Patient Engagement in a Multimodal Digital Phenotyping Study of Opioid Use Disorder.

BACKGROUND: Multiple digital data sources can capture moment-to-moment information to advance a robust understanding of opioid use disorder (OUD) behavior, ultimately creating a digital phenotype for each patient. This information can lead to individualized interventions to improve treatment for OUD. OBJECTIVE: The aim is to examine patient engagement with multiple digital phenotyping methods among patients receiving buprenorphine medication for OUD. METHODS: The study enrolled 65 patients receiving buprenorphine for OUD between June 2020 and January 2021 from 4 addiction medicine programs in an integrated health care delivery system in Northern California. Ecological momentary assessment (EMA), sensor data, and social media data were collected by smartphone, smartwatch, and social media platforms over a 12-week period. Primary engagement outcomes were meeting measures of minimum phone carry (≥8 hours per day) and watch wear (≥18 hours per day) criteria, EMA response rates, social media consent rate, and data sparsity. Descriptive analyses, bivariate, and trend tests were performed. RESULTS: The participants' average age was 37 years, 47% of them were female, and 71% of them were White. On average, participants met phone carrying criteria on 94% of study days, met watch wearing criteria on 74% of days, and wore the watch to sleep on 77% of days. The mean EMA response rate was 70%, declining from 83% to 56% from week 1 to week 12. Among participants with social media accounts, 88% of them consented to providing data; of them, 55% of Facebook, 54% of Instagram, and 57% of Twitter participants provided data. The amount of social media data available varied widely across participants. No differences by age, sex, race, or ethnicity were observed for any outcomes. CONCLUSIONS: To our knowledge, this is the first study to capture these 3 digital data sources in this clinical population. Our findings demonstrate that patients receiving buprenorphine treatment for OUD had generally high engagement with multiple digital phenotyping data sources, but this was more limited for the social media data. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.3389/fpsyt.2022.871916.

Effects of Training on Use of Stimulant Diversion Prevention Strategies by Pediatric Primary Care Providers: Results from a Cluster-Randomized Trial.

Pediatric primary care is a promising setting for reducing diversion of stimulant medications for ADHD. We tested if training pediatric primary care providers (PCPs) increased use of diversion prevention strategies with adolescents with ADHD. The study was a cluster-randomized trial in 7 pediatric primary care practices. Participants were pediatric PCPs (N = 76) at participating practices. Practices were randomized to a 1-h training in stimulant diversion prevention or treatment-as-usual. At baseline, 6 months, 12 months, and 18 months, PCPs rated how often they used four categories of strategies: patient/family education, medication management/monitoring, assessment of mental health symptoms/functioning, and assessment of risky behaviors. They completed measures of attitudes, implementation climate, knowledge/skill, and resource constraints. Generalized Estimating Equations estimated differences in outcomes by condition. Mediation analyses tested if changes in knowledge/skill mediated training effects on strategy use. PCPs in the intervention condition reported significantly greater use of patient/family education strategies at all follow-up time points. There were no differences between conditions in medication management, assessment of mental health symptoms/functioning, or assessment of risky behaviors. At 6 months, PCPs in the intervention condition reported more positive attitudes toward diversion prevention, stronger implementation climate, greater knowledge/skill, and less resource constraints. Differences in knowledge/skill persisted at 12 months and 18 months. Brief training in stimulant diversion had substantial and enduring effects on PCPs' self-reported knowledge/skill and use of patient/family education strategies to prevent diversion. Training had modest effects on attitudes, implementation climate, and resource constraints and did not change use of strategies related to medication management and assessment of mental health symptoms/functioning and risky behaviors. Changes in knowledge/skill accounted for 49% of the total effect of training on use of patient/family education strategies. Trial registration This trial is registered on ClinicalTrials.gov (NCT03080259). Posted March 15, 2017.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING: NIDA Clinical Trials Network.

Validation of the TAPS-1: A Four-Item Screening Tool to Identify Unhealthy Substance Use in Primary Care.

BACKGROUND: The Tobacco, Alcohol, Prescription Medication, and Other Substance use (TAPS) tool is a combined two-part screening and brief assessment developed for adult primary care patients. The tool's first-stage screening component (TAPS-1) consists of four items asking about past 12-month use for four substance categories, with response options of never, less than monthly, monthly, weekly, and daily or almost daily. OBJECTIVE: To validate the TAPS-1 in primary care patients. DESIGN: Participants completed the TAPS tool in self- and interviewer-administered formats, in random order. In this secondary analysis, the TAPS-1 was evaluated against DSM-5 substance use disorder (SUD) criteria to determine optimal cut-points for identifying unhealthy substance use at three severity levels (problem use, mild SUD, and moderate-to-severe SUD). PARTICIPANTS: Two thousand adult patients at five primary care sites. MAIN MEASURES: DSM-5 SUD criteria were determined via the modified Composite International Diagnostic Interview. Oral fluid was used as a biomarker of recent drug use. KEY RESULTS: Optimal frequency-of-use cut-points on the self-administered TAPS-1 for identifying SUDs were ≥ monthly use for tobacco and alcohol (sensitivity = 0.92 and 0.71, specificity = 0.80 and 0.85, AUC = 0.86 and 0.78, respectively) and any reported use for illicit drugs and prescription medication misuse (sensitivity = 0.93 and 0.89, specificity = 0.85 and 0.91, AUC = 0.89 and 0.90, respectively). The performance of the interviewer-administered format was similar. When administered first, the self-administered format yielded higher disclosure rates for past 12-month alcohol use, illicit drug use, and prescription medication misuse. Frequency of use alone did not provide sufficient information to discriminate between gradations of substance use problem severity. Among those who denied drug use on the TAPS-1, less than 4% had a drug-positive biomarker. CONCLUSIONS: The TAPS-1 can identify unhealthy substance use in primary care patients with a high level of accuracy, and may have utility in primary care for rapid triage.

Performance of the Tobacco, Alcohol, Prescription Medication, and Other Substance Use (TAPS) Tool for Substance Use Screening in Primary Care Patients.

BACKGROUND: Substance use, a leading cause of illness and death, is underidentified in medical practice. OBJECTIVE: The Tobacco, Alcohol, Prescription medication, and other Substance use (TAPS) tool was developed to address the need for a brief screening and assessment instrument that includes all commonly used substances and fits into clinical workflows. The goal of this study was to assess the performance of the TAPS tool in primary care patients. DESIGN: Multisite study, conducted within the National Drug Abuse Treatment Clinical Trials Network, comparing the TAPS tool with a reference standard measure. (ClinicalTrials.gov: NCT02110693). SETTING: 5 adult primary care clinics. PARTICIPANTS: 2000 adult patients consecutively recruited from clinic waiting areas. MEASUREMENTS: Interviewer- and self-administered versions of the TAPS tool were compared with a reference standard, the modified World Mental Health Composite International Diagnostic Interview (CIDI), which measures problem use and substance use disorder (SUD). RESULTS: Interviewer- and self-administered versions of the TAPS tool had similar diagnostic characteristics. For identifying problem use (at a cutoff of 1+), the TAPS tool had a sensitivity of 0.93 (95% CI, 0.90 to 0.95) and specificity of 0.87 (CI, 0.85 to 0.89) for tobacco and a sensitivity of 0.74 (CI, 0.70 to 0.78) and specificity of 0.79 (CI, 0.76 to 0.81) for alcohol. For problem use of illicit and prescription drugs, sensitivity ranged from 0.82 (CI, 0.76 to 0.87) for marijuana to 0.63 (CI, 0.47 to 0.78) for sedatives; specificity was 0.93 or higher. For identifying any SUD (at a cutoff of 2+), sensitivity was lower. LIMITATIONS: The low prevalence of some drug classes led to poor precision in some estimates. Research assistants were not blinded to participants' TAPS tool responses when they administered the CIDI. CONCLUSION: In a diverse population of adult primary care patients, the TAPS tool detected clinically relevant problem substance use. Although it also may detect tobacco, alcohol, and marijuana use disorders, further refinement is needed before it can be recommended broadly for SUD screening. PRIMARY FUNDING SOURCE: National Institute on Drug Abuse.

The Adolescent Community Reinforcement Approach (A-CRA) as a model paradigm for the management of adolescents with substance use disorders and co-occurring psychiatric disorders.

BACKGROUND: Integrated treatment for youth with substance use disorders (SUDs) and co-occurring psychiatric disorders is recommended; however, there are few studies that have evaluated integrated treatment approaches. METHODS: This paper includes a brief review of cognitive-behavioral and family therapies, since they have been demonstrated to be effective treatments for the disorders that commonly co-occur with substance use. It also describes how an integrated treatment paradigm has been implemented using one Empirically Supported Treatment, the Adolescent Community Reinforcement Approach (A-CRA). RESULTS: There is existing research that supports the use of several A-CRA procedures to treat substance use and commonly co-occurring psychiatric disorders. CONCLUSIONS: In the absence of further research, it is reasonable in the interim to train clinicians in treatments that incorporate components that have been found to be effective for both substance use and commonly co-occurring psychiatric disorders. These treatments can then be adapted as needed based on an individual youth's set of problems. Further research is needed to test treatments for various combinations of SUDs and psychiatric disorders (i.e., depression, trauma-related problems, conduct disorder/behavior problems, and attention-deficit/hyperactivity disorder [ADHD]).

Comparing the Performance of World Mental Health Composite International Diagnostic Interview Substance Abuse Module in Adolescents to Diagnoses Made by Pediatric Addiction Medicine Specialists.

OBJECTIVES: The World Mental Health Composite International Diagnostic Interview Substance Abuse Module (WMH-CIDI-SAM) is commonly used as a criterion standard measure for substance use disorder (SUD) diagnoses, although the accuracy of this tool when used with adolescents is unknown. The objective of this study was to evaluate the agreement between SUD diagnoses for adolescents made by WMH-CIDI-SAM and those made by specialists based on Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) ( DSM-5 ) SUD criteria during an SUD evaluation. METHODS: Adolescents aged 12 to 17 years presenting to an outpatient SUD program for youth were administered the WMH-CIDI-SAM by a trained research assistant, and results were compared with diagnoses made by experienced clinicians based on DSM-5 SUD criteria during an initial SUD evaluation. Chance-corrected concordance was estimated using the κ coefficient for the comparisons. RESULTS: The level of concordance between the WMH-CIDI-SAM interview and the clinician diagnosis based on DSM-5 SUD criteria were fair to moderate for alcohol use disorder and tobacco use disorder and poor for cannabis use disorder. Three of 11 WMH-CIDI-SAM item constructs showed poor concordance with clinician diagnosis. CONCLUSIONS: Interpreting the diagnostic criteria for SUDs, particularly cannabis use disorders, is nuanced, and the meaning of the criteria may be misunderstood by adolescents. Further evaluation of the performance of the WMH-CIDI-SAM diagnostic interview for identifying cannabis use disorders in adolescents is needed.

Identifying Adolescent Vaping With Screening to Brief Intervention and Brief Screener for Tobacco, Alcohol, and Drugs Screening Tools.

PURPOSE: This study aimed to determine whether the modified Screening to Brief Intervention (S2BI) and Brief Screener for Tobacco, Alcohol, and Drugs (BSTAD) that included e-cigarettes/vaping as examples could identify all nicotine and cannabis use or whether additional questions specifically about vaping are needed. METHODS: Between July 2020 and February 2022, adolescents recruited from primary care or an outpatient adolescent substance use disorder program were randomized to complete S2BI or BSTAD followed by specific questions about vaping. Screen questions were updated to include "vaping" in the parenthetical examples of nicotine and cannabis use. RESULTS: Data from 502 adolescent participants who completed both the S2BI or BSTAD and vaping questions were analyzed. The S2BI and BSTAD identified 92% (23/25) and 100% (16/16) of nicotine vaping and 100% (16/16) and 95.5% (21/22) of cannabis vaping, respectively. DISCUSSION: The S2BI and BSTAD tools accurately identify nicotine and cannabis use without specific questions about vaping.

Engagement, initiation, and retention in medication treatment for opioid use disorder among young adults: A narrative review of challenges and opportunities.

INTRODUCTION: Opioid Use Disorder (OUD) is a catastrophic public health problem for young adults (YAs) and their families. While medication for OUD (MOUD) is safe, effective, and recognized as the standard of care, its' uptake and success have been limited in YAs compared to older adults. METHODS: This narrative review summarizes the existing literature and highlights select studies regarding barriers to YA MOUD, potential explanations for those barriers, and strategies to overcome them. RESULTS: Barriers are prominent along the entire cascade of care, including: treatment engagement and entry, MOUD initiation, and MOUD retention. Hypothesized explanations for barriers include: developmental vulnerability, inadequate treatment system capacity, stigma against MOUD, among others. Interventions to address barriers include: promotion of family involvement, increasing provider capacity, integration of MOUD into primary care, assertive outreach, and others. CONCLUSIONS: Integrating an adapted version of family coaching from the Community Reinforcement Approach and Family Training (CRAFT) and other models into YA MOUD treatment serves as an example of an emerging novel practice that holds promise for broadening the funnel of engagement in treatment and initiation of MOUD, and enhancing treatment outcomes. This and other developmentally-informed approaches should be evaluated as part of a high-priority clinical and research agenda for improving OUD treatment for YAs.

National Institute on Drug Abuse: Dissemination of Scientific Knowledge to Improve Adolescent Health.

The wide and effective dissemination of research findings is crucial to the mission of the National Institute on Drug Abuse (NIDA). This article describes NIDA dissemination efforts and resources that are available to inform clinicians, teens, families, and educators about youth and substance use. Resources that are available include content addressing facts about youth drug use, trends in use, and stigma, in addition to substance use disorder (SUD) prevention and treatment. Information is provided about resources such as infographics, research-based practice guides, training, educational events, and online videos. How input is solicited to inform dissemination efforts is described and future directions for NIDA's dissemination efforts are outlined.

Student Perception and Preferences With Social Media for Enhanced Learning in Health Sciences Following Post-COVID-19 Era: A Cross-Sectional Study.

Background During the COVID-19 pandemic, universities worldwide pivoted to distance education, primarily online, using various blended learning tools. In the contemporary era, characterized by widespread high-speed internet and the ubiquity of social media (SM), SM has become an essential tool, especially among students. This study aimed to assess the perception, impact, and preferences of various SM platforms for learning among health sciences students in the post-COVID-19 era. Methodology The study was conducted at constituent colleges of Jouf University and Northern Border University between January and June 2022. Responses from 560 students were assessed using a self-administered, pre-validated questionnaire comprising 31 questions. These questions addressed students' perceptions, preferences, and learning modes derived from SM. Descriptive and inferential statistics evaluated the influence of SM on student learning. Results On average, students spent 3.18 hours daily on SM. YouTube (41.1%) and Instagram (37.1%) emerged as the most preferred platforms for learning. A significant 86.4% of students utilized SM for accessing subject-related texts and watching related videos. Moreover, 78.6% believed that SM platforms enhanced their subject knowledge following lectures. Logistic regression analysis indicated maximum learning benefits for students who used SM between two to three hours daily. Conclusion Social media platforms, when used judiciously, can enhance the learning experience for health sciences students in the post-COVID era. While offering opportunities to acquire new knowledge and skills, care must be taken to prevent misuse, abuse, or related health hazards.

A Brief Screening and Assessment Tool for Opioid Use in Adults: Results from a Validation Study of the Tobacco, Alcohol, Prescription Medication, and Other Substances Tool.

OBJECTIVES: This secondary analysis evaluated opioid-specific validation results of the Tobacco, Alcohol, Prescription Medication, and Other Substances (TAPS) tool for screening in primary care. METHODS: This study is a secondary data analysis of the TAPS validation study. Performance of the TAPS tool for screening for unhealthy opioid use (with a score of 1+ for heroin and/or prescription opioids representing a positive screen) was evaluated. Discriminative ability was examined in comparison with reference standard measures across the spectrum of unhealthy opioid use: timeline follow-back with and without oral fluid testing identifying past-month use and the modified Composite International Diagnostic Interview for past-year problem use, opioid use disorder (OUD), and moderate-severe OUD. RESULTS: In a sample of 2000 primary care patients, 114 screened positive for opioids on the TAPS tool. With a TAPS cutoff equal to 1+, the TAPS accurately identified past-month use, problem use, any OUD, and moderate-severe OUD (sensitivities = 68%-85%, specificities = 97%-98%, area under the curve = 0.80-0.91). When past-month use was expanded to include timeline follow-back with oral fluid testing, accuracy declined (52% sensitivity [95% confidence interval, 43%-60%], 98% specific [95% confidence interval, 97%-98%]). CONCLUSIONS: While further testing in a larger population sample may be warranted, given their brevity, simplicity, and accuracy when self-administered, the TAPS opioid items can be used in primary care settings for a spectrum of unhealthy opioid use; however, self-disclosure remains an issue in primary care settings.

Navigating post COVID-19 education: an investigative study on students' attitude and perception of their new normal learning environment.

Background: The incidence and aftermath of the COVID-19 pandemic brought about a drastic change in health professional education around the world. Traditional classrooms made way for online classrooms in order to ensure that learning continued in a safe and secure environment. However, how well health professional students perceived and accepted these changes have not been fully gauged yet. Therefore, this study aims to evaluate the perception of health professional students about their new educational climate. Methods: A modified and validated Dundee Ready Education Environment Measure (DREEM) questionnaire was used to collect data regarding student perception of their educational environment. Results: The mean DREEM scores for three time periods were in the accepted positive range of 101 to 150 indicating that most of the students perceived the changes positively. The results indicated that most students preferred blended learning over online learning or face-to-face learning alone. Areas where students were unsatisfied with their learning environment that need improvement were identified by poor item-wise scores. Conclusion: Strategic remedial measures for these concerns need to be developed to improve the quality of education received by the students. However, the results of our study indicated that most of the students were able to adapt positively to the new education environment due to the change in the circumstances during COVID.

National Institute on Drug Abuse: Dissemination of Scientific Knowledge to Improve Adolescent Health.

The wide and effective dissemination of research findings is crucial to the mission of the National Institute on Drug Abuse (NIDA). This article describes NIDA dissemination efforts and resources that are available to inform clinicians, teens, families, and educators about youth and substance use. Resources that are available include content addressing facts about youth drug use, trends in use, and stigma, in addition to substance use disorder (SUD) prevention and treatment. Information is provided about resources such as infographics, research-based practice guides, training, educational events, and online videos. How input is solicited to inform dissemination efforts is described and future directions for NIDA's dissemination efforts are outlined.

Assessment of Screening Tools to Identify Substance Use Disorders Among Adolescents.

Importance: Efficient screening tools that effectively identify substance use disorders (SUDs) among youths are needed. Objective: To evaluate the psychometric properties of 3 brief substance use screening tools (Screening to Brief Intervention [S2BI]; Brief Screener for Tobacco, Alcohol, and Drugs [BSTAD]; and Tobacco, Alcohol, Prescription Medication, and Other Substances [TAPS]) with adolescents aged 12 to 17 years. Design, Setting, and Participants: This cross-sectional validation study was conducted from July 1, 2020, to February 28, 2022. Participants aged 12 to 17 years were recruited virtually and in person from 3 health care settings in Massachusetts: (1) an outpatient adolescent SUD treatment program at a pediatric hospital, (2) an adolescent medicine program at a community pediatric practice affiliated with an academic institution, and (3) 1 of 28 participating pediatric primary care practices. Participants were randomly assigned to complete 1 of the 3 electronic screening tools via self-administration, followed by a brief electronic assessment battery and a research assistant-administered diagnostic interview as the criterion standard measure for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnoses of SUDs. Data were analyzed from May 31 to September 13, 2022. Main Outcomes and Measures: The main outcome was a DSM-5 diagnosis of tobacco/nicotine, alcohol, or cannabis use disorder as determined by the criterion standard World Mental Health Composite International Diagnostic Interview Substance Abuse Module. Classification accuracy of the 3 substance use screening tools was assessed by examining the agreement between the criterion, using sensitivity and specificity, based on cut points for each tool for use disorder, chosen a priori from previous studies. Results: This study included 798 adolescents, with a mean (SD) age of 14.6 (1.6) years. The majority of participants identified as female (415 [52.0%]) and were White (524 [65.7%]). High agreement between screening results and the criterion standard measure was observed, with area under the curve values ranging from 0.89 to 1 for nicotine, alcohol, and cannabis use disorders for each of the 3 screening tools. Conclusions and Relevance: These findings suggest that screening tools that use questions on past-year frequency of use are effective for identifying adolescents with SUDs. Future work could examine whether these tools have differing properties when used with different groups of adolescents in different settings.

Subthreshold opioid use disorder prevention (STOP) trial: a cluster randomized clinical trial: study design and methods.

BACKGROUND: Preventing progression to moderate or severe opioid use disorder (OUD) among people who exhibit risky opioid use behavior that does not meet criteria for treatment with opioid agonists or antagonists (subthreshold OUD) is poorly understood. The Subthreshold Opioid Use Disorder Prevention (STOP) Trial is designed to study the efficacy of a collaborative care intervention to reduce risky opioid use and to prevent progression to moderate or severe OUD in adult primary care patients with subthreshold OUD. METHODS: The STOP trial is a cluster randomized controlled trial, randomized at the PCP level, conducted in 5 distinct geographic sites. STOP tests the efficacy of the STOP intervention in comparison to enhanced usual care (EUC) in adult primary care patients with risky opioid use that does not meet criteria for moderate-severe OUD. The STOP intervention consists of (1) a practice-embedded nurse care manager (NCM) who provides patient participant education and supports primary care providers (PCPs) in engaging and monitoring patient-participants; (2) brief advice, delivered to patient participants by their PCP and/or prerecorded video message, about health risks of opioid misuse; and (3) up to 6 sessions of telephone health coaching to motivate and support behavior change. EUC consists of primary care treatment as usual, plus printed overdose prevention educational materials and an educational video on cancer screening. The primary outcome measure is self-reported number of days of risky (illicit or nonmedical) opioid use over 180 days, assessed monthly via text message using items from the Addiction Severity Index and the Current Opioid Misuse Measure. Secondary outcomes assess other substance use, mental health, quality of life, and healthcare utilization as well as PCP prescribing and monitoring behaviors. A mixed effects negative binomial model with a log link will be fit to estimate the difference in means between treatment and control groups using an intent-to-treat population. DISCUSSION: Given a growing interest in interventions for the management of patients with risky opioid use, and the need for primary care-based interventions, this study potentially offers a blueprint for a feasible and effective approach to improving outcomes in this population. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT04218201, January 6, 2020.

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' daily lives and their MOUD treatment response. Clinical Trial Registration: Identifier: NCT04535583.

Adolescents Treated for Attention-Deficit/Hyperactivity Disorder in Pediatric Primary Care: Characterizing Risk for Stimulant Diversion.

OBJECTIVE: To describe the clinical and psychosocial characteristics, and their hypothesized interrelations, as it pertains to risk for stimulant diversion (sharing, selling, or trading) for adolescents in pediatric primary care treatment for attention-deficit/hyperactivity disorder. METHODS: Baseline data for 341 adolescents in a cluster-randomized controlled trial of stimulant diversion prevention in pediatric primary care (NCT_03080259) were used to (1) characterize diversion and newly measured risk factors, (2) examine their associations with age and sex, and (3) test whether associations among risk factors were consistent with model-implied predictions. Data were collected through multi-informant electronic surveys from adolescents and parents. RESULTS: Diversion was rare (1%) in this sample (Mage = 15, SD = 1.5, 74% male participants). Older age was associated with being approached to divert (r = 0.25, p < 0.001) and higher risk on variables pertinent to stimulant treatment, such as treatment disclosure (r = 0.12, p < 0.05), tolerance for stimulant misuse and diversion (r = 0.17, p < 0.05), and peer norms favorable to stimulant misuse and diversion (r values = 0.15-0.34, p < 0.001). Sex differences were minimal. Variables from our conceptual model and specific to stimulants (e.g., perceived likelihood of negative consequences from diversion and schoolmate stimulant misuse/diversion) were related in multivariable regressions to hypothesized immediate precursors of diversion (e.g., diversion intentions). CONCLUSION: Although diversion was rare for these primary care-treated adolescents, risk levels appear to be higher for older adolescents. Prevention may be most effective by capitalizing on current psychosocial strengths and discussing stimulant-specific attitudes, behaviors, and social norms before vulnerability to diversion increases in the final years of high school and into college.

Use of Stimulant Diversion Prevention Strategies in Pediatric Primary Care and Associations With Provider Characteristics.

PURPOSE: Diversion of stimulant medications for ADHD is a prevalent problem. Pediatric primary care providers (PCPs) are well-positioned to reduce diversion risk among adolescents prescribed stimulants, but little is known about their use of prevention strategies. The objectives of this study were to describe the frequency with which pediatric PCPs use diversion prevention strategies and examine potential determinants (facilitators and barriers) of strategy use. METHODS: Participants were pediatric PCPs (N = 76) participating in a randomized controlled trial of stimulant diversion prevention strategies. At baseline, before randomization, PCPs rated the frequency with which they used specific strategies in each of four categories: patient/family education, medication management/monitoring, assessment of mental health symptoms/functioning, and assessment of risky behaviors. They completed measures of attitudes toward diversion prevention, subjective norms (i.e., implementation climate), and perceived behavioral control (i.e., knowledge/skill, resource constraints). Associations between determinants and strategy use were tested with correlational and regression analyses. RESULTS: PCPs used strategies for assessing mental health symptoms/functioning most frequently and patient/family education strategies least frequently. Attitudes about the effectiveness of diversion prevention, implementation climate, knowledge/skill, and resource constraints were positively correlated with the use of at least one category of strategies. In regression analysis, PCP knowledge/skill was positively associated with patient/family education, medication management, and risk assessment strategies. CONCLUSIONS: Findings suggest that improving knowledge and skill may increase the use of diversion prevention strategies by PCPs. Identifying provider-level determinants of strategy use informs implementation efforts in pediatric primary care and can facilitate efforts to prevent stimulant diversion among adolescents.

Inhibition of dynamin-2 confers endothelial barrier dysfunctions by attenuating nitric oxide production.

Hypoxia induces barrier dysfunctions in endothelial cells. Nitric oxide is an autacoid signalling molecule that confers protection against hypoxia-mediated barrier dysfunctions. Dyn-2 (dynamin-2), a large GTPase and a positive modulator of eNOS (endothelial nitric oxide synthase), plays an important role in maintaining vascular homeostasis. The present study aims to elucidate the role of dyn-2 in hypoxia-mediated leakiness of the endothelial monolayer in relation to redox milieu. Inhibition of dyn-2 by transfecting the cells with K44A, a dominant negative construct of dyn-2, elevated leakiness of the endothelial monolayer under hypoxia. Sodium nitroprusside (nitric oxide donor) and uric acid (peroxynitrite quencher) were used to evaluate the role of nitric oxide and peroxynitrite in maintaining endothelial barrier functions under hypoxia. Administration of nitric oxide and uric acid recovered hypoxia-mediated leakiness of K44A-overexpressed endothelial monolayer. Our study confirms that inhibition of dyn-2 induces leakiness in the endothelial monolayer by increasing the load of peroxynitrite under hypoxia.