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.

7) Physician and Nonphysician Health-care Provider Perspectives on Resuscitation of Suspected Drug-related Out-of-Hospital Cardiac Arrest.

Koller AC, Salcido DD, Menegazzi JJ.

Prehosp Emerg Care. 2014 May 15. [Epub ahead of print]

PMID: 24831102 [PubMed - as supplied by publisher]

Comments: A survey mostly of physicians and paramedics showing that healthcare providers manage cardiac arrest differently if it is from drug overdose versus a different etiology. This sounds quite reasonable, actually, since etiology-specific management is encouraged particularly for cardiac arrests due to “pulseless electrical activity” (that is, while we shock most arrhythmias during cardiac arrest, if there is no arrhythmia to shock we generally don’t shock and do a bunch of other things – one of those things is to guess what may be causing the cardiac arrest and administering medications to try to counteract that problem).

8) Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest.

Koller AC, Salcido DD, Callaway CW, Menegazzi JJ.

Resuscitation. 2014 Jun 26. pii: S0300-9572(14)00581-4. doi: 10.1016/j.resuscitation.2014.05.036. [Epub ahead of print]

PMID: 24973558 [PubMed - as supplied by publisher]

Comments: Overdose-related cardiac arrests are more likely to survive. They are also more likely to be younger and to receive different immediate care. These findings are consistent with the above opinion survey.

9) Two cases of intranasal naloxone self-administration in opioid overdose.

Green TC, Ray M, Bowman SE, McKenzie M, Rich JD.

Subst Abus. 2014;35(2):129-32. doi: 10.1080/08897077.2013.825691.

PMID: 24821348 [PubMed - in process]

Comments: There have been rare cases of naloxone self-administration in the setting of lay naloxone programs. This obviously should not be the goal, as most people in need of naloxone will be unconscious by the time they need it.

10) The Correlation Between Prolonged Corrected QT Interval with the Frequency of Respiratory Arrest, Endotracheal Intubation, and Mortality in Acute Methadone Overdose.

Farsi D, Mirafzal A, Hassanian-Moghaddam H, Azizi Z, Jamshidnejad N, Zehtabchi S.

Cardiovasc Toxicol. 2014 May 9. [Epub ahead of print]

PMID: 24811951 [PubMed - as supplied by publisher]

Comments: Prolonged QT interval in methadone overdose patients predicts respiratory arrest, need for intubation, and death.

11) Timing of income assistance payment and overdose patterns at a Canadian supervised injection facility.

Zlotorzynska M, Milloy MJ, Richardson L, Nguyen P, Montaner JS, Wood E, Kerr T.

Int J Drug Policy. 2014 Apr 4. pii: S0955-3959(14)00075-9. doi: 10.1016/j.drugpo.2014.03.014. [Epub ahead of print]

PMID: 24795288 [PubMed - as supplied by publisher]

Comments: People overdose when they get their monthly assistance checks. There are some programs that provide “money management” services, doling out participants monthly incomes over time – these may help to reduce binge drug use and related overdose events.

12) Intranasal naloxone for treatment of opioid overdose.

[No authors listed]

Med Lett Drugs Ther. 2014 Mar 17;56(1438):21-2. No abstract available.

PMID: 24662159 [PubMed - indexed for MEDLINE]

Comments: Unable to access.

13) Clinician beliefs and attitudes about buprenorphine/naloxone diversion.

Schuman-Olivier Z, Connery H, Griffin ML, Wyatt SA, Wartenberg AA, Borodovsky J, Renner JA Jr, Weiss RD.

Am J Addict. 2013 Nov-Dec;22(6):574-80. doi: 10.1111/j.1521-0391.2013.12024.x. Epub 2013 Apr 11.

PMID: 24131165 [PubMed - indexed for MEDLINE]

Comments: About 40% of providers think buprenorphine/naloxone diversion is a problem. I’m unable to access the article, but the abstract says providers who have experience using the medication think diversion is a result of limited access to the medication. I concur with that opinion … but I am also one of those providers.

14) Trends in quetiapine use and non-fatal quetiapine-related ambulance attendances.

Heilbronn C, Lloyd B, McElwee P, Eade A, Lubman DI.

Drug Alcohol Rev. 2013 Jul;32(4):405-11. doi: 10.1111/dar.12028. Epub 2013 Jan 27.

PMID: 23350582 [PubMed - indexed for MEDLINE]

Comments: Quetiapine is a sedating anti-psychotic that is often favored by those with opioid use disorders.

15) SMOKE IT! Promoting a change of opiate consumption pattern - from injecting to inhaling.

Stöver HJ, Schäffer D.

Harm Reduct J. 2014 Jun 27;11(1):18. [Epub ahead of print]

PMID: 24973031 [PubMed - as supplied by publisher] Free Article

Comments: Efforts to transition users from injection to smoking heroin in Europe seem to be growing in popularity with increasing evidence of effectiveness. Of note, one major limitation is the pH of different formulations of heroin. Heroin in the United States, for example, may be too acidic for most users to transition to smoking (which generally requires a “basic” acid/base balance to allow the drug to be vaporized without burning).

15) The Relationship between US Heroin Market Dynamics and Heroin-related Overdose, 1992-2008.

Unick G, Rosenblum D, Mars S, Ciccarone D.

Addiction. 2014 Jun 17. doi: 10.1111/add.12664. [Epub ahead of print]

PMID: 24938727 [PubMed - as supplied by publisher]

Comments: Purity of heroin has some association with overdose and there seems to be a difference in the geographic source of the heroin in terms of overdose risk.

16) Pharmacies as providers of expanded health services for people who inject drugs: a review of laws, policies, and barriers in six countries.

Hammett TM, Phan S, Gaggin J, Case P, Zaller N, Lutnick A, Kral AH, Fedorova EV, Heimer R, Small W, Pollini R, Beletsky L, Latkin C, Des Jarlais DC.

BMC Health Serv Res. 2014 Jun 17;14:261. doi: 10.1186/1472-6963-14-261.

PMID: 24938376 [PubMed - in process] Free PMC Article

Comments: Notwithstanding many efforts to expand the role of pharmacists in community health, the legal and social stigma surrounding injection drug use seriously limits the implementation and impact of these policy and programmatic efforts. I can only imagine this is going to get worse before it gets better, as pharmacists are increasingly being held to higher standards of evaluating the appropriateness of prescriptions for patients.

17) Risk Factors for Serious Prescription Opioid-Related Toxicity or Overdose among Veterans Health Administration Patients.

Zedler B, Xie L, Wang L, Joyce A, Vick C, Kariburyo F, Rajan P, Baser O, Murrelle L.

Pain Med. 2014 Jun 14. doi: 10.1111/pme.12480. [Epub ahead of print]

PMID: 24931395 [PubMed - as supplied by publisher]

Comments: Dose, dependence, prior overdose, liver disease and use of long-acting opioids were the primary predictors of overdose.

18) Use of a Medically Supervised Injection Facility Among Street Youth.

Hadland SE, DeBeck K, Kerr T, Nguyen P, Simo A, Montaner JS, Wood E.

J Adolesc Health. 2014 Jun 9. pii: S1054-139X(14)00191-8. doi: 10.1016/j.jadohealth.2014.04.013. [Epub ahead of print]

PMID: 24925493 [PubMed - as supplied by publisher]

Comments: INSITE serves the population of extremely high-risk, young injectors.

19) Expanded Access to Naloxone Among Firefighters, Police Officers, and Emergency Medical Technicians in Massachusetts.

Davis CS, Ruiz S, Glynn P, Picariello G, Walley AY.

Am J Public Health. 2014 Jun 12:e1-e3. [Epub ahead of print]

PMID: 24922133 [PubMed - as supplied by publisher]

Comments: This policy review is, I believe, the first publication in the scientific literature on the relatively new phenomenon of providing non-ACLS trained first responders with naloxone.

20) Clinical and radiological findings in methadone-induced delayed leukoencephalopathy.

Bileviciute-Ljungar I, Häglund V, Carlsson J, von Heijne A.

J Rehabil Med. 2014 Jun 4. doi: 10.2340/16501977-1820. [Epub ahead of print]

PMID: 24909124 [PubMed - as supplied by publisher]

Comments: Methadone overdose has resulted in a delayed leukoencephalopathy – basically a sickness in the white matter of the brain. This can result in substantial and lifelong dysfunction. There is some improvement, but it can require a fair amount of medication and still have at least moderate neurologic dysfunction that may never resolve. If you know someone who had a methadone overdose and they don’t seem to be getting better, this should be considered.

21) Reversing tragedy. Proposed legislation will increase access to an antidote to opioid overdose.

Mettner J.

Minn Med. 2014 Apr;97(4):10-1. No abstract available.

PMID: 24868924 [PubMed - indexed for MEDLINE]

Comments: Can’t access.

22) Heroin: life, death, and politics.

Jacobson J.

Am J Nurs. 2014 May;114(5):22-3. doi: 10.1097/01.NAJ.0000446774.91899.b5. No abstract available.

PMID: 24759473 [PubMed - indexed for MEDLINE]

Comments: A news article on naloxone.

23) High-risk use by patients prescribed opioids for pain and its role in overdose deaths.

Gwira Baumblatt JA, Wiedeman C, Dunn JR, Schaffner W, Paulozzi LJ, Jones TF.

JAMA Intern Med. 2014 May;174(5):796-801.

PMID: 24589873 [PubMed - indexed for MEDLINE]

Comments: Opioid overdose deaths in Tennessee had, compared to national data, an abundance of what is referred to as “doctor shopping.” Among patients prescribed opioids, 7.6% had >4 prescribers and 2.5% >4 pharmacies. While one should be cautious about overinterpreting the number of prescribers (as perhaps they were urgent care or other affiliated providers filling in for the primary prescriber), most analyses suggest that around 1% of patients fit the pharmacy criteria. These patients were the most likely to die of opioid overdose.

24) Opioid substitution treatment in pretrial prison detention: a case study from Geneva, Switzerland.

Favrod-Coune T, Baroudi M, Casillas A, Rieder JP, Gétaz L, Barro J, Gaspoz JM, Broers B, Wolff H.

Swiss Med Wkly. 2013 Nov 1;143:w13898. doi: 10.4414/smw.2013.13898.

PMID: 24186493 [PubMed - indexed for MEDLINE] Free Article

Comments: In-prison methadone maintenance.

25) Evaluation of metabolite/drug ratios in blood and urine as a tool for confirmation of a reduced tolerance in methadone-related deaths in Denmark.

Nielsen MK, Johansen SS, Linnet K.

Drug Alcohol Depend. 2013 Dec 1;133(2):447-51. doi: 10.1016/j.drugalcdep.2013.07.001. Epub 2013 Jul 25.

PMID: 23891033 [PubMed - indexed for MEDLINE]

Comments: Investigators were unable to establish a methodology that would allow them to distinguish between those who had reduced tolerance and those who did not, among methadone overdose deaths.