Sustainability of Adolescent Screening and Brief Intervention Services in Primary Care After Removal of Implementation Supports.

OBJECTIVE: Although many health care organizations have sought to increase the integration of substance use services into clinical practice, such practice changes can prove difficult to sustain. METHOD: Seven primary care clinics participated in an implementation study of screening and brief intervention (BI) services for adolescent patients (ages 12-17). All sites delivered screening and brief advice (BA) for low-risk use using a uniform protocol. Clinics were randomized to deliver BI using generalist (provider-delivered) or specialist (behavioral health clinician-delivered) models. Implementation was facilitated by multiple supporting activities (e.g., trainings, local "champion," electronic health record [EHR] integration of screening and documentation, individualized feedback, project-specific materials, etc.). Data on the penetration of screening, BA, and BI delivery (N = 14,486 adolescent patient visits) were abstracted from the EHR for the 20-month implementation phase and a 12-month sustainability phase (during which implementation supports were removed). RESULTS: Penetration of screening continued to slowly increase across the implementation-to-sustainability phases (62% vs. 70%; p = .04). Although uptake during implementation was low for BA (29%) and BI (22%), there was no significant decrease in service provision during the sustainability phase. Although overall delivery of BI was significantly higher in generalist compared with specialist sites (p < .001), sustainability did not differ by generalist versus specialist conditions. There were considerable differences in penetration across clinic sites. CONCLUSIONS: Clinics sustained a high level of substance use screening. Uptake of intervention services was low but did not decrease further following the cessation of implementation supports. This study illustrates the challenges of successfully implementing and sustaining substance use services in adolescent primary care.

Costs and Implementation Effectiveness of Generalist Versus Specialist Models for Adolescent Screening and Brief Intervention in Primary Care.

OBJECTIVE: This study analyzed the marginal service and program costs, and conducted a cost-effectiveness analysis (CEA) of two models of implementation of adolescent substance screening, brief intervention, and referral to treatment (SBIRT). METHOD: SBIRT was implemented at seven clinics in a multisite, cluster-randomized trial, through a Specialist model (behavioral health counselor-delivered brief intervention), and a Generalist model (primary care provider-delivered brief intervention). The CEA calculated marginal costs using an activity-based costing methodology for direct SBIRT services, and effectiveness was measured by the proportion of brief interventions delivered among patients who screened positive for alcohol, tobacco, or other drugs. Site-level program costs comprised start-up and maintenance (training and technical assistance). Costs were estimated in 2017 U.S. dollars. RESULTS: The marginal cost of SBIRT per patient with a positive screen for brief intervention was $6.72 in the Specialist model and $6.05 in the Generalist model. Implementation effectiveness was 7.2% (SE = 2.9%) in the Specialist model and 37.7% (SE = 5.6%) in the Generalist model. The program costs to provide SBIRT for 1 year per site were $13,548 for the Specialist site and $12,081 for the Generalist. CONCLUSIONS: The Generalist model was more effective in implementing brief intervention and less expensive than the Specialist model. Results were robust to sensitivity analysis. Brief intervention delivered by primary care providers rather than by handoff to a behavioral health counselor may ensure greater penetration and a lower cost of these services in primary care settings.

Organizational Acceptability of Implementing SBIRT for Adolescents in Primary Care.

INTRODUCTION: Adolescent illicit drug, tobacco, and alcohol use can result in sudden and long-term negative health consequences. Primary care environments present the optimal opportunity for screening and brief interventions that target prevention and curtailing use. Screening, Brief Intervention, and Referral to Treatment (SBIRT) is a service delivery method that could potentially be well-integrated into primary care settings and used to serve a high volume of adolescents. Methods: This qualitative analysis of clinic staff interviews (N = 20), collected during a large cluster-randomized trial to implement two models of adolescent SBIRT, examined barriers and facilitating factors to overall acceptability of SBIRT. This study was conducted in a large, urban Federally Qualified Health Center (FQHC) at 7 sites throughout Baltimore City, Maryland, USA. Participants from each clinic included a range of various roles and responsibilities including: medical assistants (n = 3), nurses (n = 3), primary care providers (n = 4), behavioral health counselors (n = 4), and administrators (n = 6). Results: Results indicate both barriers and facilitating factors for acceptability of SBIRT in terms of (1) universal screening, (2) provider time demands, (3) behavioral health collaboration, and (4) behavioral health caseloads. Discussion: Universal screening was acceptable to participants across organizational roles, but brief interventions and referrals to treatment were found substantially less acceptable.

Correction to Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel.

[This corrects the article DOI: 10.1021/acsmedchemlett.8b00344.].

Adolescent SBIRT implementation: Generalist vs. Specialist models of service delivery in primary care.

BACKGROUND: Drug, alcohol, and tobacco use among adolescents pose significant short- and long-term health consequences and are associated with more severe use as adults. Screening, brief intervention, and referral to treatment in primary care settings has the potential to deliver preventive interventions to a diverse range of adolescents, but optimal implementation of these services needs to be determined. The purpose of this study was to compare implementation of two different SBIRT service delivery models in primary care settings. METHODS: This cluster-randomized trial assigned 7 primary care clinics of a federally qualified health center to implement brief interventions (BI) using a Generalist model (4 sites), in which BIs were delivered by the primary care provider (PCP), or a Specialist model (3 sites), in which BIs were delivered by a behavioral health counselor (BHC) for adolescent patients ages 12-17 years. Implementation was tracked through the clinic's electronic health record, spanning 9639 clinic visits over 20 months. Multilevel logistic regression modeling was used to compare Generalist and Specialist strategies on penetration of BI for patients scoring ≥2 on the CRAFFT substance use screen, delivered by the PCP in the Generalist sites, and via warm hand-off to a BHC in the Specialist sites. RESULTS: Approximately 62% of adolescent patient visits were screened with the CRAFFT (with <4% screening positive with a CRAFFT score ≥ 2). The Generalist Condition had significantly higher self-reported penetration of BI delivery than the Specialist Condition (38% vs. 8%; Adjusted Odds Ratio = 6.53; p = .005). DISCUSSION: Despite having co-located behavioral health services at all sites, a Specialist approach to providing BI was less effectively implemented than a Generalist approach in this FQHC. BI delivered by PCPs rather than by hand-off to a BHC may ensure greater penetration of these services in primary care settings. Both implementation models provided a framework for identifying and intervening with adolescent primary care patients whose substance use might have otherwise gone undetected.

Application of System Dynamics to Inform a Model of Adolescent SBIRT Implementation in Primary Care Settings.

System dynamics (SD) modeling is used to compare and contrast strategies for effective implementation of an evidence-based adolescent behavioral health treatment in primary care settings. With qualitative and quantitative data from an on-going cluster-randomized trial in 7 federally qualified health center sites, two implementation conditions were compared: generalist vs. specialist. In the generalist approach, the primary care provider (PCP) delivered brief intervention (BI) for substance misuse (n = 4 clinics). In the specialist approach, BIs were delivered by behavioral health counselors (BHCs) (n = 3 clinics). The resultant SD model compared 'basecase' dynamics to strategic approaches to deploying continuous technical assistance (TA) and performance feedback reporting (PFR). The basecase effectively represented the SBIRT intervention, which reflected actual monthly volume of adolescent primary care visits (N = 9639), screenings (N = 5937), positive screenings (N = 246), and brief interventions (BIs; N = 50) over the 20-month implementation period. Insights gained suggest that implementation outcomes are sensitive to frequency of PFR, with bimonthly events generating the most rapid and sustained screening results. Simulated trends indicated that availability of the BHC directly impacts success of the specialist model. Similarly, understanding PCPs' perception of severity of need for intervention is key to outcomes in either condition.

A Comparison of Screening Practices for Adolescents in Primary Care After Implementation of Screening, Brief Intervention, and Referral to Treatment.

PURPOSE: The American Academy of Pediatrics recommends screening adolescents for substance use at all well-child and appropriate acute-care visits. However, many pediatric practices aim for such screenings annually at well-child visits. METHODS: As part of a larger study, 7 urban Federally Qualified Health Center clinics implemented universal screening for risky alcohol and drug use using the Car, Relax, Alone, Forget, Friends, Trouble (CRAFFT) screening tool. The present study compared uptake of screening and screening results at well-child versus acute-care visits. RESULTS: Over a period of 13 months for which encounter-level electronic medical records data were available, there were 6,346 clinic visits by 3,475 unique patients aged 12-17 years, at which 76.6% (n = 4,865) of visits had a screening for problematic substance use conducted. Rates of screening were 95.1% (2,750/2,891 involving 2,629 unique adolescents) for well-child visits and 61.2% (2,115/3,455 involving 1,535 unique adolescents) for acute-care visits. Rates of positive screening results were 9.0% (248/2,750 involving 245 unique adolescents) for well-child visits and 7.8% (164/2,115 involving 126 unique adolescents) for acute-care visits. Of the 469 unique adolescents screened only during an acute-care visit during that same period, 40 unique adolescents had positive screening results for a positive screening rate of 8.5%. CONCLUSIONS: Nearly 10% of adolescent patients screened only at acute-care visits would not have been screened if screening was implemented solely at well-child visits, and 40 adolescents reporting substance use would have been missed. The findings highlight the benefits of screening adolescents at every primary care visit to better detect and intervene in adolescents' substance use.

Disclosure of Adolescent Substance Use in Primary Care: Comparison of Routine Clinical Screening and Anonymous Research Interviews.

PURPOSE: The American Academy of Pediatrics recommends substance use screening in adolescent primary care. Many studies of substance use prevalence and screening tool validation are conducted under research protocols that differ from routine clinical screening in context, consequences, and privacy implications. METHODS: This study is a secondary analysis drawing from two projects focused on adolescent primary care patients, aged 12-17, conducted nearly contemporaneously in a Federally Qualified Health Center system. The first project conducted anonymous research interviews with patients (N = 525), while the other tracked routine clinical screening as part of a larger service implementation project (N = 5,971). Both projects assessed substance use with the CRAFFT screening tool. RESULTS: Rates of substance use disclosure and substance use problems were over three and four times higher, respectively, in the anonymous research interview sample compared to rates found in routine clinical screening (p values < .001). CONCLUSIONS: Routine clinical screening may underestimate substance use among adolescents.

Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel.

RIP2 kinase was recently identified as a therapeutic target for a variety of autoimmune diseases. We have reported previously a selective 4-aminoquinoline-based RIP2 inhibitor GSK583 and demonstrated its effectiveness in blocking downstream NOD2 signaling in cellular models, rodent in vivo models, and human ex vivo disease models. While this tool compound was valuable in validating the biological pathway, it suffered from activity at the hERG ion channel and a poor PK/PD profile thereby limiting progression of this analog. Herein, we detail our efforts to improve both this off-target liability as well as the PK/PD profile of this series of inhibitors through modulation of lipophilicity and strengthening hinge binding ability. These efforts have led to inhibitor 7, which possesses high binding affinity for the ATP pocket of RIP2 (IC50 = 1 nM) and inhibition of downstream cytokine production in human whole blood (IC50 = 10 nM) with reduced hERG activity (14 µM).

Start-Up Costs of SBIRT Implementation for Adolescents in Urban U.S. Federally Qualified Health Centers.

OBJECTIVE: Understanding the costs to implement Screening, Brief Intervention, and Referral to Treatment (SBIRT) for adolescent substance use in primary care settings is important for providers in planning for services and for decision makers considering dissemination and widespread implementation of SBIRT. We estimated the start-up costs of two models of SBIRT for adolescents in a multisite U.S. Federally Qualified Health Center (FQHC). In both models, screening was performed by a medical assistant, but models differed on delivery of brief intervention, with brief intervention delivered by a primary care provider in the generalist model and a behavioral health specialist in the specialist model. METHOD: SBIRT was implemented at seven clinics in a multisite, cluster randomized trial. SBIRT implementation costs were calculated using an activity-based costing methodology. Start-up activities were defined as (a) planning activities (e.g., changing existing electronic medical record system and tailoring service delivery protocols); and (b) initial staff training. Data collection instruments were developed to collect staff time spent in start-up activities and quantity of nonlabor resources used. RESULTS: The estimated average costs to implement SBIRT were $5,182 for the specialist model and $3,920 for the generalist model. Planning activities had the greatest impact on costs for both models. Overall, more resources were devoted to planning and training activities in specialist sites, making the specialist model costlier to implement. CONCLUSIONS: The initial investment required to implement SBIRT should not be neglected. The level of resources necessary for initial implementation depends on the delivery model and its integration into current practice.

Cardiotoxicity screening with simultaneous optogenetic pacing, voltage imaging and calcium imaging.

INTRODUCTION: The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative seeks an in vitro test to accurately predict clinical Torsades de Pointes (TdP). We developed a cardiotoxicity assay incorporating simultaneous measurement of the action potential (AP) waveform and Ca(2+) transient (CT) in human iPSC-derived cardiomyocytes (CMs). Concurrent optogenetic pacing provided a well-controlled electrophysiological background. METHODS: We used the Optopatch platform for all-optical electrophysiology (Hochbaum et al., 2014). In a monolayer culture, a subset of cells expressed a genetically encoded, calcium and voltage reporter, CaViar (Hou, Kralj, Douglass, Engert, & Cohen, 2014), while others expressed a channelrhodopsin variant, CheRiff. Optical pacing of CheRiff-expressing cells synchronized the syncytium. We screened 12 compounds (11 acute, 1 chronic) to identify electrophysiological (AP rise time, AP50, AP90, beat rate) and CT effects in spontaneously beating and paced cultures (1Hz, 2Hz). RESULTS: CaViar reported spontaneous and paced APs and CTs with high signal-to-noise ratio and low phototoxicity. Quinidine, flecainide, E-4031, digoxin and cisapride prolonged APs, while verapamil and nifedipine shortened APs. Early after depolarizations (EADs) were elicited by quinidine, flecainide and cisapride. All but four compounds (amiodarone, chromanol, nifedipine, verapamil) prolonged AP rise time. Nifedipine and verapamil decreased CT amplitude, while digoxin increased CT amplitude. Pentamidine prolonged APs after chronic exposure. DISCUSSION: The Optopatch platform provides a robust assay to measure APs and CTs in hiPSC-CMs. This addresses the CiPA mandate and will facilitate comparisons of cell-based assays to human clinical data.

Novel tricyclics (e.g., GSK945237) as potent inhibitors of bacterial type IIA topoisomerases.

During the course of our research on the lead optimisation of the NBTI (Novel Bacterial Type II Topoisomerase Inhibitors) class of antibacterials, we discovered a series of tricyclic compounds that showed good Gram-positive and Gram-negative potency. Herein we will discuss the various subunits that were investigated in this series and report advanced studies on compound 1 (GSK945237) which demonstrates good PK and in vivo efficacy properties.

SBIRT Implementation for Adolescents in Urban Federally Qualified Health Centers.

BACKGROUND: Alcohol, tobacco, and other drug use remains highly prevalent among US adolescents and is a threat to their well-being and to the public health. Evidence from clinical trials and meta-analyses supports the effectiveness of Screening, Brief Intervention and Referral to Treatment (SBIRT) for adolescents with substance misuse but primary care providers have been slow to adopt this evidence-based approach. The purpose of this paper is to describe the theoretically informed methodology of an on-going implementation study. METHODS: This study protocol is a multi-site, cluster randomized trial (N=7) guided by Proctor's conceptual model of implementation research and comparing two principal approaches to SBIRT delivery within adolescent medicine: Generalist vs. Specialist. In the Generalist Approach, the primary care provider delivers brief intervention (BI) for substance misuse. In the Specialist Approach, BIs are delivered by behavioral health counselors. The study will also examine the effectiveness of integrating HIV risk screening within an SBIRT model. Implementation Strategies employed include: integrated team development of the service delivery model, modifications to the electronic medical record, regular performance feedback and supervision. Implementation outcomes, include: Acceptability, Appropriateness, Adoption, Feasibility, Fidelity, Costs/Cost-Effectiveness, Penetration, and Sustainability. DISCUSSION: The study will fill a major gap in scientific knowledge regarding the best SBIRT implementation strategy at a time when SBIRT is poised to be brought to scale under health care reform. It will also provide novel data to inform the expansion of the SBIRT model to address HIV risk behaviors among adolescents. Finally, the study will generate important cost data that offer guidance to policymakers and clinic directors about the adoption of SBIRT in adolescent health care.

Misrepresenting the Accomplishments of Treatment.

The term "chronic relapsing disorder/disease" is viewed as an unfortunate shorthand expression that does an injustice to the accomplishments of treatment patients and treatment providers, and inadequately describes the findings from treatment evaluation research. Studies are reported that make clear relapse is not an inevitable consequence of substance abuse treatment, while substantial reductions in drug use and crime are routinely obtained consequent to treatment. It is past time to retire a term whose only virtue is brevity, and whose vices risk harm to a treatment population that is already stigmatized and a treatment system that is under frequent pressure. Thus, retiring this term provides the important benefit of recognizing the real achievements in behavior change obtained by treatment clients in conjunction with their service providers.

In Support of a National Treatment Evaluation Study.

Argument is made for the importance of conducting a national treatment evaluation to permit understanding of the nature and effectiveness of typical treatment programming. Only through such study can we hope to learn areas of success and failure of normative programming relative to population characteristics and treatment strategies, and the extent to which research-based initiatives have been adopted by the field. That information is central to efforts to draw up a research agenda appropriate to the needs of clients and the staffs responsible for their treatment, and to clarify and respond to gaps in the application of potentially useful treatment components. In spite of such need, our understanding of typical treatment programming and of its effectiveness is based on data collected from a treatment cohort of 20 years ago, although patterns of drug use, characteristics of clients, and the treatment components available have all undergone substantial change. The responsibility taken to provide such information to the field, once seen as a central task of research, needs to be reasserted to strengthen and support our treatment efforts.

Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases.

During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers.

Predicting drug-induced QT prolongation and torsades de pointes: a review of preclinical endpoint measures.

Compound-induced prolongation of the cardiac QT interval is a major concern in drug development and this unit discusses approaches that can predict QT effects prior to undertaking clinical trials. The majority of compounds that prolong the QT interval block the cardiac rapid delayed rectifier potassium current, IKr (hERG). Described in this overview are different ways to measure hERG, from recent advances in automated electrophysiology to the quantification of channel protein trafficking and binding. The contribution of other cardiac ion channels to hERG data interpretation is also discussed. In addition, endpoint measures of the integrated activity of cardiac ion channels at the single-cell, tissue, and whole-animal level, including for example the well-established action potential to the more recent beat-to-beat variability, transmural dispersion of repolarization, and field potential duration, are described in the context of their ability to predict QT prolongation and torsadogenicity in humans.

HIV sex-risk behaviors among in- versus out-of-treatment heroin-addicted adults.

BACKGROUND: Relatively limited empirical evidence exists comparing the impact on HIV sex risk behavior for patients admitted to methadone treatment programs (MTPs) as compared with nontreatment seekers. METHODS: This longitudinal cohort study examined HIV sex-risk behavior among 164 out-of-treatment heroin-dependent adults recruited from the street and 351 newly admitted MTP patients. The AIDS Risk Assessment was administered at baseline, 6 months, and 12 months. Generalized linear mixed model and generalized estimating equation analyses were used to examine the changes in sex risk behavior over time. RESULTS: The participants mean age was 41.5 years, 74.8% were African-American, 24.3% were White, and 54.4% were men. There were no significant differences between the groups in age, race, or gender. At baseline, the out-of-treatment group compared with the in-treatment group reported more sex partners (p < .001) and higher frequency of sex (p = .001). There was a group x time interaction for three of the sex-risk items and the out-of-treatment group reported having significantly more sex partners at both follow-up time points and having significantly more frequent unprotected sex while high at 6 months (all values of p < .01). CONCLUSIONS: Nontreatment seekers are at higher HIV risk than those entering MTPs and should be a focus of sex-risk reduction interventions, even if they are not interested in treatment at that time.

A comparison of attitudes toward opioid agonist treatment among short-term buprenorphine patients.

BACKGROUND: Obtaining data on attitudes toward buprenorphine and methadone of opioid-dependent individuals in the United States may help fashion approaches to increase treatment entry and improve patient outcomes. OBJECTIVES: This secondary analysis study compared attitudes toward methadone and buprenorphine of opioid-dependent adults entering short-term buprenorphine treatment (BT) with opioid-dependent adults who are either entering methadone maintenance treatment or not entering treatment. METHODS: The 417 participants included 132 individuals entering short-term BT, 191 individuals entering methadone maintenance, and 94 individuals not seeking treatment. Participants were administered an Attitudes toward Methadone scale and its companion Attitudes toward Buprenorphine scale. Demographic characteristics for the three groups were compared using χ(2) tests of independence and one-way analysis of variance. A repeated-measures multivariate analysis of variance with planned contrasts was used to compare mean attitude scores among the groups. RESULTS: Participants entering BT had significantly more positive attitudes toward buprenorphine than toward methadone (p < .001) and more positive attitudes toward BT than methadone-treatment (MT) participants and out-of-treatment (OT) participants (p < .001). In addition, BT participants had less positive attitudes toward methadone than participants entering MT (p < .001). CONCLUSIONS: Participants had a clear preference for a particular medication. Offering a choice of medications to OT individuals might enhance their likelihood of entering treatment. Treatment programs should offer a choice of medications when possible to new patients, and future comparative effectiveness research should incorporate patient preferences into clinical trials. SCIENTIFIC SIGNIFICANCE: These data contribute to our understanding of why people seek or do not seek effective pharmacotherapy for opioid addiction.