Data cleaning and harmonization of clinical trial data: Medication-assisted treatment for opioid use disorder.

Several large-scale, pragmatic clinical trials on opioid use disorder (OUD) have been completed in the National Drug Abuse Treatment Clinical Trials Network (CTN). However, the resulting data have not been harmonized between the studies to compare the patient characteristics. This paper provides lessons learned from a large-scale harmonization process that are critical for all biomedical researchers collecting new data and those tasked with combining datasets.

Empirically contrasting urine drug screening-based opioid use disorder treatment outcome definitions.

Background And Aims: A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta-analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset.

Methods: Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results.

Retention and critical outcomes among new methadone maintenance patients following extended take-home reforms: a retrospective observational cohort study.

Background: Approximately 1800 opioid treatment programs (OTPs) in the US dispense methadone to upwards of 400,000 patients with opioid use disorder (OUD) annually, operating under longstanding highly restrictive guidelines. OTPs were granted novel flexibilities beginning March 15, 2020, allowing for reduced visit frequency and extended take-home doses to minimize COVID exposure with great variation across states and sites. We sought to use electronic health records to compare retention in treatment, opioid use, and adverse events among patients newly entering methadone maintenance in the post-reform period in comparison with year-ago, unexposed, controls.

Individual-Level Risk Prediction of Return to Use During Opioid Use Disorder Treatment.

Importance: No existing model allows clinicians to predict whether patients might return to opioid use in the early stages of treatment for opioid use disorder.

Objective: To develop an individual-level prediction tool for risk of return to use in opioid use disorder.

Design, Setting, And Participants: This decision analytical model used predictive modeling with individual-level data harmonized in June 1, 2019, to October 1, 2022, from 3 multicenter, pragmatic, randomized clinical trials of at least 12 weeks' duration within the National Institute on Drug Abuse Clinical Trials Network (CTN) performed between 2006 and 2016.

Risks of returning to opioid use at treatment entry and early in opioid use disorder treatment: Role of non-opioid substances.

Objective: Patients in treatment with medications for opioid use disorder (MOUD) often report use of other substances in addition to opioids. Few studies exist that examine the relationship between use at treatment entry and early non-opioid use in opioid treatment outcome.

Methodology: We combined and harmonized three randomized, controlled MOUD clinical trials from the National Institutes of Drug Abuse (NIDA) Clinical Trials Network (CTN) (N=2197) and investigated the association of non-opioid substance use at treatment entry and during early treatment with a return to opioid use.

Exploring the performance of during-treatment substance use outcome measures in predicting longer-term psychosocial functioning and post-treatment abstinence.

Background: The selection of appropriate efficacy endpoints in clinical trials has been a long-standing challenge for the substance use disorder field. Using data from a large, multi-site National Drug Abuse Treatment Clinical Trials Network trial (CTN-0044; n=474), this secondary data analysis aimed to explore whether specific proximal (during-treatment) substance use outcome measures predict longer-term improvements in psychosocial functioning and post-treatment abstinence, and whether predictions vary depending on the specific substance (cannabis, cocaine/stimulants, opioids, and alcohol).

Methods: Generalized linear mixed models examined associations between six during-treatment substance use outcome measures and social functioning impairment (Social Adjustment Scale Self-Report) and severity of psychiatric symptoms (Brief Symptom Inventory-18) at end-of-treatment, and 3- and 6-months after treatment as well as post-treatment abstinence.

Risk of Experiencing an Overdose Event for Patients Undergoing Treatment With Medication for Opioid Use Disorder.

Objective: Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD.

Methods: Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models.

Specific polysubstance use patterns predict relapse among patients entering opioid use disorder treatment.

Introduction: While polysubstance use has consistently been associated with higher rates of relapse, few studies have examined subgroups with specific combinations and time course of polysubstance use (i.e., polysubstance use patterns).

Initiating Long-acting Injectable Naltrexone: Procedure for a Second Attempt After a First Attempt Fails.

Background And Objective: Many patients are unable to initiate long-acting injectable naltrexone (XR-NTX) on a first attempt, due to the prerequisite abstinence and withdrawal from opioids.

Methods: Thirty patients who were unable to initiate XR-NTX were recruited to receive buprenorphine for 1 week, followed by a 3-week buprenorphine taper, and an ascending titration of oral naltrexone before XR-NTX injection.

Results: Eight (27%) initiated XR-NTX, 7 (23%) transitioned to buprenorphine maintenance treatment and 15 (50%) were lost to follow up.

Patient characteristics associated with initiation of XR-naltrexone for opioid use disorder in clinical trials.

Background: Extended-release injectable naltrexone (XR-naltrexone) is effective for treatment of patients with opioid use disorder (OUD), but initiation remains a barrier due to the challenge of tolerating opioid withdrawal prior to administration. Understanding factors associated with successful initiation of XR-naltrexone could facilitate its implementation through patient-treatment matching.

Methods: We combined data from five consecutive studies that sought to initiate patients with active opioid use onto XR-naltrexone using a rapid procedure consisting of minimal buprenorphine, non-opioid medications for treating opioid withdrawal, and ascending low doses of oral naltrexone.

Predoctoral substance use disorders curricula: A survey analysis and experiential pedagogy.

Substance Use Disorders (SUD) are chronic health conditions with heritability characteristics, environmental influences, long-term management considerations and they cooccur. The US opioid epidemic is a crisis of both prescription and nonprescription opioid use. Clinicians now have access to evidence-based practices but the evolving trends require continuous attention including curriculum initiatives for dental schools.

Psychological Symptoms and Outcomes in Adults Receiving Community-based Treatment for Substance Use Disorders.

Background: Mental health issues in individuals with substance use disorders are common and can affect treatment outcomes.

Objectives: Secondary analysis of a multi-center trial of an internet-delivered psychosocial SUD treatment intervention (Therapeutic Education System; TES) to: 1) describe psychological symptoms over time, 2) explore whether treatment assignment was associated with psychological symptoms 3) explore whether psychological symptoms at baseline moderated the effect of TES on abstinence or retention at the end of treatment.

Methods: Psychological symptoms were measured using the Global Severity Index (GSI) from the Brief Symptom Inventory (BSI-18), PHQ-9, and MINI SPIN (social anxiety).

Age-Related Hearing Loss, Neuropsychological Performance, and Incident Dementia in Older Adults.

Background: Age-related hearing loss (HL) has been associated with dementia, though the neurocognitive profile of individuals with HL is poorly understood.

Objective: To characterize the neurocognitive profile of HL.

Methods: N = 8,529 participants from the National Alzheimer's Coordinating Center ≥60 years and free of cognitive impairment who were characterized as Untreated-, Treated-, or No HL.

The utility of a formative one-station objective structured clinical examination for Substance use disorders in a dental curriculum.

Substance use disorders (SUD) are chronic relapsing medical conditions characterised by compulsive substance seeking and use. They constitute a substantial disease burden globally. Labelling of persons with SUD has created barriers to treatment but there are effective management strategies.

Assessment of Prescription Opioid Medical Use and Misuse Among Parents and Their Adolescent Offspring in the US.

Importance: Limited information is available regarding the association between parental and adolescent medical prescription opioid use and misuse in the US.

Objective: To examine the associations between parental and adolescent prescription opioid medical use and misuse.

Design, Setting, And Participants: This cross-sectional, nationally representative study included 15 200 parent-adolescent dyads from the annual 2015-2017 National Survey on Drug Use and Health.

Age-Related Hearing Loss, Late-Life Depression, and Risk for Incident Dementia in Older Adults.

Background: Hearing loss (HL), late-life depression, and dementia are 3 prevalent and disabling conditions in older adults, but the interrelationships between these disorders remain poorly understood.

Methods: N = 8529 participants ≥60 years who were free of cognitive impairment at baseline were analyzed from National Alzheimer's Coordinating Center Uniform Data Set. Participants had either No HL, Untreated HL, or Treated HL.

Medical Student Attitudes Toward Substance Use Disorders Before and After a Skills-Based Screening, Brief Intervention, and Referral to Treatment (SBIRT) Curriculum.

Purpose: Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based framework for assessing and addressing risky substance use. This study evaluated the substance-related attitudes of medical students who participated in an Enhanced Pre-Clinical SBIRT Curriculum designed to reduce stigma, help students empathize with the experiences of people using alcohol and drugs, understand substance use in-context, and feel more optimistic about efforts to prevent and treat substance use disorders (SUDs).

Methods: Students (N=118; 73.

Exploring gender differences among treatment-seekers who use opioids versus alcohol and other drugs.

Identifying clinical differences between opioid users (OU) and alcohol and other drug users (AOD) may help to tailor treatment to OU, particularly among the majority of OU who are not on opioid agonist treatments. Given the dearth of research on these differences, this study explored gender differences in demographic and clinical characteristics between OU and AOD. Participants (N = 506) were from a multisite, randomized controlled clinical trial of an Internet-delivered psychosocial intervention conducted in 2010-2011.

Innovations in pre-doctoral dental education: Influencing attitudes and opinions about patients with substance use disorder.

Screening, Brief Intervention, and Referral to Treatment (SBIRT) is an evidence-based model for managing patients with substance use disorders (SUD). Historically, SUD were seen as a criminal issue and access to treatment was limited, but that paradigm is shifting and substance abuse is now being recognized as a disease state and the management of patients with SUD is increasingly within the healthcare system starting with primary healthcare settings including dental facilities. In a new training initiative, first-year dental students (DDS1) attended a 90-minute SBIRT training.

Differential Posttreatment Outcomes of Methylphenidate for Smoking Cessation for Individuals With ADHD.

Background And Objectives: In a multisite, randomized study (CTN-0029), a 3-month course of Osmotic-Release Oral System Methylphenidate (OROS-MPH) improved smoking cessation in a group of patients with higher baseline severity in Attention-Deficit/Hyperactivity Disorder (ADHD). This treatment, however, worsened smoking cessation outcome in the group with lower baseline ADHD severity. We want to examine whether this differential treatment effect persisted after OROS-MPH was discontinued.

Understanding site variability in a multisite clinical trial of a technology-delivered psychosocial intervention for substance use disorders.

Background: Significant fixed effects of site (main effects of site and/or site by treatment interactions) on primary outcome have been identified in the majority of studies performed by NIDA's National Drug Abuse Treatment Clinical Trials Network. While rarely explored, identifying patient- and site-level variables that are associated with site effects can provide information about the context in which outcome is optimized.

Methods: In a 10-site clinical trial that evaluated the effectiveness of a web-based psychosocial intervention compared to usual treatment of patients (N = 507) with substance use disorders, the primary outcome analysis revealed significant main effect of site, modeled as a fixed effect, on the outcome of abstinence (Campbell et al.

Medical Use and Misuse of Prescription Opioids in the US Adult Population: 2016-2017.

To characterize prescription opioid medical users and misusers among US adults. We used the 2016-2017 National Surveys on Drug Use and Health to compare medical prescription opioid users with misusers without prescriptions, misusers of own prescriptions, and misusers with both types of misuse. Multinomial logistic regressions identified substance use characteristics and mental and physical health characteristics that distinguished the groups.

Nonmedical Prescription Opioid Use by Parents and Adolescents in the US.

Background: To date, intergenerational patterns of nonmedical prescription opioid (NMPO) use have not been examined. We investigate the association between parental and adolescent NMPO use in the United States.

Methods: Data are from 35 000 parent-child dyads with an adolescent aged 12 to 17 years from the 2004-2012 nationally representative National Surveys on Drug Use and Health.

Cognitive functioning and treatment outcomes in a randomized controlled trial of internet-delivered drug and alcohol treatment.

Background And Objectives: Substance use disorders are associated with lower cognitive functioning, and this impairment is associated with poorer outcomes. The Therapeutic Education System (TES) is an internet-based psychosocial intervention for substance use disorders that may provide enhanced treatment for individuals with cognitive deficits. This secondary analysis investigates the association between cognitive functioning and treatment outcomes in a large (N = 507) randomized controlled effectiveness trial of TES compared to treatment-as-usual conducted within outpatient programs in the National Drug Abuse Treatment Clinical Trials Network.

Transcranial Magnetic Stimulation of Medial Prefrontal and Cingulate Cortices Reduces Cocaine Self-Administration: A Pilot Study.

Background: Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral prefrontal cortex may serve as a potential treatment for cocaine use disorder (CUD), which remains a public health problem that is refractory to treatment. The goal of this pilot study was to investigate the effect of rTMS on cocaine self-administration in the laboratory. In the self-administration sessions, CUD participants chose between cocaine and an alternative reinforcer (money) in order to directly measure cocaine-seeking behavior.