PubMed Update October/November 2016

43 papers this round, and there are some goodies in here for sure (don't miss #38!). Given the number and varied issues addressed, I divided them up into topic areas and, given the number on naloxone, I divided up the naloxone topic areas as well.

Naloxone interventions

Primary care

1) Co-prescription of naloxone as a Universal Precautions model for patients on chronic opioid therapy-Observational study.

Takeda MY, Katzman JG, Dole E, Bennett MH, Alchbli A, Duhigg D, Yonas H.

Subst Abus. 2016 Apr 19:1-6. [Epub ahead of print]

Comment: A pilot of naloxone co-prescribing.

2) Attitudes Toward Naloxone Prescribing in Clinical Settings: A Qualitative Study of Patients Prescribed High Dose Opioids for Chronic Non-Cancer Pain.

Mueller SR, Koester S, Glanz JM, Gardner EM, Binswanger IA.

J Gen Intern Med. 2016 Oct 31. [Epub ahead of print]

Comment: Shows that naloxone for patients prescribed opioids must be appropriately framed.

3) Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

Behar E, Rowe C, Santos GM, Coffa D, Turner C, Santos NC, Coffin PO.

J Gen Intern Med. 2016 Nov 4. [Epub ahead of print]

Comment: When actually implemented, providers really like adding naloxone to opioid-related care. One of five papers out of the Naloxone for Opioid Safety Evaluation of a naloxone co-prescribing study in San Francisco.

PubMed Update May 2016

19 this month. Enjoy!

1) Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme.

Tjagvad C, Skurtveit S, Linnet K, Andersen LV, Christoffersen DJ, Clausen T.

Eur Addict Res. 2016 Jun 1;22(5):249-258. [Epub ahead of print]

Comments: Patients on very high doses of methadone or also using benzodiazepines were at higher risk of death.

2) Heroin use.

Salani DA, Zdanowicz M, Joseph L.

J Psychosoc Nurs Ment Health Serv. 2016 Jun 1;54(6):30-7. doi: 10.3928/02793695-20160518-05.

Comments: Epidemiologic review.

3) Academic physicians' and medical students' perceived barriers toward bystander administered naloxone as an overdose prevention strategy.

Gatewood AK, Van Wert MJ, Andrada AP, Surkan PJ.

Addict Behav. 2016 May 17;61:40-46. doi: 10.1016/j.addbeh.2016.05.013. [Epub ahead of print]

Comments: Qualitative interviews with medical providers.

4) Patient Characteristics and Outcomes in Unintentional, Non-fatal Prescription Opioid Overdoses: A Systematic Review.

Elzey MJ, Barden SM, Edwards ES.

Pain Physician. 2016 May;19(4):215-28.

Comments: Non-fatal events are far more common, not well-predicted by risk factors, and in need of additional research.

5) Incorporation of poison center services in a state-wide overdose education and naloxone distribution program.

Doyon S, Benton C, Anderson BA, Baier M, Haas E, Hadley L, Maehr J, Rebbert-Franklin K, Olsen Y, Welsh C.

Am J Addict. 2016 Jun;25(4):301-6. doi: 10.1111/ajad.12384. Epub 2016 May 24.

Comments: Interesting case series of naloxone reversals reported to poison control. They report a 75.6% “response rate” although some of the remainder was “unknown” and was there were only 2 deaths among 78 cases, suggesting a rate closer to 97.5%. Response rate to heroin was higher than for prescription opioids. Of the 43 suspected heroin events, 31 went to the ED, 25 were discharged, and 5 required ICU care. Of 31 suspected prescription opioid 20 went to the ED, 9 were discharged, and 6 required ICU care. This is consistent with the more complicated nature of prescription opioid overdose.

6) Police Officers Can Safely and Effectively Administer Intranasal Naloxone.

Fisher R, O'Donnell D, Ray B, Rusyniak D.

Prehosp Emerg Care. 2016 May 24:1-6. [Epub ahead of print]

Comments: About a 65% response rate among 117 administrations and 1 combative individual.

PubMed Update November 2014 - February 2015

Catching up on 51 papers in 4 months. Did you miss me?

1) New Drugs of Abuse.

Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E.

Pharmacotherapy. 2014 Dec 4. doi: 10.1002/phar.1522. [Epub ahead of print]

Comment: Review of management of drug toxicities among novel, synthetic compounds.

2) Police officer attitudes towards intranasal naloxone training.

Ray B, O'Donnell D, Kahre K.

Drug Alcohol Depend. 2015 Jan 1;146:107-10. doi: 10.1016/j.drugalcdep.2014.10.026. Epub 2014 Nov 8.

Comment: Police officers like being trained to carry naloxone.

3) Intranasal naloxone administration for treatment of opioid overdose.

Robinson A, Wermeling DP.

Am J Health Syst Pharm. 2014 Dec 15;71(24):2129-35. doi: 10.2146/ajhp130798.

Comment: Review of intranasal naloxone for overdose reversal.

4) Observed transition from opioid analgesic deaths toward heroin.

Dasgupta N, Creppage K, Austin A, Ringwalt C, Sanford C, Proescholdbell SK.

Drug Alcohol Depend. 2014 Dec 1;145:238-41. doi: 10.1016/j.drugalcdep.2014.10.005. Epub 2014 Oct 18.

Comment: Heroin overdoses are increasing.

5) Brief overdose education can significantly increase accurate recognition of opioid overdose amongheroin users.

Jones JD, Roux P, Stancliff S, Matthews W, Comer SD.

Int J Drug Policy. 2014 Jan;25(1):166-70. doi: 10.1016/j.drugpo.2013.05.006. Epub 2013 Jun 15.

Comment: Brief overdose training works for naloxone distribution. This is important because many places are requiring prolonged trainings that end up limiting access to those who are unable or unwilling to invest that degree of time.

6) Brief overdose education is sufficient for naloxone distribution to opioid users.

Behar E, Santos GM, Wheeler E, Rowe C, Coffin PO.

Drug Alcohol Depend. 2015 Mar 1;148:209-12. doi: 10.1016/j.drugalcdep.2014.12.009. Epub 2014 Dec 19.

Comment: Again, brief overdose training works for naloxone distribution.

PubMed Update August-October 2014

Three months. 32 articles. Enough said.

1. Patterns and correlates of non-fatal heroin overdose at 11-year follow-up: Findings from the Australian Treatment Outcome Study.

Darke S, Marel C, Mills KL, Ross J, Slade T, Burns L, Teesson M.

Drug Alcohol Depend. 2014 Sep 16. [Epub ahead of print]

Comment: This study (the ATOS) and the team of investigators have produced some of the most powerful and useful data in substance use research. Once again they have delved into heroin overdose by following treatment patients 11 years out. At least 10.2% of the cohort had died by that time and an additional 9.4% were unaccounted for. Among the 70.1% interviewed, 67.5% had overdosed, 24.4% had experienced five or more overdoses (again suggesting that there are “overdosers” out there who are at very elevated risk of the event). In the past year before the follow-up visit, 4.9% had overdosed (11.8% of those who had used heroin in that period), 95.2% of whom had overdosed previously. Those who overdosed were more likely to report higher levels of non-heroin opiate use, as well as benzodiazepine, cocaine, and methamphetamine use.

2. A new naloxone auto-injection device to treat opioid overdose.

Simonson W.

Geriatr Nurs. 2014 Sep-Oct;35(5):381-2.

Comment: A review of the role of take-home naloxone in the form of the new autoinjector.

3. Increases in heroin overdose deaths - 28 States, 2010 to 2012.

Rudd RA, Paulozzi LJ, Bauer MJ, Burleson RW, Carlson RE, Dao D, Davis JW, Dudek J, Eichler BA, Fernandes JC, Fondario A, Gabella B, Hume B, Huntamer T, Kariisa M, Largo TW, Miles J, Newmyer A, Nitcheva D, Perez BE, Proescholdbell SK, Sabel JC, Skiba J, Slavova S, Stone K, Tharp JM, Wendling T, Wright D, Zehner AM.

MMWR Morb Mortal Wkly Rep. 2014 Oct 3;63(39):849-54.

Comment: This report demonstrates declining prescription opioid deaths (-6.6%), but heroin deaths increased so much (+101.7%) that the data actually demonstrate an overall increase in opioid overdose mortality from 2010 to 2012 (+4.3%). There is disagreement as to what is driving the increase in heroin use and overdose. Is it an inevitable consequence of increased availability of opioids? Or is it the result of growing restrictions on access to those opioids? Clearly there are elements of both, leaving us with conflicting duties when it comes to managing those already reliant upon prescription opioids. Western medical ethics is clear on this point: our patient is the person we treat, who may have been harmed by the very same prescribing behavior we are now trying to change and who may be further harmed by those changes. If we truly believe that this epidemic is “iatrogenic” (i.e. caused by medical care, akin to a surgeon leaving scissors in an abdomen), then we have to be extremely cautious and thoughtful in fixing the problem and we can never abandon the patient.

4. Working together: Expanding the availability of naloxone for peer administration to prevent opioid overdose deaths in the Australian Capital Territory and beyond.

Lenton S, Dietze P, Olsen A, Wiggins N, McDonald D, Fowlie C.

Drug Alcohol Rev. 2014 Oct 1. doi: 10.1111/dar.12198. [Epub ahead of print]

Comment: It's taken an incredibly long time for take-home naloxone to reach Australia, especially given how innovative that country has been with respect to managing drug policy and overdose.

5. Responding to opioid overdose in Rhode Island: where the medical community has gone and where we need to go.

Green TC, Bratberg J, Dauria EF, Rich JD.

R I Med J (2013). 2014 Oct 1;97(10):29-33.

Comment: The first of three articles in this post from Rhode Island, US, which has been facing a surge in opioid overdose deaths and has been responding with expanded naloxone treatment availability. This and the next two articles are free at: http://rimed.org/rimedicaljournal-2014-10.asp.

PubMed Update September 2013

12 articles this month.

1) Effectiveness of Naltrexone in the Prevention of Delayed Respiratory Arrest in Opioid-Naive Methadone-Intoxicated Patients.

Aghabiklooei A, Hassanian-Moghaddam H, Zamani N, Shadnia S, Mashayekhian M, Rahimi M, Nasouhi S, Ghoochani A.

Biomed Res Int. 2013;2013:903172. Epub 2013 Sep 9.

Comments: Interesting use of the long-acting opioid antagonist naltrexone in this study from Iran. The likely downside of this approach of course is that, in those with opioid dependence (constituting the vast majority of overdose cases), it doesn’t allow for titration of antagonist effect to minimize withdrawal symptoms.

2) An investigation of the interactions between methadone and elvitegravir/cobicistat in subjects receiving chronic methadone maintenance.

Bruce RD, Winkle P, Custodio JM, Wei X, Rhee MS, Kearney BP, Ramanathan S, Friedland GH.

Antimicrob Agents Chemother.2013 Sep 30. [Epub ahead of print]

Comments: This is a promising finding for the new HIV regimen.

3) Interaction of Different Antidepressants with Acute and Chronic Methadone in Mice, and Possible Clinical Implications.

Schreiber S, Barak Y, Hostovsky A, Baratz-Goldstein R, Volis I, Rubovitch V, Pick CG.

J MolNeurosci.2013 Sep 22. [Epub ahead of print]

Comments: Really interesting study, since many opioid overdoses occur in the presence of anti-depressant medications. These results are too preliminary to draw strong conclusions, but it’s an important pursuit.

4) Law enforcement attitudes toward overdose prevention and response.

Green TC, Zaller N, Palacios WR, Bowman SE, Ray M, Heimer R, Case P.

Drug Alcohol Depend.2013 Sep 2.doi:pii: S0376-8716(13)00334-7. 10.1016/j.drugalcdep.2013.08.018. [Epub ahead of print]

Comments: Interesting qualitative analysis of police attitudes toward lay naloxone.

5) Days of heroin use predict poor self-reported health in hospitalized heroin users.

Meshesha LZ, Tsui JI, Liebschutz JM, Crooks D, Anderson BJ, Herman DS, Stein MD.

Addict Behav. 2013 Aug 14;38(12):2884-2887. doi:

Comments: More days of heroin use is associated with worse self-reported health and worse self-reported health is associated with non-fatal overdose events.

6) Assisted injection among people who inject drugs in Thailand.

Lee WK, Ti L, Hayashi K, Kaplan K, Suwannawong P, Wood E, Kerr T.

Subst Abuse Treat Prev Policy. 2013 Sep 10;8(1):32. [Epub ahead of print]

Comments: This is a useful contribution to overdose literature. There has long been a concern that people who require assistance to inject (often women) would overdose more. This hasn’t held up in studies and this study corroborates that lack of association. It may be well worth exploring further, but thus far we don’t have any evidence that assistance with injecting increases overdose risk.

7) BET 3: Is nebulised naloxone effective in opioid overdose?

[No authors listed]

Emerg Med J. 2013 Oct;30(10):860. doi: 10.1136/emermed-2013-203100.3.

Comments: Yes, in breathing patients.

8) The lethal burden of drug overdose.

[No authors listed]

Lancet. 2013 Sep 7;382(9895):833. doi: 10.1016/S0140-6736(13)61844-9. No abstract available.

Comments: Brief commentary on opioid overdose mortality in UK and US. Notable that there is no mention of naloxone.

9) [Maintaining opioid abstinence long after inpatient treatment with opioid substitution in an addictology hospital unit].

Bouab O, Lahmek P, Meunier N, Aubin HJ, Michel L.

Rev Med Brux. 2013 May-Jun;34(3):132-40. French.

Comments: Basically inpatient withdrawal from agonist maintenance treatment.

10) The pharmacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment.

Bruce RD, Winkle P, Custodio JM, Wei LX, Rhee MS, Kearney BP, Ramanathan S, Friedland GH.

J Acquir Immune DeficSyndr. 2013 Aug 1;63(4):480-4. doi: 10.1097/QAI.0b013e3182961d31.

Comments: The new combined HIV med (Stribild) modestly increases buprenorphine levels.

11) Problem based review: The patient taking methadone.

Arora A, Williams K.

Acute Med. 2013;12(1):51-4. Review.

Comments: Methadone maintenance review.

12) Low-frequency heroin injection among out-of-treatment, street-recruited injection drug users.

Harris JL, Lorvick J, Wenger L, Wilkins T, Iguchi MY, Bourgois P, Kral AH.

J Urban Health. 2013 Apr;90(2):299-306. doi: 10.1007/s11524-012-9720-8.

Comments: Another useful contribution – infrequent heroin injectors had a lower risk of non-fatal overdose. As with most overdose epidemiology, the relationship between use frequency and overdose risk is likely complex.

News: Police host naloxone training for community

In response to a run of opioid overdoses, the Yarmouth police are co-sponsoring a training of lay persons in the community, so that there will be more naloxone in the community should future overdoses occur. 

This rapid response is made possible by the naloxone program supported by and run through the State health department, and raises the very intriguing concept that naloxone may have stark benefit in settings of overdose "outbreaks."

More OD videos - Cops, reentry, and Spanish OD training!

It seems like there are a bunch of good overdose advocacy and training videos coming out these days. 

Here's a new video from the San Francisco Police Department and Department of Public Health instructing police not to interfere with syringe access sites or naloxone distribution. (Nice narration Emalie Huriaux!)




And here's a new Spanish-language video from Boston about how to recognize overdose and respond properly. The video highlights the fact that those just released from prison or other lock-up facilities are at higher risk of OD, especially in those first two weeks.

And while we're at it, we realized that OPA didn't mention the great video, "Staying Alive on the Outside" from our friends in Rhode Island that came out a few months back. It's and English-language video that focuses on OD risk and response after prison release. 



We hope you find these useful in your work!

Police Training Video

A (really excellent) training video for police regarding Washington State's 911 Good Samaritan and Lay Naloxone law can now be found here.

The 5.5 minute video can be found directly at Seattle Police Department Training Video.

It is narrated by Captain Les Liggins of the Seattle Police Department, Mary Barbosa of the King County Prosecutor's Office, and Dr Charissa Fontinos of Public Health Seattle & King County