PubMed Update December 2017

57 for the past two months, from new ways to look at medical examiner data to an unfortunate complication of resuscitation. The fentanyl papers are at the end, as are a couple papers each addressing safe consumption spaces and opioid reformulations.

1) Wearable Biosensors to Evaluate Recurrent Opioid Toxicity After Naloxone Administration: A Hilbert Transform Approach.

Chintha KK, Indic P, Chapman B, Boyer EW, Carreiro S.

Proc Annu Hawaii Int Conf Syst Sci. 2018 Jan;2018:3247-3252. Epub 2018 Jan 3.

Comment: Unable to access. Abstract indicates that authors studied 11 participants to identify physiologic signs that naloxone effect was wearing off.

2) Using medical examiner case narratives to improve opioid overdose surveillance.

Hurstak E, Rowe C, Turner C, Behar E, Cabugao R, Lemos NP, Coffin P.

Int J Drug Policy. 2018 Jan 17;54:35-42. doi: 10.1016/j.drugpo.2017.12.017. [Epub ahead of print]

Comment: Opioid overdose surveillance is remarkably limited in its ability to explain the issue. This paper involved manual review of medical examiner case narratives in an attempt to identify consistently reported elements that could help us establish the populations at highest risk for death. This issue arose in the early 2000s, when opioid overdose deaths transitioned from heroin to prescription opioids – was it the same population, just using different substances? Was it a new population? How much of a mix was it? This paper looked at evidence of drug injection as a marker for a “heroin use” population versus non-injection, which may represent a distinct risk population.

3) Drug involvement in fatal overdoses.

Ruhm CJ.

SSM Popul Health. 2017 Jan 31;3:219-226. doi: 10.1016/j.ssmph.2017.01.009. eCollection 2017 Dec.

Comment: Recounts the transition to heroin as causal opioid and reminds us of the importance of polydrug involvement – a critical issue that has proven notoriously challenging to study.

4) Increased non-fatal overdose risk associated with involuntary drug treatment in a longitudinal study with people who inject drugs.

Rafful C, Orozco R, Rangel G, Davidson P, Werb D, Beletsky L, Strathdee SA.

Addiction. 2018 Jan 14. doi: 10.1111/add.14159. [Epub ahead of print]

Comment: Heroin users with recent involuntary treatment were nearly twice as likely to overdose.

5) Promising roles for pharmacists in addressing the U.S. opioid crisis.

Compton WM, Jones CM, Stein JB, Wargo EM.

Res Social Adm Pharm. 2017 Dec 31. pii: S1551-7411(17)30977-4. doi: 10.1016/j.sapharm.2017.12.009. [Epub ahead of print]

Comment: As addiction medicine truly becomes part of the medical system, the role for pharmacists – as well as other health professionals – becomes paramount.

6) Opioid drug poisonings in Ohio adolescents and young adults, 2002-2014.

Caupp S, Steffan J, Shi J, Wheeler KK, Spiller HA, Casavant MJ, Xiang H.

Clin Toxicol (Phila). 2018 Jan 11:1-8. doi: 10.1080/15563650.2018.1424889. [Epub ahead of print]

Comment: Demographics from the poison center.

7) Prediction Model for Two-Year Risk of Opioid Overdose Among Patients Prescribed Chronic Opioid Therapy.

Glanz JM, Narwaney KJ, Mueller SR, Gardner EM, Calcaterra SL, Xu S, Breslin K, Binswanger IA.

J Gen Intern Med. 2018 Jan 29. doi: 10.1007/s11606-017-4288-3. [Epub ahead of print]

Comment: Nice work by this team. They developed a model of overdose risk among people prescribed opioids longterm and validated it. The validation was not as good as expected, as it seems the validation population was higher risk for overdose, so the model didn’t pick up all the at-risk people. It’s also not clear that this model would transfer to other settings where the demographics of opioid use and overdose are quite different (e.g. they found that patients aged 55-65 were at lowest risk, whereas we see the opposite in San Francisco). The authors also note the important caveat that most people with the model characteristics (on long-acting opioids, tobacco use, mental health diagnoses, substance use disorders, and age via a quadratic equation) do not experience overdose, so this model should not be used to target reduced prescribing. Most interesting perhaps, opioid dose did NOT make it into their model, which points to the fallacy of focusing on that outcome as the goal of opioid stewardship efforts. Finally, the authors suggest that this model could be used to target naloxone prescription; I would suggest that this model may be a minimum guideline, although this may not account for overdose in the immediate social circle of the patient (naloxone may be used by a patient on someone else who suffers an overdose, whether a family member or friend who uses opioids or someone who accidentally or intentionally accesses the patient’s medication).

8) Drug Overdose Deaths in the United States, 1999-2016.

Hedegaard H, Warner M, Miniño AM.

NCHS Data Brief. 2017 Dec;(294):1-8.

Comment: Over 63,600 deaths in 2016, a further 21% more than 2015, and highest in West Virginia, Ohio, New Hampshire, DC, and Pennsylvania.

9) Naloxone dosage for opioid reversal: current evidence and clinical implications.

Rzasa Lynn R, Galinkin JL.

Ther Adv Drug Saf. 2018 Jan;9(1):63-88. doi: 10.1177/2042098617744161. Epub 2017 Dec 13. Review.

Comment: The naloxone dose controversy. It’s pretty clear that medical personnel should use the lowest dose they can to get effect. Lay use is more complex because it has to be simpler. The jerry-rigged nasal devise is pretty clearly insufficient for the fentanyl crisis. The other devices – from 0.4mg IM to 4mg nasal – seem to mostly work pretty consistently. Another reason for difficult resuscitations in the fentanyl era is that fentanyl overdoses may result in rapid cessation of respiration. In contrast to a heroin overdose, whereby when the witness wakes up from a ‘nod’ their friend has slowly declining respirations but still has a pulse, in the event of a fentanyl overdose the victim may have already progressed to cardiac arrest – which requires advanced medical management.

10) Diagnosis of Heroin Overdose in an 8-Year-Old Boy: Reliable Contribution of Toxicological Investigations.

Soichot M, Julliand S, Filatriau J, Hurbain A, Bourgogne E, Mihoubi A, Gourlain H, Delhotal-Landes B.

J Anal Toxicol. 2017 Dec 28. doi: 10.1093/jat/bkx111. [Epub ahead of print]

Comment: Advanced toxicology identified findings consistent with heroin exposure.

11) Measuring a Crisis: Questioning the Use of Naloxone Administrations as a Marker for Opioid Overdoses in a Large U.S. EMS System.

Grover JM, Alabdrabalnabi T, Patel MD, Bachman MW, Platts-Mills TF, Cabanas JG, Williams JG.

Prehosp Emerg Care. 2018 Jan 3:1-9. doi: 10.1080/10903127.2017.1387628. [Epub ahead of print]

Comment: Sensitivity of EMS naloxone administration for overdose was 57% and positive predictive value 60%. Unfortunately big data is failing us again – we need boots on the ground.

12) Prescription Opioid Dependence in Western New York: Using Data Analytics to Find an Answer to the Opioid Epidemic.

Sinha S, Burstein GR, Leonard KE, Murphy TF, Elkin PL.

Stud Health Technol Inform. 2017;245:594-598.

Comment: It’s a lot of work to glean good data from electronic medical records.

13) Increasing diversion of methadone in Vancouver, Canada, 2005-2015.

Reddon H, Ho J, DeBeck K, Milloy MJ, Liu Y, Dong H, Ahamad K, Wood E, Kerr T, Hayashi K.

J Subst Abuse Treat. 2018 Feb;85:10-16. doi: 10.1016/j.jsat.2017.11.010. Epub 2017 Nov 28.

Comment: The abstract seems to suggest that the increasing availability of diverted methadone is from agonist treatment, although couldn’t much of it be related to prescribing for pain, as is the case in the US?

14) Sheltering risks: Implementation of harm reduction in homeless shelters during an overdose emergency.

Wallace B, Barber K, Pauly BB.

Int J Drug Policy. 2017 Dec 28;53:83-89. doi: 10.1016/j.drugpo.2017.12.011. [Epub ahead of print]

Comment: Suggests that partial implementation of harm reduction strategies, without full engagement, carries risks.

15) Prescribing Opioid Replacement Therapy in U.S. Correctional Settings.

Farahmand P, Modesto-Lowe V, Chaplin MM.

J Am Acad Psychiatry Law. 2017 Dec;45(4):472-477.

Comment: A good idea, as the authors argue.

16) Using drugs in un/safe spaces: Impact of perceived illegality on an underground supervised injecting facility in the United States.

Davidson PJ, Lopez AM, Kral AH.

Int J Drug Policy. 2017 Dec 23;53:37-44. doi: 10.1016/j.drugpo.2017.12.005. [Epub ahead of print]

Comment: The benefit of being underground is that you’re not constrained by political / institutional factors. There are coincident risks as well.

17) Intranasal and Intramuscular Naloxone for Opioid Overdose in the Pre-Hospital Setting: A Review of Comparative Clinical and Cost-Effectiveness, and Guidelines [Internet].

Peprah K, Frey N.

Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Mar 16.

Comment: Limited to absent data.

18) Knowledge and possession of take-home naloxone kits among street-involved youth in a Canadian setting: a cohort study.

Goldman-Hasbun J, DeBeck K, Buxton JA, Nosova E, Wood E, Kerr T.

Harm Reduct J. 2017 Dec 22;14(1):79. doi: 10.1186/s12954-017-0206-6.

Comment: People become more aware of naloxone the longer and more widespread its availability – the limited knowledge in this study is, I suspect, mostly related to the relatively late uptake of take-home naloxone in Canada.

19) Treatment and Prevention of Opioid Use Disorder: Challenges and Opportunities.

McCarty D, Priest KC, Korthuis PT.

Annu Rev Public Health. 2017 Dec 22. doi: 10.1146/annurev-publhealth-040617-013526. [Epub ahead of print]

Comment: Review of current strategies in prescribing opioids and managing OUD.

20) Managing opioid overdose in pregnancy with take-home naloxone.

Blandthorn J, Bowman E, Leung L, Bonomo Y, Dietze P.

Aust N Z J Obstet Gynaecol. 2017 Dec 22. doi: 10.1111/ajo.12761. [Epub ahead of print]

Comment: Mostly the same, but there are a couple of important additional pieces to remember. First, you always need to tilt / place visibly pregnant women in emergency situations on their left side – this takes pressure off of the blood supply to the fetus. Second, you should titrate the naloxone a bit more cautiously as precipitated withdrawal could be dangerous to the fetus; that being said, maternal respiratory arrest is clearly more hazardous.

21) Opioid, Overdose.

Schiller EY, Mechanic OJ.

StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017 Jun-.
2017 Nov 28.

Comment: A basic description.

22) Effect of ageing and time since first heroin and cocaine use on mortality from external and natural causes in a Spanish cohort of drug users.

Molist G, Brugal MT, Barrio G, Mesías B, Bosque-Prous M, Parés-Badell O, de la Fuente L; Spanish Working Group for the Study of Mortality among Drug Users.

Int J Drug Policy. 2017 Dec 18;53:8-16. doi: 10.1016/j.drugpo.2017.11.011. [Epub ahead of print]

Comment: Heroin and cocaine users have greatly elevated risk of mortality. Interestingly, and consistent with decades of research, death from overdose declined with age rather than rising.

23) Opioid Crisis: No Easy Fix to Its Social and Economic Determinants.

Dasgupta N, Beletsky L, Ciccarone D.

Am J Public Health. 2017 Dec 21:e1-e5. doi: 10.2105/AJPH.2017.304187. [Epub ahead of print]

Comment: This is one of my favorite papers in a long time. It is inspired, deeply moving, and beautifully crafted. There is so much more to this than reducing opioid prescribing, providing opioid use disorder treatment, handing out naloxone, etc. This issue involves economic and social abandonment, and so much more.

24) ED Treatment of Opioid Addiction: An Opportunity to Lead.

Martin A, Mitchell A.

Acad Emerg Med. 2017 Dec 21. doi: 10.1111/acem.13367. [Epub ahead of print]

Comment: Great!

25) Abuse-deterrent opioids: an update on current approaches and considerations.

Pergolizzi JV Jr, Raffa RB, Taylor R Jr, Vacalis S.

Curr Med Res Opin. 2017 Dec 21:1-42. doi: 10.1080/03007995.2017.1419171. [Epub ahead of print]

Comment: Industry-funded promotion of novel formulations of opioids.

26) Clinical Update: The Risk of Opioid Toxicity and Naloxone Use in Operational K9s.

Palmer LE, Gautier A.

J Spec Oper Med. 2017 Winter;17(4):86-92.

Comment: I can’t access this. Naloxone is effective in canines, as well as other animals to the best of my knowledge. Exposure risks, in contrast, are being greatly exaggerated in media of late.

27) Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

Uyei J, Fiellin DA, Buchelli M, Rodriguez-Santana R, Braithwaite RS.

Lancet Public Health. 2017 Mar;2(3):e133-e140. doi: 10.1016/S2468-2667(17)30006-3. Epub 2017 Feb 10. Erratum in: Lancet Public Health. 2017 Apr;2(4):e165.

Comment: Added to naloxone distribution modeling with substance use disorder treatment referral and pre-exposure prophylaxis for HIV – an effort to merge management of syndemics as we see in practice, which can be really helpful for programmatic planning. The results appear reasonable, although I disagree with some of the model parameter estimates (e.g. overdose risk is modeled as 7.7% per year and constant – this leads to outcome estimates that are not reflected in epidemiologic data which suggests a declining overdose risk with age / some people overdose more than others).

28) A naloxone and harm reduction educational program across four years of a doctor of pharmacy program.

Maguire MA, Pavlakos RN, Mehta BH, Schmuhl KK, Beatty SJ.

Curr Pharm Teach Learn. 2018 Jan – Feb;10(1):72-77. doi: 10.1016/j.cptl.2017.09.007. Epub 2017 Oct 6.

Comment: That’s cool, and a great way to engage the profession longterm.

29) A content review of online naloxone Continuing Education courses for pharmacists in states with standing orders.

Carpenter DM, Roberts CA, Westrick SC, Ferreri SP, Kennelty KA, Look KA, Abraham O, Wilson C.

Res Social Adm Pharm. 2017 Nov 21. pii: S1551-7411(17)30649-6. doi: 10.1016/j.sapharm.2017.11.011. [Epub ahead of print]

Comment: Talking with patients about naloxone requires a bit of subtlety.

30) A cross-national analysis of the association between years of implementation of opioid substitution treatments and drug-related deaths in Europe from 1995 to 2013.

Marotta PL, McCullagh CA.

Eur J Epidemiol. 2017 Dec 12. doi: 10.1007/s10654-017-0342-z. [Epub ahead of print]

Comment: Implementation of methadone, buprenorphine, and those treatments for incarcerated populations were associate with less drug-related death.

31) Identifying gaps in the implementation of naloxone programs for laypersons in the United States.

Lambdin BH, Zibbell J, Wheeler E, Kral AH.

Int J Drug Policy. 2017 Dec 9;52:52-55. doi: 10.1016/j.drugpo.2017.11.017. [Epub ahead of print]

Comment: 8% of counties had naloxone programs, including only 13% of counties with the highest overdose rates.

32) Comparison of Two Naloxone Regimens in Addicted Methadone-Overdosed Patients, a Clinical Trial Study.

Khosravi N, Zamani N, Hassanian-Moghaddam H, Ostadi A, Rahimi M, Kabir A.

Curr Clin Pharmacol. 2017 Dec 11. doi: 10.2174/1574884713666171212112540. [Epub ahead of print]

Comment: Tintanelli is 0.1mg every 2-3 minutes. Goldfrank is escalating doses every 2-3 minutes. Goldfrank reverses faster but results in more complications due to rapid reversal.

33) Back to the core: A network approach to bolster harm reduction among persons who inject drugs.

Bouchard M, Hashimi S, Tsai K, Lampkin H, Jozaghi E.

Int J Drug Policy. 2017 Dec 8;51:95-104. doi: 10.1016/j.drugpo.2017.10.006. [Epub ahead of print]

Comment: Network interventions make a lot of sense, and are really challenging to design / test.

34) An Innovative Model for Naloxone Use Within an OTP Setting: A Prospective Cohort Study.

Katzman JG, Takeda MY, Bhatt SR, Moya Balasch M, Greenberg N, Yonas H.

J Addict Med. 2017 Dec 7. doi: 10.1097/ADM.0000000000000374. [Epub ahead of print]

Comment: Given naloxone to patients on agonist maintenance treatment leads to reversals in their immediate social networks.

35) Opiate agonist treatment to improve health of individuals with opioid use disorder in Lebanon.

Ghaddar A, Abbas Z, Haddad R.

Harm Reduct J. 2017 Dec 8;14(1):78. doi: 10.1186/s12954-017-0204-8.

Comment: Treating opioid use disorder with proven medications works in Lebanon as well.

36) Rethinking Naloxone: Overdose drug is only one part of the cycle of narcotic abuse.

Richmond NJ.

JEMS. 2017 Feb;42(2):63. No abstract available.

Comment: Can’t access and no abstract.

37) Housing and overdose: an opportunity for the scale-up of overdose prevention interventions?

Bardwell G, Collins AB, McNeil R, Boyd J.

Harm Reduct J. 2017 Dec 6;14(1):77. doi: 10.1186/s12954-017-0203-9.

Comment: Important target for overdose prevention.

38) Only One In Twenty Justice-Referred Adults In Specialty Treatment For Opioid Use Receive Methadone Or Buprenorphine.

Krawczyk N, Picher CE, Feder KA, Saloner B.

Health Aff (Millwood). 2017 Dec;36(12):2046-2053. doi: 10.1377/hlthaff.2017.0890.

Comment: Why aren’t we using the proven treatments for opioid use disorder? This is like not providing anti-hyperglycemic agents for a diabetic individual.

39) Opiate use disorders and overdose: Medical students’ experiences, satisfaction with learning, and attitudes toward community naloxone provision.

Tobin H, Klimas J, Barry T, Egan M, Bury G.

Addict Behav. 2017 Nov 22. pii: S0306-4603(17)30436-7. doi: 10.1016/j.addbeh.2017.11.028. [Epub ahead of print]

Comment: There is always a need for more education on this topic.

40) Factors associated with naloxone administration in an opioid dependent sample.

Kenney SR, Anderson BJ, Bailey GL, Stein MD.

J Subst Abuse Treat. 2018 Jan;84:17-20. doi: 10.1016/j.jsat.2017.10.008. Epub 2017 Oct 18.

Comment: Interesting analysis of people entering opioid detox. Only heroin users (i.e. no prescription opioid users) had administered naloxone and few African Americans had done so.

41) Safety and efficacy of an oxycodone vaccine: Addressing some of the unique considerations posed by opioid abuse.

Raleigh MD, Peterson SJ, Laudenbach M, Baruffaldi F, Carroll FI, Comer SD, Navarro HA, Langston TL, Runyon SP, Winston S, Pravetoni M, Pentel PR.

PLoS One. 2017 Dec 1;12(12):e0184876. doi: 10.1371/journal.pone.0184876. eCollection 2017.

Comment: Vaccines have long been a goal of some for substance use disorders. There remain many challenges.

42) Case 37-2017. A 36-Year-Old Man with Unintentional Opioid Overdose.

Raja AS, Miller ES, Flores EJ, Wakeman SE, Eng G.

N Engl J Med. 2017 Nov 30;377(22):2181-2188. doi: 10.1056/NEJMcpc1710563. Comment: Exciting to see the NEJM taking a deep dive into a patient with an opioid use disorder!

43) Elderly Man in Respiratory Arrest.

Mackle T, Rhine D.

Ann Emerg Med. 2017 Oct;70(4):599-604. doi: 10.1016/j.annemergmed.2017.04.035. No abstract available.

Comment: Gastric perforation due to resuscitation. Complications of well-intentioned medical interventions … suck.

44) Detection of Carfentanil by LC-MS-MS and Reports of Associated Fatalities in the USA.

Shanks KG, Behonick GS.

J Anal Toxicol. 2017 Jul 1;41(6):466-472. doi: 10.1093/jat/bkx042.

Comment: Go low.

45) Naloxone Access and Use for Suspected Opioid Overdoses.

[No authors listed]

Ann Emerg Med. 2017 Jul;70(1):112-113. doi: 10.1016/j.annemergmed.2017.03.031. No abstract available.

Comment: The American College of Emergency Physicians (ACEP), the National Association of EMS Physicians (NAEMSP), and the American College of Medical Toxicology (ACMT) affirm naloxone access for all emergency responders and lay persons by prescription, as well as the ability for pharmacists to furnish without prescription.

46) Acute Toxicity From Intravenous Use of the Tricyclic Antidepressant Tianeptine.

Dempsey SK, Poklis JL, Sweat K, Cumpston K, Wolf CE.

J Anal Toxicol. 2017 Jul 1;41(6):547-550. doi: 10.1093/jat/bkx034.

Comment: A tricyclic antidepressant approved in Europe (not in the US) overdose that responded to naloxone … authors presume that this was managing the tricyclic overdose although one might wonder if there was an undetected synthetic opioid on board.

Consumption spaces

47) Changes in public order after the opening of an overdose monitoring facility for people who inject drugs.

León C, Cardoso LJP, Johnston S, Mackin S, Bock B, Gaeta JM.

Int J Drug Policy. 2017 Dec 30;53:90-95. doi: 10.1016/j.drugpo.2017.12.009. [Epub ahead of print]

Comment: There were fewer people on the streets oversedated.

48) Perceptions about supervised injection facilities among people who inject drugs in Philadelphia.

Harris RE, Richardson J, Frasso R, Anderson ED.

Int J Drug Policy. 2017 Dec 10;52:56-61. doi: 10.1016/j.drugpo.2017.11.005. [Epub ahead of print]

Comment: Again, people who use drugs support a safe consumption space.

OxyContin reformulation

49) The effect of a potentially tamper-resistant oxycodone formulation on opioid use and harm: main findings of the National Opioid Medications Abuse Deterrence (NOMAD) study.

Larance B, Dobbins T, Peacock A, Ali R, Bruno R, Lintzeris N, Farrell M, Degenhardt L.

Lancet Psychiatry. 2018 Jan 10. pii: S2215-0366(18)30003-8. doi: 10.1016/S2215-0366(18)30003-8. [Epub ahead of print]

Comment: “This formulation of controlled-release oxycodone reduced tampering with pharmaceutical opioids among people who inject drugs, but did not affect population-level opioid use or harm.”

50) The impact of OxyContin reformulation at the Sydney Medically Supervised Injecting Centre: Pros and cons.

Jauncey M, Livingston M, Salmon AM, Dietze P.

Int J Drug Policy. 2017 Dec 18;53:17-22. doi: 10.1016/j.drugpo.2017.11.025. [Epub ahead of print]

Comment: More on the unintended consequence of OxyContin reformulation.

Fentanyl papers

51) The Rapid Escalation of Fentanyl in Illicit Drug Evidence in Allegheny County, Pennsylvania, 2010-2016.

Creppage KE, Yohannan J, Williams K, Buchanich JM, Songer TJ, Wisniewski SR, Fabio A.

Public Health Rep. 2018 Jan 1:33354917753119. doi: 10.1177/0033354917753119. [Epub ahead of print]

Comment: Per title.

52) Newly Emerging Drugs of Abuse and Their Detection Methods: An ACLPS Critical Review.

Liu L, Wheeler SE, Venkataramanan R, Rymer JA, Pizon AF, Lynch MJ, Tamama K.

Am J Clin Pathol. 2018 Jan 29;149(2):105-116. doi: 10.1093/ajcp/aqx138.