Tuesday, July 8, 2014

PubMed Update May/June 2014


25 papers in two months. Anyone want to help with this?

Sabzghabaee AM, Eizadi-Mood N, Yaraghi A, Zandifar S.
Arch Med Sci. 2014 May 12;10(2):309-14. doi: 10.5114/aoms.2014.42584. Epub 2014 May 13.
PMID: 24904666 [PubMed] Free PMC Article
Comments: More data to support the utility of intranasal naloxone for overdose reversal. There are, however, some odd findings that suggest caution in interpreting the paper. The authors used 0.4mg of naloxone for IV or IN administration, whereas most efforts utilize 2mg for IN administration given the lower bioavailability. Moreover, they had a higher level of consciousness in the IN group, which seems odd.

Rambod M, Elhanafi S, Mukherjee D.
Ann Noninvasive Electrocardiol. 2014 Jun 5. doi: 10.1111/anec.12171. [Epub ahead of print]
PMID: 24903622 [PubMed - as supplied by publisher]
Comments: There are cases in which opioids can result in unstable heart rhythms. Usually this is related to high dose methadone, prolongation of the QT interval and torsades de pointes. In this case, heroin plus alcohol may have resulted in electrical conduction similar to “Brugada syndrome” which, in the interest of having an image in this blog post, I’ve posted an image of here. This type of electrical conduction is usually genetic and can result in sudden death through lethal arrhythmias.


Clark AK, Wilder CM, Winstanley EL.
J Addict Med. 2014 May-Jun;8(3):153-63. doi: 10.1097/ADM.0000000000000034.
PMID: 24874759 [PubMed - in process]
Comments: An impressive review of existing data for naloxone programs. Big kudos to the authors.

Iwersen-Bergmann S, Jungen H, Andresen-Streichert H, Müller A, Elakkary S, Püschel K, Heinemann A.
Int J Legal Med. 2014 May 25. [Epub ahead of print]
PMID: 24859230 [PubMed - as supplied by publisher]
Comments: Interesting analysis of methadone-related deaths among methadone maintenance patients suggesting that, while overdose deaths are not common, many may have been related to IV use of methadone.

Liu X, Wang G, Pu H, Jing H.
Brain Res. 2014 Jul 14;1572:40-9. doi: 10.1016/j.brainres.2014.05.016. Epub 2014 May 20.
PMID: 24854119 [PubMed - in process]
Comments: Intriguing analysis of rat brains suggesting a key role of calcium in neurotoxicity related to heroin use. Do medications like verapamil, generally used to manage hypertension, have a role in preventing neurologic damage from opioids and perhaps even reducing overdose risk?

Wang KH, Fiellin DA, Becker WC.
Am J Drug Alcohol Abuse. 2014 Jul;40(4):292-303. doi: 10.3109/00952990.2014.907301. Epub 2014 May 22.
PMID: 24853143 [PubMed - in process]
Comments: Around a fifth of people using prescription opioids “non-medically” get them directly from a physician.

Tuesday, May 27, 2014

PubMed Update March/April 2014

Better late than never, right? 24 papers over two months.


Doe-Simkins M, Quinn E, Xuan Z, Sorensen-Alawad A, Hackman H, Ozonoff A, Walley AY.
BMC Public Health. 2014 Apr 1;14(1):297. [Epub ahead of print]
Comments: Sometimes naloxone is used by bystanders who have not been formally educated (or “trained”) in administering naloxone. This innovative analysis suggests that the untrained witness does a good job in lay naloxone administration.

Kuehn BM.
JAMA. 2014 Apr 23-30;311(16):1600. doi: 10.1001/jama.2014.4483. No abstract available.
Comments: The naloxone auto-injector – Evzio – has been approved and is expected to be available this summer.

3) Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an american pain society and college on problems of drug dependence clinical practice guideline.
Weimer MB, Chou R.
J Pain. 2014 Apr;15(4):366-76. doi: 10.1016/j.jpain.2014.01.496.
Comments: Basic summary is that it’s not entirely clear why there was such a surge in methadone-related deaths in the early part of the 2000s. It’s important to remember that the surge came after a surge in oxycontin-related deaths, when many payers shifted their preferred agent from oxycontin to methadone. Mortality data seems to follow the trend of the most prescribed agent.

Moore C, Lloyd G, Oretti R, Russell I, Snooks H.
BMJ Open. 2014 Mar 20;4(3):e004712. doi: 10.1136/bmjopen-2013-004712.
Comments: Outstanding, innovative design to reach those at very high risk of future overdose events. I anxiously await results.

Monday, March 3, 2014

PubMed Update February 2014

8 papers today, essentially about naloxone and heroin.

Maurer U, Kager C, Fellinger C, Loader D, Pollesböck A, Spitzer B, Jarisch R.
Subst Abuse Treat Prev Policy. 2014 Feb 27;9(1):12. [Epub ahead of print]

Comment: Seeking alternative explanations for “overdose”, the authors explored histamine levels in heroin using individuals. They found that heroin users had greater spikes in histamine levels when exposed to IV heroin compared to oral morphine. They hypothesized that this may explain why so many cases of overdose have a sublethal concentration of opioids, but this seems an overreach based on their data.


Kan M, Gall JA, Latypov A, Gray R, Alisheva D, Rakhmatova K, Sadieva AS.
Int J Drug Policy. 2014 Jan 23. pii: S0955-3959(14)00008-5. doi: 10.1016/j.drugpo.2014.01.005. [Epub ahead of print]

Comment: 47 to 81% of naloxone kits given out in Kyrgyzstan and Tajikistan were used to reverse an overdose – remarkable numbers, from 3 to 5 times higher than seen in western states.


Hansen A.
BMJ. 2014 Feb 20;348:g1686. doi: 10.1136/bmj.g1686. No abstract available.

Comment: Naloxone in Norway.


Seo S, Kwon YS, Yu K, Kim SW, Kwon OY, Kang KH, Kwon K.
Mol Med Rep. 2014 Apr;9(4):1395-9. doi: 10.3892/mmr.2014.1935. Epub 2014 Feb 7.

Comment: I can only see the abstract for this one and the science is outside of my realm – I’m unable to identify anything of apparent clinical relevance.


Bailey AM, Wermeling DP.
Ann Pharmacother. 2014 Feb 12. [Epub ahead of print]

Comment: Very helpful and relevant summary of some pharmacists experience with dispensing naloxone.


Aulet RM, Flis D, Sillman J.
Case Rep Otolaryngol. 2014;2014:962759. doi: 10.1155/2014/962759. Epub 2014 Jan 6.

Comment: Another case of opioid overdose-related sensorineural hearing loss, which means hearing loss from the cochlea (inner ear). The authors kindly run through some theories, including hypotension (e.g. reduced blood flow to the inner ear), overstimulation of kappa opioid receptors present in the cochlea, or adulteration with an ototoxic substance such as quinine.


Sarasa-Renedo A, Espelt A, Folch C, Vecino C, Majó X, Castellano Y, Casabona J, Brugal MT; Redan Study Group.
Gac Sanit. 2014 Jan 10. pii: S0213-9111(13)00227-6. doi: 10.1016/j.gaceta.2013.10.012. [Epub ahead of print]

Comment: Substance use disorder treatment programs are increasingly engaging in overdose prevention efforts – a badly needed development.


Dietze P.
Addiction. 2013 Jul;108(7):1277-8.

Comment: Interesting remarks by the author, suggesting that rather than advertising the high potency heroin, simply noting a spike in deaths and advertising overdose prevention/response strategies may be safer and more relevant to the target population.

Saturday, February 15, 2014

PubMed Update January 2014

10 papers this month, half of which relate to the United Kingdom. We continue to move forward.

Cropsey KL, Martin S, Clark CB, McCullumsmith CB, Lane PS, Hardy S, Hendricks PS, Redmond N.
J Opioid Manag. 2013 Nov-Dec;9(6):393-400.
Comments: Valuable survey of persons in the corrections system, under community supervision. Nearly half had used opioids and 40% of those had experienced an opioid overdose. Those who had overdosed were more likely to be white, female, and have higher educational attainment; they were also much more likely to have witnessed overdose, have seen someone die of overdose, and want training in overdose prevention and management.

Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC.
Spine (Phila Pa 1976). 2014 Jan 29. [Epub ahead of print]
Comments: A review of studies evaluating short term use of opioids for chronic lower back pain. The studies evaluated all have major shortcomings so we’re left with little new information.

Adrish M, Duncalf R, Diaz-Fuentes G, Venkatram S.
Am J Case Rep. 2014 Jan 15;15:22-6
Comments: Being “down” with an overdose for a prolonged period can lead to complications such as rhabdomyolysis and nerve compression. This patient developed compartment syndrome, which is to say high pressure within the fascial compartment of the buttocks, requiring surgical intervention to spare her extremity.

Tuesday, January 7, 2014

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.

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.

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.

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.

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.

Wednesday, November 27, 2013

Narcana vs Death

An amazing mural conceived of and painted by Erin Ruch and Mikey Reger, artists with Mission Minicomix, in Clarion Alley, the Mission District of San Francisco.


Monday, November 11, 2013

PubMed Update October 2013

A slight reprieve from the onslaught, only 6 articles this month – some of which are really interesting.

Wiegand T, Wax P, Smith E, Hart K, Brent J.
J Med Toxicol. 2013 Nov 1. [Epub ahead of print]
Comments: Fascinating TocIC Registry, including cases that were attended to by boarded medical toxicologists (so this would represent a tiny subset of the type of accidental drug overdoses we generally discuss on this site). I’m unable to access the full article.

De Cuyper A, Lambert M, Hantson P.
Acta Clin Belg. 2013 May-Jun;68(3):250-1. No abstract available.
Comments: Unable to access and no abstract available.

Meyer MA.
Neurol Int. 2013 Jul 22;5(3):e13. doi: 10.4081/ni.2013.e13.
Comments: There was a similar review we discussed in 2012. This is a devastating white matter neurologic disease that has been reported after severe opioid overdoses; tends to occur days to weeks after the event.

Cerdá M, Ransome Y, Keyes KM, Koenen KC, Tardiff K, Vlahov D, Galea S.
Am J Public Health. 2013 Dec;103(12):2252-60. doi: 10.2105/AJPH.2013.301347. Epub 2013 Oct 17.
Comments: Fascinating analysis of opioid analgesic overdose fatalities in New York City from 2000-2006, compared to heroin overdose deaths and non-overdose unintentional deaths. Opioid analgesic deaths basically fit in the middle in terms of neighborhood wealth and social structure, between heroin deaths (lower income, socially fragmented) and non-overdose deaths (higher income, less fragmented). This article is also the first academic publication I’ve seen that demonstrates the unique geographic nature of opioid analgesic overdose mortality in NYC – Staten Island is an epicenter, a location that was historically essentially exempt from heroin overdose death.

Okic M, Cnossen L, Crifasi JA, Long C, Mitchell EK.
J Anal Toxicol. 2013 Nov;37(9):629-35. doi: 10.1093/jat/bkt085.
Comments: Analysis of opioids in deaths in Kansas, including drug concentrations. The most notable finding is that there is a very wide range of concentrations in overdose deaths involving these agents, a result consistent with decades of toxicological literature suggesting that tolerance plays a big role on risk for overdose and subsequent death.

Williams AV, Marsden J, Strang J.
Addiction. 2013 Sep 17. doi: 10.1111/add.12360. [Epub ahead of print]

Comments: Authors randomized family members to receive just information versus a 60-minute training. They found that family members who went through the training scored higher on the standardized knowledge and attitude scales authors had previously published. Of note, naloxone was administered in witnessed overdose events for 3 out of 92 who just received information and 5 out of 95 who received the 60-minute training. This raises the very different question of what is sufficient for non-medical personnel to safely and effectively administer naloxone in the community? Information alone may be the answer to that question. While in-depth trainings are fantastic when available and accessible, requiring such activities can easily become an unnecessary obstacle to dissemination of the intervention … perhaps similar to historic requirements for extensive counseling and consent processes prior to HIV testing.

Friday, October 25, 2013

PubMed Update September 2013

12 articles this month.

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.

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.

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.

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.

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.

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.

[No authors listed]
Emerg Med J. 2013 Oct;30(10):860. doi: 10.1136/emermed-2013-203100.3.
Comments: Yes, in breathing patients.

[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.

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.

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.

Arora A, Williams K.
Acute Med. 2013;12(1):51-4. Review.
Comments: Methadone maintenance review.

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.