The Feasibility and Utility of Harnessing Digital Health to Understand Clinical Trajectories in Medication Treatment for Opioid Use Disorder: D-TECT Study Design and Methodological Considerations

Introduction: Across the U.S., the prevalence of opioid use disorder (OUD) and the rates of opioid overdoses have risen precipitously in recent years. Several effective medications for OUD (MOUD) exist and have been shown to be life-saving. A large volume of research has identified a confluence of factors that predict attrition and continued substance use during substance use disorder treatment. However, much of this literature has examined a small set of potential moderators or mediators of outcomes in MOUD treatment and may lead to over-simplified accounts of treatment non-adherence. Digital health methodologies offer great promise for capturing intensive, longitudinal ecologically-valid data from individuals in MOUD treatment to extend our understanding of factors that impact treatment engagement and outcomes. Methods: This paper describes the protocol (including the study design and methodological considerations) from a novel study supported by the National Drug Abuse Treatment Clinical Trials Network at the National Institute on Drug Abuse (NIDA). This study (D-TECT) primarily seeks to evaluate the feasibility of collecting ecological momentary assessment (EMA), smartphone and smartwatch sensor data, and social media data among patients in outpatient MOUD treatment. It secondarily seeks to examine the utility of EMA, digital sensing, and social media data (separately and compared to one another) in predicting MOUD treatment retention, opioid use events, and medication adherence [as captured in electronic health records (EHR) and EMA data]. To our knowledge, this is the first project to include all three sources of digitally derived data (EMA, digital sensing, and social media) in understanding the clinical trajectories of patients in MOUD treatment. These multiple data streams will allow us to understand the relative and combined utility of collecting digital data from these diverse data sources. The inclusion of EHR data allows us to focus on the utility of digital health data in predicting objectively measured clinical outcomes. Discussion: Results may be useful in elucidating novel relations between digital data sources and OUD treatment outcomes. It may also inform approaches to enhancing outcomes measurement in clinical trials by allowing for the assessment of dynamic interactions between individuals\u27 daily lives and their MOUD treatment response. Clinical Trial Registration: Identifier: NCT04535583

The application of digital health to the assessment and treatment of substance use disorders: The past, current, and future role of the National Drug Abuse Treatment Clinical Trials Network

The application of digital technologies to better assess, understand, and treat substance use disorders (SUDs) is a particularly promising and vibrant area of scientific research. The National Drug Abuse Treatment Clinical Trials Network (CTN), launched in 1999 by the U.S. National Institute on Drug Abuse, has supported a growing line of research that leverages digital technologies to glean new insights into SUDs and provide science-based therapeutic tools to a diverse array of persons with SUDs. This manuscript provides an overview of the breadth and impact of research conducted in the realm of digital health within the CTN. This work has included the CTN\u27s efforts to systematically embed digital screeners for SUDs into general medical settings to impact care models across the nation. This work has also included a pivotal multi-site clinical trial conducted on the CTN platform, whose data led to the very first “prescription digital therapeutic” authorized by the U.S. Food and Drug Administration (FDA) for the treatment of SUDs. Further CTN research includes the study of telehealth to increase capacity for science-based SUD treatment in rural and under-resourced communities. In addition, the CTN has supported an assessment of the feasibility of detecting cocaine-taking behavior via smartwatch sensing. And, the CTN has supported the conduct of clinical trials entirely online (including the recruitment of national and hard-to-reach/under-served participant samples online, with remote intervention delivery and data collection). Further, the CTN is supporting innovative work focused on the use of digital health technologies and data analytics to identify digital biomarkers and understand the clinical trajectories of individuals receiving medications for opioid use disorder (OUD). This manuscript concludes by outlining the many potential future opportunities to leverage the unique national CTN research network to scale-up the science on digital health to examine optimal strategies to increase the reach of science-based SUD service delivery models both within and outside of healthcare

Technology-Based Interventions in Substance Use Treatment to Promote Health Equity Among People Who Identify as African American/Black, Hispanic/Latinx, and American Indian/Alaskan Native: Protocol for a Scoping Review

BackgroundTechnology-based interventions (TBIs; ie, web-based and mobile interventions) have the potential to promote health equity in substance use treatment (SUTx) for underrepresented groups (people who identify as African American/Black, Hispanic/Latinx, and American Indian/Alaskan Native) by removing barriers and increasing access to culturally relevant effective treatments. However, technologies (emergent and more long-standing) may have unintended consequences that could perpetuate health care disparities among people who identify as a member of one of the underrepresented groups. Health care research, and SUTx research specifically, is infrequently conducted with people who identify with these groups as the main focus. Therefore, an improved understanding of the literature at the intersection of SUTx, TBIs, and underrepresented groups is warranted to avoid exacerbating inequities and to promote health equity. ObjectiveThis study aims to explore peer-reviewed literature (January 2000-March 2021) that includes people who identify as a member of one of the underrepresented groups in SUTx research using TBIs. We further seek to explore whether this subset of research is race/ethnicity conscious (does the research consider members of underrepresented groups beyond their inclusion as study participants in the introduction, methods, results, or discussion). MethodsFive electronic databases (MEDLINE, Scopus, Cochrane Library, CINAHL, and PsycInfo) were searched to identify SUTx research using TBIs, and studies were screened for eligibility at the title/abstract and full-text levels. Studies were included if their sample comprised of people who identify as a member of one of the underrepresented groups at 50% or more when combined. ResultsTitle/abstract and full-text reviews were completed in 2021. These efforts netted a sample of 185 studies that appear to meet inclusionary criteria. Due to the uniqueness of tobacco relative to other substances in the SUTx space, as well as the large number of studies netted, we plan to separately publish a scoping review on tobacco-focused studies that meet all other criteria. Filtering for tobacco-focused studies (n=31) netted a final full-text sample for a main scoping review of 154 studies. The tobacco-focused scoping review manuscript is expected to be submitted for peer review in Spring 2022. The main scoping review data extraction and data validation to confirm the accuracy and consistency of data extraction across records was completed in March 2022. We expect to publish the main scoping review findings by the end of 2022. ConclusionsResearch is needed to increase our understanding of the range and nature of TBIs being used in SUTx research studies with members of underrepresented groups. The planned scoping review will highlight research at this intersection to promote health equity. International Registered Report Identifier (IRRID)DERR1-10.2196/3450

Whole-genome sequencing of patients with rare diseases in a national health system

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare

Publisher Correction: Whole-genome sequencing of a sporadic primary immunodeficiency cohort (Nature, (2020), 583, 7814, (90-95), 10.1038/s41586-020-2265-1)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.

BACKGROUND: Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes. METHODS: We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses. FINDINGS: A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity. INTERPRETATION: This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials. FUNDING: UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR

Students' participation in collaborative research should be recognised

Letter to the editor