Addiction Medicine

Opioid Toxidrome Following Grapefruit Juice Consumption in the Setting of Methadone Maintenance Background: Methadone is a synthetic mu-opioid receptor agonist used in the treatment of chronic pain and opioid dependence. Methadone is metabolized by several cytochrome P450 isoenzymes; primarily CYP3A4, CYP2B6, and CYP2D6 before renal and fecal elimination. Exposure to substances like grapefruit juice, that inhibit these isoenzymes may result in increased blood levels of methadone, and thus may manifest clinically as unexpected opioid toxicity. Case: A 51-year-old male was found unresponsive. He was hypoxic and bradypneic with pinpoint pupils. Multiple boluses followed by infusion of naloxone were required before improvement of respiratory status. Upon awakening, the patient reported participating in an opioid treatment program where he is administered 90 mg of oral methadone daily and denied any other substance use. On further questioning, he admitted to drinking grapefruit juice (estimated to be approximately 500 mL/day) every day for 3 consecutive days before presentation. The patient was discharged home after being counseled to stop drinking grapefruit juice. Discussion: Grapefruit juice is known to be an inhibitor of the CYP3A4 isoenzyme. Various studies demonstrate that through CYP3A4 inhibition, grapefruit juice increases serum levels of opioids, such as methadone, though no clinically significant effects have been reported. Conclusions: Grapefruit juice inhibits the metabolism of methadone, raising its serum levels. To our knowledge, this is the first reported case in which the interaction between grapefruit juice and methadone was significant enough to cause an opioid toxidrome. It is, therefore, recommended that opioid treatment programs (OTPs) advise patients about this interaction before administering methadone. Send correspondence to Muhammed Ershad, MD, Hahnemann University Hospital, Philadelphia, PA 19102. E-mail: docershad@gmail.com Received 4 February, 2019 Accepted 11 March, 2019 The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Multivisceral Failure in a Context of Serotonin Syndrome Induced by MDMA: The Investigation of a Unique and Nationwide Network The occasional ingestion of 3,4-methylenedioxy-N-methylamphetamine (MDMA) presents serious risks of side effects including death through multivisceral failure in a context of serotonin syndrome. The significant increasing evolution of illicit MDMA street dosages over the past 2 decades and the difficulty for physicians to know what quantity the patients may have consumed, make MDMA a drug with unpredictable effects. Through this case report of a 16-year-old Caucasian, we made use of a unique and nationwide French health monitoring system called TREND (Recent Trends and New Drugs)—SINTES (National Identification System for Drugs and Substances), which, combined with the hair follicle test, can assist medical practitioners in rapidly establishing a precise diagnosis and consequently provide the most appropriate treatment for each individual case in a timely manner. Send correspondence to Redwan Maatoug, MD, MSc, PhD Candidate, Psychiatrist, Addictologist, La Pitié Salêtrière Hospital, 47-83 Boulevard de l'hôpital, 75013 Paris, France. E-mail: redwanmaatoug@gmail.com Received 13 December, 2018 Accepted 19 April, 2019 Disclosure: All authors declare no competing interest. © 2019 American Society of Addiction Medicine

Adolescent SBIRT Practices Among Pediatricians in Massachusetts Objectives: Adolescent Screening, Brief Intervention, and Referral to Treatment (SBIRT) in primary care is a key strategy to prevent, identify, and respond to substance use problems and disorders, including opioid and other drug addictions. Despite substantial investment in recent years to increase its implementation, few studies have reported on recent levels of SBIRT implementation among pediatricians. We aimed to assess self-reported use of the SBIRT framework with adolescent patients among Massachusetts pediatricians, and describe trends since an earlier survey. Methods: We analyzed responses to a cross-sectional survey mailed in 2017 to a representative sample of pediatricians in Massachusetts. We computed response frequencies for all SBIRT practice questions. We used the chi-square test to compare current data to data collected in 2014, as we found no demographic differences between the 2 samples. Results: Nearly all pediatricians in the 2017 sample (n = 160) reported annual screening of their adolescent patients (99%). The majority reported giving positive reinforcement (87%), brief advice (92%), counseling (90%), and referral to treatment (66%) in response to screen results. Compared with 2014, a significantly higher proportion of pediatricians in 2017 referred patients who screened positively for problematic alcohol use, but perceived barriers to screening and follow-up remain, such as insufficient time to screen and patient refusal to return. Conclusions: Among respondents to a Massachusetts pediatrician survey, we found high rates of delivering SBIRT in accordance with published guidelines, though barriers remain. Whether the content of the counseling adheres to guidelines is unknown. Send correspondence to Sharon Levy, MD, MPH, Director, Adolescent Substance Use and Addiction Program, Boston Children's Hospital, 300 Longwood Avenue, Mailstop 3114, Boston, MA 02115. E-mail: Sharon.Levy@childrens.harvard.edu. Received 7 November, 2018 Accepted 5 May, 2019 Author contributions: Dr Straus, Ms Fluett, and Ms Strother designed the survey and collected data. Dr Harris carried out data analysis. Ms Wiseblatt carried out data analysis and drafted the initial manuscript. Dr Levy designed the survey, collected data, and drafted the initial manuscript. All authors reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. Funding: Centers for Medicaid and Medicare Service, State Innovation Model grant to the Commonwealth of Massachusetts (CMS-1G1-12-001) provided support for the administration of the 2014 and 2017 survey and the analysis of results. The authors have no conflicts of interest to disclose. © 2019 American Society of Addiction Medicine

Poverty and Excess Length of Hospital Stay in Neonatal Opioid Withdrawal Syndrome Objectives: To study the impact of sociodemographic factors on length of stay (LOS) for infants with neonatal opioid withdrawal syndrome (NOWS) secondary to fetal opioid exposure. Methods: In this retrospective cohort study, we included term infants with NOWS, excluding those with other significant medical issues. Comprehensive clinical and sociodemographic data were collected. Multivariate regression modeling was used to identify factors which contributed to excess LOS, which was defined as the number of days beyond the standard monitoring and/or treatment protocol. Results: In all, 129 infants were identified; mean gestational age of 37.9 ± 1.3 weeks and mean body weight of 2880 ± 496 g. Among them, 68% of infants were exposed to opioids; 27% were exposed to methadone; and 67% required pharmacologic treatment. The degree of poverty was assessed using the Area Deprivation Index (ADI) based on the mother's address at the time of birth. Median LOS for treated infants was 23 days versus 8 days for those who did not need pharmacologic treatment. The median excess LOS was 4 days (range 0–24). Excess hospital days were strongly correlated with degree of deprivation in the mother's community (r = 0.55, P < 0.01). ADI remained a strong predictor of excess LOS, even when controlling for pharmacologic treatment, placement in state's custody, race, and gestational age at birth. Conclusions: These results suggest poverty is associated with excess LOS and that early allocation of resources for at-risk families may help to reduce overall length of hospital stay. Send correspondence to: Zachary A. Vesoulis, MD, Department of Pediatrics, Washington University School of Medicine, 1 Children's Place, St. Louis, MO 63110. E-mail: vesoulis_z@kids.wustl.edu. Received 10 January, 2019 Accepted 11 March, 2019 Funding: This work was supported by the following grants: Washington University Institute of Clinical and Translational Sciences KL2 Training Program (NIH/NCATS KL2 TR000450); the Barnes-Jewish Hospital Foundation and the Washington University Institute of Clinical and Translational Sciences Clinical and Translational Funding Program (NIH/NCATS UL1 TR000448). The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

How Might Maternal Poverty Impact the Course of Neonatal Opioid Withdrawal Syndrome? Neonatal Opioid Withdrawal Syndrome (NOWS) is an increasing problem in the midst of the current opioid epidemic, frequently associated with pharmacologic treatment and prolonged hospitalizations. NOWS is a highly variable condition with many clinical and genetic variables contributing to the clinical course. Social variables such as maternal poverty remain understudied. In this commentary, we review one of the first studies of the association between maternal poverty and infant hospital length of stay in infants with NOWS. This has important implications for designing population level interventions to improve NOWS outcomes. Send correspondence to Elisha M. Wachman, MD, Boston Medical Center, 771 Albany Street, Dowling 4103, Boston, MA 02118. E-mail: Elisha.Wachman@bmc.org Received 26 March, 2019 Accepted 31 March, 2019 Financial disclosures: No funding was provided for this manuscript. Dr Wachman has no conflicts of interest to disclose. © 2019 American Society of Addiction Medicine

The Role of Hospitalists in Treating Opioid Use Disorder No abstract available

The Role of Hospitalists in Treating Opioid Use Disorder No abstract available

Exploring the Effects of Vitamin D Supplementation on Cognitive Functions and Mental Health Status in Subjects Under Methadone Maintenance Treatment Objectives: Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT. Methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n = 32) or placebo (n = 32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables. Results: After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (β 14.50; 95% confidence interval [CI], 13.17–15.83; P < 0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (β −6.25; 95% CI, −8.60 to −3.90; P < 0.001), and significant increases in Verbal Fluency Test (β 2.82; 95% CI, 0.78–4.86; P = 0.007), Immediate Logic Memory (β 1. 32; 95% CI, 0.27–2.37; P = 0.01), Reverse Digit Span (β 2.06; 95% CI, 1.18–2.94; P < 0.001) and visual working memory (β 0.75; 95% CI, 0.33–1.16; P = 0.001). Also, vitamin D supplementation significantly improved BDI (β −2.76; 95% CI, −3.97 to −1.55; P < 0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P = 0.07) became nonsignificant, and other mental health parameters did not alter. Conclusions: Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings. Send correspondence to Zatollah Asemi, PhD, Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, Iran. E-mail: asemi_r@yahoo.com Received 8 May, 2018 Accepted 9 May, 2019 The authors report no conflicts of interest. Clinical trial registration number: www.irct.ir: IRCT2017101133079N4. © 2019 American Society of Addiction Medicine

Editor's note: Congratulations to the 2019 Author and Reviewer Award Winners No abstract available

Prenatal Practice Staff Perceptions of Three Substance Use Screening Tools for Pregnant Women Objective: There is a need to identify an acceptable and comprehensive substance use screening tool for pregnant women in the United States. This qualitative study sought to better understand prenatal practice staff perceptions of three existing substance use screening tools for use among pregnant women in an outpatient practice setting. Methods: Eight focus groups with 40 total participants were conducted with clinical and administrative staff of 2 diverse Maryland prenatal practices to determine the acceptability and usability of 3 substance use screening tools (4P's Plus, NIDA-Modified Alcohol, Smoking and Substance Involvement Screening Test, and the Substance Use Risk Profile-Pregnancy scale). The focus groups were digitally recorded, transcribed, coded, and analyzed using thematic analysis. Results: Participant perceptions of screening tools were dependent upon screening tool length, tone, comprehensiveness, subjectivity, time frame of questions, and scoring and clinician instructions. Most participants preferred the 4P's Plus screening tool because it is brief, comprehensive, easy for the patient to understand, and excludes judgmental language and subjective questions. Conclusions: These results provide valuable insight into the specific needs and preferences of prenatal practice staff as it relates to prenatal substance use screening and provides evidence that the 4P's Plus may be a preferred screening tool for standardized use in prenatal care. Send correspondence to Victoria H. Coleman-Cowger, PhD, The Emmes Company, LLC, 401N. Washington Street, Suite 700, Rockville, MD 20850. E-mail: vcolemancowger@emmes.com Received 7 December, 2018 Accepted 18 March, 2019 Funding: Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA041328. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Health Resources and Services Administration. The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

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