Dhairya Upadhyay

Background: Wearable accelerometers, which continuously record physical activity metrics, are commonly used in mobile health–enabled cardiac rehabilitation (mHealth-CR). The association between adherence to accelerometer use during mHealth-CR and improvement in clinical outcomes, such as functional capacity, is understudied. The emergence of artificial intelligence (AI) technology provides novel opportunities to investigate accelerometry use patterns in relation to mHealth-CR outcomes. Objective: In this study, we sought to use an AI clustering framework to identify distinct behavioral phenotypes of adherence to accelerometer use. We then aimed to quantify the association of these adherence phenotypes with functional capacity improvements in older adults undergoing mHealth-CR. Methods: We analyzed data from the RESILIENT (Rehabilitation at Home Using Mobile Health in Older Adults After Hospitalization for Ischemic Heart Disease) trial, the largest randomized clinical study to date comparing mHealth-CR versus usual care in older adults (aged ≥65 years). Intervention arm participants were instructed to wear a Fitbit accelerometer for the 3-month study duration. Adherence to accelerometer use was quantified as overall adherence (percentage of days worn) via k-means clustering AI-derived measures and compared with changes in 6-minute walk distance (6-MWD), adjusted for demographic and clinical covariates. Results: Among 271 participants with a mean age of 71 years (SD 8), of whom 198 (73%) were male, accelerometers were worn for an average of 76 days (95% confidence limits 73,78) over 3 months. Adjusted analyses showed a weak association between days of wear and improvement in 6-MWD, with every 30 additional days associated with an 11-meter improvement (P=.08). Our k-means clustering framework identified adherence phenotypes at two resolutions: low resolution (k=2 clusters) and high resolution (k=8 clusters). The consistently high adherence cluster trended toward a 24.6-meter improvement in 6-MWD compared to the low and declining adherence clusters (n=39; 95% CI 0.7-49.9; P=.06). The 8-cluster phenotyping revealed a richer set of adherence patterns, with the consistently high adherence cluster in this analysis having a 38.5-meter (95% CI 2.2-74.7; P=.04) improvement in 6-MWD than the low adherence cluster, as well as greater average daily steps over the 3-month intervention (mean 7518, SD 3415 vs mean 4800, SD 2920 steps; P=.008). Conclusions: A time-series AI clustering framework identified a range of behavioral phenotypes representing different degrees of adherence to accelerometer use. Regression analysis identified a weak association between the higher adherence phenotype and functional capacity improvement in older adults undergoing mHealth-CR. Our AI-derived accelerometry adherence phenotypes may offer a new approach to tailor mHealth-CR regimens to individual patients, potentially leading to better outcomes in this high-risk population. Trial Registration: ClinicalTrials.gov NCT03978130; https://clinicaltrials.gov/study/NCT03978130 International Registered Report Identifier (IRRID): RR2-10.2196/32163

BACKGROUND Wearable accelerometers, which continuously record physical activity metrics, are commonly used in mobile health–enabled cardiac rehabilitation (mHealth-CR). The association between adherence to accelerometer use during mHealth-CR and improvement in clinical outcomes, such as functional capacity, is understudied. The emergence of artificial intelligence (AI) technology provides novel opportunities to investigate accelerometry use patterns in relation to mHealth-CR outcomes. OBJECTIVE In this study, we sought to use an AI clustering framework to identify distinct behavioral phenotypes of adherence to accelerometer use. We then aimed to quantify the association of these adherence phenotypes with functional capacity improvements in older adults undergoing mHealth-CR. METHODS We analyzed data from the RESILIENT (Rehabilitation at Home Using Mobile Health in Older Adults After Hospitalization for Ischemic Heart Disease) trial, the largest randomized clinical study to date comparing mHealth-CR versus usual care in older adults (aged ≥65 years). Intervention arm participants were instructed to wear a Fitbit accelerometer for the 3-month study duration. Adherence to accelerometer use was quantified as overall adherence (percentage of days worn) via k-means clustering AI-derived measures and compared with changes in 6-minute walk distance (6-MWD), adjusted for demographic and clinical covariates. RESULTS Among 271 participants with a mean age of 71 years (SD 8), of whom 198 (73%) were male, accelerometers were worn for an average of 76 days (95% confidence limits 73,78) over 3 months. Adjusted analyses showed a weak association between days of wear and improvement in 6-MWD, with every 30 additional days associated with an 11-meter improvement (P=.08). Our k-means clustering framework identified adherence phenotypes at two resolutions: low resolution (k=2 clusters) and high resolution (k=8 clusters). The consistently high adherence cluster trended toward a 24.6-meter improvement in 6-MWD compared to the low and declining adherence clusters (n=39; 95% CI 0.7-49.9; P=.06). The 8-cluster phenotyping revealed a richer set of adherence patterns, with the consistently high adherence cluster in this analysis having a 38.5-meter (95% CI 2.2-74.7; P=.04) improvement in 6-MWD than the low adherence cluster, as well as greater average daily steps over the 3-month intervention (mean 7518, SD 3415 vs mean 4800, SD 2920 steps; P=.008). CONCLUSIONS A time-series AI clustering framework identified a range of behavioral phenotypes representing different degrees of adherence to accelerometer use. Regression analysis identified a weak association between the higher adherence phenotype and functional capacity improvement in older adults undergoing mHealth-CR. Our AI-derived accelerometry adherence phenotypes may offer a new approach to tailor mHealth-CR regimens to individual patients, potentially leading to better outcomes in this high-risk population. CLINICALTRIAL ClinicalTrials.gov NCT03978130; https://clinicaltrials.gov/study/NCT03978130 INTERNATIONAL REGISTERED REPORT RR2-10.2196/32163

The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ’s metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.