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

Dose Escalation of Naltrexone to Reduce Stress Responses Associated With Opioid Antagonist Induction: A Double-blind Randomized Trial Context: To describe the role of opioid antagonist induction in reducing stress response and withdrawal symptoms. Objective: Complexity of naltrexone induction is limiting broader applicability of opioid antagonist-assisted abstinence. The aim of this clinical trial was to assess the stress response to 2 low-dose naltrexone induction protocols under minimal oral sedation. Design: Double-blind randomized controlled trial. Setting: Open setting in-patient unit. Participants: Adults with opioid use disorder, and at least a year-long history of opioid use. Intervention protocol: Patients received either a single 12.5 mg naltrexone oral dose (SI group) or escalating dosage regimen starting from 50 μg up to a cumulative dose of 12.5 mg (ED group). Main outcome measure: Differences in cortisol and adrenocorticotropic hormone (ACTH) concentrations 1 hour after the start of naltrexone induction. Results: In all, 124 patients were enrolled and 68 remained in the trial at the point of randomization—33 in SI and 35 in ED group. Eight patients were excluded from final analysis. Plasma cortisol and ACTH concentrations were significantly higher in SI group; mean difference between groups 313 nmol/L (95% confidence interval [CI] 182–444, P < 0.001) and 36.9 pg/mL (95% CI 12.3–61.4, P = 0.004), respectively. Secondary outcomes: SI patients experienced significant increases in plasma cortisol and ACTH concentrations, and withdrawal scores. In ED group these measures remained at or below baseline throughout the 24-hour period from start of naltrexone induction. Conclusions: Contrary to a single 12.5-mg dose, the escalating naltrexone dosing regimen produced no significant increase in stress response and withdrawal scores during antagonist induction. Send correspondence to Robertas Badaras, PhD, Vilnius University Emergency Hospital, Centre of Toxicology, Siltnamiu 29, 04130 Vilnius, Lithuania. E-mail: badaras@gmail.com. Received 20 January, 2019 Revised 25 June, 2019 Accepted 4 July, 2019 Funding: Research funding from Vilnius University, Lithuania. The authors declare there is no conflicts of interest regarding this publication. 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

Prevalence and Variation of Clinically Recognized Inpatient Alcohol Withdrawal Syndrome in the Veterans Health Administration Objectives: No prior study has evaluated the prevalence or variability of alcohol withdrawal syndrome (AWS) in general hospitals in the United States. Methods: This retrospective study used secondary data from the Veterans Health Administration (VHA) to estimate the documented prevalence of clinically recognized AWS among patients engaged in VHA care who were hospitalized during fiscal year 2013. We describe variation in documented inpatient AWS by geographic region, hospital, admitting specialty, and inpatient diagnoses using International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis and/or procedure codes recorded at hospital admission, transfer, or discharge. Results: Among 469,082 eligible hospitalizations, the national prevalence of documented inpatient AWS was 5.8% (95% confidence interval [CI] 5.2%–6.4%), but there was marked variation by geographic region (4.3%–11.2%), hospital (1.4%–16.1%), admitting specialty (0.7%–19.0%), and comorbid diagnoses (1.3%–38.3%). AWS affected a high proportion of psychiatric admissions (19.0%, 95% CI 17.5%–20.4%) versus Medical (4.4%, 95% CI 4.0%–4.8%) or surgical (0.7%, 95% CI 0.6%–0.8%); though by volume, medical admissions represented the majority of hospitalizations complicated by AWS (n = 13,478 medical versus n = 12,305 psychiatric and n = 595 surgical). Clinically recognized AWS was also common during hospitalizations involving other alcohol-related disorders (38.3%, 95% CI 35.8%–40.8%), other substance use conditions (19.3%, 95% CI 17.7%–20.9%), attempted suicide (15.3%, 95% CI 13.0%–17.6%), and liver injury (13.9%, 95% CI 12.6%–15.1%). Conclusions: AWS was commonly recognized and documented during VHA hospitalizations in 2013, but varied considerably across inpatient settings. This clinical variation may, in part, reflect differences in quality of care and warrants further, more rigorous investigation. Send correspondence to Tessa L. Steel, MD, MPH, University of Washington, Division of Pulmonary, Critical Care, & Sleep Medicine, Seattle-Denver Center of Innovation (COIN), VA Puget Sound Health Care System, Seattle Division, 1660 South Columbian Way S-152, Seattle, WA 98108. E-mail: tessita@uw.edu. Received 26 May, 2019 Accepted 1 September, 2019 Funding: VA Puget Sound Health Care System Research & Development Associate Chief of Staff (ACOS) Pilot Grant Program, the Center of Excellence for Substance Abuse Treatment & Education (CESATE), and K24AA022128. 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

Caffeine Restrictions in Inpatient Psychiatric Settings: Precipitating Withdrawal? Caffeine is often restricted in locked inpatient psychiatric facilities based on concern that it may exacerbate clinical symptoms. However, psychiatric inpatients may be at particularly high risk of caffeine withdrawal during psychiatric hospitalization, which may cause undue discomfort or distress, limit their engagement in inpatient treatment, and confound the management of psychiatric illness. Psychiatric patients who regularly consume caffeine also possess a degree of caffeine tolerance which may reduce the risk of adverse effects associated with continued inpatient caffeine intake. For these reasons, it appears reasonable to allow caffeine in inpatient psychiatric settings. Send correspondence to Bryan Shapiro, MD, MPH, UCI Health Neuropsychiatric Center, 101 The City Dr. South, Orange, CA 92868. E-mail: bryan.shapiro@uci.edu Received 13 June, 2019 Accepted 20 August, 2019 The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Years of Life Lost due to Opioid Overdose in Ohio: Temporal and Geographic Patterns of Excess Mortality Objectives: The aim of the study was to quantify the burden of premature mortality because of opioid overdose in Ohio, document the role of fentanyl poisoning in contribution to this evolving epidemic, examine geographic, demographic, and temporal patterns of mortality burden within Ohio, and measure the effect of opioid overdose on lifespan in the state. Methods: A serial cross-sectional analysis was performed for all fatal opioid poisonings (N = 12,782) in the state of Ohio between January 1, 2010 and December 31, 2016. The burden of fatal opioid overdose was calculated in Years of Life Lost (YLL). YLL were mapped with respect to geographic and cultural region. The geographic spread of fentanyl poisoning was also mapped, and the shifting contribution of fentanyl poisoning to overall opioid mortality burden was assessed over time. Finally, the negative effect of opioid overdose on average lifespan was calculated. Results: Opioid overdose resulted in 508,451 total YLL. In the year 2016 alone, there were 136,679 YLL attributable to opioid poisoning. Fentanyl-related YLL rose from 7.5% of all YLL because of opioid overdose in 2010 to 69.0% in 2016. In the same year, opioid overdose lowered the lifespan of an average Ohioan by 0.97 years. Conclusions: Fatal opioid overdose accounted for over half a million YLL in Ohio during the 7-year study period. Opioid overdose mortality rose annually. Fentanyl involved overdoses accounted for a growing proportion of excess mortality. Burden was not equally distributed within the state. Two distinct geographical clusters of excess mortality were identified in the northeast and south. Send correspondence to O. Trent Hall, DO, Department of Physical Medicine and Rehabilitation, University of Michigan Medical School, University of Michigan, 325 E. Eisenhower Pkwy., Suite 200, Ann Arbor, MI 48108. E-mail: ohall@med.umich.edu. Received 23 December, 2018 Accepted 16 June, 2019 The authors declare no conflicts of interest. Dr. Hall received funding from the Recognizing and Eliminating Disparities in Addiction through Culturally Informed Healthcare (REACH) program. The REACH Program is made possible by funding to the Academy of Addiction Psychiatry (AAAP) from the Substance Abuse and Mental Health Services Administration (SAMHSA) grant no. 1H79TI08135801. The views expressed in this publication do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention of trade names, commercial practices, or organizations imply endorsement by the U.S. government. 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). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 © 2019 American Society of Addiction Medicine

Tramadol Withdrawal in the Setting of Buprenorphine Induction: A Case Report Initiating opioid use disorder treatment with buprenorphine conventionally requires the cessation of other opioid medications, including tramadol. Tramadol's spectrum of activity differs from most opioids, acting through serotonin and norepinephrine reuptake inhibition. Here, we report a case of 45-year-old man who experienced a complicated transition from tramadol to buprenorphine. We believe there were similarities to antidepressant discontinuation syndrome, which could be explained by tramadol's serotoninergic activity. Clinicians should be aware of these effects when discontinuing tramadol, even if replacing with another opioid. Send correspondence to Dale Terasaki, MD, MPH, 1693 N Quentin St. Aurora, CO 80045. E-mail: djterasaki@gmail.com Received 30 May, 2019 Accepted 25 July, 2019 The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Self-reported Health Diagnoses and Demographic Correlates With Kratom Use: Results from an Online Survey Objectives: To determine whether diagnosed pre-existing health conditions correlate with Kratom demographics and use patterns. Methods: A cross-sectional, anonymous US national online survey was conducted among 8049 Kratom users in October, 2016 to obtain demographic, health, and Kratom use pattern information. Results: People who use Kratom to mitigate illicit drug dependence self-reported less pain and better overall health than individuals who used Kratom for acute/chronic pain. Self-reported improvements in pre-existing mental health symptoms (attention deficit and hyperactivity disorder/attention deficit disorder, anxiety, bipolar disorder, post-traumatic stress disorder, and depression) attributed to Kratom use were greater than those related to somatic symptoms (back pain, rheumatoid arthritis, acute pain, chronic pain, fibromyalgia). Demographic variables, including female sex, older age, employment status, and insurance coverage correlated with increased likelihood of Kratom use. Conclusions: Kratom use may serve as a self-treatment strategy for a diverse population of patients with pre-existing health diagnoses. Healthcare providers need to be engaging with patients to address safety concerns and potential limitations of its use in clinical practice for specific health conditions. Send correspondence to Oliver Grundmann, PhD, Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1345 Center Drive, Room P6-20, Gainesville, FL 32611. E-mail: grundman@ufl.edu Received 16 March, 2019 Accepted 9 August, 2019 Financial disclosure: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors state no conflict of interest. © 2019 American Society of Addiction Medicine

Defining Low-threshold Buprenorphine Treatment Buprenorphine treatment for opioid use disorder is safe and effective, but only a fraction of Americans who need treatment receive it. One reason for this is that many buprenorphine treatment programs have rigid requirements for entry and continuation, limiting the number of people who receive treatment. “Low-threshold treatment” is a term used to describe an alternative approach that attempts to remove as many barriers to treatment as possible. However, few studies have described its essential features. In this article, we define low-threshold treatment and propose the approach be guided by the following principles: same-day treatment entry; harm-reduction approach; flexibility; and wide availability in places where people with opioid use disorder go. We discuss the evidence and rationale for these principles and directions for future research. Send correspondence to Andrea Jakubowski, MD, Division of General Internal Medicine, 3300 Kossuth Avenue, Bronx, New York, NY 10467. E-mail: ajakubow@montefiore.org Received 25 March, 2019 Accepted 16 June, 2019 Funding: The work was supported by NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA Grant Number UL1TR001073. Financial disclosure: Dr Fox is supported by R01 DA044878. The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine