Faculty Bibliography

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.

Diagnostic accuracy of the Diagnostic and Statistical Manual of Mental Disorders-oriented Child and Adolescent Symptom Inventory (CASI-4R) Psychotic Symptoms scale was tested using receiver operating characteristic analyses to identify clinically significant psychotic symptoms. Participants were new outpatients (N = 700), ages 6.0 to 12.9 years (M = 9.7, SD = 1.8) at 9 child outpatient mental health clinics, who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) Study baseline assessment. Because LAMS undersampled participants with low mania scores by design, present analyses weighted low scorers to produce unbiased estimates. Psychotic symptoms, operationally defined as a score of 3 or more for hallucinations or 4 or more for delusions based on the Schedule for Affective Disorders and Schizophrenia (K-SADS) psychosis items, occurred in 7% of youth. K-SADS diagnoses for those identified with psychotic symptoms above threshold included major depressive disorder, bipolar spectrum disorder, attention deficit/hyperactivity disorder, posttraumatic stress disorder, psychotic disorders, and autism spectrum disorder. The optimal psychosis screening cut score (maximizing sensitivity and specificity) was 2.75+ (corresponding diagnostic likelihood ratio [DiLR] = 4.29) for the parent version and 3.50+ (DiLR = 5.67) for the teacher version. The Area under the Curve for parent and teacher report was .83 and .74 (both p < .001). Parent report performed significantly better than teacher report for identifying psychotic symptoms above threshold (p = .03). The CASI-4R Psychosis subscale (J) appears clinically useful for identifying psychotic symptoms in children because of its brevity and accuracy.

Developmental ethanol exposure is a well-known cause of lifelong cognitive deficits, behavioral hyperactivity, emotional dysregulation, and more. In healthy adults, sleep is thought to have a critical involvement in each of these processes. Our previous work has demonstrated that some aspects of cognitive impairment in adult mice exposed at postnatal day 7 (P7) to ethanol (EtOH) correlate with slow-wave sleep (SWS) fragmentation (Wilson et al., 2016). We and others have also previously demonstrated that co-treatment with LiCl on the day of EtOH exposure prevents many of the anatomical and physiological impairments observed in adults. Here we explored cognitive function, diurnal rhythms (activity, temperature), SWS, and parvalbumin (PV) and perineuronal net (PNN)-positive cell densities in adult mice that had received a single day of EtOH exposure on P7 and saline-treated littermate controls. Half of the animals also received a LiCl injection on P7. The results suggest that developmental EtOH resulted in adult behavioral hyperactivity, cognitive impairment, and reduced SWS compared to saline controls. Both of these effects were reduced by LiCl treatment on the day of EtOH exposure. Finally, developmental EtOH resulted in decreased PV/PNN-expressing cells in retrosplenial (RS) cortex and dorsal CA3 hippocampus at P90. As with sleep and behavioral activity, LiCl treatment reduced this decrease in PV expression. Together, these results further clarify the long-lasting effects of developmental EtOH on adult behavior, physiology, and anatomy. Furthermore, they demonstrate the neuroprotective effects of LiCl co-treatment on this wide range of developmental EtOH's long-lasting consequences.

This is a replication, randomized control trial, that investigated the therapeutic effects of a 12-week equine-assisted (EA) intervention on the social and sensory functioning of children with autism. Reliability and stability of parent and teacher reports of children's social and sensory functioning across three assessment times were assessed, in support of the validity of observed outcomes. Furthermore, it was hypothesized that children in the EA group (n = 25) would significantly improve, relative to a wait-list control group (n = 25), in both domains of functioning. Results indicated that reports were reliable, and children in the experimental group improved in overall social and sensory functioning, as well as within specific subdomains, with "unblinded" assessment methods. Relative to the pre-assessment scores, children improved in functioning in specific areas at post-assessment and 8-weeks post-intervention. Therefore, results of the study suggest EA activities may be a beneficial modality for delivering autism-specific treatment strategies.

Objectives: The Wellness Self-Management (WSM) is an adaptation and expansion of Illness Management and Recovery (IMR), an internationally recognized best practice. In order to validate the Italian version of WSM our goals included the translation from English to Italian of the WSM workbook and the implementation of an abbreviated WSM program in an Italian day hospital setting. Methods: In a randomized controlled trial 14 patients with a diagnosis of severe mental illness were recruited and randomly assigned to two groups. Seven individuals received an abbreviated version of WSM, while the controls received Treatment as Usual. Groups did not differ for age, education, cognitive functioning and symptomatology. All patients received weekly planned treatment in the day hospital setting. After treatment, group differences on change scores were tested using ANOVA. Results: Compared to controls, at immediate post-intervention, WSM participants reported significant improvement in processing speed, psychopathology, neurocognitive and personal resources and real-life functioning. Conclusions: These results offer promising preliminary evidence that the use of an abbreviated Italian translation of the WSM workbook provides an effective complement to current mental health treatment.