PubMed Update March - May 2015

Three months. 46 papers. I’m already a month behind.

1) Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

Dahlem CH, Horstman MJ, Williams BC.

J Am Assoc Nurse Pract. 2015 Mar 26. doi: 10.1002/2327-6924.12249. [Epub ahead of print]

Comments: Naloxone programs have been providing kits to settings where homeless people receive services for many years. This is a description of a program at a homeless health clinic.

2) Quantification of morphine, morphine 6-glucuronide, buprenorphine, and the enantiomers of methadone by enantioselective mass spectrometric chromatography in whole blood.

Christoffersen DJ, Brasch-Andersen C, Thomsen JL, Worm-Leonhard M, Damkier P, Brøsen K.

Forensic Sci Med Pathol. 2015 Jun;11(2):193-201. doi: 10.1007/s12024-015-9673-9. Epub 2015 Mar 24.

Comments: It’s been awhile since we had a forensics paper here. I think this is a novel method of identifying enantiomers.

3) A Comparison of Liver Disease Mortality With HIV and Overdose Mortality Among Georgia Prisoners and Releasees: A 2-Decade Cohort Study of Prisoners Incarcerated in 1991.

Spaulding AC, Sharma A, Messina LC, Zlotorzynska M, Miller L, Binswanger IA.

Am J Public Health. 2015 May;105(5):e51-7. doi: 10.2105/AJPH.2014.302546. Epub 2015 Mar 19.

Comments: Stunningly low rate of drug overdose mortality in this cohort of prisoners in Georgia. This is one of the first times I’ve seen a paper on opioid overdose find radically different results in a different setting. I can’t access for details.

4) A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for Translating Community Programming Into Clinical Practice.

Mueller SR, Walley AY, Calcaterra SL, Glanz JM, Binswanger IA.

Subst Abus. 2015 Mar 16:1-14. [Epub ahead of print]

Comments: A review toward the end of using community distribution data to build clinical care naloxone prescription.

5) Long-term course of opioid addiction.

Hser YI, Evans E, Grella C, Ling W, Anglin D.

Harv Rev Psychiatry. 2015 Mar-Apr;23(2):76-89. doi: 10.1097/HRP.0000000000000052.

Comments: This is a systematic review of long-term studies of opioid users. Among many fascinating data reported, the length of time not using a drug of choice increases the likelihood of continuing to not use that drug. This seems obvious to many, but I don’t believe it’s been documented before. Good read for anyone looking to understand some of the longitudinal outcome data.

6) Medication-assisted treatment of opioid use disorder: review of the evidence and future directions.

Connery HS.

Harv Rev Psychiatry. 2015 Mar-Apr;23(2):63-75. doi: 10.1097/HRP.0000000000000075.

Comments: Nice review of treatment options for opioids. Strong evidence for methadone and buprenorphine. Weak evidence of naltrexone therapies – with oral increasing mortality and early but favorable evidence for injectable naltrexone.

7) The impact of chronic pain on opioid addiction treatment: a systematic review protocol.

Dennis BB, Bawor M, Paul J, Varenbut M, Daiter J, Plater C, Pare G, Marsh DC, Worster A, Desai D, Thabane L, Samaan Z.

Syst Rev. 2015 Apr 16;4(1):49. doi: 10.1186/s13643-015-0042-2.

Comments: A paper describing a planned paper. Hmm.

8) Acute fatal posthypoxic leukoencephalopathy following benzodiazepine overdose: a case report and review of the literature.

Aljarallah S, Al-Hussain F.

BMC Neurol. 2015 Apr 30;15(1):69. doi: 10.1186/s12883-015-0320-6.

Comments: Usually we see this after opioid overdose. Interesting.

9) Functional mu opioid receptor polymorphism (OPRM1 A¹¹⁸ G) associated with heroinuse outcomes in Caucasian males: A pilot study.

Woodcock EA, Lundahl LH, Burmeister M, Greenwald MK.

Am J Addict. 2015 Apr 24. doi: 10.1111/ajad.12187. [Epub ahead of print]

Comments: The 118G allele was once associated with better responsiveness to naltrexone for alcohol dependence. Interesting now to see it associated with more troubling heroin use patterns. Can’t access full article for details.

10) Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery.

Edwards ET, Edwards ES, Davis E, Mulcare M, Wiklund M, Kelley G.

Pain Ther. 2015 Apr 25. [Epub ahead of print]

Comments: The naloxone autoinjector is easier to use than the jerry-rigged intranasal device.

11) Disparity in Naloxone Administration by Emergency Medical Service Providers and the Burden of Drug Overdose in US Rural Communities.

Faul M, Dailey MW, Sugerman DE, Sasser SM, Levy B, Paulozzi LJ.

Am J Public Health. 2015 Apr 23:e1-e7. [Epub ahead of print]

Comments: Basic life support-trained EMTs generally don’t administer naloxone – and they deal with most overdoses in rural areas.

12) HIV prevention and treatment strategies can help address the overdose crisis.

Walley AY.

Prev Med. 2015 Apr 18. pii: S0091-7435(15)00109-7. doi: 10.1016/j.ypmed.2015.04.004. [Epub ahead of print]

Comments: Yup.

13) Rates of Opioid Dispensing and Overdose After Introduction of Abuse-Deterrent Extended-Release Oxycodone and Withdrawal of Propoxyphene.

Larochelle MR, Zhang F, Ross-Degnan D, Wharam JF.

JAMA Intern Med. 2015 Apr 20. doi: 10.1001/jamainternmed.2015.0914. [Epub ahead of print]

Comments: Being that I’m not a pharmaceutical company, my interest is in the welfare of people regardless of what they are putting into their bodies. Oxycodone, morphine, methadone, hydromorphone, oxymorphone, or heroin. The clear uptick in heroin use and heroin (as well as overall opioid) overdose mortality began when we started using injection-deterrent formulations (the formulations only address injection – not other potentially problematic use patterns).

14) Paramedic supplied "take home" naloxone: a randomised feasibility study.

Moore C, Lloyd G, Oretti R, Russell I, Snooks H.

Emerg Med J. 2015 May;32(5):421-2. doi: 10.1136/emermed-2015-204877.3.

Comments: Great idea. I believe the naloxone program in Inverness, Scotland, first inspired this idea by following up with overdose patients in the month after a paramedic reversal.

15) Implementing buprenorphine in addiction treatment: payer and provider perspectives in Ohio.

Molfenter T, Sherbeck C, Zehner M, Quanbeck A, McCarty D, Kim JS, Starr S.

Subst Abuse Treat Prev Policy. 2015 Mar 28;10(1):13. doi: 10.1186/s13011-015-0009-2.

Comments: Unfortunately there are multiple barriers. Physician availability, reimbursement, etc.

16) Prescription opioid abuse: Problems and responses.

Compton WM, Boyle M, Wargo E.

Prev Med. 2015 Apr 11. pii: S0091-7435(15)00103-6. doi: 10.1016/j.ypmed.2015.04.003. [Epub ahead of print]

Comments: Review of prescription opioid use problems and responses, including agonist treatment and naloxone.

17) Reducing the harm of opioid overdose with the safe use of naloxone : a pharmacologic review.

Kim HK, Nelson LS.

Expert Opin Drug Saf. 2015 Apr 12:1-10. [Epub ahead of print]

Comments: Naloxone is safe. Don’t use massive doses or people go into severe withdrawal. Lay programs generally use 0.4mg intramuscular. The intranasal 2mg dose has some variability, but is probably equivalent to 0.3-0.4mg intramuscular for many people.

18) Lessons learned from the expansion of naloxone access in Massachusetts and North Carolina.

Davis CS, Walley AY, Bridger CM.

J Law Med Ethics. 2015 Mar;43 Suppl 1:19-22. doi: 10.1111/jlme.12208.

Comments: Laws aren’t enough. Providers need education and the formulations are problematic.

19) Naloxone's basic benefit. Why the overdose-reversal drug is worth expanding beyond just ALS providers.

Furlano E.

EMS World. 2014 Oct;43(10):28-30, 32-4. No abstract available.

Comments: Basic life support-trained providers should have naloxone.

20) Predictors of participant engagement and naloxone utilization in a community-based naloxone distribution program.

Rowe C, Santos GM, Vittinghoff E, Wheeler E, Davidson P, Coffin PO.

Addiction. 2015 Apr 27. doi: 10.1111/add.12961. [Epub ahead of print]

Comments: Among recipients of take-home naloxone, those most likely to report using it to reverse an overdose are active drug users themselves. This emphasizes the top priority of getting naloxone into the hands of drug users.

21) Causes of death in a cohort treated for opioid dependence between 1985 and 2005.

Degenhardt L, Larney S, Randall D, Burns L, Hall W.

Addiction. 2014 Jan;109(1):90-9. doi: 10.1111/add.12337. Epub 2013 Oct 9.

Comments: Another stellar longitudinal paper. Overdose is of course the driver of mortality, but major organ disease-related mortality becomes a close competitor after age 45. Suicide is common, accounting for 10-15% of mortality. Another must read.

26) Lethality of Opioid Overdose in a Community Cohort of Young Heroin Users.

Espelt A, Barrio G, Álamo-Junquera D, Bravo MJ, Sarasa-Renedo A, Vallejo F, Molist G, Brugal MT.

Eur Addict Res. 2015 May 28;21(6):300-306. [Epub ahead of print]

Comments: Authors of this study from Madrid and Barcelona come to a similar conclusion as some older papers on heroin overdose – that approximately 4% are fatal. Of note, these are young heroin users, which implies events that are more likely to be witnessed. Mortality is likely higher among older users, who are more likely to be socially isolated, leading to an overall estimated mortality of approximately 10%.

27) Dynamic model of nonmedical opioid use trajectories and potential policy interventions.

Wakeland W, Nielsen A, Geissert P.

Am J Drug Alcohol Abuse. 2015 May 18:1-11. [Epub ahead of print]

Comments: I can’t access. I believe this was also presented as a poster at CPDD this year.

28) Fentanyls: Are we missing the signs? Highly potent and on the rise in Europe.

Mounteney J, Giraudon I, Denissov G, Griffiths P.

Int J Drug Policy. 2015 Apr 17. pii: S0955-3959(15)00097-3. doi: 10.1016/j.drugpo.2015.04.003. [Epub ahead of print]

Comments: Ugh. Fentanyl is scary because it is dosed in micrograms – which is really hard to do safely, especially in an illicit market.

29) Trends and characteristics of heroin overdoses in Wisconsin, 2003-2012.

Meiman J, Tomasallo C, Paulozzi L.

Drug Alcohol Depend. 2015 Jul 1;152:177-184. doi: 10.1016/j.drugalcdep.2015.04.002. Epub 2015 Apr 18.

Comments: Most states/localities saw a stark inflection point in heroin overdose events after 2010; that inflection seems less pronounced in this study.

30) 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 Mar-Apr;28(2):146-54. doi: 10.1016/j.gaceta.2013.10.012. Epub 2014 Jan 10.

Comments: Study out of Barcelona looking at predictors of less overdose prevention knowledge.

31) Griffith Edwards, the Addiction Research Unit and research on the criminal justice system.

Farrell M, Marsden J, Strang J.

Addiction. 2015 Jul;110 Suppl 2:54-8. doi: 10.1111/add.12910.

Comments: Review of Griffith Edwards’s work in the 1960s and 1970s addressing the transition from correctional to community settings. Important prelude to what’s been done over the past 20 years and what we hope will be achieved in the years to come.

32) Death matters: understanding heroin/opiate overdose risk and testing potential to prevent deaths.

Strang J.

Addiction. 2015 Jul;110 Suppl 2:27-35. doi: 10.1111/add.12904.

Comments: Let’s move on to implementation science?

33) Reversal of overdose on fentanyl being illicitly sold as heroin with naloxone nasal spray: A case report.

Fareed A, Buchanan-Cummings AM, Crampton K, Grant A, Drexler K.

Am J Addict. 2015 Jun 3. doi: 10.1111/ajad.12230. [Epub ahead of print]

Comments: Report out of the Veterans’ Administration, which is admirably taking on overdose prevention.

34) Methadone continuation versus forced withdrawal on incarceration in a combined US prison and jail: a randomised, open-label trial.

Rich JD, McKenzie M, Larney S, Wong JB, Tran L, Clarke J, Noska A, Reddy M, Zaller N.

Lancet. 2015 May 28. pii: S0140-6736(14)62338-2. doi: 10.1016/S0140-6736(14)62338-2. [Epub ahead of print]

Comments: With respect to the excellent investigators, are we really living in a world where this kind of study is either needed or permitted? “Usual care” as forced withdrawal of a life-saving medication is … leaving me speechless.

35) The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales.

Marteau D, McDonald R, Patel K.

BMJ Open. 2015 May 29;5(5):e007629. doi: 10.1136/bmjopen-2015-007629.

Comments: Buprenorphine is six times safer than methadone with regard to risk of drug overdose death. This is, of course, observational, and does not take into account differing characteristics of opioid dependent persons that may drive them to one treatment or another. Methadone is an invaluable tool for a large proportion of individuals in need.

36) Distribution of naloxone for overdose prevention to chronic pain patients.

Coe MA, Walsh SL.

Prev Med. 2015 May 27. pii: S0091-7435(15)00175-9. doi: 10.1016/j.ypmed.2015.05.016. [Epub ahead of print]

Comments: Commentary on the concept of co-prescribing naloxone to pain patients on opioids.

37) Responding to illicit drug use in family practice.

Robertson JR, Robertson AR.

Curr Opin Psychiatry. 2015 Jul;28(4):286-91. doi: 10.1097/YCO.0000000000000174.

Comments: Review of substance use issues affecting family practice providers.

38) Reducing opioid analgesic deaths in america: what health providers can do.

Agarin T, Trescot AM, Agarin A, Lesanics D, Decastro C.

Pain Physician. 2015 May-Jun;18(3):E307-22.

Comments: Nobody knows yet.

39) Opioid education and nasal naloxone rescue kits in the emergency department.

Dwyer K, Walley AY, Langlois BK, Mitchell PM, Nelson KP, Cromwell J, Bernstein E.

West J Emerg Med. 2015 May;16(3):381-284. doi: 10.5811/westjem.2015.2.24909. Epub 2015 Apr 1.

Comments: Nice initial observational study of naloxone from emergency departments. Low response rate.

40) Buprenorphine treatment for narcotic addiction: not without risks.

Sansone RA, Sansone LA.

Innov Clin Neurosci. 2015 Mar-Apr;12(3-4):32-6.

Comments: Buprenorphine is hard to overdose on in the absence of sedatives such as benzodiazepines. There is diversion, but largely to individuals already dependent on opioids who are seeking to stave off withdrawal or often self-detox. It’s about time we moved on to more sophisticated diversion research, which differentiated the type of prescription drug diversion most people have engaged in – like sharing your leftover amoxicillin or hydrocortisone cream – and more dangerous forms.

41) Coherent long-term treatment approaches-superior in the treatment of opioid dependence.

Clausen T.

Addiction. 2015 Jun;110(6):1006-7. doi: 10.1111/add.12922. No abstract available.

Comments: Nice commentary on the role and importance of agonist medications in treating opioid use disorder.

42) Economic impact of a novel naloxone autoinjector on third-party payers.

Weiss RC, Bazalo GR, Thomson H, Edwards E.

Manag Care. 2015 Feb;24(2):41-8.

Comments: I can no longer claim to have the only mathematical model of opioid overdose! This is a model from the payer perspective. Funded and co-authored by the manufacturers of the naloxone autoinjector.

43) Take home naloxone for Ireland.

Bury G.

Ir Med J. 2015 Mar;108(3):70. No abstract available.

Comments: can’t access.

44) [The message from heroin overdoses].

Pap Á, Hegedűs K.

Orv Hetil. 2015 Mar 1;156(9):352-7. doi: 10.1556/OH.2015.30091. Review. Hungarian.

Comments: Review of overdose / prevention in Hungary.

45) Out-of-hospital mortality among patients receiving methadone for noncancer pain.

Ray WA, Chung CP, Murray KT, Cooper WO, Hall K, Stein CM.

JAMA Intern Med. 2015 Mar;175(3):420-7. doi: 10.1001/jamainternmed.2014.6294.

Comments: More on the potential hazards of methadone when used for chronic noncancer pain. I remain mixed on these data. There is a mechanistic argument that methadone is more risky, but at the same time it is generally prescribed to lower income patients with less optimal insurance that doesn’t cover the more expensive long-acting opioid formulations. It’s hard to convincingly disentangle the risks of the population from the risks of the drug.

46) Increased densities of nitric oxide synthase expressing neurons in the temporal cortex and the hypothalamic paraventricular nucleus of polytoxicomanic heroin overdose victims: possible implications for heroin neurotoxicity.

Bernstein HG, Trübner K, Krebs P, Dobrowolny H, Bielau H, Steiner J, Bogerts B.

Acta Histochem. 2014 Jan;116(1):182-90. doi: 10.1016/j.acthis.2013.07.006. Epub 2013 Aug 13.

Comments: Interesting. Not sure what to make of this one.