Sarah M. Bagley

Review of the assessment and management of neonatal abstinence syndrome

Neonatal abstinence syndrome (NAS) secondary to in-utero opioid exposure is an increasing problem. Variability in assessment and treatment of NAS has been attributed to the lack of high-quality evidence to guide management of exposed neonates. This systematic review examines available evidence for NAS assessment tools, nonpharmacologic interventions, and pharmacologic management of opioid-exposed infants. There is limited data on the inter-observer reliability of NAS assessment tools due to lack of a standardized approach. In addition, most scales were developed prior to the prevalent use of prescribed prenatal concomitant medications, which can complicate NAS assessment. Nonpharmacologic interventions, particularly breastfeeding, may decrease NAS severity. Opioid medications such as morphine or methadone are recommended as first-line therapy, with phenobarbital or clonidine as second-line adjunctive therapy. Further research is needed to determine best practices for assessment, nonpharmacologic intervention, and pharmacologic management of infants with NAS in order to improve outcomes.

Overdose Education and Naloxone Rescue Kits for Family Members of Individuals Who Use Opioids: Characteristics, Motivations, and Naloxone Use.

BACKGROUND In response to the overdose epidemic, a network of support groups for family members in Massachusetts has been providing overdose education and naloxone rescue kits (OEN). The aims of this study were to describe the characteristics, motivations, and benefits of family members who receive OEN and to describe the frequency of naloxone used during an overdose rescue. METHODS This cross-sectional, multisite study surveyed attendees of community support groups for family members of opioid users where OEN training was offered using a 42-item self-administered survey that included demographics, relationship to the individual using opioids, experience with overdose, motivations to receive OEN, and naloxone rescue kit use. RESULTS Of 126 attendees who completed surveys at 8 sites, most attendees were white (95%), female (78%), married or partnered (74%), parents of an individual using opioids (85%), and providing financial support for the individual using opioids (52%). The OEN trainees (79%) were more likely than attendees not trained (21%) to be parents of an individual using opioids (91% vs. 65%, P < .05), to provide financial support to an individual using opioids (58% vs. 30%, P < .05), and to have witnessed an overdose (35% vs. 12%, P = .07). The major motivations to receive training were wanting a kit in their home (72%), education provided at the meeting (60%), and hearing about benefits from others (57%). Sixteen parents reported witnessing their child overdose, and 5 attendees had used naloxone successfully during an overdose rescue. CONCLUSIONS Support groups for families of people who use opioids are promising venues to conduct overdose prevention trainings because attendees are motivated to receive training and will use naloxone to rescue people when witnessing an overdose. Further study is warranted to understand how to optimize this approach to overdose prevention in the community setting.

Addressing Stigma in Medication Treatment of Adolescents With Opioid Use Disorder

: In September 2016, the American Academic of Pediatrics released a policy statement that adolescents with opioid use disorder should be offered pharmacotherapy with buprenorphine/naloxone, methadone, or naltrexone. In our clinical practice, however, we have encountered the perception among patients, families, and clinicians alike that medications should be used as a last resort. That we should wait until things get worse is a discarded approach. As addiction specialists, it is imperative that we prevent and identify risky use and use disorders, then intervene early and offer timely, evidence-based treatment. We suggest that adolescents deserve special attention and that specific efforts should be made to reduce the stigma associated with treating adolescents with opioid use disorder with medications to optimize those efforts.

Medication for Opioid Use Disorder After Nonfatal Opioid Overdose and Association With Mortality: A Cohort Study

The United States is in the midst of a crisis of opioid-related harms (1). Some efforts to address this crisis focus on expanding access to effective treatment of opioid use disorders (OUDs) (2). Prior nonfatal opioid overdose is a known risk factor for subsequent nonfatal and fatal overdoses (37), and engaging persons in treatment who survive an overdose may be effective in limiting subsequent fatalities. However, data on the association between treatment of OUD and mortality after a nonfatal overdose are limited to a single retrospective cohort study that analyzed enrollment in methadone maintenance treatment (MMT) at a single time point and found no association (3). The 3 medications for OUD (MOUD) approved by the U.S. Food and Drug Administration are methadone, buprenorphine, and naltrexone. Randomized controlled trials of these medications have shown consistent benefits across many outcomes, including increased treatment retention and suppression of illicit opioid use (810). A recent systematic review and meta-analysis of 19 observational cohort studies identified substantial reductions in all-cause and overdose mortality for methadone and buprenorphine (11). However, the mortality benefit in this analysis was limited to time actively retained in treatment, and the 4-week period after discontinuation was associated with an especially high risk for death. The few studies that examined mortality among patients receiving naltrexone show an unclear effect (1215). Massachusetts has been particularly affected by the opioid crisis: Opioid overdose deaths more than tripled between 2010 and 2016 (16). Through Chapter 55 of the Acts of 2015, the state legislature permitted individual-level linkage of data from 16 Massachusetts government agencies to gain a deeper understanding of the circumstances that influence fatal and nonfatal opioid overdoses (17). For this analysis, we identified a cohort of persons in the Chapter 55 data set who survived an opioid overdose and described any episodes of treatment with MOUD before and after that overdose. Specifically, we sought to determine whether treatment with MOUD, including receipt of MMT, buprenorphine, or naltrexone, was associated with reduced risk for all-cause and opioid-related mortality. Methods Study Design and Data Source We did a retrospective cohort study using the Massachusetts Chapter 55 data set, which includes data between 2011 and 2015 on residents aged 11 years or older with health insurance (as reported in the Massachusetts All-Payer Claims Database [APCD]) and represents more than 98% of Massachusetts residents. Data from APCD were linked at the individual level with records from other data sets using a multistage deterministic linkage technique described elsewhere (18). For this study, we used 7 linked Massachusetts databases: APCD, the Registry of Vital Records and Statistics, the prescription monitoring program, the Acute Hospital Case Mix, the Ambulance Trip Record Information System, the Bureau of Substance Addiction Services licensed treatment encounters, and the cancer registry. This work was mandated by Massachusetts law and conducted by a public health authority that required no institutional board review. The Boston University Medical Campus Institutional Review Board also determined that this study was not human subjects research. Cohort Selection We identified persons who had had a nonfatal opioid overdose between January 2012 and December 2014 to allow 12 months of observation before and after the overdose. We restricted the cohort to persons aged 18 years or older because access to OUD treatment substantially differs in adolescents versus adults (19). We identified opioid overdose in 2 ways. First, we identified emergency department, observation, or inpatient encounters with a medical claim containing a diagnosis code for opioid poisoning from the International Classification of Diseases, Ninth Revision, Clinical Modification (codes 965.00, 965.01, 965.02, 965.09, E850.0, E850.1, and E850.2). A study validated these codes by showing positive predictive values of 81% for identifying fatal or nonfatal opioid overdose and 94% for an opioid overdose or opioid-related adverse event (20). Second, we identified persons with an ambulance encounter for opioid overdose (available in 2013 and 2014 only). In collaboration with the Centers for Disease Control and Prevention, the Massachusetts Department of Public Health created and refined an algorithm to use with emergency medical services data to identify opioid-related overdoses; this algorithm was previously validated against internal emergency medical services data on opioid overdose events (Supplement). Supplement. Supplementary Material We examined the first qualifying event (nonfatal opioid overdose) for each person, hereafter called the index overdose. Of 20155 persons with an event, we excluded 1203 who died within 30 days after the overdose using dates of death from the Registry of Vital Records and Statistics. We excluded 1338 persons with evidence of cancer at any time in the 5 years of Chapter 55 data because of high competing risk for death. Cancer was identified using International Classification of Diseases, Ninth Revision, diagnosis codes in APCD (Supplement) or entry in the state-based cancer registry. We also excluded 46 persons whose age or sex was unknown, yielding a final cohort of 17568 persons. Key Variables We identified exposure to MOUD in monthly intervals. Exposure to MMT was identified in 2 ways: a medical claim from APCD for methadone administration via Healthcare Common Procedure Coding System code H0020 or a record of treatment with methadone in data from the Bureau of Substance Addiction Services. We used the prescription monitoring program to identify dispensing of buprenorphine or buprenorphine and naloxone combined. Naltrexone was identified via a pharmacy claim for injectable or oral naltrexone in APCD. We examined all-cause and opioid-related mortality as identified in death files. Classification of opioid-related death was based on medical examiner determination or standardized assessment by the Massachusetts Department of Public Health (Supplement). We examined potential confounding variables. We obtained patient sex and age from APCD and categorized age as 18 to 29 years, 30 to 44 years, or 45 years or older. We identified monthly dispensings of opioid analgesics and benzodiazepines from the prescription monitoring program. We identified diagnosis of anxiety or depression using International Classification of Diseases, Ninth and Tenth Revisions, diagnosis codes from APCD (Supplement). We identified OUD treatment services, including inpatient detoxification episodes and postdetoxification treatment in short- and long-term residential facilities, through the Bureau of Substance Addiction Services. Statistical Analysis To compare baseline characteristics by receipt of MOUD, we developed the following 5 categories of MOUD receipt in the 12 months after the index overdose: no MOUD during follow-up, 1 or more months of buprenorphine, 1 or more months of methadone, 1 or more months of naltrexone, and 1 or more months of 2 or 3 MOUDs combined. We compared baseline characteristics among these mutually exclusive treatment groups using 2 tests. We did time-to-event analyses for all-cause and opioid-related mortality using MOUD as a monthly time-varying exposure variable. We used 2 dichotomous classifications for MOUD exposure, with discontinuation and on treatment. Several studies have shown an increased risk for all-cause and opioid-related mortality in the 4 weeks immediately after MOUD discontinuation (11, 21). Thus, we defined a with discontinuation exposure variable, which we considered the primary classification, to attribute any effect of MOUD discontinuation on mortality to the MOUD. For this classification, persons were considered exposed to MOUD in any month in which they received it and in the month after last receipt. We defined an on treatment exposure variable as the secondary classification, in which persons were considered exposed to MOUD only in months in which they received it (Figure 1). Figure 1. MOUD exposure classification. For the primary classification (with discontinuation), MOUD exposure extends through the month after discontinuation (light and dark-green months). For the secondary classification (on treatment), exposure is limited to months in which treatment is received (light-green months only). In the illustrative examples, participant 1 is not exposed to MOUD through follow-up; participant 2 is exposed in months 12 and 712 for the primary classification and months 1 and 712 for the secondary classification. In the month of death, participant 3 would be considered exposed in the primary classification only, participant 4 would be considered exposed in both primary and secondary exposure classifications, and participant 5 would be considered not exposed to MOUD. MOUD= medication for opioid use disorder. We used an extended KaplanMeier estimator allowing for time-varying exposure to MOUD to generate cumulative incidence curves (Supplement) (22). We developed a multivariable Cox regression model of time to all-cause and opioid-related mortality. The predictors of interest were monthly receipt of MMT, buprenorphine, and naltrexone as time-varying exposure variables. Covariates were age; sex; monthly time-varying receipt of prescription opioids, benzodiazepines, and OUD treatment services; baseline characteristics, including mental health diagnoses; and prior receipt of medication or OUD treatment services. We calculated the E-value to identify the minimum strength of association that an unmeasured confounder would need to have with both treatment and outcome, conditional on the measured covariates, to explain away the observed associations between MOUD and mortality (23). We used SAS Studio, version 3.5 (SAS Institute), for analyses (Supplemen

To Improve Substance Use Disorder Prevention, Treatment and Recovery: Engage the Family

: Approximately 21 million people in the United States have a substance use disorder (SUD); the number of family members impacted by a loved ones SUD is exponentially greater. Affected family members of individuals with SUDs are at high risk for developing chronic medical and psychiatric health conditions, are high utilizers of the health care system, and have high health care expenditures. Family members play a central role in the lives of many individuals with SUDs; information given to family members can have a significant impact on persons with addiction and therefore the SUD treatment that an individual might receive. Evidence-based interventions targeting affected family members have been shown to: improve health outcomes for all family members, result in better addiction treatment outcomes, and prevent adolescent substance use. Despite mounting evidence, the health care system has been hesitant to engage families in a meaningful way. Health care providers should consider how implicit and explicit assumptions about the role of family members in SUD development, treatment, and recovery may contribute to this underlying reluctance. Antiquated policies and procedures that alienate family members should be modified (e.g., limiting phone access). Family members have a right to receive professional treatment and to be educated about the difference between mutual/peer support and evidence-based treatment options. Despite the potential for family members to move the needle on the countrys current addiction crisis they remain an underutilized resource. A paradigm shift will be required to get the current SUD care continuum to adopt a family-centric model.

Comparison of Post-Cesarean Section Opioid Analgesic Requirements in Women With Opioid Use Disorder Treated With Methadone or Buprenorphine

Objective: Buprenorphine is a highly effective treatment for opioid use disorders, but its continuation in the perioperative setting remains controversial, unlike the accepted practice of perioperative methadone continuation. Methods: We conducted a retrospective cohort study from 2006 to 2014 comparing post-cesarean section opioid analgesic requirements of women with opioid use disorders treated with methadone or buprenorphine. Preoperative, intraoperative, and postoperative opioid requirements (morphine equivalent dose [MED]), postoperative complications, and length of stay were compared between the methadone and buprenorphine groups. Results: During the 9-year study period, there were 185 women treated with methadone (mean dose 93.7 mg, SD 2.6) and 88 women treated with buprenorphine (mean dose 16.1 mg, SD 7.8). There were no statistically significant differences in MED requirements in the methadone versus buprenorphine groups: preoperative MED (11.4 mg [SD 31.5] vs 20.0 mg [SD 15.1]; mean difference [MD] 8.6, 95% confidence interval [CI] −1.9, 19.1), intraoperative MED (3.5 mg [SD 6.6] vs 5.2 mg [SD 13.7]; MD 1.8, 95% CI −1.1, 4.6), and postoperative MED during hospitalization (97.7 mg [SD 65.6] vs 85.1 mg [SD 73.0]; MD −12.6, 95% CI −31.1, 5.8). There were no statistically significant differences in postoperative complications or length of stay. Conclusions: Our study suggests that buprenorphine treatment will not interfere more than methadone with pain management after a cesarean section with no significant differences in opioid analgesic requirements, postoperative complications, or length of hospital stay. Future studies should investigate the generalizability to other surgeries.

Stigma associated with medication treatment for young adults with opioid use disorder: a case series

BackgroundOpioid-related overdose deaths have risen sharply among young adults. Despite this increase, access to evidence-based medication for opioid agonist treatment (OAT) for youth remains low. Among older adults, barriers to OAT include the paucity of buprenorphine-waivered prescribers and low rates of prescribing among waivered physicians. We have increasingly found in our clinical practice significant stigma related to using OAT to treat addiction for young adults. In this series, we describe three cases of young adults who faced significant stigma related to their treatment.Case presentationsThe first case is a young male with a history of significant trauma and a severe opioid use disorder. He started buprenorphine and has found a job, stayed abstinent, and began a healthy relationship. At each step in his recovery, he has faced resistance to taking medication from other treatment providers, directors of sober houses, and his parents. The second case is a young woman who presented to a substance use treatment program after a relapse. She was unable to restart buprenorphine despite our calling to ask that it be restarted. Ultimately, she left against medical advice and was stabilized as an outpatient on buprenorphine. The final case is a young woman who stopped buprenorphine after being told she was “not sober” while attending 12-step group but restarted after conversations with her clinical team. In each case, the patient has continued their medication treatment and are stable.ConclusionsOpioid-related deaths continue to rise among all age groups, including young adults. Stigma related to medication treatment can be a substantial barrier for many young adult patients but there are concrete steps that providers and communities can take to address this stigma.

Usefulness of the CRAFFT to diagnose alcohol or cannabis use disorders in a sample of emerging adults with past-month alcohol or cannabis use

ABSTRACT Background: Emerging adults between the ages of 18 and 25 have the highest rates of illicit drug use and heavy alcohol use. The purpose of this study was to determine the performance of the Relax, Alone, Forget, Family/Friends, Trouble (CRAFFT) screening to identify alcohol and cannabis use disorders using Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria in a sample of emerging adults who use alcohol or cannabis or both. Methods: Study participants were recruited as part of a larger intervention study of health behaviors among emerging adults between the ages of 18 and 25 reporting alcohol and/or cannabis use. As part of baseline data collection, responses to the CRAFFT (score range: 0–6) and the Structured Clinical Interview for DSM-IV (SCID) were recorded. Additional questions about craving permitted approximation with DSM-5 diagnoses of alcohol and cannabis use disorders. Results: Participants (N = 382) averaged 21 (±2.1) years of age, 47% were male, 65% were non-Latino Caucasian, and using the SCID 42% met criteria for an alcohol use disorder and 45% met criteria for cannabis use disorder. When evaluating for any alcohol use disorder alone, using a cutoff score of 4, the sensitivity was 81.4% but the specificity was only 45.3%. At a cutoff score of 4, sensitivity for identifying any cannabis use disorder alone was 83.7% and specificity was 48.6%. Conclusions: In emerging adults who report using alcohol or cannabis, the CRAFFT had low specificity for predicting alcohol or cannabis use disorder, despite using higher cut scores than previously published. The CRAFFTs utility in determining clinical substance use disorders in this population may be limited.

Childhood Health and Development in a Cohort of Infants Exposed Prenatally to Methadone or Buprenorphine

Background: Neonatal Abstinence Syndrome (NAS) due to in-utero opioid exposure is a growing problem with largely unknown long-term childhood outcomes. The objective of this study was to compare long-term outcomes of infants exposed to methadone versus buprenorphine in-utero. Method: This retrospective cohort study included all pregnant women on buprenorphine or methadone and their infants born between 2006-2010 at our institution. Inpatient data was merged with outpatient data from 2006-2014 for those infants who continued to receive their paediatric care at our institution. We estimated unadjusted risk ratios (RR) of the following outcomes in buprenorphine versus methadone exposed infants: 1) routine healthcare visits, 2) growth and feeding disorders, 3) developmental delay, 4) visual problems, 5) hearing problems, 6) behavioural/attentional problems. Results: Of 338 infants, 73.1% (N=247) continued to be followed at our hospital. The mean length of follow-up was 25.7 months (95% CI 22.9, 28.9). Infants in the buprenorphine group were less likely to be seen for hepatitis C exposure (19.6 vs. 9.2%, RR=0.60, 95% CI 0.40, 0.91) and more likely to have had a routine weight check (RR=2.14, 95% CI 1.05, 4.34). There were no differences in the incidence of developmental delay, ophthalmologic abnormalities, hearing deficits, or behavioural diagnoses between the groups. Results are limited by small sample size and lack of adjustment for confounders. Conclusion: No significant differences in paediatric outcomes at 2 years of age after in-utero methadone or buprenorphine exposure were found, but the evidence is affected by study limitations. Further studies in a large patient population are warranted.

Medication Treatment of Adolescent Opioid Use Disorder in Primary Care

1. Brittany L. Carney, MS* 2. Scott E. Hadland, MD, MPH, MS*,† 3. Sarah M. Bagley, MD, MSc*,† 1. *Department of General Internal Medicine/Pediatrics, Boston Medical Center, Boston, MA 2. †Department of Pediatrics, Boston University School of Medicine, Boston, MA 1. Medication-Assisted Treatment of Adolescents With Opioid Use Disorders. Committee on Substance Use and Prevention. Pediatrics. 2016;138(3). Available at: https://doi.org/10.1542/peds.2016-1893 2. Electronic Code of Federal Regulations, 42 CFR 8.12 - Federal Opioid Treatment Standards. § Part 8—Medication Assisted Treatment for Opioid Use Disorders. Available at: https://www.ecfr.gov/cgi-bin/text-idx?SID=25e311ab0b3ac62d80439ad2c1ba7bb2&mc=true&node=pt42.1.8&rgn=div5 3. 1. Gaither JR, 2. Leventhal JM, 3. Ryan SA, 4. Camenga DR National Trends in Hospitalizations for Opioid Poisonings Among Children and Adolescents, 1997 to 2012. Gaither JR, Leventhal JM, Ryan SA, Camenga DR. JAMA Pediatrics. 2016;170(12):1195–1201. Available at: https://doi.org/10.1001/jamapediatrics.2016.2154 [OpenUrl][1] 4. 1. Johnston LD, 2. O’Malley PM, 3. Miech RA, 4. Bachman JG, 5. Schulenberg JE Monitoring the Future National Survey Results on Drug Use, 1975-2016: Overview, Key Findings on Adolescent Drug Use. Johnston LD, O’Malley PM, Miech RA, Bachman JG, Schulenberg JE. Ann Arbor, MI: Institute for Social Research, The University of Michigan; 2017. 5. 1. Kampman K, 2. Jarvis M American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use. Kampman K, Jarvis M. J Addict Med. 2015;9(5):358–367 [OpenUrl][2][CrossRef][3][PubMed][4] 6. 1. Han B, 2. Hedden SL, 3. Lipari R, 4. Copello EAP, 5. Kroutil LK Receipt of Services for Behavioral Health Problems: Results from the 2014 National Survey on Drug Use and Health (National Survey on Drug Use and Health [NSDUH] Data Review). Han B, Hedden SL, Lipari R, Copello EAP, Kroutil LK. Available at: https://www.samhsa.gov/data/sites/default/files/NSDUH-DR-FRR3-2014/NSDUH-DR-FRR3-2014/NSDUH-DR-FRR3-2014.pdf. Published September 2015 Since 2000, a threefold increase in unintentional opioid poisonings among adolescents has followed a dramatic increase in adult opioid-related deaths. In 2016, 1 in 13 high school seniors reported past-year nonprescription use of opioids. Despite these increases, only 8.5% of adolescents received addiction treatment. In September 2016, the American Academy of Pediatrics (AAP) released a policy statement recommending that pediatricians offer medication for the treatment of severe opioid use disorder (OUD). There are 3 medications approved for OUD treatment: buprenorphine, naltrexone, and methadone. Buprenorphine and methadone are opioid agonists that decrease cravings for opioids and treat withdrawal symptoms. In addition, both provide opioid blockade, which means that if an individual uses another opioid after taking their medication, euphoric effects are blocked. Naltrexone, an opioid antagonist, blocks the opioid receptor, preventing the effects of opioid use. It may also reduce cravings for opioids. Head-to-head clinical trials of these medications in adolescents are lacking; observational data from adults suggest that of these medications, methadone may be the most effective for retention in treatment. Buprenorphine is taken daily via sublingual tablets or films and can be prescribed in pediatric primary care. The film is a dissolving strip absorbed through the buccal mucosa or tongue. Buprenorphine has 2 formulations: 1) combined with naloxone (buprenorphine/naloxone) … [1]: {openurl}?query=rft.jtitle%253DJAMA%2BPediatrics%26rft.volume%253D170%26rft.spage%253D1195%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: {openurl}?query=rft.jtitle%253DJ%2BAddict%2BMed%26rft.volume%253D9%26rft.spage%253D358%26rft_id%253Dinfo%253Adoi%252F10.1097%252FADM.0000000000000166%26rft_id%253Dinfo%253Apmid%252F26406300%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [3]: /lookup/external-ref?access_num=10.1097/ADM.0000000000000166&link_type=DOI [4]: /lookup/external-ref?access_num=26406300&link_type=MED&atom=%2Fpedsinreview%2F39%2F1%2F43.atom