Translating digital healthcare to enhance clinical management: a protocol for an observational study using a digital health technology system to monitor medication adherence and its effect on mobility in people with Parkinson's.

INTRODUCTION: In people with Parkinson's (PwP) impaired mobility is associated with an increased falls risk. To improve mobility, dopaminergic medication is typically prescribed, but complex medication regimens result in suboptimal adherence. Exploring medication adherence and its impact on mobility in PwP will provide essential insights to optimise medication regimens and improve mobility. However, this is typically assessed in controlled environments, during one-off clinical assessments. Digital health technology (DHT) presents a means to overcome this, by continuously and remotely monitoring mobility and medication adherence. This study aims to use a novel DHT system (DHTS) (comprising of a smartphone, smartwatch and inertial measurement unit (IMU)) to assess self-reported medication adherence, and its impact on digital mobility outcomes (DMOs) in PwP. METHODS AND ANALYSIS: This single-centre, UK-based study, will recruit 55 participants with Parkinson's. Participants will complete a range of clinical, and physical assessments. Participants will interact with a DHTS over 7 days, to assess self-reported medication adherence, and monitor mobility and contextual factors in the real world. Participants will complete a motor complications diary (ON-OFF-Dyskinesia) throughout the monitoring period and, at the end, a questionnaire and series of open-text questions to evaluate DHTS usability. Feasibility of the DHTS and the motor complications diary will be assessed. Validated algorithms will quantify DMOs from IMU walking activity. Time series modelling and deep learning techniques will model and predict DMO response to medication and effects of contextual factors. This study will provide essential insights into medication adherence and its effect on real-world mobility in PwP, providing insights to optimise medication regimens. ETHICS AND DISSEMINATION: Ethical approval was granted by London-142 Westminster Research Ethics Committee (REC: 21/PR/0469), protocol V.2.4. Results will be published in peer-reviewed journals. All participants will provide written, informed consent. TRIAL REGISTRATION NUMBER: ISRCTN13156149.

Can Digital Mobility Assessment Enhance the Clinical Assessment of Disease Severity in Parkinson's Disease?

BACKGROUND: Real-world walking speed (RWS) measured using wearable devices has the potential to complement the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS III) for motor assessment in Parkinson's disease (PD). OBJECTIVE: Explore cross-sectional and longitudinal differences in RWS between PD and older adults (OAs), and whether RWS was related to motor disease severity cross-sectionally, and if MDS-UPDRS III was related to RWS, longitudinally. METHODS: 88 PD and 111 OA participants from ICICLE-GAIT (UK) were included. RWS was evaluated using an accelerometer at four time points. RWS was aggregated within walking bout (WB) duration thresholds. Between-group-comparisons in RWS between PD and OAs were conducted cross-sectionally, and longitudinally with mixed effects models (MEMs). Cross-sectional association between RWS and MDS-UPDRS III was explored using linear regression, and longitudinal association explored with MEMs. RESULTS: RWS was significantly lower in PD (1.04 m/s) in comparison to OAs (1.10 m/s) cross-sectionally. RWS significantly decreased over time for both cohorts and decline was more rapid in PD by 0.02 m/s per year. Significant negative relationship between RWS and the MDS-UPDRS III only existed at a specific WB threshold (30 to 60 s, ß= - 3.94 points, p = 0.047). MDS-UPDRS III increased significantly by 1.84 points per year, which was not related to change in RWS. CONCLUSION: Digital mobility assessment of gait may add unique information to quantify disease progression remotely, but further validation in research and clinical settings is needed.

A multi-sensor wearable system for the assessment of diseased gait in real-world conditions.

Introduction: Accurately assessing people's gait, especially in real-world conditions and in case of impaired mobility, is still a challenge due to intrinsic and extrinsic factors resulting in gait complexity. To improve the estimation of gait-related digital mobility outcomes (DMOs) in real-world scenarios, this study presents a wearable multi-sensor system (INDIP), integrating complementary sensing approaches (two plantar pressure insoles, three inertial units and two distance sensors). Methods: The INDIP technical validity was assessed against stereophotogrammetry during a laboratory experimental protocol comprising structured tests (including continuous curvilinear and rectilinear walking and steps) and a simulation of daily-life activities (including intermittent gait and short walking bouts). To evaluate its performance on various gait patterns, data were collected on 128 participants from seven cohorts: healthy young and older adults, patients with Parkinson's disease, multiple sclerosis, chronic obstructive pulmonary disease, congestive heart failure, and proximal femur fracture. Moreover, INDIP usability was evaluated by recording 2.5-h of real-world unsupervised activity. Results and discussion: Excellent absolute agreement (ICC >0.95) and very limited mean absolute errors were observed for all cohorts and digital mobility outcomes (cadence ≤0.61 steps/min, stride length ≤0.02 m, walking speed ≤0.02 m/s) in the structured tests. Larger, but limited, errors were observed during the daily-life simulation (cadence 2.72-4.87 steps/min, stride length 0.04-0.06 m, walking speed 0.03-0.05 m/s). Neither major technical nor usability issues were declared during the 2.5-h acquisitions. Therefore, the INDIP system can be considered a valid and feasible solution to collect reference data for analyzing gait in real-world conditions.

Free-living monitoring of ambulatory activity after treatments for lower extremity musculoskeletal cancers using an accelerometer-based wearable - a new paradigm to outcome assessment in musculoskeletal oncology?

PURPOSE: Ambulatory activity (walking) is affected after sarcoma surgery yet is not routinely assessed. Small inexpensive accelerometers could bridge the gap. Study objectives investigated, whether in patients with lower extremity musculoskeletal tumours: (A) it was feasible to conduct ambulatory activity assessments in patient's homes using an accelerometer-based wearable (AX3, Axivity). (B) AX3 assessments produced clinically useful data, distinguished tumour sub-groups and related to existing measures. METHODS: In a prospective cross-sectional pilot, 34 patients with musculoskeletal tumours in the femur/thigh (19), pelvis/hip (3), tibia/leg (9), or ankle/foot (3) participated. Twenty-seven had limb-sparing surgery and seven amputation. Patients were assessed using a thigh-worn monitor. Summary measures of volume (total steps/day, total ambulatory bouts/day, mean bout length), pattern (alpha), and variability (S2) of ambulatory activity were derived. RESULTS: AX3 was well-tolerated and feasible to use. Outcomes compared to literature but did not distinguish tumour sub-groups. Alpha negatively correlated with disability (walking outside (r=-418, p = 0.042*), social life (r=-0.512, p = 0.010*)). Disability negatively predicted alpha (unstandardised co-efficient= -0.001, R2=0.186, p = 0.039*). CONCLUSIONS: A wearable can assess novel attributes of walking; volume, pattern, and variability after sarcoma surgery. Such outcomes provide valuable information about people's physical performance in their homes, which can guide rehabilitation. Implications for rehabilitationRoutine capture of ambulatory activity by sarcoma services in peoples' homes can provide important information about individuals "actual" physical activity levels and limitations after sarcoma surgery to inform personalised rehabilitation and care needs, including timely referral for support.Routine remote ambulatory monitoring about out of hospital activity can support personalised care for patients, including identifying high risk patients who need rapid intervention and care closer to home.Use of routine remote ambulatory monitoring could enhance delivery of evidence-based care closer to peoples' homes without disrupting their daily routine and therefore reducing patient and carer burden.Collection of data close to home using questionnaires and objective community assessment could be more cost effective and comprehensive than in-hospital assessment and could reduce the need for hospital attendance, which is of importance to vulnerable patients, particularly during the Covid-19 pandemic.

The Impact of Environment on Gait Assessment: Considerations from Real-World Gait Analysis in Dementia Subtypes.

Laboratory-based gait assessments are indicative of clinical outcomes (e.g., disease identification). Real-world gait may be more sensitive to clinical outcomes, as impairments may be exaggerated in complex environments. This study aims to investigate how different environments (e.g., lab, real world) impact gait. Different walking bout lengths in the real world will be considered proxy measures of context. Data collected in different dementia disease subtypes will be analysed as disease-specific gait impairments are reported between these groups. Thirty-two people with cognitive impairment due to Alzheimer's disease (AD), 28 due to dementia with Lewy bodies (DLB) and 25 controls were recruited. Participants wore a tri-axial accelerometer for six 10 m walks in lab settings, and continuously for seven days in the real world. Fourteen gait characteristics across five domains were measured (i.e., pace, variability, rhythm, asymmetry, postural control). In the lab, the DLB group showed greater step length variability (p = 0.008) compared to AD. Both subtypes demonstrated significant gait impairments (p < 0.01) compared to controls. In the real world, only very short walking bouts (<10 s) demonstrated different gait impairments between subtypes. The context where walking occurs impacts signatures of gait impairment in dementia subtypes. To develop real-world gait assessment as a clinical tool, algorithms and metrics must accommodate for changes in context.

An Objective Methodology for the Selection of a Device for Continuous Mobility Assessment.

Continuous monitoring by wearable technology is ideal for quantifying mobility outcomes in "real-world" conditions. Concurrent factors such as validity, usability, and acceptability of such technology need to be accounted for when choosing a monitoring device. This study proposes a bespoke methodology focused on defining a decision matrix to allow for effective decision making. A weighting system based on responses (n = 69) from a purpose-built questionnaire circulated within the IMI Mobilise-D consortium and its external collaborators was established, accounting for respondents' background and level of expertise in using wearables in clinical practice. Four domains (concurrent validity, CV; human factors, HF; wearability and usability, WU; and data capture process, CP), associated evaluation criteria, and scores were established through literature research and group discussions. While the CV was perceived as the most relevant domain (37%), the others were also considered highly relevant (WU: 30%, HF: 17%, CP: 16%). Respondents (~90%) preferred a hidden fixation and identified the lower back as an ideal sensor location for mobility outcomes. Overall, this study provides a novel, holistic, objective, as well as a standardized approach accounting for complementary aspects that should be considered by professionals and researchers when selecting a solution for continuous mobility monitoring.

Evaluating the effects of an exercise program (Staying UpRight) for older adults in long-term care on rates of falls: study protocol for a randomised controlled trial.

BACKGROUND: Falls are two to four times more frequent amongst older adults living in long-term care (LTC) than community-dwelling older adults and have deleterious consequences. It is hypothesised that a progressive exercise program targeting balance and strength will reduce fall rates when compared to a seated exercise program and do so cost effectively. METHODS/DESIGN: This is a single blind, parallel-group, randomised controlled trial with blinded assessment of outcome and intention-to-treat analysis. LTC residents (age ≥ 65 years) will be recruited from LTC facilities in New Zealand. Participants (n = 528 total, with a 1:1 allocation ratio) will be randomly assigned to either a novel exercise program (Staying UpRight), comprising strength and balance exercises designed specifically for LTC and acceptable to people with dementia (intervention group), or a seated exercise program (control group). The intervention and control group classes will be delivered for 1 h twice weekly over 1 year. The primary outcome is rate of falls (per 1000 person years) within the intervention period. Secondary outcomes will be risk of falling (the proportion of fallers per group), fall rate relative to activity exposure, hospitalisation for fall-related injury, change in gait variability, volume and patterns of ambulatory activity and change in physical performance assessed at baseline and after 6 and 12 months. Cost-effectiveness will be examined using intervention and health service costs. The trial commenced recruitment on 30 November 2018. DISCUSSION: This study evaluates the efficacy and cost-effectiveness of a progressive strength and balance exercise program for aged care residents to reduce falls. The outcomes will aid development of evidenced-based exercise programmes for this vulnerable population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618001827224. Registered on 9 November 2018. Universal trial number U1111-1217-7148.

Comparison of Walking Protocols and Gait Assessment Systems for Machine Learning-Based Classification of Parkinson's Disease.

Early diagnosis of Parkinson's diseases (PD) is challenging; applying machine learning (ML) models to gait characteristics may support the classification process. Comparing performance of ML models used in various studies can be problematic due to different walking protocols and gait assessment systems. The objective of this study was to compare the impact of walking protocols and gait assessment systems on the performance of a support vector machine (SVM) and random forest (RF) for classification of PD. 93 PD and 103 controls performed two walking protocols at their normal pace: (i) four times along a 10 m walkway (intermittent walk-IW), (ii) walking for 2 minutes on a 25 m oval circuit (continuous walk-CW). 14 gait characteristics were extracted from two different systems (an instrumented walkway-GAITRite; and an accelerometer attached at the lower back-Axivity). SVM and RF were trained on normalized data (accounting for step velocity, gender, age and BMI) and evaluated using 10-fold cross validation with area under the curve (AUC). Overall performance was higher for both systems during CW compared to IW. SVM performed better than RF. With SVM, during CW Axivity significantly outperformed GAITRite (AUC: 87.83 ± 7.81% vs. 80.49 ± 9.85%); during IW systems performed similarly. These findings suggest that choice of testing protocol and sensing system may have a direct impact on ML PD classification results and highlight the need for standardization for wide scale implementation.

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function'-in other words to develop a toolkit for assessing musculoskeletal ageing. This toolkit is envisaged as an instrument that can be used to characterise and quantify musculoskeletal function during 'normal' ageing, lend itself to use in large-scale, internationally important cohorts, and provide a set of biomarker outcome measures for epidemiological and intervention studies designed to enhance healthy musculoskeletal ageing. Such potential biomarkers include: biochemical measurements in biofluids or tissue samples, in vivo measurements of body composition, imaging of structural and physical properties, and functional tests. This review assesses candidate biomarkers of musculoskeletal ageing under these four headings, details their biological bases, strengths and limitations, and makes practical recommendations for their use. In addition, we identify gaps in the evidence base and priorities for further research on biomarkers of musculoskeletal ageing.

Towards holistic free-living assessment in Parkinson's disease: Unification of gait and fall algorithms with a single accelerometer.

Technological developments have seen the miniaturization of sensors, small enough to be embedded in wearable devices facilitating unobtrusive and longitudinal monitoring in free-living environments. Concurrently, the advances in algorithms have been ad-hoc and fragmented. To advance the mainstream use of wearable technology and improved functionality of algorithms all methodologies must be unified and robustly tested within controlled and free-living conditions. Here we present and unify a (i) gait segmentation and analysis algorithm and (ii) a fall detection algorithm. We tested the unified algorithms on a cohort of young healthy adults within a laboratory. We then deployed the algorithms on longitudinal (7 day) accelerometer-based data from an older adult with Parkinson's disease (PD) to quantify real world gait and falls. We compared instrumented falls to a self-reported falls diary to test algorithm efficiency and discuss the use of unified algorithms to impact free-living assessment in PD where accurate recognition of gait may reduce the number of automated detected falls (38/week). This informs ongoing work to use gait and related outcomes as pragmatic clinical markers.

Toward a low-cost gait analysis system for clinical and free-living assessment.

Gait is an important clinical assessment tool since changes in gait may reflect changes in general health. Measurement of gait is a complex process which has been restricted to bespoke clinical facilities until recently. The use of inexpensive wearable technologies is an attractive alternative and offers the potential to assess gait in any environment. In this paper we present the development of a low cost analysis gait system built using entirely open source components. The system is used to capture spatio-temporal gait characteristics derived from an existing conceptual model, sensitive to ageing and neurodegenerative pathology (e.g. Parkinson's disease). We demonstrate the system is suitable for use in a clinical unit and will lead to pragmatic use in a free-living (home) environment. The system consists of a wearable (tri-axial accelerometer and gyroscope) with a Raspberry Pi module for data storage and analysis. This forms ongoing work to develop gait as a low cost diagnostic in modern healthcare.

Assessment of biofeedback rehabilitation in post-stroke patients combining fMRI and gait analysis: a case study.

BACKGROUND: The ability to walk independently is a primary goal for rehabilitation after stroke. Gait analysis provides a great amount of valuable information, while functional magnetic resonance imaging (fMRI) offers a powerful approach to define networks involved in motor control. The present study reports a new methodology based on both fMRI and gait analysis outcomes in order to investigate the ability of fMRI to reflect the phases of motor learning before/after electromyographic biofeedback treatment: the preliminary fMRI results of a post stroke subject's brain activation, during passive and active ankle dorsal/plantarflexion, before and after biofeedback (BFB) rehabilitation are reported and their correlation with gait analysis data investigated. METHODS: A control subject and a post-stroke patient with chronic hemiparesis were studied. Functional magnetic resonance images were acquired during a block-design protocol on both subjects while performing passive and active ankle dorsal/plantarflexion. fMRI and gait analysis were assessed on the patient before and after electromyographic biofeedback rehabilitation treatment during gait activities. Lower limb three-dimensional kinematics, kinetics and surface electromyography were evaluated. Correlation between fMRI and gait analysis categorical variables was assessed: agreement/disagreement was assigned to each variable if the value was in/outside the normative range (gait analysis), or for presence of normal/diffuse/no activation of motor area (fMRI). RESULTS: Altered fMRI activity was found on the post-stroke patient before biofeedback rehabilitation with respect to the control one. Meanwhile the patient showed a diffuse, but more limited brain activation after treatment (less voxels). The post-stroke gait data showed a trend towards the normal range: speed, stride length, ankle power, and ankle positive work increased. Preliminary correlation analysis revealed that consistent changes were observed both for the fMRI data, and the gait analysis data after treatment (R > 0.89): this could be related to the possible effects BFB might have on the central as well as on the peripheral nervous system. CONCLUSIONS: Our findings showed that this methodology allows evaluation of the relationship between alterations in gait and brain activation of a post-stroke patient. Such methodology, if applied on a larger sample subjects, could provide information about the specific motor area involved in a rehabilitation treatment.

Within trial validation and reliability of a single tri-axial accelerometer for gait assessment.

Gait is a sensitive biomarker of decline in both cognitive and physical function. Therefore, the collection of gait data is an important feature of clinical assessments. Accelerometer-based body worn sensors are quickly becoming the preferred tool for assessing gait because they are small, useable in a wide variety of settings, offer more continuous spatio-temporal analysis and are inexpensive when compared with traditional gait assessment methodologies. The purpose of this study was to determine the validity and within test reliability of a low cost body worn movement sensor with associated algorithms to assess gait in a large group of older and younger healthy adults. We collected gait data over intermittent walks on an instrumented walkway for a within trial validation and also used the same accelerometer derived gait data for a within test reliability analysis. ICCs for validation and reliability were >0.756 and >0.965, respectively.

Biomechanical assessment of balance and posture in subjects with ankylosing spondylitis.

BACKGROUND: Ankylosing spondylitis is a major chronic rheumatic disease that predominantly affects axial joints, determining a rigid spine from the occiput to the sacrum. The dorsal hyperkyphosis may induce the patients to stand in a stooped position with consequent restriction in patients' daily living activities. The aim of this study was to develop a method for quantitatively and objectively assessing both balance and posture and their mutual relationship in ankylosing spondylitis subjects. METHODS: The data of 12 healthy and 12 ankylosing spondylitis subjects (treated with anti-TNF-α stabilized), with a mean age of 51.42 and 49.42 years; mean BMI of 23.08 and 25.44 kg/m(2) were collected. Subjects underwent a morphological examination of the spinal mobility by means of a pocket compass needle goniometer, together with an evaluation of both spinal and hip mobility (Bath Ankylosing Spondylitis Metrology Index), and disease activity (Bath Ankylosing Spondylitis Disease Activity Index). Quantitative evaluation of kinematics and balance were performed through a six cameras stereophotogrammetric system and a force plate. Kinematic models together with a test for evaluating balance in different eye level conditions were developed. Head protrusion, trunk flexion-extension, pelvic tilt, hip-knee-ankle flexion-extension were evaluated during Romberg Test, together with centre of pressure parameters. RESULTS: Each subject was able to accomplish the required task. Subjects' were comparable for demographic parameters. A significant increment was observed in ankylosing spondylitis subjects for knee joint angle with the target placed at each eye level on both sides (p < 0.042). When considering the pelvic tilt angle a statistically significant reduction was found with the target placed respectively at 10° (p = 0.034) and at 30° (p = 0.019) less than eye level. Furthermore in ankylosing spondylitis subjects both hip (p = 0.048) and ankle (p = 0.029) joints angles differs significantly. When considering the posturographic parameters significant differences were observed for ellipse, center of pressure path and mean velocity (p < 0.04). Goniometric evaluation revealed significant increment of thoracic kyphosis reduction of cervical and lumbar range of motion compared to healthy subjects. CONCLUSIONS: Our findings confirm the need to investigate both balance and posture in ankylosing spondylitis subjects. This methodology could help clinicians to plan rehabilitation treatments.