Faculty Bibliography

BACKGROUND:Alcohol and drug use are leading causes of morbidity and mortality that frequently go unidentified in medical settings. As part of a multi-phase study to implement electronic health record-integrated substance use screening in primary care clinics, we interviewed key clinical stakeholders to identify current substance use screening practices, barriers to screening, and recommendations for its implementation. METHODS:Focus groups and individual interviews were conducted with 67 stakeholders, including patients, primary care providers (faculty and resident physicians), nurses, and medical assistants, in two urban academic health systems. Themes were identified using an inductive approach, revised through an iterative process, and mapped to the Knowledge to Action (KTA) framework, which guides the implementation of new clinical practices (Graham et al. in J Contin Educ Health Prof 26(1):13-24, 2006). RESULTS:Factors affecting implementation based on KTA elements were identified from participant narratives. Identifying the problem: Participants consistently agreed that having knowledge of a patient's substance use is important because of its impacts on health and medical care, that substance use is not properly identified in medical settings currently, and that universal screening is the best approach. Assessing barriers: Patients expressed concerns about consequences of disclosing substance use, confidentiality, and the individual's own reluctance to acknowledge a substance use problem. Barriers identified by providers included individual-level factors such as lack of clinical knowledge and training, as well as systems-level factors including time pressure, resources, lack of space, and difficulty accessing addiction treatment. Adapting to the local context: Most patients and providers stated that the primary care provider should play a key role in substance use screening and interventions. Opinions diverged regarding the optimal approach to delivering screening, although most preferred a patient self-administered approach. Many providers reported that taking effective action once unhealthy substance use is identified is crucial. CONCLUSIONS:Participants expressed support for substance use screening as a valuable part of medical care, and identified individual-level as well as systems-level barriers to its implementation. These findings suggest that screening programs should clearly communicate the goals of screening to patients and proactively counteract stigma, address staff concerns regarding time and workflow, and provide education as well as treatment resources to primary care providers.

AIM/OBJECTIVE:This study assesses whether genetic variants in stress-related genes are associated with prolonged abstinence from heroin in subjects that are not in long-term methadone treatment. METHODS:Frequencies of 117 polymorphisms in 30 genes were compared between subjects with history of heroin addiction, either without agonist treatment (n = 129) or in methadone maintenance treatment (n = 923). RESULTS:SNP rs1500 downstream of CRHBP and an interaction of SNPs rs10482672 (NR3C1) and rs4234955 (NPY1R/NPY5R) were significantly associated with prolonged abstinence without agonist treatment. CONCLUSION/CONCLUSIONS:This study suggests that variability in stress-related genes may contribute to the ability of certain subjects to remain in prolonged abstinence from heroin, possibly due to higher resilience to stress.

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.

Background: With both agonist and antagonist medications available to treat opioid dependence, and with these differing markedly on a spectrum of parameters - including philosophy of treatment, need for detoxification to initiate treatment, ongoing dependence and withdrawal on stopping treatment, diversion risk, community acceptability and controlled substance restrictions - it's difficult to know which approach to take. What do we tell our patients? How should we choose? Is one approach better for some patients, the other for others? Does choice matter, do patients do better with their preferred treatment than with the alternative? CTN-0051 grows out of these questions and will establish the evidence-base to inform treatment decisions. Methods: Close to a dozen designs, including no-medication treatment-as-usual conditions, SMART designs, and designs taking choice into consideration were considered. The final design was a randomized two-arm, head-to-head effectiveness trial comparing extended-release naltrexone to buprenorphine, both FDA approved treatments, in 570 patients across 8 sites. Recruitment was from inpatient detoxification and short term residential programs. We selected a flexible point of randomization to reflect community medication initiation practices. We predicted differential induction success, and included a mitigation plan to manage the detoxification hurdle. Treatment was for up to six months with follow up visits through nine months postrandomization. The primary outcome measure was timeto- relapse, defined as 7 consecutive use-days or 4 consecutive use-weeks. Secondary outcomes included successful induction, abstinence from opioids, alcohol, tobacco and other drugs, craving, subacute withdrawal, etc., and mediators and moderators of treatment response. Results: Recruitment was completed in May 2016 with 722 participants consented and 570 randomized. Treatment visits were completed in November 2016 and follow up visits in February 2017. Women made up 30% of the population; 17% were Hispanic, 26% non-white; 69% were 25-45 years old, 15% were under 25; 57% had a high school education or less, 66% were never married, 63% were unemployed; 82% identified heroin as their primary abused opioid, 16% prescription drugs; 63% were IV users; 40% were high users defined as IV use of at least 6 bags a day, a stratification variable that we predicted to influence outcome; although all participants expressed willingness to take either medication, 29% indicated that they preferred extended-release naltrexone, and 33% buprenorphine. AEs and SAEs were those expected in this population. Data lock will be in May 2017 after which we will be able to look at outcomes data. Conclusions: We expect to be able to present comparative effectiveness data on induction success, survival without relapse, time-to-relapse, abstinence from opioids and other drugs, successful completion of 24 weeks of treatment, craving, cognitive function, and adverse events including overdose during and after treatment. Findings on the role of choice in influencing outcome, and mediators and moderators of treatment success or failure will be presented. None of these data will be available until after data-lock, precluding more specific "conclusions" per se until early summer

BACKGROUND: Alcohol and drug use is a leading cause of morbidity and mortality that frequently goes unidentified in medical settings. As part of a multi-phase study to implement the NIDA Common Data Elements for collecting substance use screening information in electronic health records (EHRs), we interviewed key clinical stakeholders with a goal of identifying barriers and facilitators affecting the implementation of substance use screening in primary care clinics. METHODS: Focus groups and individual qualitative interviews were conducted with 67 stakeholders, including primary care patients, medical providers (faculty and resident physicians, nurses), and medical assistants, in two urban academic health systems. Themes were identified, discussed, and revised through an iterative process, and mapped to the Knowledge to Action (KTA) framework (Graham, 2006), which guides the selection and implementation of new clinical practices. RESULTS: Factors affecting implementation based on KTA elements were identified from participant narratives. Identifying the problem: Participants unanimously agreed that having knowledge of a patient's substance use is important because of its impacts on health andmedical care, that substance use is not properly identified in medical settings, and that universal screening is the best approach. Adapting knowledge: The majority of patients and providers stated that the primary care provider should play a key role in substance use screening and interventions. There was discrepancy of opinion regarding the optimal approach to delivering screening. Some felt that patients should self-administer questionnaires, while others thought that patients would be more comfortable having face-to-face discussions with their primary care provider - though not with other members of the care team. Many providers reported that being able to take effective action once unhealthy substance use is identified is crucial. Assessing barriers: Patients expressed concerns about confidentiality, 'denial', and providers' lack of empathy. Barriers identified by providers included individual-level factors such as lack of knowledge and training, and systems-level factors including lack of time, resources, and space, disjointed communication between members of the medical team, and difficulty accessing addiction treatment. CONCLUSIONS: Based on these findings, we designed and are testing an implementation strategy utilizing universal screening, patient self-administered questionnaires, and EHR-integrated clinical decision support to assist providers in conducting brief motivational counseling and linking patients to behavioral health services, to address unhealthy substance use in primary care clinics