Thanks again to Rebecca Martinez, Cathleen Beliveau, Nataliya Karashchuk, and Laila Esfandiari at the Center on Substance Use and Health (www.csuhsf.org) for collaborating to produce these summaries!

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1) Opioid overdose history and awareness of naloxone in patients seeking outpatient detoxification.

Bhardwaj SB, Cochran G, Kmiec J.

J Opioid Manag. 2019 May/Jun;15(3):253-259. doi: 10.5055/jom.2019.0508.

Comments: More than half had overdosed and 52% of the total accepted naloxone. Detox is among the most important places to have naloxone available for people to take with them, given extensive data that detox dramatically increases the risk of overdose and overdose death.

2) Free trade and opioid overdose death in the United States.

Dean A, Kimmel S.

SSM Popul Health. 2019 May 23;8:100409. doi: 10.1016/j.ssmph.2019.100409. eCollection 2019 Aug.

Comments: Important analysis using CDC and Department of Labor data to demonstrate a positive association between trade-related job loss and opioid overdose death in counties across the U.S. When fentanyl is present in heroin supply, the increase in overdose deaths from the same number of job losses is even more extreme. 

3) Methodological Complexities in Quantifying Rates of Fatal Opioid-Related Overdose.

Slavova S, Delcher C, Buchanich JM, Bunn TL, Goldberger BA, Costich JF.

Curr Epidemiol Rep. 2019;6(2):263-274. doi: 10.1007/s40471-019-00201-9. Epub 2019 May 2. Review.

Comments: This review describes how the lack of standardization in investigating, certifying, and coding drug overdose-related deaths limits the accuracy of drug overdose mortality surveillance data. Lack of routine comprehensive toxicology testing, challenges in detecting and quantifying novel synthetic opioids, and variations in the specificity and completeness of drug information listed on death certificates generates bias in the data. Based on local experience in three cities and collaboration in multi-state analyses of mortality data, there are real issues comparing one location to another – or even one location over time if the medical examiner staffing changes as well. Some particularly relevant issues include coding manner of death: some code most overdoses as “undetermined” whereas others code most as “unintentional”. More important is the variation in what specific drugs are reported, as well as if a death is attributed to drugs at all when there is an additional cause of death identified.

4) Discovering major opioid-related research themes over time: A text mining technique.

Kim YM.

AMIA Jt Summits Transl Sci Proc. 2019 May 6;2019:751-760. eCollection 2019.

Comments:  Term frequencies in PubMed publications between 2000 and 2017 show that the early 2000s were marked with research on methadone maintenance treatment  and opioid research related to managing pain for HIV and cancer. Over time, research emerged on prescription opioid misuse, associated health problems, and opioid-related deaths and ED visits. The changes within opioid research publication themes mirror the emerging health concerns over time. 

5) Rapid induction onto sublingual buprenorphine after opioid overdose and successful linkage to treatment for opioid use disorder.

Herring AA, Schultz CW, Yang E, Greenwald MK.

Am J Emerg Med. 2019 May 29. pii: S0735-6757(19)30364-X. doi: 10.1016/j.ajem.2019.05.053. [Epub ahead of print] No abstract available.

Comments Unable to access full text due to Elsevier conflicts with academia. No abstract available, so assume this is a letter discussing initiation of buprenorphine immediately after overdose. This is a really exciting emerging intervention, particularly given the impressive reduction in overdose risk among people after buprenorphine dosing. Some providers actually use rapid IV buprenorphine, which is fascinating.

6) West Virginia’s model of buprenorphine expansion: Preliminary results.

Winstanley EL, Lander LR, Berry JH, Mahoney JJ 3rd, Zheng W, Herschler J, Marshalek P, Sayres S, Mason J, Haut MW.

J Subst Abuse Treat. 2019 May 8. pii: S0740-5472(19)30059-5. doi: 10.1016/j.jsat.2019.05.005. [Epub ahead of print]

Comments: Process measures for West Virginia hub and spoke model to scale up medications for substance use disorders.

7) Preparing student pharmacists to identify opioid misuse, prevent overdose and prescribe naloxone.

Skoy E, Eukel H, Frenzel J, Werremeyer A.

Curr Pharm Teach Learn. 2019 May;11(5):522-527. doi: 10.1016/j.cptl.2019.02.013. Epub 2019 May 3.

Comments: Pre-post survey suggesting that student pharmacists’ participation in an opioid misuse and overdose training program significantly increased their knowledge, self-efficacy, and perceived value of the pharmacist’s role in preventing opioid overdose. Full text not accessible. 

8) A chemically contiguous hapten approach for a heroin-fentanyl vaccine.

Natori Y, Hwang CS, Lin L, Smith LC, Zhou B, Janda KD.

Beilstein J Org Chem. 2019 May 3;15:1020-1031. doi: 10.3762/bjoc.15.100. eCollection 2019.

Comments: Drug “vaccines” are emerging again as a major pathway to develop medications for substance use disorders. There are always ethical issues with this pathway, in particular because society has a long history of forcing treatments upon people. Nonetheless, for substance use disorders that lack other good options (e.g. stimulants), the desperate need for treatments likely justifies the risk of misuse by society. This is somewhat harder to justify for opioid use disorder, which has good medications in place already. The larger issue with opioids – and fentanyl in particular – is the fact that there is actually a wide array of analogues already on the market that may not be covered by this targeted vaccine.

9) Simple minimally-invasive automatic antidote delivery device (A2D2) towards closed-loop reversal of opioid overdose.

Dhowan B, Lim J, MacLean MD, Berman AG, Kim MK, Yang Q, Linnes J, Lee CH, Goergen CJ, Lee H.

J Control Release. 2019 May 31;306:130-137. doi: 10.1016/j.jconrel.2019.05.041. [Epub ahead of print]

Comments: It’s been a real challenge to address overdoses that occur when people are alone. Closed-loop devices that alert emergency help or even administer naloxone have been considered for year.s It’s nice to see something start to move through the stages, although there is a LOT more to do before this were to make it to the real world – it’s an implant that likely requires an outpatient surgery and I’d be concerned about the need for (frequent) refill. Unable to access the full paper so may be missing some details.

10) The opioid epidemic in rural northern New England: An approach to epidemiologic, policy, and legal surveillance.

Stopka TJ, Jacque E, Kelso P, Guhn-Knight H, Nolte K, Hoskinson R Jr, Jones A, Harding J, Drew A, VanDonsel A, Friedmann PD.

Prev Med. 2019 May 31:105740. doi: 10.1016/j.ypmed.2019.05.028. [Epub ahead of print]

Comments: Geographic analysis of opioid overdose rates, HCV rates and harm reduction access in rural areas of New Hampshire, Vermont and Massachusetts. 

11) Effect of pill mill laws on opioid overdose deaths in Ohio & Tennessee: A mixed-methods case study.

Brighthaupt SC, Stone EM, Rutkow L, McGinty EE.

Prev Med. 2019 May 29;126:105736. doi: 10.1016/j.ypmed.2019.05.024. [Epub ahead of print]

Comments: Examined the impact of pill mill laws–regulations that prevent the issuing of opioid prescriptions without medical indication–on overall opioid overdose death rate and drug-specific opioid overdose death rates (prescription opioids, heroin, and synthetic opioids) in Ohio and Tennessee. Pill mill laws, even when robustly implemented, neither reduced nor increased overdose death. Full text not available. 

12) Dancing with Deterrents: Understanding the Role of Abuse-Deterrent Opioid Formulations and Naloxone in Managing Cancer Pain.

Mitchell MT.

Oncologist. 2019 May 31. pii: theoncologist.2019-0340. doi: 10.1634/theoncologist.2019-0340. [Epub ahead of print]

Comments:  Examines the use of novel “abuse-deterrent” formulas for managing cancer pain. This article acknowledges the economic barriers to patients using these more expensive formulas and warns that the novel formulas are no less prone to misuse by taking larger doses or switching to heroin. Additionally, use of naloxone as a means of harm-reduction in patients with end-stage cancer is controversial due to symptoms associated with imminent death being similar to opioid overdose; naloxone has the potential to exacerbate emotional and physical pain in this population. 

13) Naloxone urban legends and the opioid crisis: what is the role of public health?

Crabtree A, Masuda JR.

BMC Public Health. 2019 May 30;19(1):670. doi: 10.1186/s12889-019-7033-5.

Comments: This article describes and discredits sensationalized media reports about naloxone kits being used not as intended. These stories are discussed in a sociological framework of urban legends, wherein these reports incite a fear-based response against stigmatized activities and communities (there’s a long history of this related to drug use – see, for example, this excellent piece discussing a Pulitzer Prize-winning series by Washington Post journalist Janet Cooke, which led to massive manhunts for a drug dealing child, and was later determined to be entirely fraudulent). This article posits that these naloxone urban legends can be a useful tool to the public health field in understanding and addressing the underlying anxieties of the opioid crisis. 

14) Street fentanyl use: Experiences, preferences, and concordance between self-reports and urine toxicology.

Daniulaityte R, Carlson RR, Juhascik MP, Strayer KE, Sizemore IE.

Int J Drug Policy. 2019 May 27;71:3-9. doi: 10.1016/j.drugpo.2019.05.020. [Epub ahead of print]

Comments: In a sample of 60 people who self-reported heroin and non-prescription fentanyl use, nearly 90% tested positive for non-prescription fentanyl. Participants were not able to accurately identify when they were using heroin compared to when they were using non-prescription fentanyl. Study sampling and methodology were somewhat unclear from the abstract only (full text unavailable), since it does not speak to whether participants intentionally used both substances. This study took place in Dayton, Ohio, which had one of the highest overdose death rates in the country in 2017.

15) A gender-based analysis of nonmedical prescription opioid use among people who use illicit drugs.

Cheng T, Nosova E, Small W, Hogg RS, Hayashi K, DeBeck K.

Addict Behav. 2019 Oct;97:42-48. doi: 10.1016/j.addbeh.2019.05.022. Epub 2019 May 21.

Comments: Analyzed factors associated with nonmedical prescription opioid use among 1,459 people in Vancouver who use illicit drugs. There were no differences between men and women with regards to accessing prescription opioids for non-medical purposes. Those who used heroin, had overdosed, and had difficulty accessing health and social services were more likely to use prescription opioids for non-medical purposes. Unable to access full text. 

16) Opioid maintenance, weaning and detoxification techniques; where we have been, where we are now and what the future holds: an update.

Plunkett AR, Peden RM.

Pain Manag. 2019 May;9(3):297-306. doi: 10.2217/pmt-2018-0046. Epub 2019 May 29.

Comments: A review of the literature surrounding opioid use amidst changing sociological and political environments. Full text unavailable.

17) Comparing rates and characteristics of ambulance attendances related to extramedical use of pharmaceutical opioids in Australia: a protocol for a retrospective observational study.

Nielsen S, Crossin R, Middleton M, Martin C, Wilson J, Lam T, Scott D, Smith K, Lubman D.

BMJ Open. 2019 May 27;9(5):e029170. doi: 10.1136/bmjopen-2019-029170.

Comments: This article outlines the protocol for an upcoming study of non-prescription pharmaceutical opioid use in Australia using data from ambulance clinical records. Funded by a pharmaceutical company that makes tapentadol, the study outlines a particular focus on non-prescription use of tapentadol and oxycodone. 

Thanks to Rebecca Martinez, Cathleen Beliveau, Nataliya Karashchuk, and Laila Esfandiari at the Center on Substance Use and Health (www.csuhsf.org) for these summaries!

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1) The opioid crisis: Origins, trends, policies, and the roles of pharmacists.

Chisholm-Burns MA, Spivey CA, Sherwin E, Wheeler J, Hohmeier K.

Am J Health Syst Pharm. 2019 Mar 19;76(7):424-435. doi: 10.1093/ajhp/zxy089.

Comments: Pharmacist-focused history. 

2) Heroin body-packing and naloxone.

Vahabzadeh M, Banagozar Mohammadi A.

Lancet. 2019 Mar 23;393(10177):e35. doi: 10.1016/S0140-6736(19)30502-1. No abstract available.

Comments: In this case, 82 packets of heroin packed into the stomach and bowels- each weighing 20 grams and encased in 2 condoms- necessitated multiple large doses of naloxone prior to gastrotomy. Of note, naloxone is well-tolerated even at markedly high doses. While naloxone is generally administered as tenths of a milligram to a few milligrams, animal toxicity data suggest multiple grams could hypothetically be given.

3) Identification and Description of Non-Fatal Opioid Overdoses using Rhode Island EMS Data, 2016-2018.

Lasher L, Rhodes J, Viner-Brown S.

R I Med J (2013). 2019 Mar 1;102(2):41-45.

Comments: Identification of overdoses in EMS data — overview of overdose trends in RI.

4) Prescription Drug Monitoring Programs and Opioid Overdoses: Exploring Sources of Heterogeneity.

Castillo-Carniglia A, Ponicki WR, Gaidus A, Gruenewald PJ, Marshall BDL, Fink DS, Martins SS, Rivera-Aguirre A, Wintemute GJ, Cerdá M.

Epidemiology. 2019 Mar;30(2):212-220. doi: 10.1097/EDE.0000000000000950.

Comments: There have been multiple efforts to quantify the potential benefit of controlled substance monitoring programs (CSMPs). First, CSMPs are commonly and erroneously referred to as “prescription drug monitoring programs” when they do not, in fact, allow tracking of prescriptions. CSMPs are often managed by law enforcement and medical providers are mandated to use them. CSMPs are often used in a punitive rather than therapeutic manner, both for patients and providers. If CSMPs were actually “PDMPs”, then all prescription data would be available, providers would enthusiastically crave that information because it would help them manage the multiple conditions most patients have, and privacy protections would be superior because it would be vaster health data.

On to the paper. This paper found that, in places where most people were using prescribed opioids, CSMP implementation seemed to be associated with reduced prescription opioid hospitalizations. This is presumably because fewer prescription opioids were available. However, CSMPs were also associated with increased heroin hospitalizations, particularly in areas that didn’t have high rates of opioids prescribed for chronic pain. The conclusion of the authors – that CSMPs are most effective in areas with high rates of prescribed opioids – fails to account for the fact that many of these opioids were landing in those neighborhoods without as much prescribing – the very same people that turned to heroin (and then fentanyl) when they could no longer find oxycodone on the street. 

We needed vast improvements in our prescribing of opioids – there’s no doubt about that. However, it is critical to understand and admit to the unintended harms of CSMPs and other opioid stewardship efforts. If we don’t, then we will ultimately land in just as bad of a place as we started.

5) Exposures to Opioids Among Wisconsin Children and Adolescents, 2002-2016.

Creswell PD, Gibson C, Theobald J, Meiman JG.

WMJ. 2019 Apr;118(1):9-15.

Comments: Overdose rates among youth are rising in Wisconsin. Among adolescents age 13-19, the majority of hospital encounters involved prescription opioids. However, the proportion of encounters involving heroin-related overdose also increased from 10% in 2002 to 36% in 2016. 

6) Practices and concerns related to naloxone use among emergency medical service providers in a rural state: A mixed-method examination.

Kilwein TM, Wimbish LA, Gilbert L, Wambeam RA.

Prev Med Rep. 2019 Apr 28;14:100872. doi: 10.1016/j.pmedr.2019.100872. eCollection 2019 Jun.

Comments: EMS providers in remote rural areas of Wyoming report titrating naloxone more often than those in populated areas due to longer average transport times to the hospital and less law enforcement backup. Some rural EMS providers see increased naloxone use as an insufficient solution to the rise in opioid misuse, and would like to see greater efforts towards improving access to treatment and harm reduction strategies within their communities. 

7) Buprenorphine charges to uninsured patients at top-ranked U.S. hospitals.

Niforatos JD, Dorner SC, Pescatore RM, Raja AS.

Am J Emerg Med. 2019 Apr 24. pii: S0735-6757(19)30266-9. doi: 10.1016/j.ajem.2019.04.041. [Epub ahead of print] No abstract available.

Comments: An examination of the financial burden of buprenorphine prescribed in the ED setting for opioid use disorders. Full article and results were unavailable.

8) Gender differences in acute recreational drug toxicity: a case series from Oslo, Norway.

Syse VL, Brekke M, Grimsrud MM, Persett PS, Heyerdahl F, Hovda KE, Vallersnes OM.

BMC Emerg Med. 2019 Apr 29;19(1):29. doi: 10.1186/s12873-019-0244-3.

Comments: In patients treated for drug toxicity, gender differences were not pronounced. Despite relatively worse physical and mental health among women who use drugs noted in previous studies, there was no indication that this resulted in a difference in clinical manifestation or treatment when presenting with drug toxicity.

9) Rural-Urban Trends in Opioid Overdose Discharges in Missouri Emergency Departments, 2012-2016.

Coffey W, Hunter A, Mobley E, Vivolo-Kantor A.

J Rural Health. 2019 Apr 25. doi: 10.1111/jrh.12368. [Epub ahead of print]

Comments: Missouri’s overdose death rate increased by 36% from 2015 to 2016 and urban counties had both higher rates and a larger percentage increase of overdose than rural counties, including heroin overdose rates. Statewide, all rural and urban counties experienced an increase in heroin overdose morbidity. 

10) Identifying and classifying opioid-related overdoses: A validation study.

Green CA, Perrin NA, Hazlehurst B, Janoff SL, DeVeaugh-Geiss A, Carrell DS, Grijalva CG, Liang C, Enger CL, Coplan PM.

Pharmacoepidemiol Drug Saf. 2019 Apr 24. doi: 10.1002/pds.4772. [Epub ahead of print]

Comments: Code-based algorithms that detect opioid-related overdoses and classify them according to heroin involvement work well. Algorithms for classifying suicide/suicide attempts and unintentional opioid overdoses work less well, but were improved when natural language processing (NLP) was used. 

11) Should we worry that take-home naloxone availability may increase opioid use?

Tas B, Humphreys K, McDonald R, Strang J.

Addiction. 2019 Apr 23. doi: 10.1111/add.14637. [Epub ahead of print] No abstract available.

Comments: Naloxone distribution remains beneficial despite perceived negative unintended consequences.

12) Do electronic health record prompts increase take-home naloxone administration for emergency department patients after an opioid overdose?

Marino R, Landau A, Lynch M, Callaway C, Suffoletto B.

Addiction. 2019 Apr 23. doi: 10.1111/add.14635. [Epub ahead of print]

Comments: Real-time prompts from the electronic health record may increase distribution of take-home naloxone to patients following an overdose and correct racial biases in prescribing. However, as clinicians know, prompts in electronic records are ubiquitous, a point of frustration while trying to address multiple issues in limited time, and usually ignored.

13) Progress in agonist therapy for substance use disorders: Lessons learned from methadone and buprenorphine.

Jordan CJ, Cao J, Newman AH, Xi ZX.

Neuropharmacology. 2019 Apr 19. pii: S0028-3908(19)30001-2. doi: 10.1016/j.neuropharm.2019.04.015. [Epub ahead of print] Review.

Comments: Need a succinct review of the pharmacological rationale for agonist replacement therapy in the treatment of opioid and nicotine dependence? Also delves into the application of what we’ve learned about agonist therapies for potential cocaine use disorder treatment modalities like classical and atypical DAT inhibitors. 

14) Demystifying buprenorphine misuse: Has fear of diversion gotten in the way of addressing the opioid crisis?

Doernberg M BA, Krawczyk N BA, Agus D JD, Fingerhood M MD.

Subst Abus. 2019 Apr 22:1-6. doi: 10.1080/08897077.2019.1572052. [Epub ahead of print]

Comments: Policies that restrict access to buprenorphine in criminal justice and other settings due to fear of diversion constitute an unnecessary barrier to care for vulnerable populations.

15) Community Pharmacist Utilization of Legislation That Allows Impact on the Opioid Crisis in the State of Minnesota: A Mixed-Methods Approach.

Palombi L, Hawthorne AN, Lunos S, Melgaard K, Dahly A, Blue H.

J Pharm Pract. 2019 Apr 14:897190019841747. doi: 10.1177/0897190019841747. [Epub ahead of print]

Comments: Minnesota-licensed pharmacists underutilize harm reduction tools and opioid-related legislation (88.64% of respondents reported not dispensing naloxone in the past month using a protocol and 59.69% reported no naloxone distribution by any method). 

16) The impact of expanded Medicaid eligibility on access to naloxone.

Frank RG, Fry CE.

Addiction. 2019 Apr 14. doi: 10.1111/add.14634. [Epub ahead of print]

Comments: Medicaid expansion contributed to increases in naloxone prescriptions. This seems to indicate increased accessibility to those for whom cost was a barrier. 

17) A conceptual model for understanding post-release opioid-related overdose risk.

Joudrey PJ, Khan MR, Wang EA, Scheidell JD, Edelman EJ, McInnes DK, Fox AD.

Addict Sci Clin Pract. 2019 Apr 15;14(1):17. doi: 10.1186/s13722-019-0145-5. Review.

Comments: Prevention of overdose for people released from jails and prisons is multifactorial and extremely complex, and this article presents an impressive conceptual framework to better understand factors at play. Ideally, reducing overdose risks starts with reducing people’s exposure to incarceration in the first place. This article also calls for increased access to OUD treatment across the continuum of care along with better coordination between the criminal justice, healthcare and community-based systems to prevent overdose deaths. 

18) Methadone and buprenorphine pharmacokinetics and pharmacodynamics when co-administered with fostemsavir to opioid-dependent, human immunodeficiency virus seronegative participants.

Moore K, Magee M, Sevinsky H, Chang M, Lubin S, Myers E, Ackerman P, Llamoso C.

Br J Clin Pharmacol. 2019 Apr 13. doi: 10.1111/bcp.13964. [Epub ahead of print]

Comments: This study looks at the interaction between fostemsavir (FTR)–an oral prodrug of tamsavir that prevents initial HIV attachment and entry into host immune cells–and methadone/buprenorphine treatment. They found that FTR did not significantly impact MET and BUP pharmacokinetics, and thus can be administered with MET or BUP without dose adjustment. 

19) Losing the uphill battle? Emergent harm reduction interventions and barriers during the opioid overdose crisis in Canada.

Strike C, Watson TM.

Int J Drug Policy. 2019 Apr 8. pii: S0955-3959(19)30057-X. doi: 10.1016/j.drugpo.2019.02.005. [Epub ahead of print]

Comments: Harm reductions interventions are emerging in Canada and the authors argue that although this is promising, Canada needs political environments at all levels to foster innovation and drug policy experimentation to address the escalating opioid crisis.

20) Chronic pain management among people who use drugs: A health policy challenge in the context of the opioid crisis.

Dassieu L, Kaboré JL, Choinière M, Arruda N, Roy É.

Int J Drug Policy. 2019 Apr 8. pii: S0955-3959(19)30089-1. doi: 10.1016/j.drugpo.2019.03.023. [Epub ahead of print]

Comments: Patients with chronic pain who use drugs experienced frustration navigating the medical system, desired non-pharmacological therapies for their pain but often couldn’t afford them, and sometimes turned to street drugs to manage pain, resulting in a higher risk of exposure to fentanyl and overdose. Full article not available.

21) Learning from the past, looking to the future – Is there a place for injectable opioid treatment among Australia’s responses to opioid misuse?

Belackova V, Salmon AM, Jauncey M, Bell J.

Int J Drug Policy. 2019 Apr 8. pii: S0955-3959(19)30094-5. doi: 10.1016/j.drugpo.2019.01.026. [Epub ahead of print]

Comments: Yes. Arguments for piloting supervised injectable opioid treatment are: aging populations of opioid-dependent patients have not benefitted from existing treatment modalities, prescription opioids continue to be misused, and overdose rates are climbing. Developing strategies to improve sustainability of programs involve addressing patient exit strategies and cost. 

22) Overdose Risk and Client Characteristics Associated With the Injection of Buprenorphine at a Medically Supervised Injecting Center in Sydney, Australia.

Power J, Salmon AM, Latimer J, Jauncey M, Day CA.

Subst Use Misuse. 2019;54(10):1646-1653. doi: 10.1080/10826084.2019.1600147. Epub 2019 Apr 11.

Comments: This study found that risk of overdose was low for buprenorphine injection compared to other substances and no overdoses occurred when buprenorphine/naloxone was injected. Additionally, injection of mono-formulated buprenorphine and co-formulated buprenorphine-naloxone was associated with male gender, homelessness, no income/reliance upon government payments, and prior imprisonment.

23) Drug overdose deaths at work, 2011-2016.

Tiesman HM, Konda S, Cimineri L, Castillo DN.

Inj Prev. 2019 Apr 10. pii: injuryprev-2018-043104. doi: 10.1136/injuryprev-2018-043104. [Epub ahead of print]

Comments: Workplace overdose fatalities in the US were the highest in transportation and mining industries; heroin was the single most frequent drug documented in workplace overdose deaths. Deaths were low but increased 24% annually between 2011-2016 implicating that workplaces are impacted by the national opioid overdose epidemic directly.

24) Inhibitory transmission in the bed nucleus of the stria terminalis in male and female mice following morphine withdrawal.

Luster BR, Cogan ES, Schmidt KT, Pati D, Pina MM, Dange K, McElligott ZA.

Addict Biol. 2019 Apr 9. doi: 10.1111/adb.12748. [Epub ahead of print]

Comments: Mouse model comparing response to opioid withdrawal by sex in mice- some differences exist in GABAergic signaling between males and females. 

25) Management of opioid use disorder in the USA: present status and future directions.

Blanco C, Volkow ND.

Lancet. 2019 Apr 27;393(10182):1760-1772. doi: 10.1016/S0140-6736(18)33078-2. Epub 2019 Mar 14. Review.

Comments: Medications for opioid use disorder (OUD) have the potential to significantly improve OUD outcomes, however barriers to care at diagnosis, entry into treatment, and retention in treatment limit their efficacy. 

26) Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients.

Cicero TJ, Mendoza M, Cattaneo M, Dart RC, Mardekian J, Polson M, Roland CL, Schnoll SH, Webster LR, Park PW.

Postgrad Med. 2019 Apr;131(3):225-229. doi: 10.1080/00325481.2019.1585688. Epub 2019 Mar 19.

Comments:

This is an industry funded-trial to bolster the case for novel opioid products designed to try to discourage injection. They found that problematic use increase over time among those receiving either the standard opioid or their “abuse-deterrent” formulation. The analysis is, oddly, limited to confidence intervals, although these do overall suggest a greater increase in poor outcomes among the recipients of standard opioids. 

Of note, the novel formulation was the formulary choice in this clinic system. As this is not a randomized trial, there are likely differences between the two groups of people – e.g. the recipients of standard opioids may have been requesting those because of an intent to inject or insufflate the product.

1) Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011-2016.

Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M.

Natl Vital Stat Rep. 2018 Dec;67(9):1-14.

Comment: Nice summary of the data demonstrating the shift from prescribed opioids to heroin to fentanyl, with rising methamphetamine and persistent cocaine presence.

2) Enhanced Intranasal Absorption of Naltrexone by Dodecyl Maltopyranoside: Implications for the Treatment of Opioid Overdose.

Krieter P, Gyaw S, Chiang CN, Crystal R, Skolnick P.

J Clin Pharmacol. 2019 Jan 30. doi: 10.1002/jcph.1384. [Epub ahead of print]

Comment: Fascinating that the half-life of naltrexone is only 2.2 hours when administered intranasally … would be great to see that for managing alcohol use.

3) Emergency department physicians’ and pharmacists’ perspectives on take-home naloxone.

Holland TJ, Penm J, Dinh M, Aran S, Chaar B.

Drug Alcohol Rev. 2019 Jan 29. doi: 10.1111/dar.12894. [Epub ahead of print]

Comment: Qualitative assessment of opinions.

4) Take-home naloxone: a life saver in opioid overdose.

The Lancet.

Lancet. 2019 Jan 26;393(10169):296. doi: 10.1016/S0140-6736(19)30153-9. No abstract available. 

Comment: Editorial supporting take-home naloxone.

5) Feasibility and Acceptability of a Checklist and Learning Collaborative to Promote Quality and Safety in the Perinatal Care of Women with Opioid Use Disorders.

Goodman D, Zagaria AB, Flanagan V, Deselle FS, Hitchings AR, Maloney R, Small TA, Vergo AV, Bruce ML.

J Midwifery Womens Health. 2019 Jan;64(1):104-111. doi: 10.1111/jmwh.12943.

Comment: Some good changes – more naloxone provided, more counseling regarding breastfeeding, and more nicotine-replacement therapy initiated.

6) Correlates of seeking emergency medical help in the event of an overdose in British Columbia, Canada: Findings from the Take Home Naloxone program.

Karamouzian M, Kuo M, Crabtree A, Buxton JA.

Int J Drug Policy. 2019 Jan 25. pii: S0955-3959(19)30014-3. doi: 10.1016/j.drugpo.2019.01.006. [Epub ahead of print]

Comment: Great analysis of naloxone programmatic data. 55.7% of lay naloxone administrations were followed by a call for emergency medical services, again demonstrating that we do not have data showing a reduction in calling 911 when naloxone is administered. 

7) Seizures in tramadol overdoses reported in the ToxIC registry: predisposing factors and the role of naloxone.

Murray BP, Carpenter JE, Dunkley CA, Moran TP, Alfaifi M, Alsukaiti WS, Kazzi Z.

Clin Toxicol (Phila). 2019 Jan 24:1-5. doi: 10.1080/15563650.2018.1547826. [Epub ahead of print]

Comment: Tramadol is a weird drug. This analysis found that when it caused an opioid-like overdose, seizures were less likely, and that naloxone use was not associate with tramadol seizures.

8) “You Never Know What You’re Getting”: Opioid Users’ Perceptions of Fentanyl in Southwest Pennsylvania.

McLean K, Monnat SM, Rigg K, Sterner GE 3rd, Verdery A.

Subst Use Misuse. 2019 Jan 24:1-12. doi: 10.1080/10826084.2018.1552303. [Epub ahead of print]

Comment: Fentanyl use patterns are evolving – it seems to be here to stay this time.

9) Development of a Cascade of Care for responding to the opioid epidemic.

Williams AR, Nunes EV, Bisaga A, Levin FR, Olfson M.

Am J Drug Alcohol Abuse. 2019 Jan 24:1-10. doi: 10.1080/00952990.2018.1546862. [Epub ahead of print]

Comment: Nice to see this development.

10) Blockade of the human ether a-go-go related gene (hERG) potassium channel by fentanyl.

Tschirhart JN, Li W, Guo J, Zhang S.

Mol Pharmacol. 2019 Jan 21. pii: mol.118.114751. doi: 10.1124/mol.118.114751. [Epub ahead of print]

Comment: First, you gotta love the naming culture for these genes. Now the human ether a-go-go gene potassium channel effects could prolong the QT interval, which could result in ventricular arrhythmias and, ultimately, cardiac arrest. Is this playing a role in fentanyl-related deaths? Not sure. 

11) Changing risk and presentation of overdose associated with consumption of street drugs at a supervised injection site in Vancouver, Canada.

Notta D, Black B, Chu T, Joe R, Lysyshyn M.

Drug Alcohol Depend. 2019 Jan 15;196:46-50. doi: 10.1016/j.drugalcdep.2018.12.016. [Epub ahead of print]

Comment: Great use of these data. As fentanyl entered the heroin supply in Vancouver, the rate of “heroin” overdoses rose 4.8 fold. This is interesting, as fentanyl knowingly used at the Sydney injection facility was 4 times more likely than heroin to result in overdose – honestly I would have expected an even more substantial increase in “heroin” overdose events in the context of heroin contaminated with fentanyl. Notably, there was a several fold increase in overdose events for all drugs being injected in Vancouver over the period studied. They also saw an increase in rigidity (a potential complication of fentanyl) from 10.4% of “heroin” overdoses in 2010/11 to 18.9% in 2017.

12) High Prevalence of Self-Reported Exposure to Adulterated Drugs Among People Who Experienced an Opioid Overdose in Canada: A Cohort Study.

Prangnell A, Fairgrieve C, Nosova E, DeBeck K, Milloy MJ, Hayashi K.

Subst Use Misuse. 2019 Jan 20:1-6. doi: 10.1080/10826084.2018.1555257. [Epub ahead of print]

Comment: Two-thirds of people who overdosed believed their drugs had been adulterated. While the current drug supply is very dynamic, I suspect this finding would hold for overdoses in areas not heavily affected by fentanyl; that is, this is a common perception among people who have overdosed, explained by the actor-observer bias.

13) Associations between implementation of Project Lazarus and opioid analgesic dispensing and buprenorphine utilization in North Carolina, 2009-2014.

Alexandridis AA, Dasgupta N, McCort AD, Ringwalt CL, Rosamond WD, Chelminski PR, Marshall SW.

Inj Epidemiol. 2019 Jan 21;6(1):2. doi: 10.1186/s40621-018-0179-2.

Comment: Limited effects.

14) What should clinicians do as fentanyl replaces heroin?

Bisaga A.

Addiction. 2019 Jan 20. doi: 10.1111/add.14522. [Epub ahead of print] No abstract available. 

Comment: Be creative, be innovative, don’t be shy.

15) Twenty years of the methadone treatment protocol in Ireland: reflections on the role of general practice.

Delargy I, Crowley D, Van Hout MC.

Harm Reduct J. 2019 Jan 17;16(1):5. doi: 10.1186/s12954-018-0272-4. Review.

Comment: 20 years and 10,000 patients later.

16) Overdose Deaths Involving Fentanyl and Fentanyl Analogs – New York City, 2000-2017.

Colon-Berezin C, Nolan ML, Blachman-Forshay J, Paone D.

MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):37-40. doi: 10.15585/mmwr.mm6802a3.

Comment: It’s always tricky to use toxicology results in overdose mortality surveillance because there are many substances found on toxicology which may not have contributed to the death (e.g. something the patient takes medically that was at a low or appropriately therapeutic level and doesn’t interact with likely causal drugs, or something that is a by-product of decomposition). In this circumstance, however, it made sense.

17) Changes in Buprenorphine-Naloxone and Opioid Pain Reliever Prescriptions After the Affordable Care Act Medicaid Expansion.

Saloner B, Levin J, Chang HY, Jones C, Alexander GC.

JAMA Netw Open. 2018 Aug 3;1(4):e181588. doi: 10.1001/jamanetworkopen.2018.1588.

Comment: Buprenorphine treatment increased and opioid pain reliever prescriptions did not. That makes solid sense.

18) Pharmacokinetics of a novel, approved, 1.4 mg intranasal naloxone formulation for reversal of opioid overdose- a randomised controlled trial.

Skulberg AK, Åsberg A, Khiabani HZ, Røstad H, Tylleskar I, Dale O.

Addiction. 2019 Jan 14. doi: 10.1111/add.14552. [Epub ahead of print]

Comment: Intranasal 1.4mg was ~50% bioavailable, which is half as good as intramuscular, and the pharmacokinetics were similar to 0.8mg intramuscular, although the time to peak effect was about 5 minutes slower.

19) Overdose mortality rates in Croatia and factors associated with self-reported drug overdose among persons who inject drugs in three Croatian cities.

Handanagic S, Bozicevic I, Sekerija M, Rutherford GW, Begovac J.

Int J Drug Policy. 2019 Jan 11;64:95-102. doi: 10.1016/j.drugpo.2018.11.017. [Epub ahead of print]

Comment: Polydrug injection.

20) Increased Presence of Fentanyl in Cocaine-Involved Fatal Overdoses: Implications for Prevention.

Nolan ML, Shamasunder S, Colon-Berezin C, Kunins HV, Paone D.

J Urban Health. 2019 Jan 11. doi: 10.1007/s11524-018-00343-z. [Epub ahead of print]

Comment: These data suggest that fentanyl is responsible for a good amount of the increase in cocaine deaths in NYC. Was that intentionally consumed or contaminating cocaine? Given that the demographics of cocaine related deaths have historically been fairly distinct from opioid deaths in NYC, I wonder if comparing demographics would help to elucidate which is the case.

21) Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health.

Lovrecic B, Lovrecic M, Gabrovec B, Carli M, Pacini M, Maremmani AGI, Maremmani I.

Int J Environ Res Public Health. 2019 Jan 9;16(2). pii: E177. doi: 10.3390/ijerph16020177. Review.

Comment: Yup, we’re in a mess.

22) Primary Care for Persons Who Inject Drugs.

Visconti AJ, Sell J, Greenblatt AD.

Am Fam Physician. 2019 Jan 15;99(2):109-116.

Comment: Love this topic, which drove me into medicine in the first place. Excellent to see physicians, scientists, and academic publications take on this need.

23) Reversal of Pediatric Opioid Toxicity with Take-Home Naloxone: a Case Report.

Lebin JA, Chen BC, Valento MJ.

J Med Toxicol. 2019 Jan 10. doi: 10.1007/s13181-018-0695-z. [Epub ahead of print]

Comment: This may be the first journal report of pediatric reversal with take-home naloxone, but it’s not the first story … it’s been happening in the community for decades.

24) Drug Overdose Deaths Among Women Aged 30-64 Years – United States, 1999-2017.

VanHouten JP, Rudd RA, Ballesteros MF, Mack KA.

MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):1-5. doi: 10.15585/mmwr.mm6801a1.

Comment: Increased overdose mortality across the board among women.

25) Increasing Naloxone Access and Use to Prevent Opioid Overdose Death and Disability.

White ND.

Am J Lifestyle Med. 2018 Oct 20;13(1):33-35. doi: 10.1177/1559827618803874. eCollection 2019 Jan-Feb. Review.

Comment: Legislation and pronouncements have only done so much.

26) Opioid overdose detection using smartphones.

Nandakumar R, Gollakota S, Sunshine JE.

Sci Transl Med. 2019 Jan 9;11(474). pii: eaau8914. doi: 10.1126/scitranslmed.aau8914.

Comment: This is a fascinating topic. We can saturate the world with naloxone, but it still won’t prevent overdose events from becoming fatal among people who are isolated from others (e.g. marginally housed, living in hotel rooms). In San Francisco, about one-third of deaths occurred in single-room occupancy hotel units – a number that is unlikely to be significantly affected by responder interventions. To have non-invasive tools that can detect concerning vital signs could be hugely beneficial if implemented well.

27) Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study.

Lugoboni F, Zamboni L, Cibin M, Tamburin S; Gruppo InterSERT di Collaborazione Scientifica (GICS).

Eur Addict Res. 2019;25(1):10-19. doi: 10.1159/000496112. Epub 2019 Jan 9.

Comment: People who inject drugs frequently try to inject other drugs.

28) Predictive Factors of Treatment Outcomes for Hospital Care in Children with Acute Methadone Poisoning.

Atighi Y, Eizadi-Mood N, Mansourian M, Zamani A, Saffaei A, Sabzghabaee AM.

J Res Pharm Pract. 2018 Oct-Dec;7(4):200-204. doi: 10.4103/jrpp.JRPP_16_141.

Comment: Accidental opioid poisoning amoung children at home is always tragic. While our first effort has to be avoiding such events, an earlier manuscript today showed that having naloxone at home can help mitigate when they do occur.

29) Perspectives on rapid fentanyl test strips as a harm reduction practice among young adults who use drugs: a qualitative study.

Goldman JE, Waye KM, Periera KA, Krieger MS, Yedinak JL, Marshall BDL.

Harm Reduct J. 2019 Jan 8;16(1):3. doi: 10.1186/s12954-018-0276-0.

Comment: People use them and often implement some overdose prevention or management strategies when results are positive.

30) Legally Lethal Kratom: A Herbal Supplement with Overdose Potential.

Palasamudram Shekar S, Rojas EE, D’Angelo CC, Gillenwater SR, Martinez Galvis NP.

J Psychoactive Drugs. 2019 Jan 8:1-3. doi: 10.1080/02791072.2018.1562591. [Epub ahead of print]

Comment: Kratom’s another “weird” drug with some opioid properties. Took 10 days to recover – wow!

31) The importance of buprenorphine research in the opioid crisis.

Pendergrass SA, Crist RC, Jones LK, Hoch JR, Berrettini WH.

Mol Psychiatry. 2019 Jan 7. doi: 10.1038/s41380-018-0329-5. [Epub ahead of print]

Comment: Yep. Although I’d say implementation is more important.

32) Implementation of a collaborative model for opioid overdose prevention on campus.

Hill LG, Holleran Steiker LK, Mazin L, Kinzly ML.

J Am Coll Health. 2019 Jan 7:1-4. doi: 10.1080/07448481.2018.1549049. [Epub ahead of print]

Comment: Further expansion of naloxone.

33) Divergence In Recent Trends In Deaths From Intentional And Unintentional Poisoning.

Hempstead K, Phillips J.

Health Aff (Millwood). 2019 Jan;38(1):29-35. doi: 10.1377/hlthaff.2018.05186.

Comment: Notwithstanding a huge increase in unintentional opioid deaths and a shift in the causal opioids, poisoning suicide deaths have not changed during this period, again suggesting that suicide and unintentional overdose are distinct processes.

34) Medication Treatment For Opioid Use Disorders In Substance Use Treatment Facilities.

Mojtabai R, Mauro C, Wall MM, Barry CL, Olfson M.

Health Aff (Millwood). 2019 Jan;38(1):14-23. doi: 10.1377/hlthaff.2018.05162.

Comment: Uh … yeah. Please.

35) Changes in Pharmacists’ Perceptions After a Training in Opioid Misuse and Accidental Overdose Prevention.

Eukel HN, Skoy E, Werremeyer A, Burck S, Strand M.

J Contin Educ Health Prof. 2019 Jan 3. doi: 10.1097/CEH.0000000000000233. [Epub ahead of print]

Comment: More training pharmacists.

36) Commentary on Stam et al. (2019): Drugs, death and statistics.

Darke S.

Addiction. 2019 Jan 6. doi: 10.1111/add.14520. [Epub ahead of print] No abstract available. 

Comment: As usual, the author has insightful comments on overdose research and surveillance. Heroin deaths are often miscoded as morphine (or codeine?) deaths and stimulant deaths are often missed because the immediate medical cause of a cerebral hemorrhage or cardiac arrest is sufficient for the cause of death field.

37) On-site identification of psychoactive drugs by portable Raman spectroscopy during drug-checking service in electronic music events.

Gerace E, Seganti F, Luciano C, Lombardo T, Di Corcia D, Teifel H, Vincenti M, Salomone A.

Drug Alcohol Rev. 2019 Jan;38(1):50-56. doi: 10.1111/dar.12887. Epub 2019 Jan 6.

Comment: Portable drug detection is very exciting.

38) An age-based analysis of nonmedical prescription opioid use among people who use illegal drugs in Vancouver, Canada.

Cheng T, Small W, Dong H, Nosova E, Hayashi K, DeBeck K.

Subst Abuse Treat Prev Policy. 2018 Nov 27;13(1):41. doi: 10.1186/s13011-018-0180-3.

Comment: No age differences.

39) Utilizing Buprenorphine in the Emergency Department after Overdose.

Johns SE, Bowman M, Moeller FG.

Trends Pharmacol Sci. 2018 Dec;39(12):998-1000. doi: 10.1016/j.tips.2018.10.002. Review.

Comment: Good idea, when patients want it.

40) Pharmacological Research as a Key Component in Mitigating the Opioid Overdose Crisis.

Baumann MH, Kopajtic TA, Madras BK.

Trends Pharmacol Sci. 2018 Dec;39(12):995-998. doi: 10.1016/j.tips.2018.09.006. Review.

Comment: Review with focus on what new medications could provide.

41) At-a-glance – What can paramedic data tell us about the opioid crisis in Canada?

Do MT, Furlong G, Rietschlin M, Leyenaar M, Nolan M, Poirier P, Field B, Thompson W.

Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):339-342. doi: 10.24095/hpcdp.38.9.06. English, French. 

Comment: It’s tricky to track opioid overdose with paramedic calls for several reasons (e.g. diagnosis codes are preliminary in this triage service, using naloxone administration as a marker misses a lot of events that aren’t “typical” heroin overdoses, the impact of naloxone programming is unclear, etc). Nonetheless, if you can access the data in a useful way, exploring this data source is irresistible.

42) Review of Case Narratives from Fatal Overdoses Associated with Injectable Naltrexone for Opioid Dependence.

Saucier R, Wolfe D, Dasgupta N.

Drug Saf. 2018 Oct;41(10):981-988. doi: 10.1007/s40264-018-0653-3. Erratum in: Drug Saf. 2018 May 24. 

Comment: It is concerning that in overdose deaths the manufacturer placed the blame on opioid use disorder and did not consider elevated risk for overdose after treatment discontinuation. I would agree that a registry is in order.