The value of decentralized clinical trials: Inclusion, accessibility, and innovation.

In this Review, we explore the transformative potential of decentralized clinical trials (DCTs) in addressing the limitations of traditional randomized controlled trials (RCTs). We highlight the merits of DCTs fostering greater inclusivity, efficiency, and adaptability. We emphasize the challenges of RCTs, including limited participant diversity and logistical barriers, geographical constraints, and mistrust in research institutions, showing how DCTs are preferred in addressing these challenges by utilizing remote digital technologies and community providers to enable broader, more inclusive participation. Furthermore, we underscore the potential of DCTs for democratizing clinical research. We also stress the importance of addressing unresolved challenges, including data security and privacy, remote patient monitoring, and regulatory variations. Research is needed to devise standardized protocols to streamline DCT processes, explore its long-term impacts on patient outcomes, and overcome challenges through equitable stakeholder engagement.

Instructional approach, sleep, and perceived academic well-being in adolescents during COVID-19: Evidence from the NESTED study.

OBJECTIVES: At the peak of COVID-19, adolescent life was disrupted as schools adapted their instructional approaches such as online, in-person, or hybrid instruction. We and others have previously commented on how these shifts facilitated longer, later and (more developmentally appropriate) sleep. Here, we report how sleep contributed to associations between remote instruction and broader academic well-being (e.g., cognitive function, school connectedness, and stress). METHODS: Adolescents from all 50 U.S. states (n = 4068) completed online self-report surveys in fall 2020. Instructional approach was operationalized from fully in-person instruction to fully asynchronous online education. Sleep parameters included sleep timing and duration, sleep disturbances, and sleep-related impairments. Perceived academic well-being was defined as cognitive function, school connectedness, and school-related stress. Sleep and perceived academic well-being are examined across instructional approaches, in their association, and in structural models. RESULTS: Sleep and perceived academic well-being differed between hybrid and online instruction groups. Less variable or disturbed sleep was associated both with in-person instruction, and with positive outcomes in cognitive function, school connectedness, and stress domains. Sleep mediated a substantial portion of variance in perceived academic well-being attributable to instructional approach. CONCLUSION: These data highlight the need to protect both healthy sleep and in-person instruction. Appropriate sleep timing and duration, fewer sleep disturbances and sleep-related impairments accounted for a substantial degree of variance in the association between remote instruction on academic outcomes. While many students experienced "lost learning" because of COVID-19, this study joins a broader discussion of ensuring developmentally appropriate school-start times to support both sleep and achievement.

African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer's Disease Measured by pTau181.

Background: Cognitive and functional abilities in individuals with Alzheimer's disease (AD) pathology (ADP) are highly variable. Factors contributing to this variability are not well understood. Previous research indicates that higher educational attainment (EA) correlates with reduced cognitive impairments among those with ADP. While cognitive and functional impairments are correlated, they are distinguishable in their manifestations. Objective: To investigate whether levels of education are associated with functional impairments among those with ADP. Methods: This research involved 410 African American (AA) individuals (Institutional Review Boards 20070307, 01/27/2023) to ascertain whether EA correlates with functional resilience and if this effect varies between APOE ɛ4 carriers and non-carriers. Utilizing EA as a cognitive reserve proxy, CDR-FUNC as a functional difficulties measure, and blood pTau181 as an ADP proxy, the non-parametric Mann-Whitney U test assessed the relationship between EA and CDR-FUNC in individuals with advanced pTau181 levels. Results: The results showed that EA correlated with functional difficulties in AA individuals with high levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (W = 730.5, p = 0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in ɛ4 non-carriers compared to ɛ4 carriers (W = 555.5, p = 0.022). Conclusion: This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele ɛ4.

Bringing Health Care Equity to Diverse and Underserved Populations in Sleep Medicine and Research Through a Digital Health Equity Framework.

Individuals from minoritized groups are less likely to receive sleep medicine care and be the focus of sleep research. Several barriers may explain under-representation and low participation. The coronavirus disease 2019 (COVID-19) pandemic highlighted a digital divide that exacerbated disproportionate sleep health outcomes and access to sleep medicine and research opportunities among minoritized groups. The authors' team developed a digital health equity and inclusion model and revamped its culturally-tailored community outreach program to advance sleep health equity among minoritized groups. This article describes how the authors implemented their digital sleep health equity and inclusion model during the COVID-19 pandemic.

African ancestry APOE e4 non-carriers with higher educational attainment are resilient to Alzheimer disease pathology-specific blood biomarker pTau181.

Cognitive and functional abilities in individuals with Alzheimer disease (AD) pathology (ADP) show greater than expected variability. While most individuals show substantial impairments in these abilities, a considerable number show little or no impairments. Factors contributing to this variability are not well understood. For instance, multiple studies have shown that higher levels of education are associated with reduced cognitive impairments among those with ADP. However, it remains unclear whether higher levels of education are associated with functional impairments among those with ADP. We studied 410 AA individuals with advanced levels of pTau181 (a biomarker for ADP; individuals as those having log 10 (pTau181) level greater than one standard deviation above the mean) to determine whether EA (categorized as low EA for individuals with ≤ 8 years of education and high EA for those with >8 years) promotes functional resilience and whether this effect varies between APOE ε4 carriers and non-carriers. We used the four non-memory components of the Clinical Dementia Rating (CDR) to create a composite score (CDR-FUNC) to evaluate functional difficulties (scored from 0=no impairment to 12=severe). We employed the non-parametric Mann-Whitney U test to assess the relationship between EA and CDR-FUNC in advanced levels of pTau181 individuals. The results showed that EA promotes resilience to functional problems in AA individuals with advanced levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (W=730.5, p=0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in ε4 non-carriers compared to ε4 carriers (W=555.5, p=0.022). This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele ε4. The results highlight the intricate interplay of genetic and non-genetic factors in AD progression, suggesting a need for more personalized strategies to manage functional decline in AD.

The Gap Between AI and Bedside: Participatory Workshop on the Barriers to the Integration, Translation, and Adoption of Digital Health Care and AI Startup Technology Into Clinical Practice.

BACKGROUND: Artificial intelligence (AI) and digital health technological innovations from startup companies used in clinical practice can yield better health outcomes, reduce health care costs, and improve patients' experience. However, the integration, translation, and adoption of these technologies into clinical practice are plagued with many challenges and are lagging. Furthermore, explanations of the impediments to clinical translation are largely unknown and have not been systematically studied from the perspective of AI and digital health care startup founders and executives. OBJECTIVE: The aim of this paper is to describe the barriers to integrating early-stage technologies in clinical practice and health care systems from the perspectives of digital health and health care AI founders and executives. METHODS: A stakeholder focus group workshop was conducted with a sample of 10 early-stage digital health and health care AI founders and executives. Digital health, health care AI, digital health-focused venture capitalists, and physician executives were represented. Using an inductive thematic analysis approach, transcripts were organized, queried, and analyzed for thematic convergence. RESULTS: We identified the following four categories of barriers in the integration of early-stage digital health innovations into clinical practice and health care systems: (1) lack of knowledge of health system technology procurement protocols and best practices, (2) demanding regulatory and validation requirements, (3) challenges within the health system technology procurement process, and (4) disadvantages of early-stage digital health companies compared to large technology conglomerates. Recommendations from the study participants were also synthesized to create a road map to mitigate the barriers to integrating early-stage or novel digital health technologies in clinical practice. CONCLUSIONS: Early-stage digital health and health care AI entrepreneurs identified numerous barriers to integrating digital health solutions into clinical practice. Mitigation initiatives should create opportunities for early-stage digital health technology companies and health care providers to interact, develop relationships, and use evidence-based research and best practices during health care technology procurement and evaluation processes.

Health literacy and ophthalmology: A scoping review.

As of 2020, it is estimated that 43.3 million people are blind, and an additional 553 million have mild to severe vision impairment.50 At least 1 billion worldwide have a vision impairment that could have been prevented or has yet to be addressed.54 Poor health literacy may be a significant contributor to the prevalence of eye disease. With implications on disease burden, progression, and health outcomes, a greater understanding of the role health literacy plays in ophthalmology is needed. This is the first scoping review to assess the impact of health literacy on eye health outcomes and blindness, including ocular screening rates and/or follow-up rates, treatment adherence, and self-care practices. PubMed, Embase, and CINAHL databases were searched systematically through November 12, 2021, and we evaluated the association between health literacy and ophthalmic outcomes in 4 domains: clinical outcomes, treatment adherence rates, screening and/or follow-up rates, and self-care practices. There is evidence to suggest that health literacy is associated with ophthalmic outcomes in all these domains. To better understand how health literacy impacts eye health, further longitudinal studies examining the effect of health literacy (using standardized health literacy measures) on ophthalmic outcomes are needed. We believe a specific ophthalmic health literacy survey could help achieve this goal and help target interventions to ultimately improve outcomes among ophthalmology patients.

Development and Initial Validation of the Assessment of Sleep Environment (ASE): Describing and Quantifying the Impact of Subjective Environmental Factors on Sleep.

The purpose of this study was to develop and test the reliability and validity of a 13-item self-report Assessment of Sleep Environment (ASE). This study investigates the relationship between subjective experiences of environmental factors (light, temperature, safety, noise, comfort, humidity, and smell) and sleep-related parameters (insomnia symptoms, sleep quality, daytime sleepiness, and control over sleep). The ASE was developed using an iterative process, including literature searches for item generation, qualitative feedback, and pilot testing. It was psychometrically assessed using data from the Sleep and Healthy Activity Diet Environment and Socialization (SHADES) study (N = 1007 individuals ages 22-60). Reliability was determined with an internal consistency and factor analysis. Validity was evaluated by comparing ASE to questionnaires of insomnia severity, sleep quality, daytime sleepiness, sleep control, perceived stress, and neighborhood disorder. The ASE demonstrated high internal consistency and likely reflects a single factor. ASE score was associated with insomnia symptoms (B = 0.09, p < 0.0001), sleep quality (B = 0.07, p < 0.0001), and sleep control (B = -0.01, p < 0.0001), but not daytime sleepiness. The ASE was also associated with perceived stress (B = 0.20, p < 0.0001) and neighborhood disorder (B = -0.01, p < 0.0001). Among sleep environment factors, only smell was not associated with sleep quality; warmth and safety were negatively associated with sleepiness; and of the sleep environment factors, only light/dark, noise/quiet, and temperature (warm/cool) were not associated with insomnia symptoms. The ASE is a reliable and valid measure of sleep environment. Physical environment (light, temperature, safety, noise, comfort, humidity, and smell) was associated with insomnia symptoms and sleep quality but not sleepiness.

Associations of digital neuro-signatures with molecular and neuroimaging measures of brain resilience: The altoida large cohort study.

Background: Mixed results in the predictive ability of traditional biomarkers to determine cognitive functioning and changes in older adults have led to misdiagnosis and inappropriate treatment plans to address mild cognitive impairment and dementia among older adults. To address this critical gap, the primary goal of the current study is to investigate whether a digital neuro signature (DNS-br) biomarker predicted global cognitive functioning and change over time relative among cognitively impaired and cognitive healthy older adults. The secondary goal is to compare the effect size of the DNS-br biomarker on global cognitive functioning compared to traditional imaging and genomic biomarkers. The tertiary goal is to investigate which demographic and clinical factors predicted DNS-br in cognitively impaired and cognitively healthy older adults. Methods: We conducted two experiments (Study A and Study B) to assess DNS for brain resilience (DNS-br) against the established FDG-PET brain imaging signature for brain resilience, based on a 10 min digital cognitive assessment tool. Study A was a semi-naturalistic observational study that included 29 participants, age 65+, with mild to moderate mild cognitive impairment and AD diagnosis. Study B was also a semi-naturalistic observational multicenter study which included 496 participants (213 mild cognitive impairment (MCI) and 283 cognitively healthy controls (HC), a total of 525 participants-cognitively healthy (n = 283) or diagnosed with MCI (n = 213) or AD (n = 29). Results: DNS-br total score and majority of the 11 DNS-br neurocognitive subdomain scores were significantly associated with FDG-PET resilience signature, PIB ratio, cerebral gray matter and white matter volume after adjusting for multiple testing. DNS-br total score predicts cognitive impairment for the 80+ individuals in the Altoida large cohort study. We identified a significant interaction between the DNS-br total score and time, indicating that participants with higher DNS-br total score or FDG-PET in the resilience signature would show less cognitive decline over time. Conclusion: Our findings highlight that a digital biomarker predicted cognitive functioning and change, which established biomarkers are unable to reliably do. Our findings also offer possible etiologies of MCI and AD, where education did not protect against cognitive decline.