A Novel Unsupervised Machine Learning Approach to Assess Postural Dynamics in Euthymic Bipolar Disorder.

Bipolar disorder (BD) is a mood disorder with different phases alternating between euthymia, manic or hypomanic episodes, and depressive episodes. While motor abnormalities are commonly seen during depressive or manic episodes, not much attention has been paid to postural abnormalities during periods of euthymia and their association with illness burden. We collected 24-hour posture data in 32 euthymic participants diagnosed with BD using a shirt-based wearable. We extracted a set of nine time-domain features, and performed unsupervised participant clustering. We investigated the association between posture variables and 12 clinical characteristics of illness burden. Based on their postural dynamics during the daytime, evening, or nighttime, participants clustered in three clusters. Higher illness burden was associated with lower postural variability, in particular during daytime. Participants who exhibited a mostly upright sitting/standing posture during the night with frequent nighttime postural transitions had the highest number of lifetime depressive episodes. Euthymic participants with BD exhibit postural abnormalities that are associated with illness burden, especially with the number of depressive episodes. Our results contribute to understanding the role of illness burden on posture changes and sleep consolidation in periods of euthymia.

Innovative Technologies in CNS Trials: Promises and Pitfalls for Recruitment, Retention, and Representativeness.

Objective: Recruitment of a sufficiently large and representative patient sample and its retention during central nervous system (CNS) trials presents major challenges for study sponsors. Technological advances are reshaping clinical trial operations to meet these challenges, and the COVID-19 pandemic further accelerated this development. Method of Research: The International Society for CNS Clinical Trials and Methodology (ISCTM; www.isctm.org) Innovative Technologies for CNS Trials Working Group surveyed the state of technological innovations for improved recruitment and retention and assessed their promises and pitfalls. Results: Online advertisement and electronic patient registries can enhance recruitment, but challenges with sample representativeness, conversion rates from eligible prescreening to enrolled patients, data privacy and security, and patient identification remain hurdles for optimal use of these technologies. Electronic medical records (EMR) mining with artificial intelligence (AI)/machine learning (ML) methods is promising but awaits translation into trials. During the study treatment phase, technological innovations increasingly support participant retention, including adherence with the investigational treatment. Digital tools for adherence and retention support take many forms, including patient-centric communication channels between researchers and participants, real-time study reminders, and digital behavioral interventions to increase study compliance. However, such tools add technical complexities to trials, and their impact on the generalizability of results are largely unknown. Conclusion: Overall, the group found a scarcity of systematic data directly assessing the impact of technological innovations on study recruitment and retention in CNS trials, even for strategies with already high adoption, such as online recruitment. Given the added complexity and costs associated with most technological innovations, such data is needed to fully harness technologies for CNS trials and drive further adoption.

Geospatial divide in real-world EHR data: Analytical workflow to assess regional biases and potential impact on health equity.

Real-world data (RWD) like electronic health records (EHR) has great potential for secondary use by health systems and researchers. However, collected primarily for efficient health care, EHR data may not equitably represent local regions and populations, impacting the generalizability of insights learned from it. We assessed the geospatial representativeness of regions in a large health system EHR data using a spatial analysis workflow, which provides a data-driven way to quantify geospatial representation and identify adequately represented regions. We applied the workflow to investigate geospatial patterns of overweight/obesity and depression patients to find regional "hotspots" for potential targeted interventions. Our findings show the presence of geospatial bias in EHR and demonstrate the workflow to identify spatial clusters after adjusting for bias due to the geospatial representativeness. This work highlights the importance of evaluating geospatial representativeness in RWD to guide targeted deployment of limited healthcare resources and generate equitable real-world evidence.

Association of Demographic and Socioeconomic Indicators With the Use of Wearable Devices Among Children.

Importance: The use of consumer-grade wearable devices for collecting data for biomedical research may be associated with social determinants of health (SDoHs) linked to people's understanding of and willingness to join and remain engaged in remote health studies. Objective: To examine whether demographic and socioeconomic indicators are associated with willingness to join a wearable device study and adherence to wearable data collection in children. Design, Setting, and Participants: This cohort study used wearable device usage data collected from 10 414 participants (aged 11-13 years) at the year-2 follow-up (2018-2020) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, performed at 21 sites across the United States. Data were analyzed from November 2021 to July 2022. Main Outcomes and Measures: The 2 primary outcomes were (1) participant retention in the wearable device substudy and (2) total device wear time during the 21-day observation period. Associations between the primary end points and sociodemographic and economic indicators were examined. Results: The mean (SD) age of the 10 414 participants was 12.00 (0.72) years, with 5444 (52.3%) male participants. Overall, 1424 participants (13.7%) were Black; 2048 (19.7%), Hispanic; and 5615 (53.9%) White. Substantial differences were observed between the cohort that participated and shared wearable device data (wearable device cohort [WDC]; 7424 participants [71.3%]) compared with those who did not participate or share data (no wearable device cohort [NWDC]; 2900 participants [28.7%]). Black children were significantly underrepresented (-59%) in the WDC (847 [11.4%]) compared with the NWDC (577 [19.3%]; P < .001). In contrast, White children were overrepresented (+132%) in the WDC (4301 [57.9%]) vs the NWDC (1314 [43.9%]; P < .001). Children from low-income households (<$24 999) were significantly underrepresented in WDC (638 [8.6%]) compared with NWDC (492 [16.5%]; P < .001). Overall, Black children were retained for a substantially shorter duration (16 days; 95% CI, 14-17 days) compared with White children (21 days; 95% CI, 21-21 days; P < .001) in the wearable device substudy. In addition, total device wear time during the observation was notably different between Black vs White children (ß = -43.00 hours; 95% CI, -55.11 to -30.88 hours; P < .001). Conclusions and Relevance: In this cohort study, large-scale wearable device data collected from children showed considerable differences between White and Black children in terms of enrollment and daily wear time. While wearable devices provide an opportunity for real-time, high-frequency contextual monitoring of individuals' health, future studies should account for and address considerable representational bias in wearable data collection associated with demographic and SDoH factors.

Long-term participant retention and engagement patterns in an app and wearable-based multinational remote digital depression study.

Recent growth in digital technologies has enabled the recruitment and monitoring of large and diverse populations in remote health studies. However, the generalizability of inference drawn from remotely collected health data could be severely impacted by uneven participant engagement and attrition over the course of the study. We report findings on long-term participant retention and engagement patterns in a large multinational observational digital study for depression containing active (surveys) and passive sensor data collected via Android smartphones, and Fitbit devices from 614 participants for up to 2 years. Majority of participants (67.6%) continued to remain engaged in the study after 43 weeks. Unsupervised clustering of participants' study apps and Fitbit usage data showed 3 distinct engagement subgroups for each data stream. We found: (i) the least engaged group had the highest depression severity (4 PHQ8 points higher) across all data streams; (ii) the least engaged group (completed 4 bi-weekly surveys) took significantly longer to respond to survey notifications (3.8 h more) and were 5 years younger compared to the most engaged group (completed 20 bi-weekly surveys); and (iii) a considerable proportion (44.6%) of the participants who stopped completing surveys after 8 weeks continued to share passive Fitbit data for significantly longer (average 42 weeks). Additionally, multivariate survival models showed participants' age, ownership and brand of smartphones, and recruitment sites to be associated with retention in the study. Together these findings could inform the design of future digital health studies to enable equitable and balanced data collection from diverse populations.

Recruitment and Retention in Remote Research: Learnings From a Large, Decentralized Real-world Study.

BACKGROUND: Smartphones are increasingly used in health research. They provide a continuous connection between participants and researchers to monitor long-term health trajectories of large populations at a fraction of the cost of traditional research studies. However, despite the potential of using smartphones in remote research, there is an urgent need to develop effective strategies to reach, recruit, and retain the target populations in a representative and equitable manner. OBJECTIVE: We aimed to investigate the impact of combining different recruitment and incentive distribution approaches used in remote research on cohort characteristics and long-term retention. The real-world factors significantly impacting active and passive data collection were also evaluated. METHODS: We conducted a secondary data analysis of participant recruitment and retention using data from a large remote observation study aimed at understanding real-world factors linked to cold, influenza, and the impact of traumatic brain injury on daily functioning. We conducted recruitment in 2 phases between March 15, 2020, and January 4, 2022. Over 10,000 smartphone owners in the United States were recruited to provide 12 weeks of daily surveys and smartphone-based passive-sensing data. Using multivariate statistics, we investigated the potential impact of different recruitment and incentive distribution approaches on cohort characteristics. Survival analysis was used to assess the effects of sociodemographic characteristics on participant retention across the 2 recruitment phases. Associations between passive data-sharing patterns and demographic characteristics of the cohort were evaluated using logistic regression. RESULTS: We analyzed over 330,000 days of engagement data collected from 10,000 participants. Our key findings are as follows: first, the overall characteristics of participants recruited using digital advertisements on social media and news media differed significantly from those of participants recruited using crowdsourcing platforms (Prolific and Amazon Mechanical Turk; P<.001). Second, participant retention in the study varied significantly across study phases, recruitment sources, and socioeconomic and demographic factors (P<.001). Third, notable differences in passive data collection were associated with device type (Android vs iOS) and participants' sociodemographic characteristics. Black or African American participants were significantly less likely to share passive sensor data streams than non-Hispanic White participants (odds ratio 0.44-0.49, 95% CI 0.35-0.61; P<.001). Fourth, participants were more likely to adhere to baseline surveys if the surveys were administered immediately after enrollment. Fifth, technical glitches could significantly impact real-world data collection in remote settings, which can severely impact generation of reliable evidence. CONCLUSIONS: Our findings highlight several factors, such as recruitment platforms, incentive distribution frequency, the timing of baseline surveys, device heterogeneity, and technical glitches in data collection infrastructure, that could impact remote long-term data collection. Combined together, these empirical findings could help inform best practices for monitoring anomalies during real-world data collection and for recruiting and retaining target populations in a representative and equitable manner.

Real-world behavioral dataset from two fully remote smartphone-based randomized clinical trials for depression.

Most people with mental health disorders cannot receive timely and evidence-based care despite billions of dollars spent by healthcare systems. Researchers have been exploring using digital health technologies to measure behavior in real-world settings with mixed results. There is a need to create accessible and computable digital mental health datasets to advance inclusive and transparently validated research for creating robust real-world digital biomarkers of mental health. Here we share and describe one of the largest and most diverse real-world behavior datasets from over two thousand individuals across the US. The data were generated as part of the two NIMH-funded randomized clinical trials conducted to assess the effectiveness of delivering mental health care continuously remotely. The longitudinal dataset consists of self-assessment of mood, depression, anxiety, and passively gathered phone-based behavioral data streams in real-world settings. This dataset will provide a timely and long-term data resource to evaluate analytical approaches for developing digital behavioral markers and understand the effectiveness of mental health care delivered continuously and remotely.

Disentangling personalized treatment effects from "time-of-the-day" confounding in mobile health studies.

Ideally, a patient's response to medication can be monitored by measuring changes in performance of some activity. In observational studies, however, any detected association between treatment ("on-medication" vs "off-medication") and the outcome (performance in the activity) might be due to confounders. In particular, causal inferences at the personalized level are especially vulnerable to confounding effects that arise in a cyclic fashion. For quick acting medications, effects can be confounded by circadian rhythms and daily routines. Using the time-of-the-day as a surrogate for these confounders and the performance measurements as captured on a smartphone, we propose a personalized statistical approach to disentangle putative treatment and "time-of-the-day" effects, that leverages conditional independence relations spanned by causal graphical models involving the treatment, time-of-the-day, and outcome variables. Our approach is based on conditional independence tests implemented via standard and temporal linear regression models. Using synthetic data, we investigate when and how residual autocorrelation can affect the standard tests, and how time series modeling (namely, ARIMA and robust regression via HAC covariance matrix estimators) can remedy these issues. In particular, our simulations illustrate that when patients perform their activities in a paired fashion, positive autocorrelation can lead to conservative results for the standard regression approach (i.e., lead to deflated true positive detection), whereas negative autocorrelation can lead to anticonservative behavior (i.e., lead to inflated false positive detection). The adoption of time series methods, on the other hand, leads to well controlled type I error rates. We illustrate the application of our methodology with data from a Parkinson's disease mobile health study.

Correction: An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

[This corrects the article DOI: 10.2196/32165.].

Recommendations for Defining and Reporting Adherence Measured by Biometric Monitoring Technologies: Systematic Review.

BACKGROUND: Suboptimal adherence to data collection procedures or a study intervention is often the cause of a failed clinical trial. Data from connected sensors, including wearables, referred to here as biometric monitoring technologies (BioMeTs), are capable of capturing adherence to both digital therapeutics and digital data collection procedures, thereby providing the opportunity to identify the determinants of adherence and thereafter, methods to maximize adherence. OBJECTIVE: We aim to describe the methods and definitions by which adherence has been captured and reported using BioMeTs in recent years. Identifying key gaps allowed us to make recommendations regarding minimum reporting requirements and consistency of definitions for BioMeT-based adherence data. METHODS: We conducted a systematic review of studies published between 2014 and 2019, which deployed a BioMeT outside the clinical or laboratory setting for which a quantitative, nonsurrogate, sensor-based measurement of adherence was reported. After systematically screening the manuscripts for eligibility, we extracted details regarding study design, participants, the BioMeT or BioMeTs used, and the definition and units of adherence. The primary definitions of adherence were categorized as a continuous variable based on duration (highest resolution), a continuous variable based on the number of measurements completed, or a categorical variable (lowest resolution). RESULTS: Our PubMed search terms identified 940 manuscripts; 100 (10.6%) met our eligibility criteria and contained descriptions of 110 BioMeTs. During literature screening, we found that 30% (53/177) of the studies that used a BioMeT outside of the clinical or laboratory setting failed to report a sensor-based, nonsurrogate, quantitative measurement of adherence. We identified 37 unique definitions of adherence reported for the 110 BioMeTs and observed that uniformity of adherence definitions was associated with the resolution of the data reported. When adherence was reported as a continuous time-based variable, the same definition of adherence was adopted for 92% (46/50) of the tools. However, when adherence data were simplified to a categorical variable, we observed 25 unique definitions of adherence reported for 37 tools. CONCLUSIONS: We recommend that quantitative, nonsurrogate, sensor-based adherence data be reported for all BioMeTs when feasible; a clear description of the sensor or sensors used to capture adherence data, the algorithm or algorithms that convert sample-level measurements to a metric of adherence, and the analytic validation data demonstrating that BioMeT-generated adherence is an accurate and reliable measurement of actual use be provided when available; and primary adherence data be reported as a continuous variable followed by categorical definitions if needed, and that the categories adopted are supported by clinical validation data and/or consistent with previous reports.

Remote smartphone monitoring of Parkinson's disease and individual response to therapy.

Remote health assessments that gather real-world data (RWD) outside clinic settings require a clear understanding of appropriate methods for data collection, quality assessment, analysis and interpretation. Here we examine the performance and limitations of smartphones in collecting RWD in the remote mPower observational study of Parkinson's disease (PD). Within the first 6 months of study commencement, 960 participants had enrolled and performed at least five self-administered active PD symptom assessments (speeded tapping, gait/balance, phonation or memory). Task performance, especially speeded tapping, was predictive of self-reported PD status (area under the receiver operating characteristic curve (AUC) = 0.8) and correlated with in-clinic evaluation of disease severity (r = 0.71; P < 1.8 × 10-6) when compared with motor Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Although remote assessment requires careful consideration for accurate interpretation of RWD, our results support the use of smartphones and wearables in objective and personalized disease assessments.

Developing, Deploying, and Evaluating Digital Mental Health Interventions in Spaces of Online Help- and Information-Seeking.

The internet is frequently the first point of contact for people seeking support for their mental health symptoms. Digital interventions designed to be deployed through the internet have significant promise to reach diverse populations who may not have access to, or are not yet engaged in, treatment and deliver evidence-based resources to address symptoms. The liminal nature of online interactions requires designing to prioritize needs detection, intervention potency, and efficiency. Real-world implementation, data privacy and safety are equally important and can involve transparent partnerships with stakeholders in industry and non-profit organizations. This commentary highlights challenges and opportunities for research in this space, grounded in learnings from multiple research projects and teams aligned with this effort.

Artificial Intelligence: An Interprofessional Perspective on Implications for Geriatric Mental Health Research and Care.

Artificial intelligence (AI) in healthcare aims to learn patterns in large multimodal datasets within and across individuals. These patterns may either improve understanding of current clinical status or predict a future outcome. AI holds the potential to revolutionize geriatric mental health care and research by supporting diagnosis, treatment, and clinical decision-making. However, much of this momentum is driven by data and computer scientists and engineers and runs the risk of being disconnected from pragmatic issues in clinical practice. This interprofessional perspective bridges the experiences of clinical scientists and data science. We provide a brief overview of AI with the main focus on possible applications and challenges of using AI-based approaches for research and clinical care in geriatric mental health. We suggest future AI applications in geriatric mental health consider pragmatic considerations of clinical practice, methodological differences between data and clinical science, and address issues of ethics, privacy, and trust.

An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

BACKGROUND: Several app-based studies share similar characteristics of a light touch approach that recruit, enroll, and onboard via a smartphone app and attempt to minimize burden through low-friction active study tasks while emphasizing the collection of passive data with minimal human contact. However, engagement is a common challenge across these studies, reporting low retention and adherence. OBJECTIVE: This study aims to describe an alternative to a light touch digital health study that involved a participant-centric design including high friction app-based assessments, semicontinuous passive data from wearable sensors, and a digital engagement strategy centered on providing knowledge and support to participants. METHODS: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study included US frontline health care workers followed between May and November 2020. The study comprised 3 main components: (1) active and passive assessments of stress and symptoms from a smartphone app, (2) objective measured assessments of acute stress from wearable sensors, and (3) a participant codriven engagement strategy that centered on providing knowledge and support to participants. The daily participant time commitment was an average of 10 to 15 minutes. Retention and adherence are described both quantitatively and qualitatively. RESULTS: A total of 365 participants enrolled and started the study, and 81.0% (n=297) of them completed the study for a total study duration of 4 months. Average wearable sensor use was 90.6% days of total study duration. App-based daily, weekly, and every other week surveys were completed on average 69.18%, 68.37%, and 72.86% of the time, respectively. CONCLUSIONS: This study found evidence for the feasibility and acceptability of a participant-centric digital health study approach that involved building trust with participants and providing support through regular phone check-ins. In addition to high retention and adherence, the collection of large volumes of objective measured data alongside contextual self-reported subjective data was able to be collected, which is often missing from light touch digital health studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04713111; https://clinicaltrials.gov/ct2/show/NCT04713111.

Perceived Utility and Characterization of Personal Google Search Histories to Detect Data Patterns Proximal to a Suicide Attempt in Individuals Who Previously Attempted Suicide: Pilot Cohort Study.

BACKGROUND: Despite decades of research to better understand suicide risk and to develop detection and prevention methods, suicide is still one of the leading causes of death globally. While large-scale studies using real-world evidence from electronic health records can identify who is at risk, they have not been successful at pinpointing when someone is at risk. Personalized social media and online search history data, by contrast, could provide an ongoing real-world datastream revealing internal thoughts and personal states of mind. OBJECTIVE: We conducted this study to determine the feasibility and acceptability of using personalized online information-seeking behavior in the identification of risk for suicide attempts. METHODS: This was a cohort survey study to assess attitudes of participants with a prior suicide attempt about using web search data for suicide prevention purposes, dates of lifetime suicide attempts, and an optional one-time download of their past web searches on Google. The study was conducted at the University of Washington School of Medicine Psychiatry Research Offices. The main outcomes were participants' opinions on internet search data for suicide prediction and intervention and any potential change in online information-seeking behavior proximal to a suicide attempt. Individualized nonparametric association analysis was used to assess the magnitude of difference in web search data features derived from time periods proximal (7, 15, 30, and 60 days) to the suicide attempts versus the typical (baseline) search behavior of participants. RESULTS: A total of 62 participants who had attempted suicide in the past agreed to participate in the study. Internet search activity varied from person to person (median 2-24 searches per day). Changes in online search behavior proximal to suicide attempts were evident up to 60 days before attempt. For a subset of attempts (7/30, 23%) search features showed associations from 2 months to a week before the attempt. The top 3 search constructs associated with attempts were online searching patterns (9/30 attempts, 30%), semantic relatedness of search queries to suicide methods (7/30 attempts, 23%), and anger (7/30 attempts, 23%). Participants (40/59, 68%) indicated that use of this personalized web search data for prevention purposes was acceptable with noninvasive potential interventions such as connection to a real person (eg, friend, family member, or counselor); however, concerns were raised about detection accuracy, privacy, and the potential for overly invasive intervention. CONCLUSIONS: Changes in online search behavior may be a useful and acceptable means of detecting suicide risk. Personalized analysis of online information-seeking behavior showed notable changes in search behavior and search terms that are tied to early warning signs of suicide and are evident 2 months to 7 days before a suicide attempt.

Using Real-world Data for Decision Support: Recommendations from a Primary Care Provider Survey.

INTRODUCTION: The use of data from wearable sensors, smartphones, and apps holds promise as a clinical decision-making tool in health and mental health in primary care medicine. The aim of this study was to determine provider perspectives about the utility of these data for building digitally based decision-making tools. METHODS: This mixed quantitative and qualitative cross-sectional survey of a convenience sample of primary-care clinicians at Kaiser Permanente Northwest was conducted between April and July 2019 online via Institute for Translational Health Sciences' Research Electronic Data Capture. Study outcomes were 1) attitudes toward digital data, 2) willingness to use digital data to support clinical decision making, and 3) concerns and recommendations about implementing a digital tool for clinical decision making. RESULTS: This sample of 131 clinicians was largely white (n = 98) female (n = 91) physicians (n = 86). Although respondents (75.7%, n = 87) had a positive attitude toward using digital tools in their practice, 88 respondents (67.3%) voiced concerns about the possible lack of clinical utility, suspected difficulty in integration with clinical workflows, and worried about the potential burden placed on patients. Participants indicated that the accuracy of the data in detecting the need for treatment adjustments would need to be high and the tool should be clinically tested. CONCLUSIONS: Primary care providers find value in collecting real-world patient data to assist in clinical decision making, provided such information does not interfere with provider workflow or impose undue burden on patients. In addition, digital tools will need to demonstrate high accuracy, be able to integrate into current clinical workflows, and maintain the privacy and security of patients' data.

Effectiveness of Transcutaneous Electrical Nerve Stimulation Therapy on whole Salivary Flow in Patients with Xerostomia and Healthy Adults

ABSTRACT Objective: To evaluate and compare the effectiveness of transcutaneous electrical nerve stimulation (TENS) therapy on whole salivary flow in patients with xerostomia and healthy adults. Material and Methods: Thirty subjects with a history of xerostomia and subjects withunstimulated salivary flow equal to or less than 0.5 ml in 5 min were included in the study group, and 30 healthy subjects were included in the control group. Low forced spitting unstimulated saliva was collected for five minutes in a test tube fitted with a funnel. Then electrode pads of the TENS unit were applied bilaterally on skin overlying the parotid glands and at optimal intensity, stimulated saliva was collected for 5 minutes with the same method in a separate graduated test tube. The salivary flow rate (per minute) was calculated by dividing the amount of collected saliva (volume in mL) by the duration of collection period (5 minutes) and the salivary flow rates prior and after electrostimulation were compared for both groups. The Student's t-test (unpaired and paired) was performed for group-wise comparisons. Results: In study group, the mean unstimulated salivary flow rate was 0.07 ± 0.01 mL/min. There was an 85.71% increase in salivary flow (0.13 ± 0.03 mL/min) during the TENS application and the difference was highly significant (p<0.001). In control group, the mean unstimulated salivary flow rate was 0.37 ± 0.07 mL/min. There was a 21.62% increase in salivary flow (0.45 ± 0.07 mL/min) during the TENS application and the difference was highly significant (p<0.001). An increase in mean salivary flow rate both in males and females after TENS application in both groups (p<0.001) was noted. The difference between unstimulated, stimulated and mean difference in salivary flow rate between males and females was notstatistically significant in both groups (p<0.05). Conclusion: TENS can be an effective therapy in increasing whole salivary flow rates in patients with xerostomia.

Real-world longitudinal data collected from the SleepHealth mobile app study.

Conducting biomedical research using smartphones is a novel approach to studying health and disease that is only beginning to be meaningfully explored. Gathering large-scale, real-world data to track disease manifestation and long-term trajectory in this manner is quite practical and largely untapped. Researchers can assess large study cohorts using surveys and sensor-based activities that can be interspersed with participants' daily routines. In addition, this approach offers a medium for researchers to collect contextual and environmental data via device-based sensors, data aggregator frameworks, and connected wearable devices. The main aim of the SleepHealth Mobile App Study (SHMAS) was to gain a better understanding of the relationship between sleep habits and daytime functioning utilizing a novel digital health approach. Secondary goals included assessing the feasibility of a fully-remote approach to obtaining clinical characteristics of participants, evaluating data validity, and examining user retention patterns and data-sharing preferences. Here, we provide a description of data collected from 7,250 participants living in the United States who chose to share their data broadly with the study team and qualified researchers worldwide.

Evaluating the Utility of Smartphone-Based Sensor Assessments in Persons With Multiple Sclerosis in the Real-World Using an App (elevateMS): Observational, Prospective Pilot Digital Health Study.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative disease. Current monitoring practices predominantly rely on brief and infrequent assessments, which may not be representative of the real-world patient experience. Smartphone technology provides an opportunity to assess people's daily-lived experience of MS on a frequent, regular basis outside of episodic clinical evaluations. OBJECTIVE: The objectives of this study were to evaluate the feasibility and utility of capturing real-world MS-related health data remotely using a smartphone app, "elevateMS," to investigate the associations between self-reported MS severity and sensor-based active functional tests measurements, and the impact of local weather conditions on disease burden. METHODS: This was a 12-week, observational, digital health study involving 3 cohorts: self-referred participants who reported an MS diagnosis, clinic-referred participants with neurologist-confirmed MS, and participants without MS (controls). Participants downloaded the elevateMS app and completed baseline assessments, including self-reported physical ability (Patient-Determined Disease Steps [PDDS]), as well as longitudinal assessments of quality of life (Quality of Life in Neurological Disorders [Neuro-QoL] Cognitive, Upper Extremity, and Lower Extremity Function) and daily health (MS symptoms, triggers, health, mobility, pain). Participants also completed functional tests (finger-tapping, walk and balance, voice-based Digit Symbol Substitution Test [DSST], and finger-to-nose) as an independent assessment of MS-related cognition and motor activity. Local weather data were collected each time participants completed an active task. Associations between self-reported baseline/longitudinal assessments, functional tests, and weather were evaluated using linear (for cross-sectional data) and mixed-effects (for longitudinal data) regression models. RESULTS: A total of 660 individuals enrolled in the study; 31 withdrew, 495 had MS (n=359 self-referred, n=136 clinic-referred), and 134 were controls. Participation was highest in clinic-referred versus self-referred participants (median retention: 25.5 vs 7.0 days). The top 5 most common MS symptoms, reported at least once by participants with MS, were fatigue (310/495, 62.6%), weakness (222/495, 44.8%), memory/attention issues (209/495, 42.2%), and difficulty walking (205/495, 41.4%), and the most common triggers were high ambient temperature (259/495, 52.3%), stress (250/495, 50.5%), and late bedtime (221/495, 44.6%). Baseline PDDS was significantly associated with functional test performance in participants with MS (mixed model-based estimate of most significant feature across functional tests [ß]: finger-tapping: ß=-43.64, P<.001; DSST: ß=-5.47, P=.005; walk and balance: ß=-.39, P=.001; finger-to-nose: ß=.01, P=.01). Longitudinal Neuro-QoL scores were also significantly associated with functional tests (finger-tapping with Upper Extremity Function: ß=.40, P<.001; walk and balance with Lower Extremity Function: ß=-99.18, P=.02; DSST with Cognitive Function: ß=1.60, P=.03). Finally, local temperature was significantly associated with participants' test performance (finger-tapping: ß=-.14, P<.001; DSST: ß=-.06, P=.009; finger-to-nose: ß=-53.88, P<.001). CONCLUSIONS: The elevateMS study app captured the real-world experience of MS, characterized some MS symptoms, and assessed the impact of environmental factors on symptom severity. Our study provides further evidence that supports smartphone app use to monitor MS with both active assessments and patient-reported measures of disease burden. App-based tracking may provide unique and timely real-world data for clinicians and patients, resulting in improved disease insights and management.

Changes in Continuous, Long-Term Heart Rate Variability and Individualized Physiological Responses to Wellness and Vacation Interventions Using a Wearable Sensor.

There are many approaches to maintaining wellness, including taking a simple vacation to attending highly structured wellness retreats, which typically regulate the attendee's personal time and activities. In a healthy English-speaking cohort of 112 women and men (aged 30-80 years), this study examined the effects of participating in either a 6-days intensive wellness retreat based on Ayurvedic medicine principles or unstructured 6-days vacation at the same wellness center setting. Heart rate variability (HRV) was monitored continuously using a wearable ECG sensor patch for up to 7 days prior to, during, and 1-month following participation in the interventions. Additionally, salivary cortisol levels were assessed for all participants at multiple times during the day. Continual HRV monitoring data in the real-world setting was seen to be associated with demographic [HRVALF: ßAge = 0.98 (95% CI = 0.96-0.98), false discovery rate (FDR) < 0.001] and physiological characteristics [HRVPLF: ß = 0.98 (95% CI = 0.98-1), FDR =0.005] of participants. HRV features were also able to quantify known diurnal variations [HRVLF/HF: ßACT:night vs. early-morning = 2.69 (SE = 1.26), FDR < 0.001] along with notable inter- and intraperson heterogeneity in response to intervention. A statistically significant increase in HRVALF [ß = 1.48 (SE = 1.1), FDR < 0.001] was observed for all participants during the resort visit. Personalized HRV analysis at an individual level showed a distinct individualized response to intervention, further supporting the utility of using continuous real-world tracking of HRV at an individual level to objectively measure responses to potentially stressful or relaxing settings.