After an unprecedented delay, we are thrilled to release the PubMed Updates through April of 2019 (26 papers). There is much work ahead to catch up and we hope to get 2 months out every month, catching up sometime later this year.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.