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BACKGROUND: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied. METHODS: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone–bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone–bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses. RESULTS: A total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone–bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone–bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone–bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P

Background and aims Physician and pharmacist collaboration may help address the shortage of buprenorphine-waivered physicians and improve care for patients with opioid use disorder (OUD). This study investigated the feasibility and acceptability of a new collaborative care model involving buprenorphine-waivered physicians and community pharmacists. Design Nonrandomized, single-arm, open-label feasibility trial. Setting Three office-based buprenorphine treatment (OBBT) clinics and three community pharmacies in the United States. Participants Six physicians, six pharmacists, and 71 patients aged ≥18 years with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) OUD on buprenorphine maintenance. Intervention After screening, eligible patients' buprenorphine care was transferred from their OBBT physician to a community pharmacist for 6 months. Measurements Primary outcomes included recruitment, treatment retention and adherence, and opioid use. Secondary outcomes were intervention fidelity, pharmacists' use of prescription drug monitoring program (PDMP), participant safety, and satisfaction with treatment delivery. Findings A high proportion (93.4%, 71/76) of eligible participants enrolled into the study. There were high rates of treatment retention (88.7%) and adherence (95.3%) at the end of the study. The proportion of opioid-positive urine drug screens (UDSs) among complete cases (i.e. those with all six UDSs collected during 6 months) at month 6 was (4.9%, 3/61). Intervention fidelity was excellent. Pharmacists used PDMP at 96.8% of visits. There were no opioid-related safety events. Over 90% of patients endorsed that they were "very satisfied with their experience and the quality of treatment offered," that "treatment transfer from physician's office to the pharmacy was not difficult at all," and that "holding buprenorphine visits at the same place the medication is dispensed was very or extremely useful/convenient." Similarly, positive ratings of satisfaction were found among physicians/pharmacists. Conclusions A collaborative care model for people with opioid use disorder that involves buprenorphine-waivered physicians and community pharmacists appears to be feasible to operate in the United States and have high acceptability to patients.

This quality improvement study compares commonly used screening methods for alcohol and drug use among adult patients at primary care clinics to examine their association with implementation outcomes and to evaluate the best approach for implementing electronic health record–integrated screening., Key Points Question How are commonly used screening methods for alcohol and drug use associated with implementation outcomes among adult patients in primary care clinics, and what is the best approach for implementing electronic health record–integrated screening? Findings In this quality improvement study implementing systematic screening for alcohol and drug use among 93 114 patients in 6 primary care clinics, 72% of patients completed screening. Screening at any visit (in comparison with screening at annual examinations only) was associated with higher screening rates for alcohol and drug use, and self-administered screening was associated with greater detection of moderate- to high-risk alcohol use compared with staff-administered screening. Meaning These findings suggest that, to maximize the adoption of substance use screening during primary care visits, clinics can conduct screening at any visit and use self-administered screening tools to increase the detection of unhealthy alcohol use among adult patients., Importance Guidelines recommend that adult patients receive screening for alcohol and drug use during primary care visits, but the adoption of screening in routine practice remains low. Clinics frequently struggle to choose a screening approach that is best suited to their resources, workflows, and patient populations. Objective To evaluate how to best implement electronic health record (EHR)–integrated screening for substance use by comparing commonly used screening methods and examining their association with implementation outcomes. Design, Setting, and Participants This article presents the outcomes of phases 3 and 4 of a 4-phase quality improvement, implementation feasibility study in which researchers worked with stakeholders at 6 primary care clinics in 2 large urban academic health care systems to define and implement their optimal screening approach. Site A was located in New York City and comprised 2 clinics, and site B was located in Boston, Massachusetts, and comprised 4 clinics. Clinics initiated screening between January 2017 and October 2018, and 93 114 patients were eligible for screening for alcohol and drug use. Data used in the analysis were collected between January 2017 and October 2019, and analysis was performed from July 13, 2018, to March 23, 2021. Interventions Clinics integrated validated screening questions and a brief counseling script into the EHR, with implementation supported by the use of clinical champions (ie, clinicians who advocate for change, motivate others, and use their expertise to facilitate the adoption of an intervention) and the training of clinic staff. Clinics varied in their screening approaches, including the type of visit targeted for screening (any visit vs annual examinations only), the mode of administration (staff-administered vs self-administered by the patient), and the extent to which they used practice facilitation and EHR usability testing. Main Outcomes and Measures Data from the EHRs were extracted quarterly for 12 months to measure implementation outcomes. The primary outcome was screening rate for alcohol and drug use. Secondary outcomes were the prevalence of unhealthy alcohol and drug use detected via screening, and clinician adoption of a brief counseling script. Results Patients of the 6 clinics had a mean (SD) age ranging from 48.9 (17.3) years at clinic B2 to 59.1 (16.7) years at clinic B3, were predominantly female (52.4% at clinic A1 to 64.6% at clinic A2), and were English speaking. Racial diversity varied by location. Of the 93,114 patients with primary care visits, 71.8% received screening for alcohol use, and 70.5% received screening for drug use. Screening at any visit (implemented at site A) in comparison with screening at annual examinations only (implemented at site B) was associated with higher screening rates for alcohol use (90.3%-94.7% vs 24.2%-72.0%, respectively) and drug use (89.6%-93.9% vs 24.6%-69.8%). The 5 clinics that used a self-administered screening approach had a higher detection rate for moderate- to high-risk alcohol use (14.7%-36.6%) compared with the 1 clinic that used a staff-administered screening approach (1.6%). The detection of moderate- to high-risk drug use was low across all clinics (0.5%-1.0%). Clinics with more robust practice facilitation and EHR usability testing had somewhat greater adoption of the counseling script for patients with moderate-high risk alcohol or drug use (1.4%-12.5% vs 0.1%-1.1%). Conclusions and Relevance In this quality improvement study, EHR-integrated screening was feasible to implement in all clinics and unhealthy alcohol use was detected more frequently when self-administered screening was used at any primary care visit. The detection of drug use was low at all clinics, as was clinician adoption of counseling. These findings can be used to inform the decision-making of health care systems that are seeking to implement screening for substance use. Trial Registration ClinicalTrials.gov Identifier: NCT02963948

Background Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment: Episodes Data Set – Admissions. Methods Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings.

Background There is a need for screening and brief assessment instruments to identify primary care patients with substance use problems. This study's aim was to examine the performance of a two-step screening and brief assessment instrument, the TAPS Tool, compared to the WHO ASSIST. Methods Two thousand adult primary care patients recruited from five primary care clinics in four Eastern US states completed the TAPS Tool followed by the ASSIST. The ability of the TAPS Tool to identify moderate- and high-risk use scores on the ASSIST was examined using sensitivity and specificity analyses. Results The interviewer and self-administered computer tablet versions of the TAPS Tool generated similar results. The interviewer-administered version (at cut-off of 2), had acceptable sensitivity and specificity for high-risk tobacco (0.90 and 0.77) and alcohol (0.87 and 0.80) use. For illicit drugs, sensitivities were > 0.82 and specificities > 0.92. The TAPS (at a cut-off of 1) had good sensitivity and specificity for moderate-risk tobacco use (0.83 and 0.97) and alcohol (0.83 and 0.74). Among illicit drugs, sensitivity was acceptable for moderate-risk of marijuana (0.71), while it was low for all other illicit drugs and non-medical use of prescription medications. Specificities were 0.97 or higher for all illicit drugs and prescription medications. Conclusions The TAPS Tool identified adult primary care patients with high-risk ASSIST scores for all substances as well moderate-risk users of tobacco, alcohol, and marijuana, although it did not perform well in identifying patients with moderate-risk use of other drugs or non-medical use of prescription medications. The advantages of the TAPS Tool over the ASSIST are its more limited number of items and focus solely on substance use in the past 3 months.

Importance There are no approved drug treatments for autosomal dominant retinitis pigmentosa, a relentlessly progressive cause of adult and childhood blindness. Objectives To evaluate the potential efficacy and assess the safety of orally administered valproic acid (VPA) in the treatment of autosomal dominant retinitis pigmentosa. Design, Setting, and Participants Multicenter, phase 2, prospective, interventional, placebo-controlled, double-masked randomized clinical trial. The study took place in 6 US academic retinal degeneration centers. Individuals with genetically characterized autosomal dominant retinitis pigmentosa were randomly assigned to receive treatment or placebo for 12 months. Analyses were intention-to-treat. Interventions Oral VPA 500 mg to 1000 mg daily for 12 months or placebo. Main Outcomes and Measures The primary outcome measure was determined prior to study initiation as the change in visual field area (assessed by the III4e isopter, semiautomated kinetic perimetry) between baseline and month 12. Results The mean (SD) age of the 90 participants was 50.4 (11.6) years. Forty-four (48.9%) were women, 87 (96.7%) were white, and 79 (87.8%) were non-Hispanic. Seventy-nine participants (87.8%) completed the study (42 [95.5%] received placebo and 37 [80.4%] received VPA). Forty-two (46.7%) had a rhodopsin mutation. Most adverse events were mild, although 7 serious adverse events unrelated to VPA were reported. The difference between the VPA and placebo arms for mean change in the primary outcome was −150.43 degree2(95% CI, −290.5 to −10.03;P = .035). Conclusions and Relevance This negative value indicates that the VPA arm had worse outcomes than the placebo group. This study brings to light the key methodological considerations that should be applied to the rigorous evaluation of treatments for these conditions. This study does not provide support for the use of VPA in the treatment of autosomal dominant retinitis pigmentosa. Trial Registration ClinicalTrials.gov Identifier:NCT01233609

Computer-delivered interventions have the potential to improve access to quality addiction treatment care. The objective of this study was to evaluate the effectiveness of the Therapeutic Education System (TES), an Internet-delivered behavioral intervention that includes motivational incentives, as a clinician-extender in the treatment of substance use disorders.Adult men and women (N=507) entering 10 outpatient addiction treatment programs were randomly assigned to receive 12 weeks of either treatment as usual (N=252) or treatment as usual plus TES, with the intervention substituting for about 2 hours of standard care per week (N=255). TES consists of 62 computerized interactive modules covering skills for achieving and maintaining abstinence, plus prize-based motivational incentives contingent on abstinence and treatment adherence. Treatment as usual consisted of individual and group counseling at the participating programs. The primary outcome measures were abstinence from drugs and heavy drinking (measured by twice-weekly urine drug screens and self-report) and time to dropout from treatment.Compared with patients in the treatment-as-usual group, those in the TES group had a lower dropout rate (hazard ratio=0.72, 95% CI=0.57, 0.92) and a greater abstinence rate (odds ratio=1.62, 95% CI=1.12, 2.35). This effect was more pronounced among patients who had a positive urine drug or breath alcohol screen at study entry (N=228) (odds ratio=2.18, 95% CI=1.30, 3.68).Internet-delivered interventions such as TES have the potential to expand access and improve addiction treatment outcomes. Additional research is needed to assess effectiveness in non-specialty clinical settings and to differentiate the effects of the community reinforcement approach and contingency management components of TES.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with an estimated prevalence of 10–15% in Western countries. • Diagnosis of IBS is based upon the presence of abdominal discomfort/pain with changes in bowel habits. In clinical practice and research, IBS patients are • subgrouped on the basis of differences in bowel habits. Approximately 1/3 of IBS patients suffer with IBS and constipation (IBS-C). Current therapies for IBS-C tend to target relieving individual symptoms of constipation, abdominal pain or bloating rather than the totality of IBS symptoms. • Lubiprostone, a selective activator of type-2 chloride channels (CIC-2), is approved for the treatment of chronic idiopathic constipation in adults and for the • treatment of IBS-C in adult women. Lubiprostone enhances fluid secretion into the intestinal lumen without altering serum electrolyte levels. • Patients with IBS may exhibit abnormal gut permeability and an associated intestinal inflammatory response. Lubiprostone stimulates recovery of mucosal • barrier function in animal models suggesting a possible mechanism for the clinical improvement observed in patients on this drug.* Given the intermittent nature of IBS-C symptoms, short-term interventions for symptomatic relief of IBS-C may be appropriate in some patients. Such • interventions need to be efficacious and not associated with rebound effects following discontinuation of treatment.