PubMed Update March - May 2015

Three months. 46 papers. I’m already a month behind.

1) Development and implementation of intranasal naloxone opioid overdose response protocol at a homeless health clinic.

Dahlem CH, Horstman MJ, Williams BC.

J Am Assoc Nurse Pract. 2015 Mar 26. doi: 10.1002/2327-6924.12249. [Epub ahead of print]

Comments: Naloxone programs have been providing kits to settings where homeless people receive services for many years. This is a description of a program at a homeless health clinic.

2) Quantification of morphine, morphine 6-glucuronide, buprenorphine, and the enantiomers of methadone by enantioselective mass spectrometric chromatography in whole blood.

Christoffersen DJ, Brasch-Andersen C, Thomsen JL, Worm-Leonhard M, Damkier P, Brøsen K.

Forensic Sci Med Pathol. 2015 Jun;11(2):193-201. doi: 10.1007/s12024-015-9673-9. Epub 2015 Mar 24.

Comments: It’s been awhile since we had a forensics paper here. I think this is a novel method of identifying enantiomers.

3) 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.

Comments: Stunningly low rate of drug overdose mortality in this cohort of prisoners in Georgia. This is one of the first times I’ve seen a paper on opioid overdose find radically different results in a different setting. I can’t access for details.

4) A Review of Opioid Overdose Prevention and Naloxone Prescribing: Implications for Translating Community Programming Into Clinical Practice.

Mueller SR, Walley AY, Calcaterra SL, Glanz JM, Binswanger IA.

Subst Abus. 2015 Mar 16:1-14. [Epub ahead of print]

Comments: A review toward the end of using community distribution data to build clinical care naloxone prescription.

5) Long-term course of opioid addiction.

Hser YI, Evans E, Grella C, Ling W, Anglin D.

Harv Rev Psychiatry. 2015 Mar-Apr;23(2):76-89. doi: 10.1097/HRP.0000000000000052.

Comments: This is a systematic review of long-term studies of opioid users. Among many fascinating data reported, the length of time not using a drug of choice increases the likelihood of continuing to not use that drug. This seems obvious to many, but I don’t believe it’s been documented before. Good read for anyone looking to understand some of the longitudinal outcome data.

PubMed Update August-October 2014

Three months. 32 articles. Enough said.

1. Patterns and correlates of non-fatal heroin overdose at 11-year follow-up: Findings from the Australian Treatment Outcome Study.

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

Drug Alcohol Depend. 2014 Sep 16. [Epub ahead of print]

Comment: This study (the ATOS) and the team of investigators have produced some of the most powerful and useful data in substance use research. Once again they have delved into heroin overdose by following treatment patients 11 years out. At least 10.2% of the cohort had died by that time and an additional 9.4% were unaccounted for. Among the 70.1% interviewed, 67.5% had overdosed, 24.4% had experienced five or more overdoses (again suggesting that there are “overdosers” out there who are at very elevated risk of the event). In the past year before the follow-up visit, 4.9% had overdosed (11.8% of those who had used heroin in that period), 95.2% of whom had overdosed previously. Those who overdosed were more likely to report higher levels of non-heroin opiate use, as well as benzodiazepine, cocaine, and methamphetamine use.

2. A new naloxone auto-injection device to treat opioid overdose.

Simonson W.

Geriatr Nurs. 2014 Sep-Oct;35(5):381-2.

Comment: A review of the role of take-home naloxone in the form of the new autoinjector.

3. Increases in heroin overdose deaths - 28 States, 2010 to 2012.

Rudd RA, Paulozzi LJ, Bauer MJ, Burleson RW, Carlson RE, Dao D, Davis JW, Dudek J, Eichler BA, Fernandes JC, Fondario A, Gabella B, Hume B, Huntamer T, Kariisa M, Largo TW, Miles J, Newmyer A, Nitcheva D, Perez BE, Proescholdbell SK, Sabel JC, Skiba J, Slavova S, Stone K, Tharp JM, Wendling T, Wright D, Zehner AM.

MMWR Morb Mortal Wkly Rep. 2014 Oct 3;63(39):849-54.

Comment: This report demonstrates declining prescription opioid deaths (-6.6%), but heroin deaths increased so much (+101.7%) that the data actually demonstrate an overall increase in opioid overdose mortality from 2010 to 2012 (+4.3%). There is disagreement as to what is driving the increase in heroin use and overdose. Is it an inevitable consequence of increased availability of opioids? Or is it the result of growing restrictions on access to those opioids? Clearly there are elements of both, leaving us with conflicting duties when it comes to managing those already reliant upon prescription opioids. Western medical ethics is clear on this point: our patient is the person we treat, who may have been harmed by the very same prescribing behavior we are now trying to change and who may be further harmed by those changes. If we truly believe that this epidemic is “iatrogenic” (i.e. caused by medical care, akin to a surgeon leaving scissors in an abdomen), then we have to be extremely cautious and thoughtful in fixing the problem and we can never abandon the patient.

4. Working together: Expanding the availability of naloxone for peer administration to prevent opioid overdose deaths in the Australian Capital Territory and beyond.

Lenton S, Dietze P, Olsen A, Wiggins N, McDonald D, Fowlie C.

Drug Alcohol Rev. 2014 Oct 1. doi: 10.1111/dar.12198. [Epub ahead of print]

Comment: It's taken an incredibly long time for take-home naloxone to reach Australia, especially given how innovative that country has been with respect to managing drug policy and overdose.

5. Responding to opioid overdose in Rhode Island: where the medical community has gone and where we need to go.

Green TC, Bratberg J, Dauria EF, Rich JD.

R I Med J (2013). 2014 Oct 1;97(10):29-33.

Comment: The first of three articles in this post from Rhode Island, US, which has been facing a surge in opioid overdose deaths and has been responding with expanded naloxone treatment availability. This and the next two articles are free at: http://rimed.org/rimedicaljournal-2014-10.asp.

PubMed Update November/December 2013

We close out 2013 with an impressive 25 papers in the final two months for a total count of 89 papers. Some interesting new approaches and perspectives, including a paper on the underappreciated role of adulterants, a couple of naltrexone papers, and lots of lay naloxone.

1) The Whole Is Just the Sum of Its Parts: Limited Polydrug Use Among the "Big Three" Expensive Drugs in the United States.

Caulkins JP, Everingham S, Kilmer B, Midgette G.

Curr Drug Abuse Rev. 2013 Dec 5. [Epub ahead of print]

Comments: Somewhat surprising data suggesting relatively separate markets for heroin, cocaine and methamphetamine.

2) A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence.

Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L.

Drug Alcohol Rev. 2013 Dec 3. doi: 10.1111/dar.12095. [Epub ahead of print]

Comments: A systematic review concluding that the data for naltrexone implants for opioid dependence are insufficient for use outside of clinical trials.

3) Trends and Regional Variation in Opioid Overdose Mortality Among Veterans Health Administration Patients, Fiscal Year 2001 to 2009.

Bohnert AS, Ilgen MA, Trafton JA, Kerns RD, Eisenberg A, Ganoczy D, Blow FC.

Clin J Pain. 2013 Nov 25. [Epub ahead of print]

Comments: What happened with opioid analgesic overdose deaths in the United States also happened in among veterans receiving care in the Veterans’ Administration.

4) The Dueling Obligations of Opioid Stewardship.

Coffin P, Banta-Green C.

Ann Intern Med. 2013 Dec 10. doi: 10.7326/M13-2781. [Epub ahead of print] No abstract available.

Comments: Commentary on the reliance on opioids and minimizing the potential harms of stewardship efforts.

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 April 2013

10 papers this time. Good stuff.

1. Take-Home Emergency Naloxone to Prevent Heroin Overdose Deaths after Prison Release: Rationale and Practicalities for the N-ALIVE Randomized Trial.

Strang J, Bird SM, Parmar MK.

J Urban Health. 2013 May 1. [Epub ahead of print]

Comment: Really interesting article on the design of the N-ALIVE trial of naloxone provision to prisoners pre-release.

2. Determination of dextromethorphan and levomethorphan in seized heroin samples by enantioselective HPLC and electronic CD.

Tedesco D, Di Pietra AM, Rossi F, Garagnani M, Del Borrello E, Bertucci C, Andrisano V.

J Pharm Biomed Anal. 2013 Apr 6;81-82C:76-79. doi: 10.1016/j.jpba.2013.03.024. [Epub ahead of print]

Comment: Methods paper demonstrating methorphan in some heroin samples involved in overdose death.

3. All-cause mortality in criminal justice clients with substance use problems-A prospective follow-up study.

Hakansson A, Berglund M.

Drug Alcohol Depend. 2013 Apr 24. doi:pii: S0376-8716(13)00109-9. 10.1016/j.drugalcdep.2013.03.014. [Epub ahead of print]

Comments: Another analysis of post-release mortality among prisoners, in which the largest group (39%) of deaths were due to accidental or undetermined intent poisoning.

4. Changing law from barrier to facilitator of opioid overdose prevention.

Davis C, Webb D, Burris S.

J Law Med Ethics. 2013 Mar;41 Suppl 1:33-6. doi: 10.1111/jlme.12035.

Comments: Excellent analysis of naloxone and Good Samaritan legislation.

PubMed Update December 2012 - January 2013

This is a really exciting time for research into overdose in general and naloxone in particular. 15 papers this time.

1. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.

Walley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A.

BMJ. 2013 Jan 30;346:f174. doi: 10.1136/bmj.f174.

Comments: A long-awaited paper for which the authors deserve high praise, as they have produced the first real evidence of naloxone effectiveness and arguably the most important contribution to naloxone literature to-date. Although not randomized, the interrupted time series analysis is respectable and the results are impressive.

2. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal.

Coffin PO, Sullivan SD.

Ann Intern Med. 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.

Comments: I’ve wanted to write this paper for about a decade, when I thought about cost-effectiveness as three to four calculations on the back of a napkin, rather than years of work and RAM-straining matrices. There’s a long way to go with overdose research that will certainly contribute to future iterations of the model. In the meantime, this is probably a fair, if quite conservative, initial estimate. There is one sensitivity analysis – in which naloxone results in behavior change such that overdose risk is lower – which I suspect may be closer to the actual truth.

3. Naloxone for heroin overdose reversal.

Ann Intern Med. 2013 Jan 1;158(1):I-30. doi: 10.7326/0003-4819-158-1-201301010-00001. No abstract available.

Comments: An excellent editorial from our colleagues at NIDA and the FDA.

4. Prescription opioid use among addictions treatment patients: Nonmedical use for pain relief vs. other forms of nonmedical use.

Bohnert AS, Eisenberg A, Whiteside L, Price A, McCabe SE, Ilgen MA.

Addict Behav. 2012 Nov 23;38(3):1776-1781. doi: 10.1016/j.addbeh.2012.11.005. [Epub ahead of print]

Comments: Survey of prescription opioid use among treatment program patients. Use for reasons other than pain relief was associated with overdose as well as use of several other agents that increase the risk of overdose.

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.