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.

6. Ethanol Reversal of Tolerance to the Respiratory Depressant Effects of Morphine.

Hill R, Lyndon A, Withey S, Roberts J, Kershaw Y, MacLachlan J, Lingford-Hughes A, Kelly E, Bailey C, Hickman M, Henderson G.

Neuropsychopharmacology. 2015 Jul 14. doi: 10.1038/npp.2015.201. [Epub ahead of print]

Comment: Okay, this is a very cool mouse study. They gave morphine to mice until they developed tolerance. The tolerance to respiratory depression effects of morphine were reversed by ethanol. Methadone and buprenorphine seemed to protect mice from this reversal of tolerance effect. Very cool. This is why I do these reviews.

7. Overdose Education and Naloxone for Patients Prescribed Opioids in Primary Care: A Qualitative Study of Primary Care Staff.

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

J Gen Intern Med. 2015 Jun 9. [Epub ahead of print]

Comment: Interesting initial look at prescriber concerns regarding prescribing naloxone from primary care practices. Issues are knowledge about lay use, uncertainty about who to prescribe to, logistical barriers, fears about offending patients, fears about risky use, and discomfort with their own opioid prescribing practices.

8. Methadone overdose causing acute cerebellitis and multi-organ damage.

Rando J, Szari S, Kumar G, Lingadevaru H.

Am J Emerg Med. 2015 Jun 18. pii: S0735-6757(15)00509-4. doi: 10.1016/j.ajem.2015.06.032. [Epub ahead of print] No abstract available.

Comment: A very sad case in which a 14 year old boy accessed his mother’s methadone (apparently prescribed for pain) and had severe disease of the cerebellum as a result. When we speak of opioid overdose, we are generally talking about respiratory depression, but there are some complications that can be unique to particular opioids.

9. Vital Signs: Demographic and Substance Use Trends Among Heroin Users - United States, 2002-2013.

Jones CM, Logan J, Gladden RM, Bohm MK.

MMWR Morb Mortal Wkly Rep. 2015 Jul 10;64(26):719-25.

Comment: Just after 2010 there was a big uptick in heroin use and overdose mortality. Again, this suggests that the increases in heroin use and sequelae were not simply the inevitable consequence of increased opioid dependence, but resulted from – or were substantially contributed to by – restrictions on prescription opioids. It is essential to recognize this in order to minimize the harms of the new/emerging paradigm of opioid prescribing.

10. High uptake of naloxone-based overdose prevention training among previously incarcerated syringe-exchange program participants.

Barocas JA, Baker L, Hull SJ, Stokes S, Westergaard RP.

Drug Alcohol Depend. 2015 Jun 24. pii: S0376-8716(15)00322-1. doi: 10.1016/j.drugalcdep.2015.06.023. [Epub ahead of print]

Comment: People who have been incarcerated are more likely to access naloxone programs. This is consistent with the aims of naloxone programming.

11. Messaging to Increase Public Support for Naloxone Distribution Policies in the United States: Results from a Randomized Survey Experiment.

Bachhuber MA, McGinty EE, Kennedy-Hendricks A, Niederdeppe J, Barry CL.

PLoS One. 2015 Jul 1;10(7):e0130050. doi: 10.1371/journal.pone.0130050. eCollection 2015.

Comment: Useful study testing different approaches to providing information about naloxone programming. The finding that adding sympathetic narratives to factual information roughly doubles support for the programs is consistent with recent experience in which personal exposure to the tragedy of opioid overdose has led many people in positions of power to advocate for naloxone programming.

12. Can differences in the type, nature or amount of polysubstance use explain the increased risk of non-fatal overdose among psychologically distressed people who inject drugs?

Betts KS, McIlwraith F, Dietze P, Whittaker E, Burns L, Cogger S, Alati R.

Drug Alcohol Depend. 2015 Jun 22. pii: S0376-8716(15)00319-1. doi: 10.1016/j.drugalcdep.2015.06.020. [Epub ahead of print]

Comment: This is fascinating. Polysubstance use research is an underdeveloped (and surprisingly challenging) avenue of research. The finding that those with less psychological distress are protected by a combination of agonist maintenance and prescription drug use is of particular interest…

13. Duration of opioid receptor blockade determines biotherapeutic response.

McLaughlin PJ, Zagon IS.

Biochem Pharmacol. 2015 Jun 25. pii: S0006-2952(15)00332-9. doi: 10.1016/j.bcp.2015.06.016. [Epub ahead of print]

Comment: This isn’t really about overdose or even substance use, but it’s about naloxone and naltrexone – opioid blockers – and it’s intriguing. There are some other potential therapeutic roles for opioid blockade, related to complications of diabetes, autoimmune disorders, and cancer.

14. Chiral analysis of methorphan in opiate-overdose related deaths by using capillary electrophoresis.

Bertaso A, Musile G, Gottardo R, Seri C, Tagliaro F.

J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Jul 19;1000:130-135. doi: 10.1016/j.jchromb.2015.07.024.

Comment: Methorphan, a codeine analog and related to dextromethorphan, is being added to heroin sometimes. This paper describes how to test for it.

15. Naloxone-does over-antagonism matter? Evidence of iatrogenic harm after emergency treatment of heroin/opioid overdose.

Neale J, Strang J.

Addiction. 2015 Jun 27. doi: 10.1111/add.13027. [Epub ahead of print]

Comment: Medical professionals are generally cautious in administering naloxone these days because we know it makes patients miserable. Low doses and, if in a monitored setting, only using it when oxygen saturation begins to decline helps to minimize the untoward effects. In this study naloxone had a bad rap but respondents often didn’t know that it had been administered because it was done cautiously.

16. Technology: Barriers to misuse.

Dolgin E.

Nature. 2015 Jun 25;522(7557):S60-1. doi: 10.1038/522S60a. No abstract available.

Comment: There’s a serious problem with the term “abuse-deterrent formulations.” These are formulations of opioids that are more difficult to inject - or in some cases insufflate. They should really be referred to as “injection-deterrent formulations.” They don’t prevent somebody from developing an opioid habit. This article instead reads more like a press release for “abuse-deterrent formulations.”

17. Incidence and predictors of non-fatal drug overdose after release from prison among people who inject drugs in Queensland, Australia.

Winter RJ, Stoové M, Degenhardt L, Hellard ME, Spelman T, Jenkinson R, McCarthy DR, Kinner SA.

Drug Alcohol Depend. 2015 Aug 1;153:43-9. doi: 10.1016/j.drugalcdep.2015.06.011. Epub 2015 Jun 16.

Comment: People overdose after they leave prison.

18. The Supply of Physicians Waivered to Prescribe Buprenorphine for Opioid Use Disorders in the United States: A State-Level Analysis.

Knudsen HK.

J Stud Alcohol Drugs. 2015 Jul;76(4):644-54.

Comment: The average U.S. state has 8 physicians per 100,000 residents able to prescribe buprenorphine for opioid dependence. This rate is even worse in many states, from a low of 1.9 in Nebraska to a high of 27.9 in Vermont. Appalachia – probably the region with the most urgent need – has a rate of 3 to 11 / 100,000 residents. We really need to do something about this waiver situation.

19. Drug use patterns predict risk of non-fatal overdose among street-involved youth in a Canadian setting.

Mitra G, Wood E, Nguyen P, Kerr T, DeBeck K.

Drug Alcohol Depend. 2015 Aug 1;153:135-9. doi: 10.1016/j.drugalcdep.2015.05.035. Epub 2015 May 28.

Comment: This is a sample of street-involved youth – 17.1% injected heroin. Any opioid use was associated with overdose, but interestingly prescription opioid use was a stronger predictor than heroin. That’s surprising. The relatively low overall rate of overdose – 7.67/100,000 person years is not surprising given the distribution of substance use.

20. The Epidemic of Prescription Opioid Abuse, the Subsequent Rising Prevalence of Heroin Use, and the Federal Response.

Kanouse AB, Compton P.

J Pain Palliat Care Pharmacother. 2015 Jun;29(2):102-14. doi: 10.3109/15360288.2015.1037521.

Comment: This leaves some holes in the story, such as the role of reduced access to prescription opioids has had in rising heroin use. Another issue is the suggestion in the text that police getting naloxone has led to 10,000 lay reversals. These were lay person – aka drug user – reversals. It’s frustrating to see this misinformation being spread in the literature.

21. Association between non-fatal opioid overdose and encounters with healthcare and criminal justice systems: Identifying opportunities for intervention.

Wagner KD, Liu L, Davidson PJ, Cuevas-Mota J, Armenta RF, Garfein RS.

Drug Alcohol Depend. 2015 Aug 1;153:215-20. doi: 10.1016/j.drugalcdep.2015.05.026. Epub 2015 May 27.

Comment: Criminal justice and hospital-related opportunities for naloxone distribution.

22. Harm Reduction: Front Line Public Health.

Stancliff S, Phillips BW, Maghsoudi N, Joseph H.

J Addict Dis. 2015 Jun 16:0. [Epub ahead of print]

Comment: Excellent harm reduction review.

23. Intranasal naloxone administration by police first responders is associated with decreased opioid overdose deaths.

Rando J, Broering D, Olson JE, Marco C, Evans SB.

Am J Emerg Med. 2015 May 29. pii: S0735-6757(15)00443-X. doi: 10.1016/j.ajem.2015.05.022. [Epub ahead of print]

Comment: Naloxone should be in the hands of first responders. Even more important, however, is that naloxone is in the hands of people who use drugs – who are much more likely to be present at the time of an overdose. If the data from this paper are scientific evidence that naloxone given to first responders is associated with reduced mortality, then we had much stronger evidence for giving it to drug users in the late 20^th century. Neither of those statements is true.

24. Heroin use, HIV-risk, and criminal behavior in Baltimore: Findings from Clinical Research.

Schwartz RP, Kelly SM, Gryczynski J, Mitchell SG, O'Grady KE, Jaffe JH.

J Addict Dis. 2015 Jun 16:0. [Epub ahead of print]

Comment: Interesting data and experience out of Baltimore with harm reduction interventions.

25. Engaging Law Enforcement in Overdose Reversal Initiatives: Authorization and Liability for Naloxone Administration.

Davis CS, Carr D, Southwell JK, Beletsky L.

Am J Public Health. 2015 Aug;105(8):1530-7. doi: 10.2105/AJPH.2015.302638. Epub 2015 Jun 11.

Comment: Review of police and naloxone administration.

26. Prehospital Naloxone Administration as a Public Health Surveillance Tool: A Retrospective Validation Study.

Lindstrom HA, Clemency BM, Snyder R, Consiglio JD, May PR, Moscati RM.

Prehosp Disaster Med. 2015 Jun 10:1-5. [Epub ahead of print]

Comment: Interesting paper. Pre-hospital naloxone administrations are more likely for heroin overdose than prescription opioid overdose.

27. Accidental methadone intoxication masquerading as asthma exacerbation with respiratory arrest in a six-year-old boy.

Swenson O.

Del Med J. 2015 May;87(5):147-9.

Comment: Keep your eyes out for pinpoint pupils.

28. Asystolic Cardiac Arrest of Unknown Duration in Profound Hypothermia and Polysubstance Overdose: A Case Report of Complete Recovery.

Lubana SS, Genin DI, Singh N, De La Cruz A.

Am J Case Rep. 2015 Jun 8;16:353-6. doi: 10.12659/AJCR.893880.

Comment: Survival after cardiac arrest in opioid overdose is thought to be quite uncommon.

29. Economic impact of a novel naloxone autoinjector on third-party payers.

Weiss RC, Bazalo GR, Thomson H, Edwards E.

Manag Care. 2015 Feb;24(2):41-8.

Comment: This model attempts to estimate the cost to payers of the naloxone autoinjector, accounting for anticipated savings. There are some serious issues with this model that are quite disappointing. As a minor example, authors used “80%” as the likelihood naloxone would be administered. This assumption was based on a qualitative paper estimating the likelihood that naloxone would be administered if a heroin user was carrying it. In this paper it was used as the likelihood that the autoinjector would be used in an overdose if it had been prescribed. For a model such as this, that’s a quite different parameter.

30. A comparison of liver disease mortality with HIV and overdose mortality among Georgia prisoners and releasees: a 2-decade cohort study of prisoners incarcerated in 1991.

Spaulding AC, Sharma A, Messina LC, Zlotorzynska M, Miller L, Binswanger IA.

Am J Public Health. 2015 May;105(5):e51-7. doi: 10.2105/AJPH.2014.302546. Epub 2015 Mar 19.

Comment: Another paper from the analysis of mortality among prisoners in the state of Georgia (not the country). Overdose was only a minor contributor, in contrast to many other prison releasee studies.

31. Overdose reversal.

Spencer S.

Am J Nurs. 2015 Jan;115(1):13. doi: 10.1097/01.NAJ.0000459609.86788.ac. No abstract available.

Comment: Letter I’m unable to access.

32. Safety studies of post-surgical buprenorphine therapy for mice.

Traul KA, Romero JB, Brayton C, DeTolla L, Forbes-McBean N, Halquist MS, Karnes HT, Sarabia-Estrada R, Tomlinson MJ, Tyler BM, Ye X, Zadnik P, Guarnieri M.

Lab Anim. 2015 Apr;49(2):100-10. doi: 10.1177/0023677214554216. Epub 2014 Oct 10.

Comment: Mice can handle remarkably high doses of buprenorphine without adverse effects.

33. An overview of the patterns of prescription opioid use, costs and related harms in Australia.

Blanch B, Pearson SA, Haber PS.

Br J Clin Pharmacol. 2014 Nov;78(5):1159-66. doi: 10.1111/bcp.12446. Review.

Comment: Review of opioid use and death rates in Australia, illustrating something that looks like a very mild version of what’s happened in the U.S.

34. Gender differences in mortality and risk factors in a 13-year cohort study of street-recruited injecting drug users.

Gjersing L, Bretteville-Jensen AL.

BMC Public Health. 2014 May 10;14:440. doi: 10.1186/1471-2458-14-440.

Comment: Study in Norway of mortality among injectors recruited in 1997 and followed for 13 years, comparing men to women. Overdose was the leading cause of death. Men had a higher mortality rate but women had higher early mortality.