Wrist-worn sensor-based measurements for drug effect detection with small samples in people with Lewy Body Dementia.

INTRODUCTION: Few late-stage clinical trials in Parkinson's disease (PD) have produced evidence on the clinical validity of sensor-based digital measurements of daily life activities to detect responses to treatment. The objective of this study was to assess whether digital measures from patients with mild-to-moderate Lewy Body Dementia demonstrate treatment effects during a randomized Phase 2 trial. METHODS: Substudy within a 12-week trial of mevidalen (placebo vs 10, 30, or 75 mg), where 70/344 patients (comparable to the overall population) wore a wrist-worn multi-sensor device. RESULTS: Treatment effects were statistically significant by conventional clinical assessments (Movement Disorder Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] sum of Parts I-III and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC] scores) in the full study cohort at Week 12, but not in the substudy. However, digital measurements detected significant effects in the substudy cohort at week 6, persisting to week 12. CONCLUSIONS: Digital measurements detected treatment effects in a smaller cohort over a shorter period than conventional clinical assessments. TRIAL REGISTRATION: clinicaltrials.gov, NCT03305809.

Analytical and clinical validity of wearable, multi-sensor technology for assessment of motor function in patients with Parkinson's disease in Japan.

Continuous, objective monitoring of motor signs and symptoms may help improve tracking of disease progression and treatment response in Parkinson's disease (PD). This study assessed the analytical and clinical validity of multi-sensor smartwatch measurements in hospitalized and home-based settings (96 patients with PD; mean wear time 19 h/day) using a twice-daily virtual motor examination (VME) at times representing medication OFF/ON states. Digital measurement performance was better during inpatient clinical assessments for composite V-scores than single-sensor-derived features for bradykinesia (Spearman |r|= 0.63, reliability = 0.72), tremor (|r|= 0.41, reliability = 0.65), and overall motor features (|r|= 0.70, reliability = 0.67). Composite levodopa effect sizes during hospitalization were 0.51-1.44 for clinical assessments and 0.56-1.37 for VMEs. Reliability of digital measurements during home-based VMEs was 0.62-0.80 for scores derived from weekly averages and 0.24-0.66 for daily measurements. These results show that unsupervised digital measurements of motor features with wrist-worn sensors are sensitive to medication state and are reliable in naturalistic settings.Trial Registration: Japan Pharmaceutical Information Center Clinical Trials Information (JAPIC-CTI): JapicCTI-194825; Registered June 25, 2019.

Virtual exam for Parkinson's disease enables frequent and reliable remote measurements of motor function.

Sensor-based remote monitoring could help better track Parkinson's disease (PD) progression, and measure patients' response to putative disease-modifying therapeutic interventions. To be useful, the remotely-collected measurements should be valid, reliable, and sensitive to change, and people with PD must engage with the technology. We developed a smartwatch-based active assessment that enables unsupervised measurement of motor signs of PD. Participants with early-stage PD (N = 388, 64% men, average age 63) wore a smartwatch for a median of 390 days. Participants performed unsupervised motor tasks both in-clinic (once) and remotely (twice weekly for one year). Dropout rate was 5.4%. Median wear-time was 21.1 h/day, and 59% of per-protocol remote assessments were completed. Analytical validation was established for in-clinic measurements, which showed moderate-to-strong correlations with consensus MDS-UPDRS Part III ratings for rest tremor (⍴ = 0.70), bradykinesia (⍴ = -0.62), and gait (⍴ = -0.46). Test-retest reliability of remote measurements, aggregated monthly, was good-to-excellent (ICC = 0.75-0.96). Remote measurements were sensitive to the known effects of dopaminergic medication (on vs off Cohen's d = 0.19-0.54). Of note, in-clinic assessments often did not reflect the patients' typical status at home. This demonstrates the feasibility of smartwatch-based unsupervised active tests, and establishes the analytical validity of associated digital measurements. Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally. Sensitivity to medication-induced change and improved reliability imply that these methods could help reduce sample sizes needed to demonstrate a response to therapeutic interventions or disease progression.

A holistic approach for suppression of COVID-19 spread in workplaces and universities.

As society has moved past the initial phase of the COVID-19 crisis that relied on broad-spectrum shutdowns as a stopgap method, industries and institutions have faced the daunting question of how to return to a stabilized state of activities and more fully reopen the economy. A core problem is how to return people to their workplaces and educational institutions in a manner that is safe, ethical, grounded in science, and takes into account the unique factors and needs of each organization and community. In this paper, we introduce an epidemiological model (the "Community-Workplace" model) that accounts for SARS-CoV-2 transmission within the workplace, within the surrounding community, and between them. We use this multi-group deterministic compartmental model to consider various testing strategies that, together with symptom screening, exposure tracking, and nonpharmaceutical interventions (NPI) such as mask wearing and physical distancing, aim to reduce disease spread in the workplace. Our framework is designed to be adaptable to a variety of specific workplace environments to support planning efforts as reopenings continue. Using this model, we consider a number of case studies, including an office workplace, a factory floor, and a university campus. Analysis of these cases illustrates that continuous testing can help a workplace avoid an outbreak by reducing undetected infectiousness even in high-contact environments. We find that a university setting, where individuals spend more time on campus and have a higher contact load, requires more testing to remain safe, compared to a factory or office setting. Under the modeling assumptions, we find that maintaining a prevalence below 3% can be achieved in an office setting by testing its workforce every two weeks, whereas achieving this same goal for a university could require as much as fourfold more testing (i.e., testing the entire campus population twice a week). Our model also simulates the dynamics of reduced spread that result from the introduction of mitigation measures when test results reveal the early stages of a workplace outbreak. We use this to show that a vigilant university that has the ability to quickly react to outbreaks can be justified in implementing testing at the same rate as a lower-risk office workplace. Finally, we quantify the devastating impact that an outbreak in a small-town college could have on the surrounding community, which supports the notion that communities can be better protected by supporting their local places of business in preventing onsite spread of disease.

Effect of match-run frequencies on the number of transplants and waiting times in kidney exchange.

Numerous kidney exchange (kidney paired donation [KPD]) registries in the United States have gradually shifted to high-frequency match-runs, raising the question of whether this harms the number of transplants. We conducted simulations using clinical data from 2 KPD registries-the Alliance for Paired Donation, which runs multihospital exchanges, and Methodist San Antonio, which runs single-center exchanges-to study how the frequency of match-runs impacts the number of transplants and the average waiting times. We simulate the options facing each of the 2 registries by repeated resampling from their historical pools of patient-donor pairs and nondirected donors, with arrival and departure rates corresponding to the historical data. We find that longer intervals between match-runs do not increase the total number of transplants, and that prioritizing highly sensitized patients is more effective than waiting longer between match-runs for transplanting highly sensitized patients. While we do not find that frequent match-runs result in fewer transplanted pairs, we do find that increasing arrival rates of new pairs improves both the fraction of transplanted pairs and waiting times.