Developing better digital health measures of Parkinson's disease using free living data and a crowdsourced data analysis challenge.

One of the promising opportunities of digital health is its potential to lead to more holistic understandings of diseases by interacting with the daily life of patients and through the collection of large amounts of real-world data. Validating and benchmarking indicators of disease severity in the home setting is difficult, however, given the large number of confounders present in the real world and the challenges in collecting ground truth data in the home. Here we leverage two datasets collected from patients with Parkinson's disease, which couples continuous wrist-worn accelerometer data with frequent symptom reports in the home setting, to develop digital biomarkers of symptom severity. Using these data, we performed a public benchmarking challenge in which participants were asked to build measures of severity across 3 symptoms (on/off medication, dyskinesia, and tremor). 42 teams participated and performance was improved over baseline models for each subchallenge. Additional ensemble modeling across submissions further improved performance, and the top models validated in a subset of patients whose symptoms were observed and rated by trained clinicians.

Miniaturized wireless, skin-integrated sensor networks for quantifying full-body movement behaviors and vital signs in infants.

Early identification of atypical infant movement behaviors consistent with underlying neuromotor pathologies can expedite timely enrollment in therapeutic interventions that exploit inherent neuroplasticity to promote recovery. Traditional neuromotor assessments rely on qualitative evaluations performed by specially trained personnel, mostly available in tertiary medical centers or specialized facilities. Such approaches are high in cost, require geographic proximity to advanced healthcare resources, and yield mostly qualitative insight. This paper introduces a simple, low-cost alternative in the form of a technology customized for quantitatively capturing continuous, full-body kinematics of infants during free living conditions at home or in clinical settings while simultaneously recording essential vital signs data. The system consists of a wireless network of small, flexible inertial sensors placed at strategic locations across the body and operated in a wide-bandwidth and time-synchronized fashion. The data serve as the basis for reconstructing three-dimensional motions in avatar form without the need for video recordings and associated privacy concerns, for remote visual assessments by experts. These quantitative measurements can also be presented in graphical format and analyzed with machine-learning techniques, with potential to automate and systematize traditional motor assessments. Clinical implementations with infants at low and at elevated risks for atypical neuromotor development illustrates application of this system in quantitative and semiquantitative assessments of patterns of gross motor skills, along with body temperature, heart rate, and respiratory rate, from long-term and follow-up measurements over a 3-mo period following birth. The engineering aspects are compatible for scaled deployment, with the potential to improve health outcomes for children worldwide via early, pragmatic detection methods.

A smartphone-based online system for fall detection with alert notifications and contextual information of real-life falls.

BACKGROUND: Falls are a leading cause of accidental deaths and injuries worldwide. The risk of falling is especially high for individuals suffering from balance impairments. Retrospective surveys and studies of simulated falling in lab conditions are frequently used and are informative, but prospective information about real-life falls remains sparse. Such data are essential to address fall risks and develop fall detection and alert systems. Here we present the results of a prospective study investigating a proof-of-concept, smartphone-based, online system for fall detection and notification. METHODS: The system uses the smartphone's accelerometer and gyroscope to monitor the participants' motion, and falls are detected using a regularized logistic regression. Data on falls and near-fall events (i.e., stumbles) is stored in a cloud server and fall-related variables are logged onto a web portal developed for data exploration, including the event time and weather, fall probability, and the faller's location and activity before the fall. RESULTS: In total, 23 individuals with an elevated risk of falling carried the phones for 2070 days in which the model classified 14,904,000 events. The system detected 27 of the 37 falls that occurred (sensitivity = 73.0 %) and resulted in one false alarm every 46 days (specificity > 99.9 %, precision = 37.5 %). 42.2 % of the events falsely classified as falls were validated as stumbles. CONCLUSIONS: The system's performance shows the potential of using smartphones for fall detection and notification in real-life. Apart from functioning as a practical fall monitoring instrument, this system may serve as a valuable research tool, enable future studies to scale their ability to capture fall-related data, and help researchers and clinicians to investigate real-falls.

Combining Accelerometer and GPS Features to Evaluate Community Mobility in Knee Ankle Foot Orthoses (KAFO) Users.

Orthotic and assistive devices such as knee ankle foot orthoses (KAFO), come in a variety of forms and fits, with several levels of available features that could help users perform daily activities more naturally. However, objective data on the actual use of these devices outside of the research lab is usually not obtained. Such data could enhance traditional lab-based outcome measures and inform clinical decision-making when prescribing new orthotic and assistive technology. Here, we link data from a GPS unit and an accelerometer mounted on the orthotic device to quantify its usage in the community and examine the correlations with clinical metrics. We collected data from 14 individuals over a period of 2 months as they used their personal KAFO first, and then a novel research KAFO; for each device we quantified number of steps, cadence, time spent at community locations and time wearing the KAFO at those locations. Sensor-derived metrics showed that mobility patterns differed widely between participants (mean steps: 591.3, SD =704.2). The novel KAFO generally enabled participants to walk faster during clinical tests ( ∆6 Minute-Walk-Test=71.5m, p=0.006). However, some participants wore the novel device less often despite improved performance on these clinical measures, leading to poor correlation between changes in clinical outcome measures and changes in community mobility ( ∆6 Minute-Walk-Test - ∆ Community Steps: r=0.09, p=0.76). Our results suggest that some traditional clinical outcome measures may not be associated with the actual wear time of an assistive device in the community, and obtaining personalized data from real-world use through wearable technology is valuable.

Automated, multiparametric monitoring of respiratory biomarkers and vital signs in clinical and home settings for COVID-19 patients.

Capabilities in continuous monitoring of key physiological parameters of disease have never been more important than in the context of the global COVID-19 pandemic. Soft, skin-mounted electronics that incorporate high-bandwidth, miniaturized motion sensors enable digital, wireless measurements of mechanoacoustic (MA) signatures of both core vital signs (heart rate, respiratory rate, and temperature) and underexplored biomarkers (coughing count) with high fidelity and immunity to ambient noises. This paper summarizes an effort that integrates such MA sensors with a cloud data infrastructure and a set of analytics approaches based on digital filtering and convolutional neural networks for monitoring of COVID-19 infections in sick and healthy individuals in the hospital and the home. Unique features are in quantitative measurements of coughing and other vocal events, as indicators of both disease and infectiousness. Systematic imaging studies demonstrate correlations between the time and intensity of coughing, speaking, and laughing and the total droplet production, as an approximate indicator of the probability for disease spread. The sensors, deployed on COVID-19 patients along with healthy controls in both inpatient and home settings, record coughing frequency and intensity continuously, along with a collection of other biometrics. The results indicate a decaying trend of coughing frequency and intensity through the course of disease recovery, but with wide variations across patient populations. The methodology creates opportunities to study patterns in biometrics across individuals and among different demographic groups.

Rapid Screening of Physiological Changes Associated With COVID-19 Using Soft-Wearables and Structured Activities: A Pilot Study.

OBJECTIVE: Controlling the spread of the COVID-19 pandemic largely depends on scaling up the testing infrastructure for identifying infected individuals. Consumer-grade wearables may present a solution to detect the presence of infections in the population, but the current paradigm requires collecting physiological data continuously and for long periods of time on each individual, which poses limitations in the context of rapid screening. Technology: Here, we propose a novel paradigm based on recording the physiological responses elicited by a short (~2 minutes) sequence of activities (i.e. "snapshot"), to detect symptoms associated with COVID-19. We employed a novel body-conforming soft wearable sensor placed on the suprasternal notch to capture data on physical activity, cardio-respiratory function, and cough sounds. RESULTS: We performed a pilot study in a cohort of individuals (n=14) who tested positive for COVID-19 and detected altered heart rate, respiration rate and heart rate variability, relative to a group of healthy individuals (n=14) with no known exposure. Logistic regression classifiers were trained on individual and combined sets of physiological features (heartbeat and respiration dynamics, walking cadence, and cough frequency spectrum) at discriminating COVID-positive participants from the healthy group. Combining features yielded an AUC of 0.94 (95% CI=[0.92, 0.96]) using a leave-one-subject-out cross validation scheme. Conclusions and Clinical Impact: These results, although preliminary, suggest that a sensor-based snapshot paradigm may be a promising approach for non-invasive and repeatable testing to alert individuals that need further screening.

Role of data measurement characteristics in the accurate detection of Parkinson's disease symptoms using wearable sensors.

BACKGROUND: Parkinson's disease (PD) is a progressive neurological disease, with characteristic motor symptoms such as tremor and bradykinesia. There is a growing interest to continuously monitor these and other symptoms through body-worn sensor technology. However, limited battery life and memory capacity hinder the potential for continuous, long-term monitoring with these devices. There is little information available on the relative value of adding sensors, increasing sampling rate, or computing complex signal features, all of which may improve accuracy of symptom detection at the expense of computational resources. Here we build on a previous study to investigate the relationship between data measurement characteristics and accuracy when using wearable sensor data to classify tremor and bradykinesia in patients with PD. METHODS: Thirteen individuals with PD wore a flexible, skin-mounted sensor (collecting tri-axial accelerometer and gyroscope data) and a commercial smart watch (collecting tri-axial accelerometer data) on their predominantly affected hand. The participants performed a series of standardized motor tasks, during which a clinician scored the severity of tremor and bradykinesia in that limb. Machine learning models were trained on scored data to classify tremor and bradykinesia. Model performance was compared when using different types of sensors (accelerometer and/or gyroscope), different data sampling rates (up to 62.5 Hz), and different categories of pre-engineered features (up to 148 features). Performance was also compared between the flexible sensor and smart watch for each analysis. RESULTS: First, there was no effect of device type for classifying tremor symptoms (p > 0.34), but bradykinesia models incorporating gyroscope data performed slightly better (up to 0.05 AUROC) than other models (p = 0.01). Second, model performance decreased with sampling frequency (p < 0.001) for tremor, but not bradykinesia (p > 0.47). Finally, model performance for both symptoms was maintained after substantially reducing the feature set. CONCLUSIONS: Our findings demonstrate the ability to simplify measurement characteristics from body-worn sensors while maintaining performance in PD symptom detection. Understanding the trade-off between model performance and data resolution is crucial to design efficient, accurate wearable sensing systems. This approach may improve the feasibility of long-term, continuous, and real-time monitoring of PD symptoms by reducing computational burden on wearable devices.

Automating sleep stage classification using wireless, wearable sensors.

Polysomnography (PSG) is the current gold standard in high-resolution sleep monitoring; however, this method is obtrusive, expensive, and time-consuming. Conversely, commercially available wrist monitors such as ActiWatch can monitor sleep for multiple days and at low cost, but often overestimate sleep and cannot differentiate between sleep stages, such as rapid eye movement (REM) and non-REM. Wireless wearable sensors are a promising alternative for their portability and access to high-resolution data for customizable analytics. We present a multimodal sensor system measuring hand acceleration, electrocardiography, and distal skin temperature that outperforms the ActiWatch, detecting wake and sleep with a recall of 74.4% and 90.0%, respectively, as well as wake, non-REM, and REM with recall of 73.3%, 59.0%, and 56.0%, respectively. This approach will enable clinicians and researchers to more easily, accurately, and inexpensively assess long-term sleep patterns, diagnose sleep disorders, and monitor risk factors for disease in both laboratory and home settings.

Association of sleep with neurobehavioral impairments during inpatient rehabilitation after traumatic brain injury.

BACKGROUND: Sleep disturbance is a common sequela after traumatic brain injury (TBI). Many of the impairments following TBI may be exacerbated by impaired sleep-wake cycle regulation. OBJECTIVES: To investigate the relationship between total sleep time (TST), measured by wrist actigraphy and observational sleep logs, and neurobehavioral impairments during inpatient rehabilitation after TBI. METHODS: Twenty-five subjects undergoing inpatient rehabilitation for traumatic brain injury were included. TST was measured using wrist actigraphy and observational sleep logs. Neurobehavioral impairments were assessed using the Neurobehavioral Rating Scale-Revised (NRS-R), a multidimensional clinician-based assessment. RESULTS: Of 25 subjects enrolled, 23 subjects completed the study. A significant negative correlation was found between total NRS-R and TST calculated by observational sleep logs (r = -0.28, p = 0.007). The association between total NRS-R and TST, as calculated by actigraphy, was not significantly correlated (R = -0.01, p = 0.921). CONCLUSIONS: Sleep disturbance during inpatient rehabilitation is associated with neurobehavioral impairments after TBI. TST measured by actigraphy may be limited by sleep detection algorithms that have not been validated in certain patient populations. Considerations should be made regarding the feasibility of using wearable sensors in patients with cognitive and behavioral impairments. Challenges regarding actigraphy for sleep monitoring in the brain injury population are discussed.

Wearable sensors for Parkinson's disease: which data are worth collecting for training symptom detection models.

Machine learning algorithms that use data streams captured from soft wearable sensors have the potential to automatically detect PD symptoms and inform clinicians about the progression of disease. However, these algorithms must be trained with annotated data from clinical experts who can recognize symptoms, and collecting such data are costly. Understanding how many sensors and how much labeled data are required is key to successfully deploying these models outside of the clinic. Here we recorded movement data using 6 flexible wearable sensors in 20 individuals with PD over the course of multiple clinical assessments conducted on 1 day and repeated 2 weeks later. Participants performed 13 common tasks, such as walking or typing, and a clinician rated the severity of symptoms (bradykinesia and tremor). We then trained convolutional neural networks and statistical ensembles to detect whether a segment of movement showed signs of bradykinesia or tremor based on data from tasks performed by other individuals. Our results show that a single wearable sensor on the back of the hand is sufficient for detecting bradykinesia and tremor in the upper extremities, whereas using sensors on both sides does not improve performance. Increasing the amount of training data by adding other individuals can lead to improved performance, but repeating assessments with the same individuals-even at different medication states-does not substantially improve detection across days. Our results suggest that PD symptoms can be detected during a variety of activities and are best modeled by a dataset incorporating many individuals.

Addendum of: Fall Detection in Individuals With Lower Limb Amputations Using Mobile Phones: Machine Learning Enhances Robustness for Real-World Applications.

[This corrects the article DOI: 10.2196/mhealth.8201.].

Fall Detection in Individuals With Lower Limb Amputations Using Mobile Phones: Machine Learning Enhances Robustness for Real-World Applications.

BACKGROUND: Automatically detecting falls with mobile phones provides an opportunity for rapid response to injuries and better knowledge of what precipitated the fall and its consequences. This is beneficial for populations that are prone to falling, such as people with lower limb amputations. Prior studies have focused on fall detection in able-bodied individuals using data from a laboratory setting. Such approaches may provide a limited ability to detect falls in amputees and in real-world scenarios. OBJECTIVE: The aim was to develop a classifier that uses data from able-bodied individuals to detect falls in individuals with a lower limb amputation, while they freely carry the mobile phone in different locations and during free-living. METHODS: We obtained 861 simulated indoor and outdoor falls from 10 young control (non-amputee) individuals and 6 individuals with a lower limb amputation. In addition, we recorded a broad database of activities of daily living, including data from three participants' free-living routines. Sensor readings (accelerometer and gyroscope) from a mobile phone were recorded as participants freely carried it in three common locations-on the waist, in a pocket, and in the hand. A set of 40 features were computed from the sensors data and four classifiers were trained and combined through stacking to detect falls. We compared the performance of two population-specific models, trained and tested on either able-bodied or amputee participants, with that of a model trained on able-bodied participants and tested on amputees. A simple threshold-based classifier was used to benchmark our machine-learning classifier. RESULTS: The accuracy of fall detection in amputees for a model trained on control individuals (sensitivity: mean 0.989, 1.96*standard error of the mean [SEM] 0.017; specificity: mean 0.968, SEM 0.025) was not statistically different (P=.69) from that of a model trained on the amputee population (sensitivity: mean 0.984, SEM 0.016; specificity: mean 0.965, SEM 0.022). Detection of falls in control individuals yielded similar results (sensitivity: mean 0.979, SEM 0.022; specificity: mean 0.991, SEM 0.012). A mean 2.2 (SD 1.7) false alarms per day were obtained when evaluating the model (vs mean 122.1, SD 166.1 based on thresholds) on data recorded as participants carried the phone during their daily routine for two or more days. Machine-learning classifiers outperformed the threshold-based one (P<.001). CONCLUSIONS: A mobile phone-based fall detection model can use data from non-amputee individuals to detect falls in individuals walking with a prosthesis. We successfully detected falls when the mobile phone was carried across multiple locations and without a predetermined orientation. Furthermore, the number of false alarms yielded by the model over a longer period of time was reasonably low. This moves the application of mobile phone-based fall detection systems closer to a real-world use case scenario.

Activity Recognition for Persons With Stroke Using Mobile Phone Technology: Toward Improved Performance in a Home Setting.

BACKGROUND: Smartphones contain sensors that measure movement-related data, making them promising tools for monitoring physical activity after a stroke. Activity recognition (AR) systems are typically trained on movement data from healthy individuals collected in a laboratory setting. However, movement patterns change after a stroke (eg, gait impairment), and activities may be performed differently at home than in a lab. Thus, it is important to validate AR for gait-impaired stroke patients in a home setting for accurate clinical predictions. OBJECTIVE: In this study, we sought to evaluate AR performance in a home setting for individuals who had suffered a stroke, by using different sets of training activities. Specifically, we compared AR performance for persons with stroke while varying the origin of training data, based on either population (healthy persons or persons with stoke) or environment (laboratory or home setting). METHODS: Thirty individuals with stroke and fifteen healthy subjects performed a series of mobility-related activities, either in a laboratory or at home, while wearing a smartphone. A custom-built app collected signals from the phone's accelerometer, gyroscope, and barometer sensors, and subjects self-labeled the mobility activities. We trained a random forest AR model using either healthy or stroke activity data. Primary measures of AR performance were (1) the mean recall of activities and (2) the misclassification of stationary and ambulatory activities. RESULTS: A classifier trained on stroke activity data performed better than one trained on healthy activity data, improving average recall from 53% to 75%. The healthy-trained classifier performance declined with gait impairment severity, more often misclassifying ambulatory activities as stationary ones. The classifier trained on in-lab activities had a lower average recall for at-home activities (56%) than for in-lab activities collected on a different day (77%). CONCLUSIONS: Stroke-based training data is needed for high quality AR among gait-impaired individuals with stroke. Additionally, AR systems for home and community monitoring would likely benefit from including at-home activities in the training data.

Accelerometry-enabled measurement of walking performance with a robotic exoskeleton: a pilot study.

BACKGROUND: Clinical scores for evaluating walking skills with lower limb exoskeletons are often based on a single variable, such as distance walked or speed, even in cases where a host of features are measured. We investigated how to combine multiple features such that the resulting score has high discriminatory power, in particular with few patients. A new score is introduced that allows quantifying the walking ability of patients with spinal cord injury when using a powered exoskeleton. METHODS: Four spinal cord injury patients were trained to walk over ground with the ReWalk™ exoskeleton. Body accelerations during use of the device were recorded by a wearable accelerometer and 4 features to evaluate walking skills were computed. The new score is the Gaussian naïve Bayes surprise, which evaluates patients relative to the features' distribution measured in 7 expert users of the ReWalk™. We compared our score based on all the features with a standard outcome measure, which is based on number of steps only. RESULTS: All 4 patients improved over the course of training, as their scores trended towards the expert users' scores. The combined score (Gaussian naïve surprise) was considerably more discriminative than the one using only walked distance (steps). At the end of training, 3 out of 4 patients were significantly different from the experts, according to the combined score (p < .001, Wilcoxon Signed-Rank Test). In contrast, all but one patient were scored as experts when number of steps was the only feature. CONCLUSION: Integrating multiple features could provide a more robust metric to measure patients' skills while they learn to walk with a robotic exoskeleton. Testing this approach with other features and more subjects remains as future work.

Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.