUSION: The Discrete Turn Algorithm may be particularly useful to characterize turns when the turn angle is unknown, i.e., during free-living conditions. The Merged Turn algorithm is recommended for clinical tasks in which the single-turn angle is known, especially for patients who hesitate while turning.

Laboratory versus daily life gait characteristics in patients with multiple sclerosis, Parkinson's disease, and matched controls.

BACKGROUND AND PURPOSE: Recent findings suggest that a gait assessment at a discrete moment in a clinic or laboratory setting may not reflect functional, everyday mobility. As a step towards better understanding gait during daily life in neurological populations, we compared gait measures that best discriminated people with multiple sclerosis (MS) and people with Parkinson's Disease (PD) from their respective, age-matched, healthy control subjects (MS-Ctl, PD-Ctl) in laboratory tests versus a week of daily life monitoring. METHODS: We recruited 15 people with MS (age mean ± SD: 49 ± 10 years), 16 MS-Ctl (45 ± 11 years), 16 people with idiopathic PD (71 ± 5 years), and 15 PD-Ctl (69 ± 7 years). Subjects wore 3 inertial sensors (one each foot and lower back) in the laboratory followed by 7 days during daily life. Mann-Whitney U test and area under the curve (AUC) compared differences between PD and PD-Ctl, and between MS and MS-Ctl in the laboratory and in daily life. RESULTS: Participants wore sensors for 60-68 h in daily life. Measures that best discriminated gait characteristics in people with MS and PD from their respective control groups were different between the laboratory gait test and a week of daily life. Specifically, the toe-off angle best discriminated MS versus MS-Ctl in the laboratory (AUC [95% CI] = 0.80 [0.63-0.96]) whereas gait speed in daily life (AUC = 0.84 [0.69-1.00]). In contrast, the lumbar coronal range of motion best discriminated PD versus PD-Ctl in the laboratory (AUC = 0.78 [0.59-0.96]) whereas foot-strike angle in daily life (AUC = 0.84 [0.70-0.98]). AUCs were larger in daily life compared to the laboratory. CONCLUSIONS: Larger AUC for daily life gait measures compared to the laboratory gait measures suggest that daily life monitoring may be more sensitive to impairments from neurological disease, but each neurological disease may require different gait outcome measures.

Effect of Bout Length on Gait Measures in People with and without Parkinson's Disease during Daily Life.

Although the use of wearable technology to characterize gait disorders in daily life is increasing, there is no consensus on which specific gait bout length should be used to characterize gait. Clinical trialists using daily life gait quality as study outcomes need to understand how gait bout length affects the sensitivity and specificity of measures to discriminate pathological gait as well as the reliability of gait measures across gait bout lengths. We investigated whether Parkinson's disease (PD) affects how gait characteristics change as bout length changes, and how gait bout length affects the reliability and discriminative ability of gait measures to identify gait impairments in people with PD compared to neurotypical Old Adults (OA). We recruited 29 people with PD and 20 neurotypical OA of similar age for this study. Subjects wore 3 inertial sensors, one on each foot and one over the lumbar spine all day, for 7 days. To investigate which gait bout lengths should be included to extract gait measures, we determined the range of gait bout lengths available across all subjects. To investigate if the effect of bout length on each gait measure is similar or not between subjects with PD and OA, we used a growth curve analysis. For reliability and discriminative ability of each gait measure as a function of gait bout length, we used the intraclass correlation coefficient (ICC) and area under the curve (AUC), respectively. Ninety percent of subjects walked with a bout length of less than 53 strides during the week, and the majority (>50%) of gait bouts consisted of less than 12 strides. Although bout length affected all gait measures, the effects depended on the specific measure and sometimes differed for PD versus OA. Specifically, people with PD did not increase/decrease cadence and swing duration with bout length in the same way as OA. ICC and AUC characteristics tended to be larger for shorter than longer gait bouts. Our findings suggest that PD interferes with the scaling of cadence and swing duration with gait bout length. Whereas control subjects gradually increased cadence and decreased swing duration as bout length increased, participants with PD started with higher than normal cadence and shorter than normal stride duration for the smallest bouts, and cadence and stride duration changed little as bout length increased, so differences between PD and OA disappeared for the longer bout lengths. Gait measures extracted from shorter bouts are more common, more reliable, and more discriminative, suggesting that shorter gait bouts should be used to extract potential digital biomarkers for people with PD.

Inter-Rater Agreement of Biofield Tuning: Testing a Novel Health Assessment Procedure.

Objectives: Practitioners of Biofield Tuning assess health status of their clients by detecting off-the-body biofield perturbations using tuning fork (TF) vibrations. This study tested inter-rater agreement (IRA) on location of these perturbations. Design: Three Biofield Tuning practitioners, in randomized order, identified locations of the 4-5 "strongest" perturbations along each of 4 sites for the same series of 10 research subjects. Setting/Location: An Integrative Health and Medicine Center in La Jolla, CA. Subjects: Adult volunteers with no serious current illness and no prior experience of a Biofield Tuning session. Interventions: Practitioners used an activated 174 Hz unweighted TF to "comb" the same four sites per subject, located on the left and right sides of the base of the spine and the heart. Outcome Measures: Practitioners identified and vocalized the distance from the body of perturbations along each site. Distances were recorded by a research assistant in the clinic room. No health information related to perturbation sites was discussed with the subjects. Results: Practitioners reported 6.3 ± 0.6 (mean ± standard deviation) perturbations per combed site per subject, with no significant difference among the raters. The overall level of IRA was low based initially on a first-pass, nonstatistical, analysis of results, with "agreement" defined within a tolerance of ±2 inches. In this approach agreement was 33%. More rigorous statistical analysis, including a statistical test using a Monte Carlo approach, strongly supported the conclusion of poor IRA. Conclusions: IRA was low despite attempts to balance the real-world practice of Biofield Tuning with the constraints of research. For example, while IRA necessitates multiple assessments of the same subject, no information exists as to whether an initial assessment may affect subsequent assessments. Our study exemplifies the challenges faced when attempting to fit interventions with incompletely understood procedures and mechanisms into conventional research designs.

Digital Biomarkers of Mobility in Parkinson's Disease During Daily Living.

BACKGROUND: Identifying digital biomarkers of mobility is important for clinical trials in Parkinson's disease (PD). OBJECTIVE: To determine which digital outcome measures of mobility discriminate mobility in people with PD from healthy control (HC) subjects over a week of continuous monitoring. METHODS: We recruited 29 people with PD, and 27 age-matched HC subjects. Subjects were asked to wear three inertial sensors (Opal by APDM) attached to both feet and to the lumbar region, and a subset of subjects also wore two wrist sensors, for a week of continuous monitoring. We derived 43 digital outcome measures of mobility grouped into five domains. An Area Under Curve (AUC) was calculated for each digital outcome measures of mobility, and logistic regression employing a 'best subsets selection strategy' was used to find combinations of measures that discriminated mobility in PD from HC. RESULTS: Duration of recordings was 66±14 hours in the PD and 59±16 hours in the HC. Out of a total of 43 digital outcome measures of mobility, we found six digital outcome measures of mobility with AUC > 0.80. Turn angle (AUC = 0.89, 95% CI: 0.79-0.97) and swing time variability (AUC = 0.87, 95% CI: 0.75-0.96) were the most discriminative individual measures. Turning measures were most consistently selected via the best subsets strategy to discriminate people with PD from HC, followed by gait variability measures. CONCLUSION: Clinical studies and clinical practice with digital biomarkers of daily life mobility in PD should include turning and variability measures.

Quantity and quality of gait and turning in people with multiple sclerosis, Parkinson's disease and matched controls during daily living.

Clinical trials need to specify which specific gait characteristics to monitor as mobility measures for each neurological disorder. As a first step, this study aimed to investigate a set of measures from daily-life monitoring that best discriminate mobility between people with multiple sclerosis (MS) and age-matched healthy control subjects (MS-Ctl) and between people with Parkinson's disease (PD) and age-matched healthy control subjects (PD-Ctl). Further, we investigated how these discriminative measures relate to the disease severity of MS or PD. We recruited 13 people with MS, 21 MS-Ctl, 29 people with idiopathic PD, and 20 PD-Ctl. Subjects wore 3 inertial sensors on their feet and the lumbar back for a week. The Area Under Curves (AUC) from the receiver operator characteristic (ROC) plot was calculated for each measure to determine the objective measures that best separated the MS and PD groups from their respective control cohorts. Adherence wearing the sensors was similar among groups for 58-66 h of recording (p = 0.14). Quantity of mobility (activity measures, such as a median number of strides per gait bout, AUC = 0.93) best discriminated mobility impairments in MS from MS-Ctl. In contrast, quality of mobility (such as turn angle, AUC = 0.90) best discriminated mobility impairments in PD from PD-Ctl. Mobility measures with AUC > 0.80 were correlated with MS and PD clinical scores of disease severity. Thus, measures characterizing mobility impairments differ for MS versus PD during daily life suggesting that mobility measures for clinical trials and clinical practice need to be specific to each neurological disorder.