PubMed Update October 2015

28 in a month.

1) Clinical Presentation and the Outcome of Therapy in a Cohort of Patients with Methadone Toxicity in Iran.

Eizadi-Mood N, Yaraghi A, Sharifian Z, Feizi A, Hedaiaty M, Sabzghabaee AM.

Mater Sociomed. 2015 Aug;27(4):276-9. doi: 10.5455/msm.2015.27.276-279.

Comments: Some interesting data on methadone toxicity in Iran. Length of stay was 33 hours (median). 90.3% survived. There were several complications. GCS on admission predicted survival. Useful data for economic modeling …

2) Overdose prevention for prisoners in New York: a novel program and collaboration.

Zucker H, Annucci AJ, Stancliff S, Catania H.

Harm Reduct J. 2015 Nov 5;12(1):51. doi: 10.1186/s12954-015-0084-8.

PMID: 26541987 Free Article

Comments: Early report describing the establishment of a prison naloxone program in NY. Some of the most important work happening in this area…

3) Response to "Quality Assessment Errors and Study Misclassification Threaten Systematic Review Validity: Community Opioid Overdose Prevention and Naloxone Distribution Programs Review".

Winstanley EL, Clark A, Wilder CM.

J Addict Med. 2015 Dec;9(6):503-4. doi: 10.1097/ADM.0000000000000160. No abstract available.

Comments: Can’t access. Meh.

4) Quality Assessment Errors and Study Misclassification Threaten Systematic Review Validity: Community Opioid Overdose Prevention and Naloxone Distribution Programs Review: Re: Clark AK, Wilder CM, Winstanley EL. A systematic review of community opioid overdose prevention and naloxone distribution programs. J Addict Med 2014 May-June;8(3): 153-163.

Orkin AM, Bingham K, Buick JE, Klaiman M, Leece P, Kouyoumdjian F.

J Addict Med. 2015 Dec;9(6):502-3. doi: 10.1097/ADM.0000000000000161. No abstract available.

Comments: Also can’t access.

5) Implementation of an inpatient opioid overdose prevention program.

Clark A, Winstanley EL, Martsolf DS, Rosen M.

Addict Behav. 2015 Oct 8;53:141-145. doi: 10.1016/j.addbeh.2015.10.006. [Epub ahead of print] No abstract available.

Comments: Authors report on development of an electronic book on overdose prevention for use in addiction treatment settings.

6) Evaluation of knowledge and confidence following opioid overdose prevention training: A comparison of types of training participants and naloxone administration methods.

Ashrafioun L, Gamble S, Herrmann M, Baciewicz G.

Subst Abus. 2015 Oct 29:0. [Epub ahead of print]

Comments: Those trained in intranasal naloxone were more confident than those trained in injectable. That is odd, as studies suggest that injectable is easier than intranasal.

7) Methadone related deaths compared to all prescription related deaths.

Lev R, Petro S, Lee A, Lee O, Lucas J, Castillo EM, Egnatios J, Vilke GM.

Forensic Sci Int. 2015 Oct 22;257:347-352. doi: 10.1016/j.forsciint.2015.09.021. [Epub ahead of print]

Comments: The lack of data from methadone maintenance programs makes it quite challenging to interpret some of the methadone-related mortality data.

8) Exploring the life-saving potential of naloxone: A systematic review and descriptive meta-analysis of take home naloxone (THN) programmes for opioid users.

McAuley A, Aucott L, Matheson C.

Int J Drug Policy. 2015 Oct 1. pii: S0955-3959(15)00306-0. doi: 10.1016/j.drugpo.2015.09.011. [Epub ahead of print]

Comments: 9% of kits were likely to be used for overdose rescue. That looks like a rather low number, but it’s over a 3-month period. I suspect the annual rate is closer to 20% +/- 5%.

9) Legal changes to increase access to naloxone for opioid overdose reversal in the United States.

Davis CS, Carr D.

Drug Alcohol Depend. 2015 Oct 22. pii: S0376-8716(15)01695-6. doi: 10.1016/j.drugalcdep.2015.10.013. [Epub ahead of print]

Comments: Great paper, title says it all.

10) Understanding Heroin Overdose: A Study of the Acute Respiratory Depressant Effects of Injected Pharmaceutical Heroin.

Jolley CJ, Bell J, Rafferty GF, Moxham J, Strang J.

PLoS One. 2015 Oct 23;10(10):e0140995. doi: 10.1371/journal.pone.0140995. eCollection 2015.

Comments: I like this study. The physiology of “overdose” is totally fascinating and nowhere near as simple as it seems.

11) Hair testing in postmortem diagnosis of substance abuse: An unusual case of slow-release oral morphine abuse in an adolescent.

Baillif-Couniou V, Kintz P, Sastre C, Pok PP, Chèze M, Pépin G, Leonetti G, Pelissier-Alicot AL.

J Forensic Leg Med. 2015 Sep 4;36:172-176. doi: 10.1016/j.jflm.2015.08.014. [Epub ahead of print]

Comments: Morphine overdose in an adolescent in France. It’s news there because they don’t see people dying of prescription opioids like in the U.S.

12) Effects of acute and repeated administration of oxycodone and naloxone-precipitated withdrawal on Intracranial Self-Stimulation (ICSS) in rats.

Wiebelhaus JM, Walentiny DM, Beardsley PM.

J Pharmacol Exp Ther. 2015 Oct 21. pii: jpet.115.228940. [Epub ahead of print]

Comments: Oxycodone works like other opioids.

13) Risk factors associated with benzodiazepine use among people who inject drugs in an urban Canadian setting.

Tucker D, Hayashi K, Milloy MJ, Nolan S, Dong H, Kerr T, Wood E.

Addict Behav. 2015 Oct 9;52:103-107. doi: 10.1016/j.addbeh.2015.10.002. [Epub ahead of print]

Comments: Benzo use is associated with lots of risk factors for negative health outcomes, including blood-borne virus transmission, among drug users.

14) Commentary on Gjersing & Bretteville-Jensen (2015): EMS-treated opioid overdose-an important opportunity for saving lives.

Dailey M.

Addiction. 2015 Nov;110(11):1775-6. doi: 10.1111/add.13093. No abstract available.

Comments: Nice commentary, pointing out the opportunities for intervention among those who contact the medical system with an overdose.

15) Flumazenil, naloxone and the 'coma cocktail'.

Sivilotti ML.

Br J Clin Pharmacol. 2015 Aug 7. doi: 10.1111/bcp.12731. [Epub ahead of print] Review.

Comments: Fascinating differences between benzo and opioid-induced respiratory depression. Benzos cause apnea usually because the upper airway is blocked or collapses – so respiratory support is the need – and the antidote can lead to seizures. Opioids are different and naloxone much safer.

16) Opioid Therapy and Sleep Disorders: Risks and Mitigation Strategies.

Cheatle MD, Webster LR.

Pain Med. 2015 Oct;16 Suppl 1:S22-6. doi: 10.1111/pme.12910. Review.

Comments: Opioids might be dangerous with sleep disorders.

17) More than just someone to inject drugs with: Injecting within primary injection partnerships.

Morris MD, Bates A, Andrew E, Hahn J, Page K, Maher L.

Drug Alcohol Depend. 2015 Nov 1;156:275-81. doi: 10.1016/j.drugalcdep.2015.09.025. Epub 2015 Sep 30.

Comments: Injection partnerships can have divergent benefits and risks.

18) A True Antidote.

Berlin J.

Tex Med. 2015 Oct 1;111(10):41-7.

Comments: Naloxone in Texas!

19) The effect of prescription opioid injection on the risk of non-fatal overdose among people who inject drugs.

Lake S, Hayashi K, Buxton J, Milloy MJ, Dong H, Wood E, Montaner J, Kerr T.

Drug Alcohol Depend. 2015 Nov 1;156:297-303. doi: 10.1016/j.drugalcdep.2015.09.026. Epub 2015 Sep 30.

Comments: Interesting analysis – injecting prescription opioids didn’t by itself increase overdose risk. Injecting of both prescription opioids and heroin did, however. So there is probably some protection offered by the known doses and constituents in prescription opioids.

20) Worldwide Prevalence and Trends in Unintentional Drug Overdose: A Systematic Review of the Literature.

Martins SS, Sampson L, Cerdá M, Galea S.

Am J Public Health. 2015 Nov;105(11):e29-49. doi: 10.2105/AJPH.2015.302843.

Comments: Nice summary of global data looking at some basic overdose results. Mean/median rate of witnessed overdose in a drug user’s lifetime = 73/70%. Lifetime prevalence of experienced overdose was mean of 45.4% and median of 47%. Population-based overdose mortality rates varied from 0.4-46.6 / 100,000 person years (note, this is population based).

21) An Overdose Antidote Goes Mainstream.

Humphreys K.

Health Aff (Millwood). 2015 Oct 1;34(10):1624-7. doi: 10.1377/hlthaff.2015.0934.

Comments: Review of naloxone based on summer 2015 FDA meeting.

22) Is immunotherapy an opportunity for effective treatment of drug addiction?

Zalewska-Kaszubska J.

Vaccine. 2015 Oct 2. pii: S0264-410X(15)01369-9. doi: 10.1016/j.vaccine.2015.09.079. [Epub ahead of print] Review.

Comments: Really interesting idea – use antibodies against drugs, like cocaine, to manage overdose on those drugs. Excellent.

23) Involvement of Opioid Receptors in the Lipid Rescue of Bupivacaine-Induced Cardiotoxicity.

Partownavid P, Sharma S, Li J, Umar S, Rahman S, Eghbali M.

Anesth Analg. 2015 Aug;121(2):340-7. doi: 10.1213/ANE.0000000000000788.

Comments: Opioid receptors are required for rescuing people from the cardiac toxicity of bupivacaine overdose.

24) New drugs of abuse.

Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E.

Pharmacotherapy. 2015 Feb;35(2):189-97. doi: 10.1002/phar.1522. Epub 2014 Dec 4. Review.

Comments: Desomorphine. Blech.

25) What we know, and don't know, about the impact of state policy and systems-level interventions on prescription drug overdose.

Haegerich TM, Paulozzi LJ, Manns BJ, Jones CM.

Drug Alcohol Depend. 2014 Dec 1;145:34-47. doi: 10.1016/j.drugalcdep.2014.10.001. Epub 2014 Oct 14. Review.

Comments: Not much.

26) Access to harm reduction and HIV-related treatment services inside Indian prisons: experiences of formerly incarcerated injecting drug users.

Chakrapani V, Kamei R, Kipgen H, Kh JK.

Int J Prison Health. 2013;9(2):82-91. doi: 10.1108/17449201311326952.

Comments: Access is … no there.

27) Low Expression of D2R and Wntless Correlates With High Motivation for Heroin.

Tacelosky DM, Alexander DN, Morse M, Hajnal A, Berg A, Levenson R, Grigson PS.

Behav Neurosci. 2015 Oct 26. [Epub ahead of print]

Comments: Holding drug exposure constant, reducing dopamine D2 receptors or that other thing (Wntless) results in more opioid craving.

28) The misuse and abuse of prescription medications: part 1 current trends.

Allread V, Paul S.

MD Advis. 2014 Fall;7(4):12-20. Review.

Comments: Can’t access. Review for New Jersey and rest of US regarding prescription opioids and heroin use.

PubMed Update September 2015

Twelve this month. Enjoy!

1) Correlates of Opioid Use in Adults With Self-Reported Drug Use Recruited From Public Safety-Net Primary Care Clinics.

Ries R, Krupski A, West II, Maynard C, Bumgardner K, Donovan D, Dunn C, Roy-Byrne P.

J Addict Med. 2015 Oct;9(5):417-26. doi: 10.1097/ADM.0000000000000151.

Comment: Can’t access the full article, but the abstract suggests a fascinating look into opioid-using safety net primary care patients.

2) Suicide Risk of Heroin Dependent Subjects in Lebanon.

Kazour F, Soufia M, Rohayem J, Richa S.

Community Ment Health J. 2015 Sep 30. [Epub ahead of print]

Comment: Most studies of heroin users find that heroin is *not* the usual method of suicide attempts. Interestingly, this study finds something quite different, with nearly half of attempts being through heroin use in Lebanon.

3) Trends and characteristics of accidental and intentional codeine overdose deaths in Australia.

Roxburgh A, Hall WD, Burns L, Pilgrim J, Saar E, Nielsen S, Degenhardt L.

Med J Aust. 2015 Oct 5;203(7):299.

Comment: Interesting paper exploring deaths related to one, low-potency, opioid. Those deaths seemed to be increasing, over a third were intentional (that’s much higher than other opioids), and a remarkably high proportion were polydrug – which makes sense since it would be tough to die from codeine alone.

4) American Society of Addiction Medicine (ASAM) National Practice Guideline for the Use of Medications in the Treatment of Addiction Involving Opioid Use.

Kampman K, Jarvis M.

J Addict Med. 2015 Oct;9(5):358-67. doi: 10.1097/ADM.0000000000000166.

Comment: Another that I can’t access but whose abstract looks compelling.

5) Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.

Kharasch ED, Regina KJ, Blood J, Friedel C.

Anesthesiology. 2015 Sep 19. [Epub ahead of print]

Comment: Ah, the complexities of methadone. Genetic differences in hepatic metabolism are more prominent in oral than intravenous methadone.

PubMed Update August 2015

Sixteen in August. Back on schedule (thanks to jetlag).

1) Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies.

Hawk KF, Vaca FE, D'Onofrio G.

Yale J Biol Med. 2015 Sep 3;88(3):235-245. eCollection 2015 Sep. Review.

Comment: Can’t access full article. Appears to be a review of harm reduction strategies for opioid overdose prevention.

2) Prescription Opioid Misuse, Abuse, and Treatment in the United States: An Update.

Brady KT, McCauley JL, Back SE.

Am J Psychiatry. 2015 Sep 4:appiajp201515020262. [Epub ahead of print]

Comment: Appropriately draws attention to the problem now faced in the United States: we are cutting back on opioid prescribing to try to limit further opioid dependence, but effectively abandoning many of the people who are already dependent.

3) Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series.

DeVido J, Connery H, Hill KP.

J Opioid Manag. 2015 Jul-Aug;11(4):363-6. doi: 10.5055/jom.2015.0285.

Comment: Two case reports of sleep-disordered breathing among buprenorphine patients suggesting that buprenorphine may contribute to sleep apnea.

4) Buprenorphine infrequently found in fatal overdose in New York City.

Paone D, Tuazon E, Stajic M, Sampson B, Allen B, Mantha S, Kunins H.

Drug Alcohol Depend. 2015 Aug 15. pii: S0376-8716(15)01598-7. doi: 10.1016/j.drugalcdep.2015.08.007. [Epub ahead of print]

Comment: Actually, none of the decedents tested positive for buprenorphine - very few (2) were found to have positive toxicology for norbuprenorphine, a metabolite demonstrating recent – but not recent enough to be causal – consumption of buprenorphine. This is not surprising since it’s tough to overdose on buprenorphine. Nice work.

5) Risk Factors for Mortality and Endotracheal Intubation after Methadone Intoxication.

Hassanian-Moghaddam H, Soltaninejad K, Shadnia S, Kabir A, Movahed M, Mirafzal A.

Basic Clin Pharmacol Toxicol. 2015 Aug 24. doi: 10.1111/bcpt.12476. [Epub ahead of print]

Comment: Lower consciousness/respirations once in the emergency room were associated with increased likelihood of being intubated and/or dying from methadone overdose. This is interesting in the context of previous papers included on this blog that demonstrate lower likelihood of such outcomes when naloxone is administered in the field. Is it time to think of naloxone as an automated electronic defibrillator?

6) The characteristics of a cohort who tamper with prescribed and diverted opioid medications.

Larance B, Lintzeris N, Bruno R, Peacock A, Cama E, Ali R, Kihas I, Hordern A, White N, Degenhardt L.

J Subst Abuse Treat. 2015 Jun 24. pii: S0740-5472(15)00137-3. doi: 10.1016/j.jsat.2015.06.001. [Epub ahead of print]

Comment: This is a complex population. Although risk outcomes appear closer to those of someone who uses heroin than those of someone prescribed opioids, the clinical characteristics overlap substantially with the latter group.

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.

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 November 2014 - February 2015

Catching up on 51 papers in 4 months. Did you miss me?

1) New Drugs of Abuse.

Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E.

Pharmacotherapy. 2014 Dec 4. doi: 10.1002/phar.1522. [Epub ahead of print]

Comment: Review of management of drug toxicities among novel, synthetic compounds.

2) Police officer attitudes towards intranasal naloxone training.

Ray B, O'Donnell D, Kahre K.

Drug Alcohol Depend. 2015 Jan 1;146:107-10. doi: 10.1016/j.drugalcdep.2014.10.026. Epub 2014 Nov 8.

Comment: Police officers like being trained to carry naloxone.

3) Intranasal naloxone administration for treatment of opioid overdose.

Robinson A, Wermeling DP.

Am J Health Syst Pharm. 2014 Dec 15;71(24):2129-35. doi: 10.2146/ajhp130798.

Comment: Review of intranasal naloxone for overdose reversal.

4) Observed transition from opioid analgesic deaths toward heroin.

Dasgupta N, Creppage K, Austin A, Ringwalt C, Sanford C, Proescholdbell SK.

Drug Alcohol Depend. 2014 Dec 1;145:238-41. doi: 10.1016/j.drugalcdep.2014.10.005. Epub 2014 Oct 18.

Comment: Heroin overdoses are increasing.

5) Brief overdose education can significantly increase accurate recognition of opioid overdose amongheroin users.

Jones JD, Roux P, Stancliff S, Matthews W, Comer SD.

Int J Drug Policy. 2014 Jan;25(1):166-70. doi: 10.1016/j.drugpo.2013.05.006. Epub 2013 Jun 15.

Comment: Brief overdose training works for naloxone distribution. This is important because many places are requiring prolonged trainings that end up limiting access to those who are unable or unwilling to invest that degree of time.

6) Brief overdose education is sufficient for naloxone distribution to opioid users.

Behar E, Santos GM, Wheeler E, Rowe C, Coffin PO.

Drug Alcohol Depend. 2015 Mar 1;148:209-12. doi: 10.1016/j.drugalcdep.2014.12.009. Epub 2014 Dec 19.

Comment: Again, brief overdose training works for naloxone distribution.