PubMed Update December 2012 - January 2013

This is a really exciting time for research into overdose in general and naloxone in particular. 15 papers this time.

1. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.

Walley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A.

BMJ. 2013 Jan 30;346:f174. doi: 10.1136/bmj.f174.

Comments: A long-awaited paper for which the authors deserve high praise, as they have produced the first real evidence of naloxone effectiveness and arguably the most important contribution to naloxone literature to-date. Although not randomized, the interrupted time series analysis is respectable and the results are impressive.

2. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal.

Coffin PO, Sullivan SD.

Ann Intern Med. 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.

Comments: I’ve wanted to write this paper for about a decade, when I thought about cost-effectiveness as three to four calculations on the back of a napkin, rather than years of work and RAM-straining matrices. There’s a long way to go with overdose research that will certainly contribute to future iterations of the model. In the meantime, this is probably a fair, if quite conservative, initial estimate. There is one sensitivity analysis – in which naloxone results in behavior change such that overdose risk is lower – which I suspect may be closer to the actual truth.

3. Naloxone for heroin overdose reversal.

Ann Intern Med. 2013 Jan 1;158(1):I-30. doi: 10.7326/0003-4819-158-1-201301010-00001. No abstract available.

Comments: An excellent editorial from our colleagues at NIDA and the FDA.

4. Prescription opioid use among addictions treatment patients: Nonmedical use for pain relief vs. other forms of nonmedical use.

Bohnert AS, Eisenberg A, Whiteside L, Price A, McCabe SE, Ilgen MA.

Addict Behav. 2012 Nov 23;38(3):1776-1781. doi: 10.1016/j.addbeh.2012.11.005. [Epub ahead of print]

Comments: Survey of prescription opioid use among treatment program patients. Use for reasons other than pain relief was associated with overdose as well as use of several other agents that increase the risk of overdose.

5. Opioid-induced respiratory depression in paediatrics: a review of case reports.

Niesters M, Overdyk F, Smith T, Aarts L, Dahan A.

Br J Anaesth. 2012 Dec 17. [Epub ahead of print]

Comments: Very intriguing review of opioid overdose cases among children, identifying three issues associated with respiratory depression: renal dysfunction, CYP2D6 polymorphism resulting in rapid accumulation of morphine as a codeine metabolite, and obstructive sleep apnea.

6. Buprenorphine prescribing practices and exposures reported to a poison center - utah, 2002-2011.

Centers for Disease Control and Prevention (CDC).

MMWR Morb Mortal Wkly Rep. 2012 Dec 14;61:997-1001.

Comments:

7. Gender and strain contributions to the variability of buprenorphine-related respiratory toxicity in mice.

Alhaddad H, Cisternino S, Saubamea B, Schlatter J, Chiadmi F, Risède P, Smirnova M, Cochois-Guégan V, Tournier N, Baud FJ, Mégarbane B.

Toxicology. 2013 Jan 29. doi:pii: S0300-483X(13)00018-8. 10.1016/j.tox.2013.01.013. [Epub ahead of print]

Comments: An effort to identify biologic mechanisms for gender variability to buprenorphine respiratory depression.

8. Fentanyl-associated Fatalities Among Illicit Drug Users in Wayne County, Michigan (July 2005-May 2006).

Algren DA, Monteilh CP, Punja M, Schier JG, Belson M, Hepler BR, Schmidt CJ, Miller CE, Patel M, Paulozzi LJ, Straetemans M, Rubin C.

J Med Toxicol. 2013 Jan 29. [Epub ahead of print]

Comments: An analysis from the fentanyl-laced heroin overdose fatality epidemic that struck the eastern United States from 2005-2007. This epidemic was substantial and deserves mention in any modern history of overdose in North America as it led to the active engagement of several federal agencies in addressing overdose.

9. Prescription opioid mortality trends in New York City, 1990-2006: Examining the emergence of an epidemic.

Cerdá M, Ransome Y, Keyes KM, Koenen KC, Tracy M, Tardiff KJ, Vlahov D, Galea S.

Drug Alcohol Depend. 2013 Jan 25. doi:pii: S0376-8716(13)00003-3. 10.1016/j.drugalcdep.2012.12.027. [Epub ahead of print]

Comments: Interesting analysis of demographic characteristics among opioid overdose decedents in New York City as the epidemic of prescription opioid overdose emerged (largely among Caucasians).

10. Diversity in causes and characteristics of drug-induced deaths in an urban setting.

Gjersing L, Jonassen KV, Biong S, Ravndal E, Waal H, Bramness JG, Clausen T.

Scand J Public Health. 2013 Jan 9. [Epub ahead of print]

Comments: Basic and important epidemiology of drug-related deaths in Oslo. Mostly opioids, lots of contact with social services prior to death.

11. National trends in pharmaceutical opioid related overdose deaths compared to other substance related overdose deaths: 1999-2009.

Calcaterra S, Glanz J, Binswanger IA.

Drug Alcohol Depend. 2013 Jan 4. doi:pii: S0376-8716(12)00459-0. 10.1016/j.drugalcdep.2012.11.018. [Epub ahead of print]

Comments: Nice analysis of WONDER data on opioid overdose death, comparing heroin to prescription opioids. As we know, the current epidemic is opioid analgesics, although there has been a more recent increase in heroin deaths – likely due to the transition that often occurs from opioid analgesics to heroin.

12. Buprenorphine prescribing practices and exposures reported to a poison center--Utah, 2002-2011.

Centers for Disease Control and Prevention (CDC).

MMWR Morb Mortal Wkly Rep. 2012 Dec 14;61(49):997-1001.

Comments: Useful analysis of buprenorphine toxicity events in the setting of increased buprenorphine prescription. The rate of toxic events has actually decreased (from 0.27 to 0.008 per patient prescribed buprenorphine).

13. Methadone toxicity and possible induction and enhanced elimination in a premature neonate.

George M, Kitzmiller JP, Ewald MB, O'Donell KA, Becter ML, Salhanick S.

J Med Toxicol. 2012 Dec;8(4):432-5. doi: 10.1007/s13181-012-0249-8.

Comments: Case report of a massive methadone overdose in a neonate. I can’t access so don’t know if it was iatrogenic.

14. Improvement in the detection of adverse drug events by the use of electronic health and prescription records: An evaluation of two trigger tools.

Nwulu U, Nirantharakumar K, Odesanya R, McDowell SE, Coleman JJ.

Eur J Clin Pharmacol. 2013 Feb;69(2):255-9. doi: 10.1007/s00228-012-1327-1. Epub 2012 Jun 17.

Comments: An intriguing look at electronic record “triggers” to identify adverse events. Administration of naloxone had a positive-predictive value of 91% for opioid overmedication. This is a secondary care setting, not an emergency setting. In an emergency or field setting, such a trigger may still have a high positive predictive value, but the negative predictive value is likely inadequate to justify its use for out-of-hospital overdose detection.

15. Patternsof prescription drug misuse among young injection drugusers.

Lankenau SE, Teti M, Silva K, Bloom JJ, Harocopos A, Treese M.

J Urban Health. 2012 Dec;89(6):1004-16. doi: 10.1007/s11524-012-9691-9.

Comments: Interesting qualitative analysis of prescription opioid use among young injectors.