A Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Clinical Study to Evaluate the Efficacy and Safety of a Nicotine Mint Lozenge (2 and 4 mg) in Smoking Cessation Objective: To evaluate the efficacy in smoking cessation and safety of 2 and 4 mg nicotine mint lozenges in Chinese adult smokers. Methods: This was a multicenter, randomized, stratified, double-blind, placebo-controlled, parallel-group study. The low-dependence stratum included 483 smokers (241 randomized to active 2 mg nicotine lozenge and 242 to placebo lozenge). The high-dependence stratum included 240 smokers (120 randomized to active 4 mg nicotine lozenge and 120 to placebo lozenge). The primary endpoint was successful smoking cessation at 6 weeks postquit, defined as continuous abstinence from smoking for the 28-day period up to and including the 6-week visit (verified by CO measurement). Cochran–Mantel–Haenszel tests were performed to compare quit rates between active nicotine and placebo separately for the high-dependence and low-dependence strata. Results: The primary analysis showed that in the low-dependence (2 mg) stratum, 59 subjects (24.5%) of 241 in the active nicotine group and 52 subjects (21.5%) of 242 in the placebo group were successful quitters (P = .3851). In the high-dependence (4 mg) stratum, 37 subjects (30.8%) of 120 in the active nicotine group and 24 subjects (20.2%) of 119 in the placebo group were successful quitters (P = .0565). Conclusions: The 4 mg nicotine lozenge provided a directionally significant improvement in smoking cessation rates compared with placebo in Chinese adult smokers with high nicotine dependence for the primary endpoint. The 2 mg nicotine lozenge provided higher, but nonsignificant, smoking cessation rates than placebo. Both nicotine lozenges were generally well tolerated in Chinese adult smokers. Send correspondence to Chen Wang, MD, PhD, China-Japan Friendship Hospital, 2 Yinghuayuan E St, Chaoyang Qu, Beijing, 100029, China. E-mail: cyh-birm@263.net Received 20 September, 2018 Accepted 28 April, 2019 Current affiliation: Accenture, Berwyn, PA, USA. On behalf of the following Principal Investigators: Chunxue Bai (Zhongshan Hospital Fudan University, Shanghai); Kejing Ying (Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou); Ping Chen (General Hospital of Shenyang Military District PLA, Shenyang); Qiang Li (Changhai Hospital, Second Medical Military University, Shanghai); Nanshan Zhong (The First Affiliated Hospital of Guangzhou Medical University, Guangzhou); Gengzhi Ge (The 2nd Hospital of Tainjin Medical University, Tianjin); Jiangtao Lin (China-Japan Friendship Hospital, Beijing); Baoyuan Chen (Tianjin Medical University General Hospital, Tianjin). This study was sponsored by Tianjin Sino-American SmithKline & French Laboratory Ltd. Medical writing assistance was provided by Peloton Advantage, LLC, an OPEN Health company, and was funded by GlaxoSmithKline Consumer Healthcare. GlaxoSmithKline Consumer Healthcare provided a full review of the article. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.journaladdictionmedicine.com). © 2019 American Society of Addiction Medicine

Sustained-release Oral Hydromorphone for the Treatment of Opioid Use Disorder Objectives: In 2017, almost 50,000 Americans and over 4000 Canadians died from an opioid overdose. Accordingly, an urgent need exists to improve access to evidence-based treatment for opioid addiction, and also to develop and evaluate alternative treatment options for opioid use disorder (OUD). We present a case of a patient with OUD who was successfully switched and managed on oral hydromorphone after development of a prolonged QTc interval on methadone. Case: A 51-year-old man with longstanding polysubstance use presented to an urban hospital in Vancouver, Canada, for management of alcohol intoxication and hyponatremia. At the time of admission, the patient was stable on 100 mg of methadone daily, but was found to have a persistently elevated QTc (>550 milliseconds), putting him at increased risk for Torsades de Pointes. In an effort to find an alternative opioid agonist therapy for maintenance, a trial of slow-release oral morphine was attempted, but discontinued due to the development of myoclonus. Once-daily sustained-release oral hydromorphone was then started, which was found to manage cravings well without notable side effects. Discussion: The case presented offers promise for the use of once-daily sustained-release oral hydromorphone as a viable treatment option for patients with OUD for whom first-line therapies are not suitable or tolerated. This case report is the first to our knowledge to demonstrate the successful use of oral hydromorphone for treatment of opioid use disorder. Send correspondence to Seonaid Nolan, MD, Assistant Professor, University of British Columbia, Clinician Scientist, British Columbia Centre on Substance Use, 553B-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. E-mail: Seonaid.nolan@bccsu.ubc.ca Received 8 July, 2019 Accepted 22 September, 2019 Disclosure: S.N. is supported by a Michael Smith Foundation for Health Research Health Professional Investigator award. The other authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Sexual Abuse and Future Mental Health Hospitalization in a Swedish National Sample of Men Who Use Opioids Objective: Experiences of trauma, specifically sexual abuse, have been linked to both mental health and substance use disorders. This study used 14 years of Swedish health registry data to select a sample of adult men who reported frequent opioid use and assessed if those with a self-reported history of sexual abuse had a higher likelihood of hospitalization for a mental health disorder. Methods: A Swedish longitudinal (2003–2017) registry study linked Addiction Severity Index (ASI) assessments completed with individuals who sought treatment for substance use disorders with data on hospitalizations for mental health disorders, and assessed associations with self-reported histories of sexual abuse among men who reported sustained and frequent use of opioids (n = 1862). Cox regression methods tested associations and controlled for age, and the 7 ASI composite scores: family and social relationships, employment, alcohol use, drug use, legal, physical health, and mental health. Results: The ASI composite score for mental health (hazard ratio [HR] 16.6, P < 0.001) and a history of sexual abuse (HR 1.93, P < 0.001) were associated with an elevated risk of future mental health hospitalization. Conclusion: Both the ASI composite scores for mental health and self-reported history of sexual abuse reflected complex needs among men who used opioids and increased risk for mental health hospitalization. Treatment providers should strive to provide integrated care and address the negative aspects of victimization. Send correspondence to Marcus Blom Nilsson, Department of Social Work, Umeå University, SE-901 87 Umeå, Sweden. E-mail: Marcus.Blom.Nilsson@umu.se Received 11 February, 2019 Accepted 12 September, 2019 Funding: A grant from the Swedish Research Council for Health, Working Life and Welfare (Grant No. 2016–07213) supported the analysis and manuscript preparation. The contributing authors have no financial interests affecting this manuscript and certify that there are no conflicts of interest, including relationships and affiliations relevant to the subject matter or materials discussed in the manuscript. © 2019 American Society of Addiction Medicine

Pharmacological and Psychosocial Treatment of Adults with Gambling Disorder: A Meta-Review Background and Objectives: Gambling disorder (GD) leads to impaired socioeconomical functioning and increased social costs. Although the research on GD has been rising over the years, approved treatment guidelines are currently not available. The aim of this study was to systematically review the literature on the pharmacological and psychosocial treatment of adults with GD, and to identify possible agreed-upon standards of care. Methods: MEDLINE, PubMed, Cochrane, Web of Science, Embase, and CINAHL electronic databases were searched up to April 2019 for systematic reviews on pharmacological, psychosocial, and combined treatment of adults with GD. Twenty-six studies were eventually included in this meta-review. Results: Studies reported promising results of opioid antagonists and mood stabilizers in reducing GD-related symptomatology. Lithium was particularly effective in subjects with comorbid bipolar disorders. Cognitive behavioral therapy (CBT) was the most commonly used psychological intervention and reduced global severity, gambling frequency, and financial loss. Motivational interviewing (MI) seemed to improve several GD domains, alone or in combination with CBT. Self-help interventions (SHIs) showed some efficacy in promoting treatment-seeking, and in combination with other treatments. Conclusions: We found moderate evidence of effect for CBT, but weaker evidence for pharmacotherapy and SHIs. Results suggested some efficacy for MI in the short but not in the long term. It is likely that certain interventions might be more effective than others on specific features of GD. Further studies are needed to compare the efficacy and acceptability of individual and combined psychosocial and pharmacological interventions, to deliver patient-tailored treatments. Send correspondence to Marco Di Nicola, MD, PhD, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, L.go Agostino Gemelli 8, 00168 Rome, Italy. E-mail: marcodinicola.md@gmail.com Received 19 February, 2019 Accepted 4 July, 2019 Funding: The study was conducted without receiving any form of funding. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.journaladdictionmedicine.com). Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.journaladdictionmedicine.com). © 2019 American Society of Addiction Medicine

Comparing Reasons for Starting and Stopping Methadone, Buprenorphine, and Naltrexone Treatment Among a Sample of White Individuals With Opioid Use Disorder Objectives: Despite their efficacy, medications for opioid use disorder (MOUD) are underutilized in the United States. Nonetheless, few studies have explored reasons why individuals choose to start MOUD or discontinue MOUD after starting, especially extended-release naltrexone. We sought to identify reasons why individuals start and stop MOUD, including the differences between starting and stopping the 3 most common formulations: methadone, sublingual buprenorphine, and extended-release naltrexone. Methods: We conducted 31 semistructured interviews over the phone with a sample of white individuals with a history of MOUD utilization. Participants were recruited using snowball sampling from 8 US states. Interviews were audio-recorded, transcribed, coded in Dedoose software, and analyzed using thematic analysis and modified event structure analysis. Results: Participants primarily learned about methadone and buprenorphine from other individuals with OUD. Participants primarily became interested in starting buprenorphine and methadone after seeing the medications work effectively in peers, though methadone was perceived as a last resort. In contrast, participants primarily learned about and became interested in naltrexone after receiving information from health practitioners. Participants frequently stopped MOUD to prevent medication or health service dependence. Participants also felt stigma and external pressure to stop buprenorphine and methadone, but not naltrexone. Some participants identified relapse and medication termination by health providers or the criminal justice system as reasons for stopping MOUD. Conclusions: Given the frequency with which participants identified informal peer education as a reason for starting methadone and buprenorphine, peers with MOUD experience may be a trusted source of information for individuals seeking OUD treatment. Further research is needed to assess whether incorporating peer support specialists with MOUD experience into formal SUD treatment would expand MOUD utilization, retain patients in treatment, and/or improve OUD treatment outcomes. Send correspondence to Olivia Randall-Kosich, MHA, Doctoral Fellow, Department of Health Policy and Behavioral Sciences, Georgia State University, 14 Marietta St. NW, Suite 232, Atlanta, GA 30303. E-mail: orandallkosich1@gsu.edu Received 1 April, 2019 Accepted 22 September, 2019 Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Perceptions of Alcohol Risk Among HIV/Hepatitis C Coinfected Patients Objectives: We examined how patient perceptions of alcohol risk, provider discussions about alcohol, and treatment of hepatitis C virus (HCV) differed among HIV–HCV coinfected patients in primary care. Methods: Between April, 2016 and April, 2017, we conducted a screening survey with patients in an HIV primary care clinic in Seattle, Washington, who had chronic HCV coinfection or a history of chronic HCV infection who had successfully cleared their infection with treatment. Results: Of 225 participants, 84 (37%) were active drinkers (drank ≥2–4 times/mo in past 3 months). Of those with little to no use for ≥3 months, 65 (29%) were former drinkers with a history of alcohol use and 76 were abstainers with no such history. Former drinkers and abstainers were more likely than active drinkers to perceive that any drinking was unsafe (69% vs 58% vs 31%; P < 0.001). Former drinkers were more likely to report a physician's recommendation to stop drinking than active drinkers (63% vs 47%; P = 0.05). The great majority (87%) of former drinkers decided to stop or reduce drinking on their own (most often in response to a nonhealth life event) and only 13% acknowledged doing so on their doctor's prompting. HCV treatment was not associated with former or active drinking status. Conclusions: Our findings underscore the importance of educating not only HIV–HCV patients about the effects of alcohol use but also HIV clinicians about delivering consistent counseling about alcohol avoidance. Understanding the reasons that HIV–HCV coinfected persons make changes in their alcohol use could drive novel interventions that reduce the negative consequences of drinking. Send correspondence to Michael Stein, MD, Boston University School of Public Health, 715 Albany Street, Boston, MA 02118. E-mail: mdstein@bu.edu. Received 17 April, 2019 Accepted 21 September, 2019 Funding: Research described in this paper was supported by National Institute on Alcohol Abuse and Alcoholism (NIAAA), grant number R01-AA023726. Disclosure: The authors report no conflict of interest. The authors alone are responsible for the content and writing of this paper. © 2019 American Society of Addiction Medicine

Preliminary Results of Psychiatric Inpatients Referred to an Addiction Medicine Consult Service No abstract available

Long-term Outcomes of Injection Drug-related Infective Endocarditis Among People Who Inject Drugs Objectives: Infective endocarditis (IE) among people who inject drugs is associated with high rates of mortality and repeat episodes of endocarditis. We sought to report on longer-term clinical outcomes of patients with IE who were offered buprenorphine or methadone treatment for opioid use disorder (OUD) at their initial hospital admission. Methods: Individuals with OUD hospitalized between 2013 and 2015 with IE were included for the retrospective study. The following data were extracted from the medical record: sociodemographic data, mortality, repeat episodes of endocarditis, and evidence of ongoing buprenorphine and methadone treatment. The impact of medication use on mortality and repeat episode of endocarditis was examined using survival analysis. Results: Overall, 26 individuals were included in the study. The mean duration of follow-up was 45.0 months (SD 7.2, range 34.0–56.0). During the index admission, 8 received buprenorphine, 8 received methadone, and 10 declined medications. During the follow-up period, 4 (15.4%) individuals died and 10 (38.5%) individuals experienced a repeat episode of endocarditis. Survival analysis of mortality (log-rank P = 0.066) and repeat episode of endocarditis (log-rank P = 0.86) comparing those who received buprenorphine, received methadone, and declined medication did not differ significantly. Conclusions: Initiation of medication treatment alone may not be sufficient to impact long-term mortality and rates of repeat episode of endocarditis. More research is needed to identify optimal treatment strategies for people who inject drugs with IE. Send correspondence to Joji Suzuki, MD, Brigham and Women's Hospital, 60 Fenwood Rd, Boston, MA 02115. E-mail: jsuzuki2@bwh.harvard.edu. Received 7 March, 2019 Accepted 16 July, 2019 Funding: This work was supported by National Institutes of Health (grant numbers K23DA042326 [J.S.], K24DA022288 [R.W.]). The authors declare no conflicts of interest. © 2019 American Society of Addiction Medicine

Improving Outcomes for People With Injection Drug-related Endocarditis: Are Medications for Opioid Use Disorder Enough? No abstract available

Inappropriate Opioid Prescribing in Oregon's Coordinated Care Organizations Objectives: The objective of this study is to identify demographic and clinical characteristics of patients with a pain diagnosis who fill potentially inappropriate opioid prescriptions within the Oregon Medicaid population. Methods: Using de-identified Oregon Medicaid claims data (2010–2014), a series of logistic regression models was estimated to identify factors associated with receipt of potential inappropriate opioid prescriptions among patients with acute or chronic pain. Analyses included a total of 204,364 records, representing 118,671 unique patients. Results: The percentage of patients with a pain diagnosis filling at least 1 inappropriate opioid prescription decreased over the study period, falling from 32.5% in 2010 to 22.3% in 2014. Multivariate logistic regression results indicated that white and older enrollees were more likely to fill an inappropriate prescription over the study period. The odds of filling an inappropriate opioid prescription were also greater for patients with chronic health conditions, psychiatric disorders, and substance use disorder. Results were similar for patients diagnosed with either acute or chronic pain, chronic pain only, or acute pain only. Conclusions: Inappropriate opioid prescribing for patients with pain diagnoses decreased over the study period, which stands in stark contrast to other state Medicaid programs. However, in 2014, almost 23% of patients in the Oregon Medicaid program filled at least 1 inappropriate opioid prescription, suggesting additional strategies are needed to further reduce potential inappropriate prescribing. Medicaid programs may consider adopting enhanced prescription drug monitoring program features, enacting pain clinic legislation, and implementing additional prior authorization policies to reduce inappropriate prescribing of opioids. Send correspondence to Amanda J. Abraham, PhD, University of Georgia, Department of Public Administration and Policy, Athens, GA 30602. E-mail: aabraham@uga.edu. Received 5 January, 2019 Accepted 4 August, 2019 Funding: NIH/NIDA R33 DA035640-05: Oregon's Coordinated Care Organizations Integrate Care for Drug Use Disorders. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.journaladdictionmedicine.com). © 2019 American Society of Addiction Medicine