PubMed Update March - May 2015

Three months. 46 papers. I’m already a month behind.

1) Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

Dahlem CH, Horstman MJ, Williams BC.

J Am Assoc Nurse Pract. 2015 Mar 26. doi: 10.1002/2327-6924.12249. [Epub ahead of print]

Comments: Naloxone programs have been providing kits to settings where homeless people receive services for many years. This is a description of a program at a homeless health clinic.

2) Quantification of morphine, morphine 6-glucuronide, buprenorphine, and the enantiomers of methadone by enantioselective mass spectrometric chromatography in whole blood.

Christoffersen DJ, Brasch-Andersen C, Thomsen JL, Worm-Leonhard M, Damkier P, Brøsen K.

Forensic Sci Med Pathol. 2015 Jun;11(2):193-201. doi: 10.1007/s12024-015-9673-9. Epub 2015 Mar 24.

Comments: It’s been awhile since we had a forensics paper here. I think this is a novel method of identifying enantiomers.

3) A Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991.

Spaulding AC, Sharma A, Messina LC, Zlotorzynska M, Miller L, Binswanger IA.

Am J Public Health. 2015 May;105(5):e51-7. doi: 10.2105/AJPH.2014.302546. Epub 2015 Mar 19.

Comments: Stunningly low rate of drug overdose mortality in this cohort of prisoners in Georgia. This is one of the first times I’ve seen a paper on opioid overdose find radically different results in a different setting. I can’t access for details.

4) A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for Translating Community Programming Into Clinical Practice.

Mueller SR, Walley AY, Calcaterra SL, Glanz JM, Binswanger IA.

Subst Abus. 2015 Mar 16:1-14. [Epub ahead of print]

Comments: A review toward the end of using community distribution data to build clinical care naloxone prescription.

5) Long-term course of opioid addiction.

Hser YI, Evans E, Grella C, Ling W, Anglin D.

Harv Rev Psychiatry. 2015 Mar-Apr;23(2):76-89. doi: 10.1097/HRP.0000000000000052.

Comments: This is a systematic review of long-term studies of opioid users. Among many fascinating data reported, the length of time not using a drug of choice increases the likelihood of continuing to not use that drug. This seems obvious to many, but I don’t believe it’s been documented before. Good read for anyone looking to understand some of the longitudinal outcome data.

PubMed Update July 2014

Hooray for a mere 7 paper reprieve this month.

1) Underrepresentation of Heroin Involvement in Unintentional Drug Overdose Deaths in Allegheny County, PA.

Mertz KJ, Janssen JK, Williams KE.

J Forensic Sci. 2014 Jul 16. doi: 10.1111/1556-4029.12541. [Epub ahead of print]

Comments: This manuscript presents critical and very concerning results regarding interpretation of our prescription opioid overdose epidemic. Morphine and codeine are commonly present and without 6-MAM (a third heroin metabolite) present at sufficient levels those deaths are coded as morphine and codeine. On this review of 112 such deaths, 66% met criteria for heroin involvement based on a history of heroin use (which may not be sufficient given the frequent use of other opioids among heroin users), drug paraphernalia or stamp bags, track marks, and detection of 6-MAM (generally at very low levels). Good toxicologists always check for 6-MAM so that shouldn’t be a major issue, but it is conceivable that some of these morphine/codeine cases are in fact heroin – an important caveat as we respond to the epidemic.

2) Legislative strategies other than legalizing illicit opioids may help to reduce overdose fatalities.

Trafton JA, Oliva EM.

Addiction. 2014 Aug;109(8):1243-4. doi: 10.1111/add.12585. No abstract available.

Comments: Authors argue that Good Samaritan and naloxone legislation may be effective strategies to reduce overdose.

3) Prevalence and factors associated with HIV infection among injection drug users at methadone clinics in Taipei, Taiwan.

Yen YF, Yen MY, Lin T, Li LH, Jiang XR, Chou P, Deng CY.

BMC Public Health. 2014 Jul 4;14(1):682. doi: 10.1186/1471-2458-14-682.

Comments: Again, HIV infection is associated with a history of overdose among persons who inject drugs.

4) Methadone toxicity in a poisoning referral center.

Taheri F, Yaraghi A, Sabzghabaee AM, Moudi M, Eizadi-Mood N, Gheshlaghi F, Farajzadegan Z.

J Res Pharm Pract. 2013 Jul;2(3):130-4. doi: 10.4103/2279-042X.122387.

Comments: an analysis of methadone poisonings in Iran. Among 385 patients, 57.7% of cases were “intentional” and demonstrated high rates of psychiatric disorders (25.8%). Among the full cohort, 40% had opioid use disorders and 25.5% were in a methadone program.

PubMed Update November/December 2013

We close out 2013 with an impressive 25 papers in the final two months for a total count of 89 papers. Some interesting new approaches and perspectives, including a paper on the underappreciated role of adulterants, a couple of naltrexone papers, and lots of lay naloxone.

1) The Whole Is Just the Sum of Its Parts: Limited Polydrug Use Among the "Big Three" Expensive Drugs in the United States.

Caulkins JP, Everingham S, Kilmer B, Midgette G.

Curr Drug Abuse Rev. 2013 Dec 5. [Epub ahead of print]

Comments: Somewhat surprising data suggesting relatively separate markets for heroin, cocaine and methamphetamine.

2) A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence.

Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L.

Drug Alcohol Rev. 2013 Dec 3. doi: 10.1111/dar.12095. [Epub ahead of print]

Comments: A systematic review concluding that the data for naltrexone implants for opioid dependence are insufficient for use outside of clinical trials.

3) Trends and Regional Variation in Opioid Overdose Mortality Among Veterans Health Administration Patients, Fiscal Year 2001 to 2009.

Bohnert AS, Ilgen MA, Trafton JA, Kerns RD, Eisenberg A, Ganoczy D, Blow FC.

Clin J Pain. 2013 Nov 25. [Epub ahead of print]

Comments: What happened with opioid analgesic overdose deaths in the United States also happened in among veterans receiving care in the Veterans’ Administration.

4) The Dueling Obligations of Opioid Stewardship.

Coffin P, Banta-Green C.

Ann Intern Med. 2013 Dec 10. doi: 10.7326/M13-2781. [Epub ahead of print] No abstract available.

Comments: Commentary on the reliance on opioids and minimizing the potential harms of stewardship efforts.

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.

PubMed Update: Another Year in Overdose

Another year in overdose, September 2012-August 2013, generally in reverse chronological order, and following the same loosely-formed categories as last year. 

Once again, this is opioid focused and misses anything not listed in the PubMed database – which means it misses many interesting papers to which you are warmly welcomed to post links!

This year there were 99 papers, up from 81 in the preceding 12 months. 

Administering naloxone at an overdose is associated with less syringe sharing

Presented today at the International AIDS Conference:


UPDATE: We now have a link to a PDF of the poster if you'd like a higher-resolution view or to download.