PubMed Update December 2016 / January 2017

49 in two months. Enjoy!

1) Multiple Fentanyl Overdoses - New Haven, Connecticut, June 23, 2016.

Tomassoni AJ, Hawk KF, Jubanyik K, Nogee DP, Durant T, Lynch KL, Patel R, Dinh D, Ulrich A, D'Onofrio G.

MMWR Morb Mortal Wkly Rep. 2017 Feb 3;66(4):107-111. doi: 10.15585/mm6604a4.

Comments: Nice description of an outbreak of and public health response to insufflated fentanyl causing severe overdose.

2) Patient Simulation for Assessment of Layperson Management of Opioid Overdose With Intranasal Naloxone in a Recently Released Prisoner Cohort.

Kobayashi L, Green TC, Bowman SE, Ray MC, McKenzie MS, Rich JD.

Simul Healthc. 2017 Feb;12(1):22-27. doi: 10.1097/SIH.0000000000000182.

Comments: Interesting and rigorous way to evaluate overdose knowledge after naloxone provision.

3) Pharmacokinetics of a new, nasal formulation of naloxone.

Tylleskar I, Skulberg AK, Nilsen T, Skarra S, Jansook P, Dale O.

Eur J Clin Pharmacol. 2017 Jan 31. doi: 10.1007/s00228-016-2191-1. [Epub ahead of print]

Comments: Data from another nasal naloxone in development.

4) In response to: Do heroin overdose patients require observation after receiving naloxone?

Eggleston W, Clemency BM.

Clin Toxicol (Phila). 2017 Jan 31:1-3. doi: 10.1080/15563650.2017.1284336. [Epub ahead of print] No abstract available.

Comments: Authors note that data on the safety of discharging patients after an hour of observation may not apply in the current era of synthetic opioids.

5) Pharmacists' role in opioid overdose: Kentucky pharmacists' willingness to participate in naloxone dispensing.

Freeman PR, Goodin A, Troske S, Strahl A, Fallin A, Green TC.

J Am Pharm Assoc (2003). 2017 Jan 28. pii: S1544-3191(16)31004-4. doi: 10.1016/j.japh.2016.12.064. [Epub ahead of print]

Comments: Mixed opinions.

6) 'Naloxone works': The politics of knowledge in 'evidence-based' drug policy.

Lancaster K, Treloar C, Ritter A.

Health (London). 2017 Jan 1:1363459316688520. doi: 10.1177/1363459316688520. [Epub ahead of print]

Comments: Interesting article on whose knowledge matters.

PubMed Update July 2016

11 papers this month, including an announcement that naloxone is now over-the-counter in Australia.

1) Factors associated with knowledge of a Good Samaritan Law among young adults who use prescription opioids non-medically.

Evans TI, Hadland SE, Clark MA, Green TC, Marshall BD.

Harm Reduct J. 2016 Jul 26;13(1):24. doi: 10.1186/s12954-016-0113-2.

Comments: Less than half knew about it.

2) Reasons for Benzodiazepine Use Among Persons Seeking Opioid Detoxification.

Stein MD, Kanabar M, Anderson BJ, Lembke A, Bailey GL.

J Subst Abuse Treat. 2016 Sep;68:57-61. doi: 10.1016/j.jsat.2016.06.008. Epub 2016 Jun 16.

Comments: Important work, as there’s an effort to also reduce benzodiazepine prescribing among people who are on opioids. Understanding the drivers of BDZ use should be helpful in structuring interventions. Anxiety and managing opioid withdrawal were two main reasons.

3) Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths - United States, 2002-2014.

Jones CM, Baldwin GT, Manocchio T, White JO, Mack KA.

MMWR Morb Mortal Wkly Rep. 2016 Jul 8;65(26):667-71. doi: 10.15585/mmwr.mm6526a2.

Comments: Interesting analysis of methadone prescribing, overdose, and diversion. It seems that efforts to reduce methadone, beginning in 2006, corresponded with reduced diversion and overdose; unfortunate that opioid overdose death overall continued to escalate.

4) Determinants of willingness to enroll in opioid agonist treatment among opioid dependent people who inject drugs in Ukraine.

Makarenko I, Mazhnaya A, Polonsky M, Marcus R, Bojko MJ, Filippovych S, Springer S, Dvoriak S, Altice FL.

Drug Alcohol Depend. 2016 Aug 1;165:213-20. doi: 10.1016/j.drugalcdep.2016.06.011. Epub 2016 Jun 17.

Comments: Barriers to enrolling in agonist treatment in Ukraine.

PubMed Update March 2016

23 this month.

1) Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria.

McDonald R, Strang J.

Addiction. 2016 Mar 30. doi: 10.1111/add.13326. [Epub ahead of print] Review.

Comments: Take-home naloxone meets all Bradford Hill criteria for causality in reducing opioid overdose mortality. Incidence of fatality among overdoses in the setting of take-home naloxone was 0.8%.

2) Managing Opioid Abuse in Older Adults: Clinical Considerations and Challenges.

Loreck D, Brandt NJ, DiPaula B.

J Gerontol Nurs. 2016 Apr 1;42(4):10-5. doi: 10.3928/00989134-20160314-04.

Comments: A review of the U.S. situation and treatments for opioid use disorder.

3) Years of potential life lost amongst heroin users in the Australian Treatment Outcome Study cohort, 2001-2015.

Darke S, Marel C, Mills KL, Ross J, Slade T, Tessson M.

Drug Alcohol Depend. 2016 May 1;162:206-10. doi: 10.1016/j.drugalcdep.2016.03.010. Epub 2016 Mar 18.

Comments: Heroin use is associated with 25-50 years of life lost. Over half of deaths and nearly two-thirds of years of life lost were due to opioid overdose.

4) Risk factors for unnatural death: Fatal accidental intoxication, undetermined intent and suicide: Register follow-up in a criminal justice population with substance use problems.

Olsson MO, Bradvik L, Öjehagen A, Hakansson A.

Drug Alcohol Depend. 2016 May 1;162:176-81. doi: 10.1016/j.drugalcdep.2016.03.009. Epub 2016 Mar 17.

Comments: Accidental overdose death and suicide are distinct entities, with distinct predictive variables. This is important.

5) An Initial evaluation of law enforcement overdose training in Rhode Island.

Saucier CD, Zaller N, Macmadu A, Green TC.

Drug Alcohol Depend. 2016 May 1;162:211-8. doi: 10.1016/j.drugalcdep.2016.03.011. Epub 2016 Mar 19.

Comments: Harm reduction programs training law enforcement, a critical step forward.

PubMed Update February 2016

Ten articles for February 2016.

1) As opioid overdose deaths reach record highs, call for systematic changes grows louder.

[No authors listed]

ED Manag. 2016 Feb;28(2):13-9.

Comments: Review of the new CDC opioid prescribing guidelines.

2) Australia reschedules naloxone for opioid overdose.

Lenton SR, Dietze PM, Jauncey M.

Med J Aust. 2016 Mar 7;204(4):146-7. No abstract available.

Comments: Naloxone can now be over the counter in Australia, but there’s some work to be done in product design.

3) Science Over Stigma: Saving Lives-Implementation of Naloxone Use in the School Setting.

King R.

NASN Sch Nurse. 2016 Mar;31(2):96-101. doi: 10.1177/1942602X16628890.

Comments: Naloxone for school nurses in Delaware.

4) Electrocardiogram Abnormality Associated with Methadone Overdose.

Agahi M, Shakoori V, Marashi SM.

Sultan Qaboos Univ Med J. 2016 Feb;16(1):e113-4. doi: 10.18295/squmj.2016.16.01.022. Epub 2016 Feb 2. No abstract available.

Comments: Long QT interval is a side effect of high methadone doses.

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 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 June 2013

13 new papers this month, from drug development to naloxone programming, epidemiology to practice management, toxicology to supply side drug control.

1) Illicit drug overdose - Prevalence and acute management.

Li W, Gunja N.

Aust Fam Physician. 2013 Jul;42(7):481-5.

Comment: Unable to access.  Appears to be a general review of managing illicit drug toxicities.

2) Development and implementation of an opioid overdose prevention and response program in Toronto, Ontario.

Leece PN, Hopkins S, Marshall C, Orkin A, Gassanov MA, Shahin RM.

Can J Public Health. 2013 Apr 18;104(3):e200-4.

Comment: Unable to access. There have been several papers describing the initial experience of naloxone programs and this is a welcome addition to that literature.

3) Vital signs: overdoses of prescription opioid pain relievers and other drugs among women - United States, 1999-2010.

Centers for Disease Control and Prevention (CDC).

MMWR Morb Mortal Wkly Rep. 2013 Jul 5;62(26):537-42.

Comment: A review of drug overdose mortality data among women, demonstrating that women have been particularly affected by the recent epidemic.

4) Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal in Russian cities.

Coffin PO, Sullivan SD.

J Med Econ. 2013 Jun 19. [Epub ahead of print]

Comments: An adaptation of the model developed for the United States, taking into account structural differences, epidemiologic data, and costs in Russia. Because of limitations in emergency medical services in Russia, the high rate at which overdoses are witnessed, and the very low costs of naloxone, this intervention is likely to be even more cost-effective in Russia than it appears to be in the United States.