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 October/November 2016

43 papers this round, and there are some goodies in here for sure (don't miss #38!). Given the number and varied issues addressed, I divided them up into topic areas and, given the number on naloxone, I divided up the naloxone topic areas as well.

Naloxone interventions

Primary care

1) Co-prescription of naloxone as a Universal Precautions model for patients on chronic opioid therapy-Observational study.

Takeda MY, Katzman JG, Dole E, Bennett MH, Alchbli A, Duhigg D, Yonas H.

Subst Abus. 2016 Apr 19:1-6. [Epub ahead of print]

Comment: A pilot of naloxone co-prescribing.

2) Attitudes Toward Naloxone Prescribing in Clinical Settings: A Qualitative Study of Patients Prescribed High Dose Opioids for Chronic Non-Cancer Pain.

Mueller SR, Koester S, Glanz JM, Gardner EM, Binswanger IA.

J Gen Intern Med. 2016 Oct 31. [Epub ahead of print]

Comment: Shows that naloxone for patients prescribed opioids must be appropriately framed.

3) Acceptability of Naloxone Co-Prescription Among Primary Care Providers Treating Patients on Long-Term Opioid Therapy for Pain.

Behar E, Rowe C, Santos GM, Coffa D, Turner C, Santos NC, Coffin PO.

J Gen Intern Med. 2016 Nov 4. [Epub ahead of print]

Comment: When actually implemented, providers really like adding naloxone to opioid-related care. One of five papers out of the Naloxone for Opioid Safety Evaluation of a naloxone co-prescribing study in San Francisco.

PubMed Update May 2016

19 this month. Enjoy!

1) Methadone-Related Overdose Deaths in a Liberal Opioid Maintenance Treatment Programme.

Tjagvad C, Skurtveit S, Linnet K, Andersen LV, Christoffersen DJ, Clausen T.

Eur Addict Res. 2016 Jun 1;22(5):249-258. [Epub ahead of print]

Comments: Patients on very high doses of methadone or also using benzodiazepines were at higher risk of death.

2) Heroin use.

Salani DA, Zdanowicz M, Joseph L.

J Psychosoc Nurs Ment Health Serv. 2016 Jun 1;54(6):30-7. doi: 10.3928/02793695-20160518-05.

Comments: Epidemiologic review.

3) Academic physicians' and medical students' perceived barriers toward bystander administered naloxone as an overdose prevention strategy.

Gatewood AK, Van Wert MJ, Andrada AP, Surkan PJ.

Addict Behav. 2016 May 17;61:40-46. doi: 10.1016/j.addbeh.2016.05.013. [Epub ahead of print]

Comments: Qualitative interviews with medical providers.

4) Patient Characteristics and Outcomes in Unintentional, Non-fatal Prescription Opioid Overdoses: A Systematic Review.

Elzey MJ, Barden SM, Edwards ES.

Pain Physician. 2016 May;19(4):215-28.

Comments: Non-fatal events are far more common, not well-predicted by risk factors, and in need of additional research.

5) Incorporation of poison center services in a state-wide overdose education and naloxone distribution program.

Doyon S, Benton C, Anderson BA, Baier M, Haas E, Hadley L, Maehr J, Rebbert-Franklin K, Olsen Y, Welsh C.

Am J Addict. 2016 Jun;25(4):301-6. doi: 10.1111/ajad.12384. Epub 2016 May 24.

Comments: Interesting case series of naloxone reversals reported to poison control. They report a 75.6% “response rate” although some of the remainder was “unknown” and was there were only 2 deaths among 78 cases, suggesting a rate closer to 97.5%. Response rate to heroin was higher than for prescription opioids. Of the 43 suspected heroin events, 31 went to the ED, 25 were discharged, and 5 required ICU care. Of 31 suspected prescription opioid 20 went to the ED, 9 were discharged, and 6 required ICU care. This is consistent with the more complicated nature of prescription opioid overdose.

6) Police Officers Can Safely and Effectively Administer Intranasal Naloxone.

Fisher R, O'Donnell D, Ray B, Rusyniak D.

Prehosp Emerg Care. 2016 May 24:1-6. [Epub ahead of print]

Comments: About a 65% response rate among 117 administrations and 1 combative individual.

PubMed Update June - July 2015

Great stuff this time! 34 in two months.

1. Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014.

Wheeler E, Jones TS, Gilbert MK, Davidson PJ.

MMWR Morb Mortal Wkly Rep. 2015 Jun 19;64(23):631-5.

Comment: The long-awaited sequel to 2010’s blockbuster naloxone MMWR report! 152,283 laypersons trained and 26,463 overdose reversals reported to naloxone programs through 2014.

2. Heroin-related overdose: The unexplored influences of markets, marketing and source-types in the United States.

Mars SG, Fessel JN, Bourgois P, Montero F, Karandinos G, Ciccarone D.

Soc Sci Med. 2015 Jun 30;140:44-53. doi: 10.1016/j.socscimed.2015.06.032. [Epub ahead of print]

Comment: Interesting use of qualitative data exploring the role of heroin markets on overdose risk, suggesting that factors such as open-air versus behind-closed-door markets can affect risk.

3. Risk factors for concurrent use of benzodiazepines and opioids among individuals under community corrections supervision.

Cropsey KL, Stevens EN, Valera P, Brendan Clark C, Bulls HW, Nair P, Lane PS.

Drug Alcohol Depend. 2015 Jul 10. pii: S0376-8716(15)00352-X. doi: 10.1016/j.drugalcdep.2015.06.038. [Epub ahead of print]

Comment: There’s a movement toward not prescribing opioids with benzodiazepines at all. This makes some sense from an overdose prevention perspective, however the impact of such a policy is unknown. Those who require both opioids and benzodiazepines generally have far more complex and substantial mental health challenges. Just removing one or the other of the agents may results in worsening mental health or even increased rates of self-harm. Or not. Nobody knows.

4. Drug quality assessment practices and communication of drug alerts among people who use drugs.

Soukup-Baljak Y, Greer AM, Amlani A, Sampson O, Buxton JA.

Int J Drug Policy. 2015 Jul 2. pii: S0955-3959(15)00200-5. doi: 10.1016/j.drugpo.2015.06.006. [Epub ahead of print]

Comment: This is interesting, particularly in an era of frequent high-potency batches of heroin or even pure fentanyl derivatives. Subjects recommend using words like “dangerous” or “lethal” instead of “potent” which can be misconstrued as desirable. They also emphasized timeliness. As one of the first studies to really look at this issue, this paper is well worth the read.

5. Opioid Overdose Deaths in the City and County of San Francisco: Prevalence, Distribution, and Disparities.

Visconti AJ, Santos GM, Lemos NP, Burke C, Coffin PO.

J Urban Health. 2015 Jun 16. [Epub ahead of print]

Comment: Epidemiology of opioid overdose mortality in San Francisco – the first since Pete Davidson’s seminal geocoding paper in 2003 that led SF to refocus overdose prevention efforts to the hardest hit neighborhoods. This paper documents that heroin overdose is now remarkably rare in San Francisco, although for me it raises more questions than it answers.

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 January 2014

10 papers this month, half of which relate to the United Kingdom. We continue to move forward.

1) Characterization of opioid overdose and response in a high-risk community corrections sample: A preliminary study.

Cropsey KL, Martin S, Clark CB, McCullumsmith CB, Lane PS, Hardy S, Hendricks PS, Redmond N.

J Opioid Manag. 2013 Nov-Dec;9(6):393-400.

Comments: Valuable survey of persons in the corrections system, under community supervision. Nearly half had used opioids and 40% of those had experienced an opioid overdose. Those who had overdosed were more likely to be white, female, and have higher educational attainment; they were also much more likely to have witnessed overdose, have seen someone die of overdose, and want training in overdose prevention and management.

2) Opioids Compared to Placebo or Other Treatments for Chronic Low Back Pain: An Update of the Cochrane Review.

Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC.

Spine (Phila Pa 1976). 2014 Jan 29. [Epub ahead of print]

Comments: A review of studies evaluating short term use of opioids for chronic lower back pain. The studies evaluated all have major shortcomings so we’re left with little new information.

3) Opioid overdose with gluteal compartment syndrome and acute peripheral neuropathy.

Adrish M, Duncalf R, Diaz-Fuentes G, Venkatram S.

Am J Case Rep. 2014 Jan 15;15:22-6

Comments: Being “down” with an overdose for a prolonged period can lead to complications such as rhabdomyolysis and nerve compression. This patient developed compartment syndrome, which is to say high pressure within the fascial compartment of the buttocks, requiring surgical intervention to spare her extremity.

PubMed Update: Another Year in Overdose

Another year in overdose, September 2012-August 2013, generally in reverse chronological order, and following the same loosely-formed categories as last year. 

Once again, this is opioid focused and misses anything not listed in the PubMed database – which means it misses many interesting papers to which you are warmly welcomed to post links!

This year there were 99 papers, up from 81 in the preceding 12 months. 

PubMed Update July 2013

8 papers this month. Police, pharmacology, prisons, methadone, money, and plants. Enjoy!

1) Police Officers' and Paramedics' Experiences with Overdose and Their Knowledge and Opinions of Washington State's Drug Overdose-Naloxone-Good Samaritan Law.

Banta-Green CJ, Beletsky L, Schoeppe JA, Coffin PO, Kuszler PC.

J Urban Health. 2013 Jul 31. [Epub ahead of print]

Comment: Expands on the limited data we have regarding police and paramedics knowledge and opinions regarding opioid overdose prevention initiatives.

2) [Heroin].

Demaret I, Lemaître A, Ansseau M.

Rev Med Liege. 2013 May-Jun;68(5-6):287-93. French.

Comment: Only saw the abstract, but appears to be a nice summary of heroin, particularly overdose risk factors.

3) Potential P-glycoprotein Pharmacokinetic Interaction of Telaprevir With Morphine or Methadone.

Fudin J, Fontenelle DV, Fudin HR, Carlyn C, Hinden DA, Ashley CC.

J Pain Palliat Care Pharmacother. 2013 Jul 24. [Epub ahead of print]

Comment: Some potential interactions of the HCV protease inhibitor with selected opioids. Hopefully we won’t be using telaprevir too much longer as more advanced, effective, and easily tolerated regimens are expected as early as the end of 2013.

4) Non-fatal overdose among adult prisoners with a history of injecting drug use in two Australian states.

Moore E, Winter R, Indig D, Greenberg D, Kinner SA.

Drug Alcohol Depend. 2013 Jul 15. doi:pii: S0376-8716(13)00220-2.

Comments: Survey of prisoners lifetime history of overdose.

5) Factors associated with high-frequency illicit methadone use among rural Appalachian drug users.

Hall MT, Leukefeld CG, Havens JR.

Am J Drug Alcohol Abuse. 2013 Jul;39(4):241-6. doi:

Comment: I can’t access this article, but have some concerns about the utility of the analysis of covariates presented in the abstract.

6) Methadone-Related Overdose Deaths in Rural Virginia: 1997 to 2003.

Wunsch MJ, Nuzzo PA, Behonick G, Massello W, Walsh SL.

J Addict Med. 2013 Jul 8. [Epub ahead of print]

Comments: Analysis of methadone-related deaths.

7) The Economic Burden of Opioid-Related Poisoning in the United States.

Inocencio TJ, Carroll NV, Read EJ, Holdford DA.

Pain Med. 2013 Jul 10. doi: 10.1111/pme.12183. [Epub ahead of print]

Comments: Intriguing analysis of costs of opioid overdose, focusing on the costs to the healthcare system.

8) A drug fatality involving Kratom.

Neerman MF, Frost RE, Deking J.

J Forensic Sci. 2013 Jan;58 Suppl 1:S278-9. doi: 10.1111/1556-4029.12009. Epub 2012 Oct 19.

Comments: Kratom is a plant that grows in North America (this case is from Texas) and many other parts of the world. Its use is prohibited in Thailand. It acts as a mu-opioid receptor agonist.

The Scottish Highland Overdose Prevention Programme Goes to Prison

Lisa Ross

NHS Highland Clinical Harm Reduction Nurse Specialist / Naloxone Lead

In July 2009, I started the Highland programme in Inverness, in the north of Scotland, to deliver overdose prevention services to those at risk of opiate overdose, their friends and family members, and staff working with those at risk. The program is part of the Scottish National Health Service, our universal public health care system. 

Trainees were given a supply of naloxone for intramuscular administration to take home and use in the event of witnessing an opiate overdose. The programme also included Inverness prison; those who were identified as at risk were trained whilst in prison and given a naloxone pack on their liberation date.

The Programme was rolled out after the first year throughout the Highland area. To date over 900 kits have been supplied and there have been over 200 recorded uses of naloxone with successful reversal of the overdose state. In 2012, the programme was developed to include supply of naloxone for intranasal administration.

Last year I also started to develop a network of peer trainers; one of the aims of this was to increase uptake to those at risk, particularly those who had not previously engaged with the programme. Peer trainers are ideally placed to deliver this training; after all they hold the most experience and are far more likely to engage with the identified target group.

This again included Inverness Prison; I trained a peer trainer as a trainer and he now delivers the training in prison to those at risk. The results of this have been hugely positive so far. In a short space of time he has managed to engage with more individuals and deliver the training to them than the health and addictions staff have managed throughout the year. This is even more impressive when we consider the prison is in its fourth year of delivering this intervention and supplies of naloxone were starting to decrease given that the majority of people had already been trained. Or so we thought!

There will be the opportunity for the peer trainer to continue delivering the programme upon his own liberation, working in the community with the Harm Reduction Service and the community peer trainers.

My ongoing intention for the programme is to increase the number of peer trainers throughout Highland; there is no doubt that when it comes to overdose prevention and Naloxone training; peer trainers can have the maximum impact.

More OD videos - Cops, reentry, and Spanish OD training!

It seems like there are a bunch of good overdose advocacy and training videos coming out these days. 

Here's a new video from the San Francisco Police Department and Department of Public Health instructing police not to interfere with syringe access sites or naloxone distribution. (Nice narration Emalie Huriaux!)




And here's a new Spanish-language video from Boston about how to recognize overdose and respond properly. The video highlights the fact that those just released from prison or other lock-up facilities are at higher risk of OD, especially in those first two weeks.

And while we're at it, we realized that OPA didn't mention the great video, "Staying Alive on the Outside" from our friends in Rhode Island that came out a few months back. It's and English-language video that focuses on OD risk and response after prison release. 



We hope you find these useful in your work!

PubMed Update: A Year in Overdose

Here is a summary of our first year of PubMed updates. This list is NOT comprehensive and focuses on opioids at the expense of stimulant issues. There are some excellent papers not listed in the PubMed database (e.g. a couple of great papers out of Scotland we’ve discussed here and many conference abstracts).

So … there were an impressive 81 papers! Basic epidemiology and opioid analgesics dominate, but the list is quite diverse. I’ve roughly categorized papers, but many would fit into multiple categories, and I have not updated the comments …

EPIDEMIOLOGY

1) Drug overdose deaths --- Florida, 2003-2009
Centers for Disease Control and Prevention
MMWR Morb Mortal Wkly Rep. 2011 Jul 8; 60(26):869-72

Comments: Again, oxycodone has arisen as a major source of overdose mortality. The use characteristics that lead to mortality, however, remain unexplained.

2) Characteristics of drug users who witness many overdoses: Implications for overdose prevention.

Bohnert AS, Tracy M, Galea S. Drug Alcohol Depend. 2011 Aug 10.

Comment: Another analysis from a non-fatal overdose survey in Harlem and the South Bronx. There have been some concerning results in terms of witness management of overdose from this study. We know that those who have overdosed are at higher risk of overdose and from a 2005 analysis also know that they are less likely to contact emergency medical services when they witness an overdose. Now we know that these findings apply to those who witness multiple overdoses as well (they appear to be almost the same population). Authors propose that prior negative experiences with medical service might dissuade contact at future overdoses, although perhaps successful prior lay resuscitation efforts also discourage calling for help.

3) Drug-Related Death Following Release from Prison: A Brief Review of the Literature with Recommendations for Practice.

Leach D, Oliver P. Curr Drug Abuse Rev. 2011 Aug 12. [Epub ahead of print]

Comment: I don’t have access to the full article and hope that naloxone distribution is discussed as one of the options.

4) Mortality among Substance-using Mothers in California: A 10-year Prospective Study.

Hser Y, Kagihara J, Huang D, Evans E, Messina N. Addiction. 2011 Aug 10

Comment: Mortality among pregnant or parenting women seeking substance abuse treatment (including heroin, cocaine, alcohol, marijuana, and methamphetamine) over ten years was 8.4x higher than the general population, the largest portion of which was from overdose (29%). The authors do not breakdown overdose by primary drug problem (i.e. can’t tell if most of the overdoses were among heroin users or if they were more evenly distributed).

5) An analysis of the root causes for opioid-related overdose deaths in the United States.

Webster LR, Cochella S, Dasgupta N, Fakata KL, Fine PG, Fishman SM, Grey T, Johnson EM, Lee LK, Passik SD, Peppin J, Porucznik CA, Ray A, Schnoll SH, Stieg RL, Wakeland W.

Pain Med. 2011 Jun;12 Suppl 2:S26-35.

Comment: A review of structural and individual factors related to opioid overdose increases in the U.S.