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 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 May/June 2014

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

1) Naloxone therapy in opioid overdose patients: intranasal or intravenous? A randomized clinical trial.

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.

2) Brugada Phenocopy in Concomitant Ethanol and Heroin Overdose.

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.

3) A systematic review of community opioid overdose prevention and naloxone distribution programs.

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.

4) Intravenous methadone application as a serious risk factor for an overdose death: methadone-related fatalities in Hamburg from 2007 to 2012.

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.

5) Abnormal intracellular calcium homeostasis associated with vulnerability in the nerve cells from heroin-dependent rat.

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?

6) Source of prescription drugs used nonmedically in rural and urban populations.

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.

PubMed Update March/April 2014

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

1) Overdose rescues by trained and untrained participants and change in opioid use among substance-using participants in overdose education and naloxone distribution programs: a retrospective cohort study.

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.

2) Easy-to-use overdose antidote earns fast-track approval.

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.

4) Paramedic-supplied 'Take Home' Naloxone: protocol for cluster randomised feasibility study.

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.

PubMed Update February 2014

8 papers today, essentially about naloxone and heroin.

1) Risk of anaphylaxis in opioid dependent persons: effects of heroin versus substitution substance.

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.

2) Effective use of naloxone among people who inject drugs in Kyrgyzstan and Tajikistan using pharmacy- and community-based distribution approaches.

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.

3) Norway tries naloxone in spray form to prevent deaths from drug overdose.

Hansen A.

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

Comment: Naloxone in Norway.

4) Naloxone induces endoplasmic reticulum stress in PC12 cells.

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.

5) Naloxone for Opioid Overdose Prevention: Pharmacists' Role in Community-Based Practice Settings.

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.

6) A case of heroin induced sensorineural hearing loss.

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.

7) Overdose prevention in injecting opioid users: The role of substance abuse treatment and training programs.

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.

8) Commentary on Kerr et al. (2013): advertising high-potency heroin.

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.

PubMed Update January 2014

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

1) Characterization of opioid overdose and response in a high-risk community corrections sample: A preliminary study.

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.

2) Opioids Compared to Placebo or Other Treatments for Chronic Low Back Pain: An Update of the Cochrane Review.

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.

3) Opioid overdose with gluteal compartment syndrome and acute peripheral neuropathy.

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.

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.