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: 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.

Embarking on a Cost Analysis of Opioid Overdose Morbidity and Mortality in the U.S.

By Leo Beletsky and Andrea Sorensen

Much attention has been devoted in recent years to the alarming increase in morbidity and mortality related to opioid overdose.  Between 2004 and 2007 there was a nearly fourfold increase in the use of prescription opioids in the US, and in at least five states this is now the leading cause of unintentional injury death.[1]  Data such as the number of emergency room visits and deaths attributable to opioid overdose have raised awareness among states and the federal government that there is much work needed in preventing and addressing this epidemic.

A growing body of research and reports addressing this issue have focused on, for example, the severity of this problem in particular states, the trends of a particular opiate such as methadone[2], or the societal cost of drug addiction more broadly.  Lacking from this literature is an assessment of the overall costs that result from the increased overdose morbidity and mortality.  Thus, we intend to perform a cost-of-illness analysis by assessing the costs associated with emergency room visits, lost productivity due to hospitalization, and costs to society resulting from premature deaths.  Data permitting, we will focus on the annual cost in 2008—the most recent year for which healthcare cost data are available. 

We are currently working to collect data and information from a wide variety of sources in order to provide a national cost estimate and range.  Our costs will include healthcare costs/medical expenses; the economic impact from days of work lost due to hospitalization; and the costs associated with lives lost and premature death.  Thus, we will take into account both direct (medical) and indirect (lost productivity and lost lives) to estimate this annual cost burden.

We are relying on DAWN statistics for Emergency room visit data, which provides a breakdown of the annual number of ER visits attributable to opioid/opiate abuse.  DAWN also provides data for the cost of an average hospital stay for accidental poisoning and substance abuse stays, as well as the average length of stay by condition.  This will allow us to calculate the cost per episode that we can use to determine the entire direct health care cost component.  The average length of hospital stay data will also be used to determine lost productivity due to hospitalization.

Prevalence of premature death will be determined using the National Vital Statistics System data.  We will calculate the premature death costs based on previously established methods used in similar cost analysis research:  we will rely on the value of statistical life (VSL) determined by Aldy and Viscusi (2003)—a value that has been used widely in other similar cost studies.  In addition, we will calculate projected lost earnings based on the number of deaths attributable to opioid overdose in each age group, using life expectancy data and estimated earnings data (for each age group).  International Classification of Diseases (ICD) 10th Revision, T-40.0—T40.6 are of interest for this analysis. The overall category ICD -10 T40 includes Poisoning by narcotics and psychodysleptics (hallucinogens).  We have yet to locate this mortality data.  While there are many summary reports published by the CDC, finding specific breakdowns of mortality causes has proven challenging to pinpoint.  It looks as though the Healthcare Cost and Utilization Project (HCUP) offers databases available for purchase that might contain this information (http://www.hcup-us.ahrq.gov/tech_assist/centdist.jsp).  

Questions that have emerged during our initial stage of gathering data and defining costs include selecting proper ICD categories and determining the accuracy of deaths attributable to prescription opioid overdose, as earlier research has found that death certificates might fail to specify this as the reason of death, thus underestimating the actual number.[3]

Our goal is for this cost analysis to inform policymaking and funding decisions.  Our findings can help state and Federal government agencies and other funders quantify the costs of opioid overdose morbidity and loss of life.  Cost estimation is important for setting priorities in prevention programming, surveillance, and research particularly at a time of particularly scarce public health resources. Quantifying this piece can also provide an important component in future benefit-cost preventative treatment studies. 

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[1] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5842a1.htm

[2] http://www.cdc.gov/nchs/data/hestat/poisoning/poisoning.htm

[3] http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5842a1.htm