PubMed Update October 2015

28 in a month.

1) Clinical Presentation and the Outcome of Therapy in a Cohort of Patients with Methadone Toxicity in Iran.

Eizadi-Mood N, Yaraghi A, Sharifian Z, Feizi A, Hedaiaty M, Sabzghabaee AM.

Mater Sociomed. 2015 Aug;27(4):276-9. doi: 10.5455/msm.2015.27.276-279.

Comments: Some interesting data on methadone toxicity in Iran. Length of stay was 33 hours (median). 90.3% survived. There were several complications. GCS on admission predicted survival. Useful data for economic modeling …

2) Overdose prevention for prisoners in New York: a novel program and collaboration.

Zucker H, Annucci AJ, Stancliff S, Catania H.

Harm Reduct J. 2015 Nov 5;12(1):51. doi: 10.1186/s12954-015-0084-8.

PMID: 26541987 Free Article

Comments: Early report describing the establishment of a prison naloxone program in NY. Some of the most important work happening in this area…

3) Response to "Quality Assessment Errors and Study Misclassification Threaten Systematic Review Validity: Community Opioid Overdose Prevention and Naloxone Distribution Programs Review".

Winstanley EL, Clark A, Wilder CM.

J Addict Med. 2015 Dec;9(6):503-4. doi: 10.1097/ADM.0000000000000160. No abstract available.

Comments: Can’t access. Meh.

4) Quality Assessment Errors and Study Misclassification Threaten Systematic Review Validity: Community Opioid Overdose Prevention and Naloxone Distribution Programs Review: Re: Clark AK, Wilder CM, Winstanley EL. A systematic review of community opioid overdose prevention and naloxone distribution programs. J Addict Med 2014 May-June;8(3): 153-163.

Orkin AM, Bingham K, Buick JE, Klaiman M, Leece P, Kouyoumdjian F.

J Addict Med. 2015 Dec;9(6):502-3. doi: 10.1097/ADM.0000000000000161. No abstract available.

Comments: Also can’t access.

5) Implementation of an inpatient opioid overdose prevention program.

Clark A, Winstanley EL, Martsolf DS, Rosen M.

Addict Behav. 2015 Oct 8;53:141-145. doi: 10.1016/j.addbeh.2015.10.006. [Epub ahead of print] No abstract available.

Comments: Authors report on development of an electronic book on overdose prevention for use in addiction treatment settings.

6) Evaluation of knowledge and confidence following opioid overdose prevention training: A comparison of types of training participants and naloxone administration methods.

Ashrafioun L, Gamble S, Herrmann M, Baciewicz G.

Subst Abus. 2015 Oct 29:0. [Epub ahead of print]

Comments: Those trained in intranasal naloxone were more confident than those trained in injectable. That is odd, as studies suggest that injectable is easier than intranasal.

7) Methadone related deaths compared to all prescription related deaths.

Lev R, Petro S, Lee A, Lee O, Lucas J, Castillo EM, Egnatios J, Vilke GM.

Forensic Sci Int. 2015 Oct 22;257:347-352. doi: 10.1016/j.forsciint.2015.09.021. [Epub ahead of print]

Comments: The lack of data from methadone maintenance programs makes it quite challenging to interpret some of the methadone-related mortality data.

8) Exploring the life-saving potential of naloxone: A systematic review and descriptive meta-analysis of take home naloxone (THN) programmes for opioid users.

McAuley A, Aucott L, Matheson C.

Int J Drug Policy. 2015 Oct 1. pii: S0955-3959(15)00306-0. doi: 10.1016/j.drugpo.2015.09.011. [Epub ahead of print]

Comments: 9% of kits were likely to be used for overdose rescue. That looks like a rather low number, but it’s over a 3-month period. I suspect the annual rate is closer to 20% +/- 5%.

9) Legal changes to increase access to naloxone for opioid overdose reversal in the United States.

Davis CS, Carr D.

Drug Alcohol Depend. 2015 Oct 22. pii: S0376-8716(15)01695-6. doi: 10.1016/j.drugalcdep.2015.10.013. [Epub ahead of print]

Comments: Great paper, title says it all.

10) Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

Jolley CJ, Bell J, Rafferty GF, Moxham J, Strang J.

PLoS One. 2015 Oct 23;10(10):e0140995. doi: 10.1371/journal.pone.0140995. eCollection 2015.

Comments: I like this study. The physiology of “overdose” is totally fascinating and nowhere near as simple as it seems.

11) Hair testing in postmortem diagnosis of substance abuse: An unusual case of slow-release oral morphine abuse in an adolescent.

Baillif-Couniou V, Kintz P, Sastre C, Pok PP, Chèze M, Pépin G, Leonetti G, Pelissier-Alicot AL.

J Forensic Leg Med. 2015 Sep 4;36:172-176. doi: 10.1016/j.jflm.2015.08.014. [Epub ahead of print]

Comments: Morphine overdose in an adolescent in France. It’s news there because they don’t see people dying of prescription opioids like in the U.S.

12) Effects of acute and repeated administration of oxycodone and naloxone-precipitated withdrawal on Intracranial Self-Stimulation (ICSS) in rats.

Wiebelhaus JM, Walentiny DM, Beardsley PM.

J Pharmacol Exp Ther. 2015 Oct 21. pii: jpet.115.228940. [Epub ahead of print]

Comments: Oxycodone works like other opioids.

13) Risk factors associated with benzodiazepine use among people who inject drugs in an urban Canadian setting.

Tucker D, Hayashi K, Milloy MJ, Nolan S, Dong H, Kerr T, Wood E.

Addict Behav. 2015 Oct 9;52:103-107. doi: 10.1016/j.addbeh.2015.10.002. [Epub ahead of print]

Comments: Benzo use is associated with lots of risk factors for negative health outcomes, including blood-borne virus transmission, among drug users.

14) Commentary on Gjersing & Bretteville-Jensen (2015): EMS-treated opioid overdose-an important opportunity for saving lives.

Dailey M.

Addiction. 2015 Nov;110(11):1775-6. doi: 10.1111/add.13093. No abstract available.

Comments: Nice commentary, pointing out the opportunities for intervention among those who contact the medical system with an overdose.

15) Flumazenil, naloxone and the 'coma cocktail'.

Sivilotti ML.

Br J Clin Pharmacol. 2015 Aug 7. doi: 10.1111/bcp.12731. [Epub ahead of print] Review.

Comments: Fascinating differences between benzo and opioid-induced respiratory depression. Benzos cause apnea usually because the upper airway is blocked or collapses – so respiratory support is the need – and the antidote can lead to seizures. Opioids are different and naloxone much safer.

16) Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies.

Cheatle MD, Webster LR.

Pain Med. 2015 Oct;16 Suppl 1:S22-6. doi: 10.1111/pme.12910. Review.

Comments: Opioids might be dangerous with sleep disorders.

17) More than just someone to inject drugs with: Injecting within primary injection partnerships.

Morris MD, Bates A, Andrew E, Hahn J, Page K, Maher L.

Drug Alcohol Depend. 2015 Nov 1;156:275-81. doi: 10.1016/j.drugalcdep.2015.09.025. Epub 2015 Sep 30.

Comments: Injection partnerships can have divergent benefits and risks.

18) A True Antidote.

Berlin J.

Tex Med. 2015 Oct 1;111(10):41-7.

Comments: Naloxone in Texas!

19) The effect of prescription opioid injection on the risk of non-fatal overdose among people who inject drugs.

Lake S, Hayashi K, Buxton J, Milloy MJ, Dong H, Wood E, Montaner J, Kerr T.

Drug Alcohol Depend. 2015 Nov 1;156:297-303. doi: 10.1016/j.drugalcdep.2015.09.026. Epub 2015 Sep 30.

Comments: Interesting analysis – injecting prescription opioids didn’t by itself increase overdose risk. Injecting of both prescription opioids and heroin did, however. So there is probably some protection offered by the known doses and constituents in prescription opioids.

20) Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature.

Martins SS, Sampson L, Cerdá M, Galea S.

Am J Public Health. 2015 Nov;105(11):e29-49. doi: 10.2105/AJPH.2015.302843.

Comments: Nice summary of global data looking at some basic overdose results. Mean/median rate of witnessed overdose in a drug user’s lifetime = 73/70%. Lifetime prevalence of experienced overdose was mean of 45.4% and median of 47%. Population-based overdose mortality rates varied from 0.4-46.6 / 100,000 person years (note, this is population based).

21) An Overdose Antidote Goes Mainstream.

Humphreys K.

Health Aff (Millwood). 2015 Oct 1;34(10):1624-7. doi: 10.1377/hlthaff.2015.0934.

Comments: Review of naloxone based on summer 2015 FDA meeting.

22) Is immunotherapy an opportunity for effective treatment of drug addiction?

Zalewska-Kaszubska J.

Vaccine. 2015 Oct 2. pii: S0264-410X(15)01369-9. doi: 10.1016/j.vaccine.2015.09.079. [Epub ahead of print] Review.

Comments: Really interesting idea – use antibodies against drugs, like cocaine, to manage overdose on those drugs. Excellent.

23) Involvement of Opioid Receptors in the Lipid Rescue of Bupivacaine-Induced Cardiotoxicity.

Partownavid P, Sharma S, Li J, Umar S, Rahman S, Eghbali M.

Anesth Analg. 2015 Aug;121(2):340-7. doi: 10.1213/ANE.0000000000000788.

Comments: Opioid receptors are required for rescuing people from the cardiac toxicity of bupivacaine overdose.

24) New drugs of abuse.

Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E.

Pharmacotherapy. 2015 Feb;35(2):189-97. doi: 10.1002/phar.1522. Epub 2014 Dec 4. Review.

Comments: Desomorphine. Blech.

25) What we know, and don't know, about the impact of state policy and systems-level interventions on prescription drug overdose.

Haegerich TM, Paulozzi LJ, Manns BJ, Jones CM.

Drug Alcohol Depend. 2014 Dec 1;145:34-47. doi: 10.1016/j.drugalcdep.2014.10.001. Epub 2014 Oct 14. Review.

Comments: Not much.

26) Access to harm reduction and HIV-related treatment services inside Indian prisons: experiences of formerly incarcerated injecting drug users.

Chakrapani V, Kamei R, Kipgen H, Kh JK.

Int J Prison Health. 2013;9(2):82-91. doi: 10.1108/17449201311326952.

Comments: Access is … no there.

27) Low Expression of D2R and Wntless Correlates With High Motivation for Heroin.

Tacelosky DM, Alexander DN, Morse M, Hajnal A, Berg A, Levenson R, Grigson PS.

Behav Neurosci. 2015 Oct 26. [Epub ahead of print]

Comments: Holding drug exposure constant, reducing dopamine D2 receptors or that other thing (Wntless) results in more opioid craving.

28) The misuse and abuse of prescription medications: part 1 current trends.

Allread V, Paul S.

MD Advis. 2014 Fall;7(4):12-20. Review.

Comments: Can’t access. Review for New Jersey and rest of US regarding prescription opioids and heroin use.

PubMed Update August 2015

Sixteen in August. Back on schedule (thanks to jetlag).

1) Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies.

Hawk KF, Vaca FE, D'Onofrio G.

Yale J Biol Med. 2015 Sep 3;88(3):235-245. eCollection 2015 Sep. Review.

Comment: Can’t access full article. Appears to be a review of harm reduction strategies for opioid overdose prevention.

2) Prescription Opioid Misuse, Abuse, and Treatment in the United States: An Update.

Brady KT, McCauley JL, Back SE.

Am J Psychiatry. 2015 Sep 4:appiajp201515020262. [Epub ahead of print]

Comment: Appropriately draws attention to the problem now faced in the United States: we are cutting back on opioid prescribing to try to limit further opioid dependence, but effectively abandoning many of the people who are already dependent.

3) Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series.

DeVido J, Connery H, Hill KP.

J Opioid Manag. 2015 Jul-Aug;11(4):363-6. doi: 10.5055/jom.2015.0285.

Comment: Two case reports of sleep-disordered breathing among buprenorphine patients suggesting that buprenorphine may contribute to sleep apnea.

4) Buprenorphine infrequently found in fatal overdose in New York City.

Paone D, Tuazon E, Stajic M, Sampson B, Allen B, Mantha S, Kunins H.

Drug Alcohol Depend. 2015 Aug 15. pii: S0376-8716(15)01598-7. doi: 10.1016/j.drugalcdep.2015.08.007. [Epub ahead of print]

Comment: Actually, none of the decedents tested positive for buprenorphine - very few (2) were found to have positive toxicology for norbuprenorphine, a metabolite demonstrating recent – but not recent enough to be causal – consumption of buprenorphine. This is not surprising since it’s tough to overdose on buprenorphine. Nice work.

5) Risk Factors for Mortality and Endotracheal Intubation after Methadone Intoxication.

Hassanian-Moghaddam H, Soltaninejad K, Shadnia S, Kabir A, Movahed M, Mirafzal A.

Basic Clin Pharmacol Toxicol. 2015 Aug 24. doi: 10.1111/bcpt.12476. [Epub ahead of print]

Comment: Lower consciousness/respirations once in the emergency room were associated with increased likelihood of being intubated and/or dying from methadone overdose. This is interesting in the context of previous papers included on this blog that demonstrate lower likelihood of such outcomes when naloxone is administered in the field. Is it time to think of naloxone as an automated electronic defibrillator?

6) The characteristics of a cohort who tamper with prescribed and diverted opioid medications.

Larance B, Lintzeris N, Bruno R, Peacock A, Cama E, Ali R, Kihas I, Hordern A, White N, Degenhardt L.

J Subst Abuse Treat. 2015 Jun 24. pii: S0740-5472(15)00137-3. doi: 10.1016/j.jsat.2015.06.001. [Epub ahead of print]

Comment: This is a complex population. Although risk outcomes appear closer to those of someone who uses heroin than those of someone prescribed opioids, the clinical characteristics overlap substantially with the latter group.

PubMed Update September 2013

12 articles this month.

1) Effectiveness of Naltrexone in the Prevention of Delayed Respiratory Arrest in Opioid-Naive Methadone-Intoxicated Patients.

Aghabiklooei A, Hassanian-Moghaddam H, Zamani N, Shadnia S, Mashayekhian M, Rahimi M, Nasouhi S, Ghoochani A.

Biomed Res Int. 2013;2013:903172. Epub 2013 Sep 9.

Comments: Interesting use of the long-acting opioid antagonist naltrexone in this study from Iran. The likely downside of this approach of course is that, in those with opioid dependence (constituting the vast majority of overdose cases), it doesn’t allow for titration of antagonist effect to minimize withdrawal symptoms.

2) An investigation of the interactions between methadone and elvitegravir/cobicistat in subjects receiving chronic methadone maintenance.

Bruce RD, Winkle P, Custodio JM, Wei X, Rhee MS, Kearney BP, Ramanathan S, Friedland GH.

Antimicrob Agents Chemother.2013 Sep 30. [Epub ahead of print]

Comments: This is a promising finding for the new HIV regimen.

3) Interaction of Different Antidepressants with Acute and Chronic Methadone in Mice, and Possible Clinical Implications.

Schreiber S, Barak Y, Hostovsky A, Baratz-Goldstein R, Volis I, Rubovitch V, Pick CG.

J MolNeurosci.2013 Sep 22. [Epub ahead of print]

Comments: Really interesting study, since many opioid overdoses occur in the presence of anti-depressant medications. These results are too preliminary to draw strong conclusions, but it’s an important pursuit.

4) Law enforcement attitudes toward overdose prevention and response.

Green TC, Zaller N, Palacios WR, Bowman SE, Ray M, Heimer R, Case P.

Drug Alcohol Depend.2013 Sep 2.doi:pii: S0376-8716(13)00334-7. 10.1016/j.drugalcdep.2013.08.018. [Epub ahead of print]

Comments: Interesting qualitative analysis of police attitudes toward lay naloxone.

5) Days of heroin use predict poor self-reported health in hospitalized heroin users.

Meshesha LZ, Tsui JI, Liebschutz JM, Crooks D, Anderson BJ, Herman DS, Stein MD.

Addict Behav. 2013 Aug 14;38(12):2884-2887. doi:

Comments: More days of heroin use is associated with worse self-reported health and worse self-reported health is associated with non-fatal overdose events.

6) Assisted injection among people who inject drugs in Thailand.

Lee WK, Ti L, Hayashi K, Kaplan K, Suwannawong P, Wood E, Kerr T.

Subst Abuse Treat Prev Policy. 2013 Sep 10;8(1):32. [Epub ahead of print]

Comments: This is a useful contribution to overdose literature. There has long been a concern that people who require assistance to inject (often women) would overdose more. This hasn’t held up in studies and this study corroborates that lack of association. It may be well worth exploring further, but thus far we don’t have any evidence that assistance with injecting increases overdose risk.

7) BET 3: Is nebulised naloxone effective in opioid overdose?

[No authors listed]

Emerg Med J. 2013 Oct;30(10):860. doi: 10.1136/emermed-2013-203100.3.

Comments: Yes, in breathing patients.

8) The lethal burden of drug overdose.

[No authors listed]

Lancet. 2013 Sep 7;382(9895):833. doi: 10.1016/S0140-6736(13)61844-9. No abstract available.

Comments: Brief commentary on opioid overdose mortality in UK and US. Notable that there is no mention of naloxone.

9) [Maintaining opioid abstinence long after inpatient treatment with opioid substitution in an addictology hospital unit].

Bouab O, Lahmek P, Meunier N, Aubin HJ, Michel L.

Rev Med Brux. 2013 May-Jun;34(3):132-40. French.

Comments: Basically inpatient withdrawal from agonist maintenance treatment.

10) The pharmacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment.

Bruce RD, Winkle P, Custodio JM, Wei LX, Rhee MS, Kearney BP, Ramanathan S, Friedland GH.

J Acquir Immune DeficSyndr. 2013 Aug 1;63(4):480-4. doi: 10.1097/QAI.0b013e3182961d31.

Comments: The new combined HIV med (Stribild) modestly increases buprenorphine levels.

11) Problem based review: The patient taking methadone.

Arora A, Williams K.

Acute Med. 2013;12(1):51-4. Review.

Comments: Methadone maintenance review.

12) Low-frequency heroin injection among out-of-treatment, street-recruited injection drug users.

Harris JL, Lorvick J, Wenger L, Wilkins T, Iguchi MY, Bourgois P, Kral AH.

J Urban Health. 2013 Apr;90(2):299-306. doi: 10.1007/s11524-012-9720-8.

Comments: Another useful contribution – infrequent heroin injectors had a lower risk of non-fatal overdose. As with most overdose epidemiology, the relationship between use frequency and overdose risk is likely complex.