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. Outcome definitions were derived from clinical trials that are among the most influential in the OUD treatment field. Outcome functions were applied to a harmonized dataset from three large-scale National Drug Abuse Treatment Clinical Trials Network (CTN) studies, which tested various medication for OUD (MOUD) options (n = 2492). Hierarchical clustering was employed to empirically contrast outcome definitions. RESULTS: The optimal number of clusters identified was three. Cluster 1, comprising eight definitions focused on detecting opioid-positive UDS, did not include missing UDS in outcome calculations, potentially resulting in inflated rates of treatment success. Cluster 2, with the highest variability, included 10 definitions characterized by strict criteria for treatment success, relying heavily on UDS results from either a brief period or a single study visit. The 43 definitions in Cluster 3 represented a diverse range of outcomes, conceptualized as measuring abstinence, use reduction and relapse. These definitions potentially offer more balanced measures of treatment success or failure, as they avoid the extreme methodologies characteristic of Clusters 1 and 2. CONCLUSIONS: Clinical trials using urine drug screening (UDS) for objective substance use assessment in outcome definitions should consider (1) incorporating missing UDS data in outcome computation and (2) avoiding over-reliance on UDS data confined to a short time frame or the occurrence of a single positive urine test following a period of abstinence.

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. The clinical trials covered a variety of treatment settings, including federally licensed treatment sites, physician practices, and inpatient treatment facilities. All 3 trials enrolled adult participants older than 18 years, with broad pragmatic inclusion and few exclusion criteria except for major medical and unstable psychiatric comorbidities. Intervention: All participants received 1 of 3 medications for opioid use disorder: methadone, buprenorphine, or extended-release naltrexone. Main Outcomes and Measures: Predictive models were developed for return to use, which was defined as 4 consecutive weeks of urine drug screen (UDS) results either missing or positive for nonprescribed opioids by week 12 of treatment. Results: The overall sample included 2199 trial participants (mean [SD] age, 35.3 [10.7] years; 728 women [33.1%] and 1471 men [66.9%]). The final model based on 4 predictors at treatment entry (heroin use days, morphine- and cocaine-positive UDS results, and heroin injection in the past 30 days) yielded an area under the receiver operating characteristic curve (AUROC) of 0.67 (95% CI, 0.62-0.71). Adding UDS in the first 3 treatment weeks improved model performance (AUROC, 0.82; 95% CI, 0.78-0.85). A simplified score (CTN-0094 OUD Return-to-Use Risk Score) provided good clinical risk stratification wherein patients with weekly opioid-negative UDS results in the 3 weeks after treatment initiation had a 13% risk of return to use compared with 85% for those with 3 weeks of opioid-positive or missing UDS results (AUROC, 0.80; 95% CI, 0.76-0.84). Conclusions and Relevance: The prediction model described in this study may be a universal risk measure for return to opioid use by treatment week 3. Interventions to prevent return to regular use should focus on this critical early treatment period.

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. Methods: Retrospective observational cohort study across 9 OTPs, geographically dispersed, in the National Institute of Drug Abuse (NIDA) Clinical Trials Network. Newly enrolled patients between April 15 and October 14, 2020 (post-COVID, reform period) v. March 15-September 14, 2019 (pre-COVID, control period) were assessed. The primary outcome was 6-month retention. Secondary outcomes were opioid use and adverse events including emergency department visits, hospitalizations, and overdose. Findings: 821 individuals were newly admitted in the post-COVID and year-ago control periods, average age of 38.3 (SD 11.1), 58.9% male. The only difference across pre- and post-reform groups was the prevalence of psychostimulant use disorder (25.7% vs 32.9%, p = 0.02). Retention was non-inferior (60.0% vs 60.1%) as were hazards of adverse events in the aggregate (X2 (1) = 0.55, p = 0.46) in the post-COVID period. However, rates of month-level opioid use were higher among post-COVID intakes compared to pre-COVID controls (64.8% vs 51.1%, p < 0.001). Moderator analyses accounting for stimulant use and site-level variation in take-home schedules did not change findings. Interpretation: Policies allowing for extended take-home schedules were not associated with worse retention or adverse events despite slightly elevated rates of measured opioid use while in care. Relaxed guidelines were not associated with measurable increased harms and findings could inform future studies with prospective trials. Funding: USDHHSNIDACTNUG1DA013035-15.

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. The trials compared MOUD treatment (buprenorphine, methadone, extended-release naltrexone) in populations with opioid use disorder (OUD). Non-opioid substances were identified through harmonizing self-reported use. The primary outcomes were markers of return to opioid use by 12 weeks. RESULTS: When treatment cohorts were adjusted, no association between self-reported treatment entry use of non-opioid substances and week-12 opioid use was detected. During the first month of treatment, higher use of cocaine (OR 1.41 [1.18-1.69]) and amphetamine (OR 1.70 [1.27-2.26]) was found to be associated with higher likelihood of illicit opioid use by week 12. Exploratory analyses of potential treatment cohort-by-predictor interactions showed that those with heavier cocaine use had a lower rate of returning to opioid use in the extended-release naltrexone group than in the methadone group. CONCLUSION: Substance use other than opioids at treatment entry is not associated with relapse. Use of cocaine or amphetamines during the first few weeks of MOUD treatment may signal a worse outcome, suggesting a need for additional interventions.

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. RESULTS: Maximum days of consecutive abstinence, proportion of days abstinent, ≥3 weeks of continuous abstinence, and the proportion of urine specimens negative for the primary substance were associated with post-treatment psychiatric and social functioning improvement and abstinence. However, only the effects of abstinence during the last 4 weeks of the treatment period on all three post-treatment outcomes was stable over time and did not differ between primary substance groups. In contrast, complete abstinence during the 12-week treatment period was not consistently associated with functioning improvements. CONCLUSIONS: Substance use outcome measures capturing the duration of primary substance abstinence during treatment are suitable predictors of post-treatment abstinence and longer-term psychosocial functioning improvement. Binary outcomes, such as end-of-treatment abstinence, may be particularly stable predictors and attractive given their ease of computation and straightforward clinical interpretability.

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. RESULTS: By week 24, 39 participants had ≥1 overdose event. The observed frequency of having an overdose event was 15 (5.30%) among 283 patients assigned to naltrexone, eight (1.51%) among 529 patients assigned to methadone, and 16 (1.15%) among 1,387 patients assigned to buprenorphine. Notably, 27.9% of patients assigned to extended-release naltrexone never initiated the medication, and their overdose rate was 8.9% (7/79), compared with 3.9% (8/204) among those who initiated naltrexone. Controlling for sociodemographic and time-varying medication adherence variables and baseline substance use, a proportional hazard model did not show a significant effect of naltrexone assignment. Significantly higher probabilities of experiencing an overdose event were observed among patients with baseline benzodiazepine use (hazard ratio=3.36, 95% CI=1.76, 6.42) and those who either were never inducted on their assigned study medication (hazard ratio=6.64, 95% CI=2.12, 19.54) or stopped their medication after initial induction (hazard ratio=4.04, 95% CI=1.54, 10.65). CONCLUSIONS: Among patients with opioid use disorder seeking medication treatment, the risk of overdose events over the next 24 weeks is elevated among those who fail to initiate or discontinue medication and those who report benzodiazepine use at baseline.

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. Associations between patient characteristics and initiating naltrexone were estimated with logistic regression models. To evaluate whether associations differed between inpatient and outpatient settings, patient characteristic-by-setting interactions were also estimated. RESULTS: 409 patients were included in the analyses and 228 (56%) received the first injection. A significantly greater percent of inpatients (62%) vs outpatients (48%) initiated XR-naltrexone. Initiation success was significantly more likely on an inpatient basis for heroin (60.9% inpatient vs 36.2% outpatient), intravenous (56.3% inpatient vs 22.5% outpatient), and speedball users (68.1% inpatient vs 32.3% outpatient). Prescription opioid users showed similar, higher initiation rates across settings (68.9% inpatient; 73.7% outpatient). CONCLUSIONS: An inpatient setting may be the preferred strategy for rapid initiation of XR-naltrexone for opioid users with greater severity, including heroin or speedball injection users or those who use opioids intravenously. Initiation on an outpatient basis may be more likely to succeed for prescription opioid users.

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. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: A second attempt at XR- NTX initiation using buprenorphine stabilization and cross taper may be a reasonable approach for some patients.

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). This study aimed to classify and compare polysubstance use patterns, and their associations with relapse to regular opioid use in 2637 participants in three large opioid use disorder (OUD) treatment trials. Methods: We explored the daily patterns of self-reported substance use in the 28 days prior to treatment entry. Market basket analysis (MBA) and repeated measure latent class analysis (RMLCA) were used to examine the subgroups of polysubstance use patterns, and multiple logistic regression was used to examine associations between identified classes and relapse. Results: MBA and RMLCA identified 34 "associations rules " and 6 classes, respectively. Specific combinations of polysubstance use and time course (high baseline use and rapid decrease of use prior to initiation) predicts a worse relapse outcome. MBA showed individuals who co-used cocaine, heroin, prescription opioids, and cannabis had a higher risk for relapse (OR = 2.82, 95%CI = 1.13, 7.03). In RMLCA, higher risk of relapse was observed in individuals who presented with high baseline prescription opioid (OR = 1.9, 95% CI = 1.3, 2.76) or heroin use (OR = 3.54, 95%CI = 1.86, 6.72), although use decreased in both cases prior to treatment initiation. Conclusions: Our analyses identified subgroups with distinct patterns of polysubstance use. Different patterns of polysubstance use differentially predict relapse outcomes. Interventions tailored to these individuals with specific polysubstance use patterns prior to treatment initiation may increase the effectiveness of relapse prevention.

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. The purpose of this study was to obtain information about the content and educational strategies of current SUD curricula, beneficial educational products for a standardized curriculum and perceived barriers toward standardization. Invitations were sent to 64 US dental schools describing the purpose of this study and a link to complete the survey was provided. Fully completed responses were received from 32 (50.0%) of the schools. Descriptive statistics was used to analyze the data. Most dental schools surveyed (81.3%) have a curriculum for SUD with classroom lectures being the most commonly used teaching method (96.2%), followed by online modules (42.3%). About 30% of the responding schools provided additional educational experiences. Instruction occurred mostly in second (73.1%) and third (77.0%) academic years. Opioids, alcohol, nicotine, and marijuana were the most frequently taught substance classes. Curriculum standardization with online modules (81.3%), case-based exercises (59.4%), and simulation with standardized patients (43.8%) was considered desirable to improve student competency in the management of patients with SUD. Lack of time (62.5%), space (56.3%), and faculty (50.0%) were cited as the most common barriers to curriculum initiatives. Experiential and achievable options for improving SUD curriculum were highlighted.

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). Zero-inflated-negative-binomial models given high numbers of "0" GSI scores and multivariate logistic regression models were run to estimate the effect of the interaction between treatment and baseline psychological symptoms. RESULTS: The mean age was 35, 37.9% were female, 56.0% were white. Fifty-four percent had a negative urine drug or breath alcohol screen at baseline. Mean GSI score at baseline was 13.5 (SD = 12.6). GSI scores significantly improved (p<.0001) over time. Treatment was not significantly associated with GSI scores (aIRR = 0.97, 95%CI = 0.85-1.11). Those with social anxiety at baseline had a higher likelihood of achieving abstinence when receiving TES compared to TAU (b = 1.2071, SE = 0.6109, p = 0.0482). CONCLUSIONS: Psychological symptoms may improve over time in individuals seeking treatment for SUD, and for those with social anxiety, technology-based treatments may result in a better response. Examining the effect of SUD treatment on broader psychological outcomes in addition to abstinence may help clinicians provide more individualized care for those with co-occurring conditions.

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. Outcomes included executive function (Trail Making Test [TMT] Part B), episodic memory (Immediate/Delayed Recall), language fluency (Vegetables, Boston Naming Test), and conversion to dementia. Regression models were fit to examine associations between HL and neurocognitive performance at baseline. Cox proportional hazards models examined the links between HL, neurocognitive scores, and development of dementia over follow-up. RESULTS: At baseline, those with Untreated HL (versus No HL) had worse neurocognitive performance per standardized difference on executive function (TMT Part B [mean difference = 0.05 (95% CI 0.00, 0.10)]) and language fluency (Vegetables [mean difference = -0.07 (95% CI -0.14, -0.01)], Boston Naming Test [mean difference = -0.07 (95% CI -0.13, -0.01)]). No differences in these neurocognitive performance scores were demonstrated between Treated HL and No HL groups other than MMSE [mean difference = -0.06 (95% CI -0.12, 0.00)]. Through follow-up, executive dysfunction differed by hearing group (χ2(2) = 46.08, p < 0.0001) and was present among 39.12% in No HL, 44.85% in Untreated HL, and 49.40% in Treated HL. Worse performance across all cognitive domains predicted incident dementia. CONCLUSION: The observed association between Untreated HL and lower cognitive ability that improved when hearing aids were worn may reflect an inability to hear the test instructions. Future studies using cognitive assessments validated for use in HL are needed to evaluate the neuropsychological profile of HL and identify individuals at risk for dementia.

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. The dental profession has embraced reforms designed to address the SUD epidemic by promoting continuing education for practitioners and initiating curriculum changes in dental schools. Screening, Brief Intervention and Referral to Treatment (SBIRT) is an evidence-based model for managing patients with SUD. The use of a formative 1-station Objective Structured Clinical Examination (OSCE) for learning and assessment in SBIRT, operationalised with the MD3 rating scale is presented in this study. In 3 years of implementation, the SBIRT OSCE successfully integrated into the curriculum of the College of Dental Medicine, Columbia University. Mean score of total adherent behaviours was 11.80 (SD =4.23) (range: 2 - 24) and Cronbach's coefficient alpha for across-items reliability in adherent behaviours was 0.66. Adherent behaviours correlated with the global ratings (r = 0.66). Mean of global rating scores were 2.90 (SD =1.01) for collaboration and 2.97 (SD =1.00) for empathy and the global rating scores correlated with each other (r = 0.85). Histograms of global rating scores resembled normal distribution. The 1-station OSCE is a good model for learning about SBIRT. Psychometric analysis was useful in understanding the underlying construct of the MD3 rating scale and supported its reliability, validity and utility in dental education.

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. Data were collected from January 6, 2015, to December 20, 2017, and analyzed from October 4, 2019, to October 15, 2020. Exposures: Parental past 12-month exclusive medical prescription opioid use and any misuse (ie, using without a prescription or in any way not directed by a physician). Main Outcomes and Measures: Adolescent past 12-month medical prescription opioid use or misuse. Multivariable regressions estimated associations between parental and offspring medical prescription opioid use or misuse, controlling for sociodemographic and psychosocial variables. Results: Respondents included 9400 mother-child and 5800 father-child dyads in the same household; children were aged 12 to 17 years (52.8% male; mean [SD] age, 14.5 [1.7] years). Controlling for other factors, parental medical prescription opioid use was associated with adolescent prescription opioid medical use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.06-1.53) and misuse (aOR, 1.53; 95% CI, 1.07-2.25), whereas parental misuse was not. Parental medical prescription stimulant use was associated with adolescent medical prescription opioid use (aOR, 1.40; 95% CI, 1.02-1.91). Parental marijuana use (aOR, 1.84; 95% CI, 1.13-2.99), parent-adolescent conflict (aOR, 1.26; 95% CI, 1.05-1.52), and adolescent depression (aOR, 1.75; 95% CI, 1.26-2.44) were associated with adolescent prescription opioid misuse. Adolescent delinquency (aOR, 1.55; 95% CI, 1.38-1.74) and perceived schoolmates' drug use (aOR, 2.87; 95% CI, 1.95-4.23) were also associated with adolescent misuse and more weakly with medical use (aORs, 1.13 [95% CI, 1.05-1.22] and 1.61 [95% CI, 1.32-1.96], respectively). Conclusions and Relevance: Youth use of prescription opioids is in part a structural/environmental issue. The findings of this study suggest that parental medical prescription opioid use is associated with offspring prescription opioid use, whereas parental misuse is not. Restricting physicians' opioid prescribing to parents is a crucial public health goal. In addition, parents could be educated on the risks of their prescription opioid use for offspring and on practices to mitigate risk, including safe medication storage and disposal. Screening for parental prescription opioid use could be part of pediatric practice. Addressing adolescent mental health could also reduce adolescent prescription opioid misuse.

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. Primary outcomes included depression (15-item Geriatric Depression Scale ≥5) and conversion to dementia. A longitudinal logistic model was fit to examine the association between HL and changes in depressive symptoms across time. Two Cox proportional hazards models were used to examine HL and the development of dementia: Model A included only baseline variables and Model B included time-varying depression to evaluate for the direct effect of changes in depression on dementia over time. RESULTS: Treated HL (vs no HL) had increased risk for depression (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.04-1.54, p = .02) and conversion to dementia (hazard ratio [HR] = 1.29, 95% CI = 1.03-1.62, p = .03). Baseline depression was a strong independent predictor of conversion to dementia (HR = 2.32, 95% CI = 1.77-3.05, p < .0001). Development/persistence of depression over time was also associated with dementia (HR = 1.89, 95% CI = 1.47-2.42, p < .0001), but only accounted for 6% of the direct hearing-dementia relationship (Model A logHR = 0.26 [SE = 0.12] to Model B logHR = 0.24 [SE = 0.12]) suggesting no significant mediation effect of depression. CONCLUSIONS: Both HL and depression are independent risk factors for eventual conversion to dementia. Further understanding the mechanisms linking these later-life disorders may identify targets for early interventions to alter the clinical trajectories of at-risk individuals.

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; 73.8% of eligible) completed the Attitudes and Opinions Survey for alcohol and drugs before and after this 2-year, multi-modality curriculum. The authors classified attitudes as "positive" or "negative" and grouped students by pre-post attitudinal change: persistently negative, persistently positive, negative-to-positive, positive-to-negative. Using chi-square tests, the authors assessed differences by sex, race/ethnicity, and whether students had a family member or friend with an SUD. RESULTS: Most students (>90%) reported persistently positive attitudes regarding physicians in recovery, societal contributions of patients with SUDs; ability to learn from such patients; and general attitudes toward SUD treatment. This skewed distribution precluded the investigation of subgroup differences. Fewer students reported persistently positive attitudes regarding SUD patients' healthcare utilization (alcohol 58.5%; drug 57.8%) and impact on other patients' care (alcohol 73.7%; drug 72.4%), compared to other attitudinal domains (at p-values < 0.0001 in the McNemar's tests). Approximately, 1 in 5 students reported more negative healthcare utilization attitudes on follow-up. There were no demographic differences in these two attitudinal domains. CONCLUSION: Unlike previous studies of medical student attitudes, most students who participated in the Enhanced Pre-Clinical SBIRT Curriculum reported an enduring appreciation for the educational and societal contributions of patients with SUDs. Attitudes toward healthcare utilization and the impact of patients with SUDs on the care of other patients were more resistant to change, possibly due to the predominance of acute-care inpatient settings in clinical training.

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. Logistic regression models explored differences in demographic and clinical characteristics by substance use category within and between women and men. Women OU were more likely to be younger, White, employed, benzodiazepine users, and less likely to have children or use cocaine and cannabis than women AOD. Men OU, compared to men AOD, were more likely to be younger, White, younger at first abuse/dependence, benzodiazepine users, and reported greater psychological distress, but were less likely to be involved in criminal justice or use stimulants. Interactions by gender and substance use were also detected for age of first abuse/dependence, employment, and criminal justice involvement. These findings provide a nuanced understanding of gender differences within substance use groups to inform providers for OU seeking treatment.

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. An Attitudes and Opinion Survey (AOS) consisting of 8 questions that separately assesses DDS1 attitudes toward alcohol and drug use disorders was utilized to evaluate the training. Assenting DDS1 anonymously completed the AOS before and following the training. Over 3 years, we analyzed changes in the AOS of 230 DDS1 using Chi-squared test for bivariate comparison. We then applied a Bonferroni correction to the P-values. Response rate was 95.5%. The SBIRT training improved DDS1 attitudes and opinions toward patients with SUD with respect to all AOS questions. There was a statistically significant improvement (P < 0.003) in DDS1 attitudes and opinions with respect to whether other patients care suffers because of time and resources spent on patients with SUD and whether the SBIRT training provided adequate education to prepare DDS1 to manage patients with SUD. SBIRT training is relevant to dental education. It fills an important educational gap and is a suitable model for other dental schools.

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. METHODS: We conducted a secondary analysis of the 1-month follow-up data from CTN-0029 after the discontinuation of OROS-MPH (N = 134). Nicotine patch was tapered during this month. We tested whether OROS-MPH had an effect on self-reported 7-day abstinence by week, as well as possible treatment by baseline ADHD severity interactions. RESULTS: Abstinence diminished overall in time after the end of the treatment. In the high baseline severity group, patients who received OROS-MPH had an advantage in 7-day abstinence at week 15 (40% for OROS-MPH vs 20% for placebo, odds ratio = 2.63, P = .028). In the lower severity group (n = 121), no difference was detected (29% for OROS-MPH vs 32% for placebo, P = 1.00) between the two treatment groups. There was also a significant treatment by baseline ADHD severity interaction (P = .03). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: OROS-MPH promotes abstinence beyond the course of treatment for patients with more severe ADHD, while the paradoxical effects in the lower baseline severity group is not persistent after medication discontinuation. Targeting ADHD in smoking cessation as a comorbidity therefore can have broader impact with more precise patient selection. (Am J Addict).

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., 2014). In the current analysis, we use a two-level, hierarchical generalized linear model (HGLM) to identify patient- and site-level variables associated with abstinence outcome, while modeling site as a random factor. RESULTS: The site-specific percentage of patients abstinent in the last 4 weeks of the study varied from 6.1% to 40%. However, only 6.7% (p = 0.08) of variability in end-of-study abstinence was accounted for by site, indicating a small-moderate effect. Among patient-level predictors, older age (OR = 1.40; 95% CI = 1.15, 1.71; p = 0.0009), abstinence at baseline (OR = 2.77; 95% CI = 1.73, 4.45; p < 0.0001), and among site-level predictors, higher annual clinic admissions (OR = 1.28; 95% CI = 1.03, 1.59; p = 0.0251) were significantly associated with increased likelihood of abstinence. When controlling for these three variables in a HGLM, only patient age and abstinence at baseline remained significant, and random factor site explained only 1.4% of variability in end-of-study abstinence, a 79% reduction in magnitude. CONCLUSIONS: The findings suggest that only some amount of variability in abstinence outcomes among sites can be explained by a combination of patient- and site-level variables. Our findings support the case that variability between sites is a natural phenomenon, and our methodological recommendation is that site be modeled as a random factor when analyzing multi-site clinical trials.