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 OverdoseWith 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 receivingnaloxone?

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.

7) Development and applications of the Veterans Health Administration’s Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdoseand suicide.

Oliva EM, Bowe T, Tavakoli S, Martins S, Lewis ET, Paik M, Wiechers I, Henderson P, Harvey M, Avoundjian T, Medhanie A, Trafton JA.

Psychol Serv. 2017 Feb;14(1):34-49. doi: 10.1037/ser0000099.

Comments: Can’t access the full article, but abstract describes a compelling effort to use EMRs in the VA system to identify patients for overdose prevention.

8) Commentary: Hypnotic Medications and Suicide: Risk, Mechanisms, Mitigation, and the FDA.

Ruan X, Luo JJ, Kaye AD.

Front Psychiatry. 2017 Jan 13;7:210. doi: 10.3389/fpsyt.2016.00210. No abstract available.

Comments: Authors respond to associations between certain medications and suicide, noting that associations are not causation and suggesting that they are can lead to a “nocebo” effect, causing the symptoms among those who read the warnings.

9) Buprenorphine prescribing practice trends and attitudes among New York providers.

Kermack A, Flannery M, Tofighi B, McNeely J, Lee JD.

J Subst Abuse Treat. 2017 Mar;74:1-6. doi: 10.1016/j.jsat.2016.10.005.

Comments: Major barriers were prior authorization (oy, it’s way past time for prior auths to be eliminated for bup), and limited clinic space and support. Utilizing home inductions is a great way to deal with the second concern. A lack of psychiatric support is the third noted concern, although data support buprenorphine provision with or without counseling.

10) Effect of tamoxifen and brain penetrant PKC and JNK inhibitors on tolerance to opioid-induced respiratory depression in mice.

Withey SL, Hill R, Lyndon A, Dewey WL, Kelly E, Henderson G.

J Pharmacol Exp Ther. 2017 Jan 27. pii: jpet.116.238329. doi: 10.1124/jpet.116.238329. [Epub ahead of print]

Comments: Investigators concluded that protein kinase C mediates tolerance to the respiratory depressive effects of morphine, and PKC blockers (like tamoxifen) reverse that tolerance and could therefore increase the risk of opioid overdose.

11) Examining Fatal Opioid Overdoses in Marion County, Indiana.

Ray B, Quinet K, Dickinson T, Watson DP, Ballew A.

J Urban Health. 2017 Jan 26. doi: 10.1007/s11524-016-0113-2. [Epub ahead of print]

Comments: Reduced opioid prescribing appears to have reduced death from prescribed opioids but increased deaths from illicit opioids.

12) Identifying Patients for Overdose Prevention With ICD-9 Classification in the Emergency Department, Massachusetts, 2013-2014.

Ellison J, Walley AY, Feldman JA, Bernstein E, Mitchell PM, Koppelman EA, Drainoni ML.

Public Health Rep. 2016 Sep;131(5):671-675. doi: 10.1177/0033354916661981.

Comments: Using ICD-9 codes in ED visits identified 4.6% of patients with opioid poisoning or abuse/dependency codes. An additional 14.7% were prescribed opioids in the ED.

13) A case of massive methadone overdose presented with refractory hypoglycemia.

Li AT, Chu FK.

Clin Toxicol (Phila). 2017 Mar;55(3):233. doi: 10.1080/15563650.2016.1277236. No abstract available.

Comments: Fascinating complication of methadone toxicity.

14) Social mixing and correlates of injection frequency among opioid use partnerships.

Rowe C, Santos GM, Raymond HF, Coffin PO.

Int J Drug Policy. 2017 Jan 20;41:80-88. doi: 10.1016/j.drugpo.2016.11.016. [Epub ahead of print]

Comments: Identifies network correlates of frequent injection and witnessing overdose.

15) Development of an Opioid-Related Overdose Risk Behavior Scale (ORBS).

Pouget ER, Bennett AS, Elliott L, Wolfson-Stofko B, Almeñana R, Britton PC, Rosenblum A.

Subst Abus. 2017 Jan 23:0. doi: 10.1080/08897077.2017.1282914. [Epub ahead of print]

Comments: An interesting scale for opioid overdose risk. Would be great to see a prospective validation.

16) Lack of overlap and large discrepancies in the characteristics of the deceased in two sources of drug death. A linkage study of the Cause of Death and the Police Registries in Norway 2007-2009.

Amundsen EJ.

Int J Drug Policy. 2017 Jan 19;41:74-79. doi: 10.1016/j.drugpo.2016.12.016. [Epub ahead of print]

Comments: Interesting, if not surprising, results. Police registries didn’t include older, female, prescription opioid-involved drug deaths.

17) The pharmacist’s role in overdose: Using mapping technologies to analyzenaloxone and pharmacy distribution.

Burrell A, Ethun L, Fawcett JA, Rickard-Aasen S, Williams K, Kearney SM, Pringle JL.

J Am Pharm Assoc (2003). 2017 Jan 18. pii: S1544-3191(16)30889-5. doi: 10.1016/j.japh.2016.11.006. [Epub ahead of print]

Comments: Can’t access the full paper. They mapped overdose deaths and pharmacies carrying naloxone in Allegheny County, PA, finding that areas with more overdose were more likely to have pharmacies with naloxone.

18) Pharmaceutical opioid use among oral and intravenous users in Australia: A qualitative comparative study.

Dertadian G, Iversen J, Dixon TC, Sotiropoulos K, Maher L.

Int J Drug Policy. 2017 Jan 17;41:51-58. doi: 10.1016/j.drugpo.2016.12.007. [Epub ahead of print]

Comments: Oral opioid users were more well-off and resourced than those who injected.

19) Adult clonidine overdose: prolonged bradycardia and central nervous system depression, but not severe toxicity.

Isbister GK, Heppell SP, Page CB, Ryan NM.

Clin Toxicol (Phila). 2017 Mar;55(3):187-192. doi: 10.1080/15563650.2016.1277234.

Comments: Clonidine is a blood pressure medication often used to blunt the symptoms of opioid withdrawal during detoxification. Toxicity includes altered mental status and slow heart rate, which does not respond to naloxone.

20) High risk injecting behaviour among people who inject pharmaceutical opioids in Australia.

Iversen J, Dertadian G, Geddes L, Maher L.

Int J Drug Policy. 2017 Jan 16;42:1-6. doi: 10.1016/j.drugpo.2016.12.004. [Epub ahead of print]

Comments: Opioid injectors who had injected opioid analgesics in the past 6 months had elevated risk behaviors and overdose frequency. This may seem to be in contrast to a paper out of Vancouver last year, which showed that opioid analgesic-only injectors had a risk of overdose similar to those who consumed the drugs orally. However the Vancouver paper found those who injected heroin as well as opioid analgesics had just as much risk of overdose as those who injected heroin. I’m not entirely certain how to put these two stories together, but perhaps the answer is that any injection of drugs obtained on the street brings similar overdose risk.

21) Characterization and Management of Patients with Heroin versus Non-HeroinOpioid Overdoses: Experience at an Academic Medical Center.

Morizio KM, Baum RA, Dugan A, Marin JE, Bailey AM.

Pharmacotherapy. 2017 Jan 18. doi: 10.1002/phar.1902. [Epub ahead of print]

Comments: Looking at those admitted for an overdose is a quite narrow subset of events. In this study from Kentucky, this subset – those admitted for heroin overdose generally didn’t need naloxone once admitted – whereas others ended up on naloxone drips in the intensive care unit. 19% had a repeat admission and 7.6% had a repeat admission for an overdose on the same drug within the 5 year study period. I would have expected a higher rate of readmission.

22) Trends in naloxone prescriptions prescribed after implementation of a National Academic Detailing Service in the Veterans Health Administration: A preliminary analysis.

Bounthavong M, Harvey MA, Wells DL, Popish SJ, Himstreet J, Oliva EM, Kay CL, Lau MK, Randeria-Noor PP, Phillips AG, Christopher ML.

J Am Pharm Assoc (2003). 2017 Jan 11. pii: S1544-3191(16)30886-X. doi: 10.1016/j.japh.2016.11.003. [Epub ahead of print]

Comments: Academic detailing is a neat development in medical education. The basic idea is to use similar tactics as the pharmaceutical industry does to promote evidence-based and public health-oriented education for physicians, nurse practitioners, physician assistants, and pharmacists. This paper demonstrated a benefit in terms of naloxone prescribing among VA providers.

23) Prevalence and correlates of fentanyl-contaminated heroin exposure among young adults who use prescription opioids non-medically.

Macmadu A, Carroll JJ, Hadland SE, Green TC, Marshall BD.

Addict Behav. 2017 May;68:35-38. doi: 10.1016/j.addbeh.2017.01.014.

Comments: I struggle to find the silver lining of fentanyl-containing street opioids.

24) Blockade of Serotonin 5-HT2A Receptors Suppresses Behavioral Sensitization andNaloxone-Precipitated Withdrawal Symptoms in Morphine-Treated Mice.

Pang G, Wu X, Tao X, Mao R, Liu X, Zhang YM, Li G, Stackman RW Jr, Dong L, Zhang G.

Front Pharmacol. 2016 Dec 26;7:514. doi: 10.3389/fphar.2016.00514.

Comments: If I follow the abstract, blocking serotonin 2a receptors suppressed withdrawal symptoms when naloxone is administered to morphine-dependent mice. Interesting new direction.

25) State legal innovations to encourage naloxone dispensing.

Davis C, Carr D.

J Am Pharm Assoc (2003). 2017 Jan 7. pii: S1544-3191(16)30890-1. doi: 10.1016/j.japh.2016.11.007. [Epub ahead of print]

Comments: As of August 2016, 44 states allow third-party administration of naloxone, 42 states allow a standing order or similar mechanism to enhance distribution, and 5 states allow pharmacists to furnish naloxone without a prescription. Although providing naloxone is no more prone to liability than any other medication, 36 states provide additional civil liability protection for those providing naloxone, 32 provide additional criminal liability protections, and 31 explicitly state that providing naloxone cannot be ground for professional disciplinary action.

26) Is Kratom the New ‘Legal High’ on the Block?: The Case of an Emerging Opioid Receptor Agonist with Substance Abuse Potential.

Chang-Chien GC, Odonkor CA, Amorapanth P.

Pain Physician. 2017 Jan-Feb;20(1):E195-E198.

Comments: Kratom is a largely unregulated opioid receptor agonist that comes in the form of dietary supplements.

27) A review: Fentanyl and non-pharmaceutical fentanyls.

Suzuki J, El-Haddad S.

Drug Alcohol Depend. 2017 Feb 1;171:107-116. doi: 10.1016/j.drugalcdep.2016.11.033. Review.

Comments: Again, I struggle to see the silver lining.

28) The implementation of a naloxone rescue program in university students.

Panther SG, Bray BS, White JR.

J Am Pharm Assoc (2003). 2017 Jan 4. pii: S1544-3191(16)30885-8. doi: 10.1016/j.japh.2016.11.002. [Epub ahead of print]

Comments: Education strategies for overdose prevention among students.

29) Opioid overdose prevention and naloxone rescue kits: what we know and what we don’t know.

Kerensky T, Walley AY.

Addict Sci Clin Pract. 2017 Jan 7;12(1):4. doi: 10.1186/s13722-016-0068-3. Review.

Comments: A review of naloxone programming.

30) Trajectories of heroin use: 10-11-year findings from the Australian Treatment Outcome Study.

Teesson M, Marel C, Darke S, Ross J, Slade T, Burns L, Lynskey M, Memedovic S, White J, Mills KL.

Addiction. 2017 Jan 6. doi: 10.1111/add.13747. [Epub ahead of print]

Comments: About a fifth continue to use at high levels, about a fifth stopped using early on and remained abstinent. This study continues to provide incredibly useful information.

31) Naloxone administration for suspected opioid overdose: An expanded scope of practice by a basic life support collegiate-based emergency medical services agency.

Jeffery RM, Dickinson L, Ng ND, DeGeorge LM, Nable JV.

J Am Coll Health. 2017 Jan 6:1-5. doi: 10.1080/07448481.2016.1277730. [Epub ahead of print]

Comments: Title says it all.

32) QuickStats: Rates of Drug Overdose Deaths Involving Heroin,* by Selected Age Groups – United States, 2006-2015.

[No authors listed]

MMWR Morb Mortal Wkly Rep. 2017 Jan 6;65(52):1497. doi: 10.15585/mmwr.mm6552a12.

Comments: The increase, really starting in 2011, is across age groups, most pronounced in those 25-54 years of age.

33) Increases in Drug and Opioid-Involved Overdose Deaths – United States, 2010-2015.

Rudd RA, Seth P, David F, Scholl L.

MMWR Morb Mortal Wkly Rep. 2016 Dec 30;65(5051):1445-1452. doi: 10.15585/mmwr.mm655051e1.

Comments: The rising fentanyl deaths are a tragedy. The rising heroin deaths may be somewhat expected as access to prescribed opioids declined. The lack of a decline – and actual increase – in other opioid analgesics is surprising.

34) Lack of respiratory depression in paracetamol-codeine combination overdoses.

Heppell SP, Isbister GK.

Br J Clin Pharmacol. 2016 Dec 30. doi: 10.1111/bcp.13224. [Epub ahead of print]

Comments: Interesting paper. The role of codeine formulations in opioid overdose death is still a bit murky. They can clearly contribute in a polydrug death, but can they result in death on their own, absent acetaminophen toxicity?

35) Experiences of peer-trainers in a take-home naloxone program: Results from a qualitative study.

Marshall C, Perreault M, Archambault L, Milton D.

Int J Drug Policy. 2016 Dec 24;41:19-28. doi: 10.1016/j.drugpo.2016.11.015. [Epub ahead of print]

Comments: This is the second qualitative paper finding empowerment through naloxone programs.

36) Opioid Overdose Prevention Training with Naloxone, an Adjunct to Basic Life Support Training for First Year Medical Students.

Berland N, Fox A, Tofighi B, Hanley K.

Subst Abus. 2016 Dec 27:0. doi: 10.1080/08897077.2016.1275925. [Epub ahead of print]

Comments: Training early med students in overdose prevention and naloxone is a great idea. Although there wasn’t a significant change in attitude toward drug users, I don’t understand how they used the scale. The text reads that it was scored from 1 (disagree) to 6 (agree), but the questions switch back and forth with regard to what is a favorable response. If the total score if higher with more favorable attitudes toward drug users (unsure if that’s the case), the participants already had a fairly favorable attitude.

37) Do More Robust Prescription Drug Monitoring Programs Reduce Prescription Opioid Overdose?

Pardo B.

Addiction. 2016 Dec 23. doi: 10.1111/add.13741. [Epub ahead of print]

Comments: The paper concludes that states with PDMPs and medical marijuana dispensaries have fewer prescription opioid overdoses. It’s a complex, ecologic analysis. Unfortunately these ecologic analyses have proven very problematic lately, and this one, as an example, doesn’t account for law enforcement against grossly overprescribing providers.

38) Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2010-2014.

Warner M, Trinidad JP, Bastian BA, Minino AM, Hedegaard H.

Natl Vital Stat Rep. 2016 Dec;65(10):1-15.

Comments: Useful analysis of drugs mentioned in medical examiner reports of drug-related deaths. Top drugs were opioids (heroin, oxycodone, methadone, morphine, hydrocodone, fentanyl), benzodiazepines (alprazolam, diazepam), and stimulants (cocaine, methamphetamine). Almost half (48%) had more than one drug listed.

39) The Rising Price of Naloxone – Risks to Efforts to Stem Overdose Deaths.

Gupta R, Shah ND, Ross JS.

N Engl J Med. 2016 Dec 8;375(23):2213-2215. No abstract available.

Comments: While it’s nice to think that this is unique to naloxone, the truth – that pricing in the entire pharmaceutical market is out of control – is far more disturbing.

40) Intravenous use of intranasal naloxone: A case of overdose reversal.

Das S, Shah N, Ghadiali M.

Subst Abus. 2016 Dec 7:1-4. doi: 10.1080/08897077.2016.1267686. [Epub ahead of print]

Comments: This involved the old jerry-rigged naloxone that is losing favor due to difficulties with use when an easier to use nasal spray is now available.

41) The Prevalence of Paraphernalia Found at the Scene of Drug-Related Deaths.

Lozano JG, Healy NL, Kimberley Molina D.

J Forensic Sci. 2016 Dec 6. doi: 10.1111/1556-4029.13329. [Epub ahead of print]

Comments: I find this paper fascinating, yet tautological. By reading the narrative on drug-related deaths, authors found presence of paraphernalia to be associated with the death being drug-related. However, the presence of that paraphernalia is part of why the medical examiner determined the death to be drug-related. I’m not sure what else we’ve learned.

42) The Portapotty Experiment: Neoliberal approaches to the intertwined epidemics of opioid-related overdose and HIV/HCV, and why we need cultural anthropologists in the South Bronx.

Wolfson-Stofko B, Curtis R, Fuentes F, Manchess E, Del Rio-Cumba A, Bennett AS.

Dialect Anthropol. 2016 Dec;40(4):395-410.

Comments: Interesting story about efforts to create safer spaces for injecting.

43) Small state takes big steps in opioid-overdose reversal.

Traynor K.

Am J Health Syst Pharm. 2016 Jun 1;73(11):734-8. doi: 10.2146/news160033. No abstract available.

Comments: A story about Vermont’s efforts with naloxone.

44) HIV and drugs: a common, common-sense agenda for 2016.

Buse K, Albers E, Phurailatpam S.

Lancet Glob Health. 2016 May;4(5):e292-3. doi: 10.1016/S2214-109X(16)00043-7. No abstract available.

Comments: A call for humane action.

45) Altered Mental Status in a 14-Year-Old Girl.

Guimera AL, Kulkarni D.

Pediatr Rev. 2016 Apr;37(4):175-6. doi: 10.1542/pir.2015-0164. No abstract available.

Comments: Can’t access.

46) Linkage to Primary Care for Persons First Receiving Injectable Naltrexone During Inpatient Opioid Detoxification.

Stein MD, Risi MM, Bailey GL, Anderson BJ.

J Subst Abuse Treat. 2016 May;64:44-6. doi: 10.1016/j.jsat.2016.01.007.

Comments: 55% followed up for a second injection, 32% got a third injection. This type of dropoff from injectable naltrexone therapy is not uncommon.

47) The liability risks of naloxone access expansion should be the least of our worries.

Humphreys K.

Am J Drug Alcohol Abuse. 2016 Mar;42(2):115-6. doi: 10.3109/00952990.2015.1137299. No abstract available.

Comments: We’ve contorted ourselves in odd ways to protect providers and users from a hypothetical liability that may never come to pass.

48) From risk reduction to implementation: Addressing the opioid epidemic and continued challenges to our field.

Binswanger IA, Gordon AJ.

Subst Abus. 2016;37(1):1-3. doi: 10.1080/08897077.2015.1134152. No abstract available.

Comments: A commentary on a series of articles in the journal addressing naloxone, overdose, and opioid prescribing.

49) Who gets antidotes? choosing the chosen few.

Buckley NA, Dawson AH, Juurlink DN, Isbister GK.

Br J Clin Pharmacol. 2016 Mar;81(3):402-7. doi: 10.1111/bcp.12894. Review.

Comments: How to provide an antidote to a suspected poisoning is an art form. For example, if a patient suffering from opioid overdose is stable and closely monitored, the main indication for naloxone administration would be worsening oxygenation (i.e. reversing the opioid and causing withdrawal may not be necessary). This is good practice, but unfortunately adds to the confusion and challenges in surveillance efforts.