Sunday, November 16, 2014

PubMed Update August-October 2014

Three months. 32 articles. Enough said.

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.

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.

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.

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.

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:

Samuels E.
R I Med J (2013). 2014 Oct 1;97(10):38-9.
Comment: A brief summary of an ED-based naloxone prescription program in Rhode Island, US. I like the emerging use of the term “naloxone rescue kit.”

Bowman S, Engelman A, Koziol J, Mahoney L, Maxwell C, McKenzie M.
R I Med J (2013). 2014 Oct 1;97(10):34-7.
Comment: A third article on the response in Rhode Island.

Lovegrove MC, Mathew J, Hampp C, Governale L, Wysowski DK, Budnitz DS.
Pediatrics. 2014 Oct;134(4):e1009-16. doi: 10.1542/peds.2014-0840. Epub 2014 Sep 15.
Comment: From 2007-2011 in the US, there were 9,490 hospitalizations among children <6 years of age, 17.6% of which involved opioids. Interestingly, buprenorphine was the most frequent opioid. There are some limitations to this study, including the absence of non-oral ingestions and the lack of narrative detail for the cases.

Davis CS, Southwell JK, Niehaus VR, Walley AY, Dailey MW.
Acad Emerg Med. 2014 Oct;21(10):1173-1177.
Comment: Most states don’t allow basic life support-trained emergency medical responders to administer naloxone.

Stein BD, Gordon AJ, Dick AW, Burns RM, Pacula RL, Farmer CM, Leslie DL, Sorbero M.
J Subst Abuse Treat. 2014 Aug 2.
Comment: 43% of US counties have no buprenorphine treatment providers. Hello?

Richards-Waugh LL, Primerano DA, Dementieva Y, Kraner JC, Rankin GO.
J Anal Toxicol. 2014 Oct;38(8):541-7.
Comment: There’s much to be learned about risks for opioid overdose mortality. This study evaluated the role of CYP450 isoform known as CYP3A4, involved in hepatic metabolism. Some people are slow metabolizers – single nucleotide polymorphisms (aka common “mutations”) rs2242480 and rs2740574 were more common in methadone-only deaths but not in methadone+benzodiazepine deaths, suggesting that these genetic variations may play a role in overdose risk.

Hirsch A, Proescholdbell SK, Bronson W, Dasgupta N.
Pain Med. 2014 Jul;15(7):1187-95.
Comment: The majority of prescription opioid overdose decedents had filled a prescription for that opioid within 60 days of their death. This has to be an argument for co-prescribing naloxone.

Roth AM, Armenta RA, Wagner KD, Roesch SC, Bluthenthal RN, Cuevas-Mota J, Garfein RS.
Subst Use Misuse. 2014 Oct 14. [Epub ahead of print]
Comment: Opioid overdose and HCV appear to be associated in this analysis. This is an interesting area of work. We are quickly learning that people who witness overdoses – and thus people most likely to use naloxone to reverse an overdose – are very high risk persons themselves. This makes logical sense but can make interpreting risk data among naloxone recipients quite challenging.

Aghabiklooei A, Edalatparvar M, Zamani N, Mostafazadeh B.
J Toxicol. 2014;2014:341826. doi: 10.1155/2014/341826. Epub 2014 Aug 12.
Comment: Fascinating study out of Iran. Methadone overdose cases ultimately died from renal failure related to rhabdomyolysis. This likely means that overdose cases were “down” for a while, where the pressure of their bodies on the ground/floor resulted in muscle breakdown, causing release of muscle metabolites that damaged the kidneys. Although they were revived (at least somewhat), the kidney damage from that downtime was ultimately fatal.

Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L.
Drug Alcohol Rev. 2014 Mar;33(2):115-28. doi: 10.1111/dar.12095. Epub 2013 Dec 3. Review.
Comment: Authors contend that long-acting naltrexone formulations for opioid dependence should be limited to clinical trials only. The depot injection of naltrexone was approved in the US for this indication in 2012 based on a study conducted in Russia. While oral naltrexone clearly should not be used for opioid dependence – as there is a very high overdose death rate after discontinuation of treatment – the long-acting formulations may overcome that by allowing for a slower “tapering” off of the medication when treatment is discontinued. There are several studies in process or planning in the US which should provide more useful data to guide us on the safety of this therapy.

Matheson C, Pflanz-Sinclair C, Aucott L, Wilson P, Watson R, Malloy S, Dickie E, McAuley A.
BMC Fam Pract. 2014 Jan 15;15:12. doi: 10.1186/1471-2296-15-12.
Comment: A survey of primary care providers in Scotland (with a fairly low response rate of 55% that biases the results) found limited awareness of the concept of prescribing naloxone.

Oluwajenyo Banjo MPHc, Tzemis D, Al-Qutub D, Amlani A, Kesselring S, Buxton JA.
CMAJ Open. 2014 Jul 22;2(3):E153-61. doi: 10.9778/cmajo.20140008. eCollection 2014 Jul.
Comment: In the first 20 months, take-home naloxone in British Columbia opened in 40 sites, trained 1,318 participants, distributed 836 kits and reported 85 reversed overdose events. They ran into issues with finding providers willing to prescribe, recruiting some high-risk populations (like pain patients), and getting convincing participants it was safe to call emergency medical services.

Weisberg DF, Becker WC, Fiellin DA, Stannard C.
Int J Drug Policy. 2014 Jul 30.
Comment: An interesting comparison of the US and UK in opioid prescribing and the risks for resultant opioid use disorder and overdose epidemics. Authors suggest that limited use of benzodiazepines and ready access to methadone may be helping to buffer the UK from the effects of opioid prescribing seen in the US.

Walker R, Maxwell JC, Adinoff B, Carmody T, Coton CE, Tirado CF.
J Ethn Subst Abuse. 2014;13(3):258-72. doi: 10.1080/15332640.2014.883582.
Comment: 74% of Hispanic adolescents in treatment for “cheese heroin” dependence reported a prior overdose (70% of females, 80% of males).

Klimas J, O'Reilly M, Egan M, Tobin H, Bury G.
Am J Emerg Med. 2014 Jul 31.
Comment: Ambulances in Dublin Ireland attended 469 opioid overdoses, 2.8% of which were fatal and 26% of which were among persons who had been attended to for at least one prior overdose. These are useful data for understanding the epidemiology of EMS-attended overdose cases.

Zuckerman M, Weisberg SN, Boyer EW.
Prehosp Emerg Care. 2014 Oct-Dec;18(4):550-4
Davis CS, Banta-Green CJ, Coffin P, Dailey MW, Walley AY.
Prehosp Emerg Care. 2014 Aug 25. [Epub ahead of print].
Comment: The lead article is a case report of an overdose that didn’t respond to initial paramedic-administered intranasal naloxone and an unrelated opinion piece critiquing both intranasal and take-home naloxone. There are randomized trials of intranasal naloxone and high-quality observational studies of take-home naloxone that are useful in this discussion – this article constitutes neither. The response letter pointing out these and other concerns has an entire page of disclosures because the lead article authors and journal editor determined that federal research funding is a conflict of interest. The disclosures are worth a read.

Frank D, Mateu-Gelabert P, Guarino H, Bennett A, Wendel T, Jessell L, Teper A.
Int J Drug Policy. 2014 Jul 31.
Comment: Qualitative interviews among young prescription opioid users in New York City identified substantial experiences with personal and witnessed overdose and little to no connection with the networks and services that provide overdose prevention services.

Richert T.
Int J Drug Policy. 2014 Jul 21.
Comment: Qualitative interviews with heroin users in Sweden identifies concerns with responding to overdose (in a setting without naloxone access) including police harassment and not wanting to disturb a high.

Lin RJ, Reid MC, Chused AE, Evans AT.
Am J Hosp Palliat Care. 2014 Aug 8. pii: 1049909114546545. [Epub ahead of print]
Comment: Authors reviewed pain management in a New York City hospital. Over 6 months, they found 5 cases of naloxone administration for an in-hospital opioid overdose related to prescribed opioids.

Seaman EL, Levy MJ, Lee Jenkins J, Godar CC, Seaman KG.
Prehosp Disaster Med. 2014 Aug 4:1-5. [Epub ahead of print]
Comment: Younger adolescents use prescription drugs, older adolescents use illicit drugs.

Crocker-Buque T, Lovitt C.
Lancet. 2014 Jul 26;384(9940):308. doi: 10.1016/S0140-6736(14)61240-X. No abstract available.
Comment: A letter calling for lay naloxone in the UK.

Knopf A.
Behav Healthc. 2014 May-Jun;34(3):48-9. No abstract available.
Comment: Unable to access.

Akce M, Suneja A, Genord C, Singal B, Hopper JA.
J Opioid Manag. 2014 Sep-Oct;10(5):337-44. doi: 10.5055/jom.2014.0223.
Comment: Can’t access full article. An educational intervention among hospital residents had no impact on pain. Naloxone use was an outcome but is not reported in the abstract.

Pichot C, Petitjeans F, Ghignone M, Quintin L.
Anaesthesiol Intensive Ther. 2014 Oct 27. doi: 10.5603/AIT.a2014.0053. [Epub ahead of print]
Comment: Interesting successful case report of non-invasive ventilation in an opioid overdose with severe respiratory failure.

Traul KA, Romero JB, Brayton C, DeTolla L, Forbes-McBean N, Halquist MS, Karnes HT, Sarabia-Estrada R, Tomlinson MJ, Tyler BM, Ye X, Zadnik P, Guarnieri M.
Lab Anim. 2014 Oct 10. pii: 0023677214554216. [Epub ahead of print]
Comment: Can’t access full article. The abstract is confusing to me, but it appears to involve efforts to improve analgesia for lab mice through use of buprenorphine. Unlike human studies, investigators here conducted intentional overdoses.

Berger FH, Nieboer KH, Goh GS, Pinto A, Scaglione M.
Radiol Med. 2014 Oct 10. [Epub ahead of print]
Comment: Lots of badness can result from this.

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