PubMed Update November 2015 - January 2016

We have 35 articles for your viewing this time, with apologies for the delay in getting this out. Thanks to Traci Green for offering to help out and for reviewing this post.

1) Management of patients with issues related to opioid safety, efficacy and/or misuse: a case series from an integrated, interdisciplinary clinic.

Becker WC, Merlin JS, Manhapra A, Edens EL.

Addict Sci Clin Pract. 2016 Jan 28;11(1):3. doi: 10.1186/s13722-016-0050-0.

Comment: Fascinating article. Worth a read if you’re interested in management of pain and opioids.

2) Circumstances and contexts of heroin initiation following non-medical opioid analgesic use in New York City.

Harocopos A, Allen B, Paone D.

Int J Drug Policy. 2015 Dec 29. pii: S0955-3959(15)00374-6. doi: 10.1016/j.drugpo.2015.12.021. [Epub ahead of print]

Comment: Great to see some of the path from prescription opioids to heroin. Makes sense that first step is moving from a drug co-formulated with acetaminophen.

3) Emergency Department-Based Opioid Harm Reduction: moving physicians from willing to doing.

Samuels EA, Dwyer K, Mello MJ, Baird J, Kellogg A, Bernstein E.

Acad Emerg Med. 2016 Jan 27. doi: 10.1111/acem.12910. [Epub ahead of print]

Comment: To get EDs to enhance practices will require pressure from the top.

4) Internal Medicine Resident Knowledge, Attitudes and Barriers to Naloxone Prescription in Hospital and Clinic Settings.

Wilson JD, Spicyn N, Matson P, Alvanzo A, Feldman L.

Subst Abus. 2016 Jan 28:0. [Epub ahead of print]

Comment: Nice article from Baltimore finding that young physicians are ready and willing to prescribe naloxone, but aren’t routinely doing so yet.

5) Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?

Strang J, McDonald R, Tas B, Day E.
Addiction. 2016 Feb 3. doi: 10.1111/add.13209. [Epub ahead of print]

Comment: There are significant issues with this proscriptive publication. First, as noted in the disclosures, the author has interest as an inventor in a patent on a new formulation of naloxone owned by his employer that would address the concerns upon which he bases his conclusions. This is a quite a conflict of interest for an academic commentary that directs clinicians in how to act.

Second, a quote from the Discussion section describes where the authors have gone off course:

“In this situation [lay naloxone administration] the failure of effect of i.n. naloxone, for whatever reason, can delay the time to naloxone injection until an ambulance arrives.”

And what would occur if there was no naloxone, besides delay in the time of naloxone administration until an ambulance arrives? As we know from experience, getting a needle into places like pre-release prison is impossible in most settings – whereas getting the nasal device was achievable. While we have long sought a superior nasal device, the absence of such a product did not obviate the benefits of nasal naloxone. The authors’ views in this case are, I believe, inconsistent with public health aims.

Third, the authors ignore the years of on-the-ground experience that emergency medical providers in the United States have with the jerry-rigged nasal naloxone device in question. Numerous systems adopted the product because it took the risk of needle-sticks out of the equation and was as - or nearly as - effective as when injected. Some investigators have suggested, and many anesthesiologists would agree, that this relatively low dose of naloxone may be all that is needed in most cases since the goal isn't to restore a Glasgow Coma Scale of 15 - that may actually complicate lay management of overdose - but to restore breathing. (On a slight tangent, some have suggested the fascinating hypothesis that the clinical response to nasal naloxone - which is better than would be expected based on peripheral blood concentrations - may be due to exposure to naloxone through the cribriform plate directly into the central nervous system.) 

Finally, to suggest that there are ethical concerns in having used this device to expand access because it was not the perfect device ignores the reality of overdose – this isn’t something we can wait to address until everything is perfect. People’s lives are on the line. Public health providers would have been at far greater fault if they had done nothing. The lead author, based in England where naloxone provision has long been delayed, should be well aware of this problem.

This "debate" seems particularly odd from the U.S. perspective, where off-label prescription and use of medications is authorized by the Food and Drug Administration and common practice. This paper is apparently the first salvo in a discussion that will involve four additional papers coming out in April.

6) Naloxone (Narcan) nasal spray for opioid overdose.

[No authors listed]

Med Lett Drugs Ther. 2016 Jan 4;58(1485):1-2. No abstract available.

Comment: As a follow-up to the oddly-timed prior article, we finally have an approved intranasal device. This is exciting and the product is priced within reach of a lot of insurers – less so community programs unfortunately. The one other potential issue is the pharmacokinetic data for this product, which suggest that the recipient may be exposed to the equivalent of around five times the standard 0.4mg intramuscular dose. Hopefully this won’t be an issue at all – and perhaps will instead be helpful for the fentanyl overdoses  seen with increasing frequency – but we will have to keep close watch for problems related to precipitated withdrawal.

7) Legal regimes surrounding naloxone access: considerations for prescribers.

Brodrick JE, Brodrick CK, Adinoff B.

Am J Drug Alcohol Abuse. 2016 Jan 25:1-12. [Epub ahead of print]

Comment: Another legal review of naloxone access.

8) A Systematic Review on the Use of Psychosocial Interventions in Conjunction With Medications for the Treatment of Opioid Addiction.

Dugosh K, Abraham A, Seymour B, McLoyd K, Chalk M, Festinger D.

J Addict Med. 2016 Jan 19. [Epub ahead of print]

Comment: I like the title of this article, as it hints at the primacy of medication.

9) Neighborhood-Level and Spatial Characteristics Associated with Lay Naloxone Reversal Events and Opioid Overdose Deaths.

Rowe C, Santos GM, Vittinghoff E, Wheeler E, Davidson P, Coffin PO.

J Urban Health. 2016 Jan 22. [Epub ahead of print]

Comment: How can we use geocoding data to enhance the public health response to overdose surveillance?

10) Relationship between Nonmedical Prescription-Opioid Use and Heroin Use.

Compton WM, Jones CM, Baldwin GT.

N Engl J Med. 2016 Jan 14;374(2):154-63. doi: 10.1056/NEJMra1508490. Review. No abstract available.

Comment: Interesting take on the trend of increasing heroin-related deaths. Most likely there is truth to both sides of this argument – opioid prescribing got lots of people hooked and taking away the opioids leaves a hole filled by illicit opioids.

11) Evaluation of Overdose Prevention Trainings in NYC: Knowledge and Self-efficacy among Participants Twelve Months after Training.

Maldjian L, Siegler A, Kunins HV.

Subst Abus. 2016 Jan 5:0. [Epub ahead of print]

Comment: Happy we have these data, and the lack of an age or racial differentiation in knowledge is very promising. The conclusions – that we need to improve training – is based on a pre-set idea of what knowledge is necessary to effectively respond to an overdose. I’m not sure we know that, so it’s hard to say that the trainings are insufficient. Also, with regard to the finding that some participants didn’t know naloxone could reverse opioids besides heroin, I’m curious if that finding translates to some emergency medical providers as well...

12) Risk factors of prescription opioid overdose among Colorado Medicaid beneficiaries.

Dilokthornsakul P, Moore G, Campbell JD, Lodge R, Traugott C, Zerzan J, Allen R, Page RL 2nd.

J Pain. 2015 Dec 22. pii: S1526-5900(15)00985-2. doi: 10.1016/j.jpain.2015.12.006. [Epub ahead of print]

Comment: Dose, use of methadone, substance use disorder, other psychiatric illness, benzodiazepine use, and number of pharmacies utilized.

13) An Initial Evaluation of Web-Based Opioid Overdose Education.

Roe SS, Banta-Green CJ.

Subst Use Misuse. 2015 Dec 28:1-8. [Epub ahead of print]

Comment: Web-based naloxone training!

14) Focused use of drug screening in overdose patients increases impact on management.

Erdmann A, Werner D, Hugli O, Yersin B.

Swiss Med Wkly. 2015 Dec 28;145:w14242. doi: 10.4414/smw.2015.14242. eCollection 2015.

Comment: Drug screening helps manage toxidromes in the ED.

15) An Evaluation of Naloxone Use for Opioid Overdoses in West Virginia: A Literature Review.

Beheshti A, Lucas L, Dunz T, Haydash M, Chiodi H, Edmiston B, Ford C, Bohn N, Stein JH, Berrett A, Sobota B, Horzempa J.

Am Med J. 2015 Jul 9;6(1):9-13.

Comment: Naloxone emerging in West Virginia, which has a remarkably high rate of opioid overdose mortality.

16) Opioid Overdose Deaths and Florida's Crackdown on Pill Mills.

Kennedy-Hendricks A, Richey M, McGinty EE, Stuart EA, Barry CL, Webster DW.

Am J Public Health. 2016 Feb;106(2):291-7. doi: 10.2105/AJPH.2015.302953. Epub 2015 Dec 21.

Comment: While we usually discuss health system-related interventions on this site, there have been a few times when law enforcement-related activities have resulted in many lives saved. The Florida example described here is one of those. Another was in 2007, when the DEA shut down a fentanyl manufacturer in Mexico, ending a dramatic spate of deaths on the eastern seaboard.

17) Non-fatal overdoses and related risk factors among people who inject drugs in St. Petersburg, Russia and Kohtla-Järve, Estonia.

Uusküla A, Raag M, Vorobjov S, Rüütel K, Lyubimova A, Levina OS, Heimer R.

BMC Public Health. 2015 Dec 18;15(1):1255. doi: 10.1186/s12889-015-2604-6.

Comment: Exciting to see these important data. Unfortunately the health of drug users – and the ability to study or intervene – has only worsened in Russia.

18) Barriers to Implementation of Opioid Overdose Prevention Programs in Ohio.

Winstanley EL, Clark A, Feinberg J, Wilder CM.

Subst Abus. 2015 Dec 18:0. [Epub ahead of print]

Comment: Drug use is stigmatized and naloxone’s too expensive.

19) Patient Perspectives on an Opioid Overdose Education and Naloxone Distribution Program in the US Department of Veterans Affairs.

Oliva EM, Nevedal A, Lewis ET, McCaa MD, Cochran MF, Konicki PE, Davis CS, Wilder C.

Subst Abus. 2015 Dec 16:0. [Epub ahead of print]

Comment: Fascinating focus groups on naloxone among veterans.

20) Mortality in the Melbourne injecting drug user cohort study (MIX).

Nambiar D, Agius PA, Stoové M, Hickman M, Dietze P.

Harm Reduct J. 2015 Dec 9;12:55. doi: 10.1186/s12954-015-0089-3.

Comment: Mortality rate was 1.0/100person-years, associated with prior incarceration, recent need for emergency care, and recent overdose. Only half of the deaths were likely accidental overdose, suggesting overall a lower rate of opioid overdose mortality than is standard in the literature – perhaps because 36% were in agonist maintenance treatment.

21) A Question About the Safety of Buprenorphine/Naloxone and Benzodiazepine Drugs.

Howland RH.

J Psychosoc Nurs Ment Health Serv. 2015 Dec 1;53(12):11-4. doi: 10.3928/02793695-20151117-01.

Comment: Buprenorphine is safer than other opioids.

22) Effectiveness of Scotland's national naloxone programme for reducing opioid-related deaths: a before (2006-10) versus after (2011-13) comparison.

Bird SM, McAuley A, Perry S, Hunter C.

Addiction. 2015 Dec 7. doi: 10.1111/add.13265. [Epub ahead of print]

Comment: Very exciting data from Scotland supporting naloxone among inmates pre-release to reduce opioid-related mortality.

23) Naloxone Administration in US Emergency Departments, 2000-2011.

Frank JW, Levy C, Calcaterra SL, Hoppe JA, Binswanger IA.

J Med Toxicol. 2015 Nov 30. [Epub ahead of print]

Comment: Tough to interpret these data. Only a minority of opioid overdose cases had naloxone administered – this makes sense since overdose can often be safely managed without naloxone in monitored settings. In 14% of cases where naloxone was administered, an opioid agonist was also provided – this would surely be a high rate of iatrogenic overdose … Can’t access full article.

24) Mortality Risk Among Heroin Abusers: Clients and Non-clients of Public Treatment Centers for Drug Addiction.

Pavarin RM.

Subst Use Misuse. 2015;50(13):1690-6. doi: 10.3109/10826084.2015.1027932. Epub 2015 Nov 23.

Comment: The mortality rate was even higher among the cohort of Italian heroin users who sought treatment compared to those just accessing emergency care. This is fascinating. And only 17% of deaths were from opioid overdose.

25) The rise of opioid abuse in Iowa.

Strickler K.

Iowa Med. 2015 Summer;105(3):10-1. No abstract available.

Comment: Can’t access and no abstract.

26) Development and process evaluation of an educational intervention for overdose prevention and naloxone distribution by general practice trainees.

Klimas J, Egan M, Tobin H, Coleman N, Bury G.

BMC Med Educ. 2015 Nov 20;15(1):206. doi: 10.1186/s12909-015-0487-y.

Comment: Authors utilized the British OOKS/OOAS scales to test their training efficacy.

27) Acetylfentanyl: An Emerging Drug of Abuse.

Rogers JS, Rehrer SJ, Hoot NR.

J Emerg Med. 2015 Nov 14. pii: S0736-4679(15)01148-8. doi: 10.1016/j.jemermed.2015.10.014. [Epub ahead of print]

Comment: Case report of acetyl-fentanyl overdose targeted at emergency providers.

28) Response to Bird et al.: The importance of post-release engagement in treatment in estimating impacts on post-release deaths.

Larney S, Degenhardt L, Farrell M.

Addiction. 2015 Nov 21. doi: 10.1111/add.13208. [Epub ahead of print] No abstract available.

Comment: Opioid agonist treatment in prison helps too.

29) Why the FUSS (Fentanyl Urine Screen Study)? A cross-sectional survey to characterize an emerging threat to people who use drugs in British Columbia, Canada.

Amlani A, McKee G, Khamis N, Raghukumar G, Tsang E, Buxton JA.

Harm Reduct J. 2015 Nov 14;12:54. doi: 10.1186/s12954-015-0088-4.

Comment: 29% of participants tested positive for fentanyl while 73% denied any use – this adulterant is not good news.

30) Emergence of methadone as a street drug in St. Petersburg, Russia.

Heimer R, Lyubimova A, Barbour R, Levina OS.

Int J Drug Policy. 2016 Jan;27:97-104. doi: 10.1016/j.drugpo.2015.10.001. Epub 2015 Oct 19.

Comment: Even when in the illicit market (because it’s not legal in Russia), methadone use is associated with reduced HIV risk behaviors.

31) Short-Term Outcomes for Opiate and Crack Users Accessing Treatment: The Effects of Criminal Justice Referral and Crack Use.

Jones A, Hayhurst KP, Millar T, Pierce M, Dunn G, Donmall M.

Eur Addict Res. 2016;22(3):145-52. doi: 10.1159/000438987. Epub 2015 Nov 17.

Comment: Improvements in drug use behaviors were not mediated by whether or not treatment was due to criminal justice referral.

32) Risk factors for opioid overdose and awareness of overdose risk among veterans prescribed chronic opioids for addiction or pain.

Wilder CM, Miller SC, Tiffany E, Winhusen T, Winstanley EL, Stein MD.

J Addict Dis. 2016 Jan-Mar;35(1):42-51. doi: 10.1080/10550887.2016.1107264.

Comment: Pain patients underestimate overdose risk.

33) Do drug seizures predict drug-related emergency department presentations or arrests for drug use and possession?

Wan WY, Weatherburn D, Wardlaw G, Sarafidis V, Sara G.

Int J Drug Policy. 2016 Jan;27:74-81. doi: 10.1016/j.drugpo.2015.09.012. Epub 2015 Oct 23.

Comment: Overall, it appears that more drug supply leads to more overdoses. This is a critical issue certainly worthy of additional investigation.

34) Heroin deaths increase by two thirds in two years, UK figures show.

Wise J.

BMJ. 2015 Sep 3;351:h4754. doi: 10.1136/bmj.h4754. No abstract available.

Comment: Increased deaths in England and Wales is concerning. A smaller increase also occurred in Scotland, again suggesting that naloxone programming – while perhaps able to blunt spikes in mortality – can’t avoid the problem altogether.

35) The benefits and potential drawbacks in the approval of EVZIO for lay reversal of opioid overdose.

Beletsky L.

Am J Prev Med. 2015 Mar;48(3):357-9. doi: 10.1016/j.amepre.2014.09.011. Epub 2014 Dec 26. Review. No abstract available.

Comment: Great commentary, emphasizing both the pricing of naloxone and the need for a broader program to prevent overdose mortality.