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) Overdoseprevention 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 populationbased).

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.

6) Mortality risk of opioid substitution therapy with methadone versus buprenorphine: a retrospective cohort study.

Kimber J, Larney S, Hickman M, Randall D, Degenhardt L.

Lancet Psychiatry. 2015 Sep 15. pii: S2215-0366(15)00366-1. doi: 10.1016/S2215-0366(15)00366-1. [Epub ahead of print]

Comment: There is likely a mortality benefit to buprenorphine in the initiation of treatment, but after that methadone and buprenorphine are comparable. I’ll admit that I’m a bit surprised by that – I would have expected an ongoing relative benefit to buprenorphine (there was a possible benefit to buprenorphine in all-cause mortality during the treatment time). Of note for treatment programs, even if the eventual treatment is methadone, it may be possible to avert the initiation mortality risk by starting with buprenorphine because the subsequent switch to methadone doesn’t come with the mortality risk.

7) Use of Naloxone by Emergency Medical Services during Opioid Drug Overdose Resuscitation Efforts.

Sumner SA, Mercado-Crespo MC, Spelke MB, Paulozzi L, Sugerman DE, Hillis SD, Stanley C.

Prehosp Emerg Care. 2015 Sep 18:1-6. [Epub ahead of print]

Comment: Really interesting analysis of medical examiner records. They looked at opioid overdose decedents who had undergone resuscitation efforts and then looked to see if they had received naloxone during those paramedic efforts. Naloxone was given in two-thirds of cases and was much more likely to be given to younger men with evidence of illicit drug use. Should paramedics be more willing to use naloxone in settings that don’t look like a “classic heroin overdose”? Or would that have negative effects? This is a really interesting topic for emergency medicine.

8) Heroin overdose resuscitation with naloxone: patient uses own prescribed supply to save the life of a peer.

Winston I, McDonald R, Tas B, Strang J.

BMJ Case Rep. 2015 Sep 14;2015. pii: bcr2015210391. doi: 10.1136/bcr-2015-210391.

Comment: I can’t access this but the abstract purports that it is the “first-ever account” of a lay person titrating naloxone to respiratory function. Not to be snooty, but that’s really old news.

9) Illicit drug use and harms, and related interventions and policy in Canada: A narrative review of select key indicators and developments since 2000.

Fischer B, Murphy Y, Rudzinski K, MacPherson D.

Int J Drug Policy. 2015 Aug 14. pii: S0955-3959(15)00242-X. doi: 10.1016/j.drugpo.2015.08.007. [Epub ahead of print]

Comment: Canada’s conflicted drug policy.

10) Suicidal risk among patients enrolled in methadone maintenance treatment: HCV status and implications for suicide prevention (ANRS Methaville).

Michel L, Lions C, Maradan G, Mora M, Marcellin F, Morel A, Spire B, Roux P, Carrieri PM; Methaville Study Group.

Compr Psychiatry. 2015 Oct;62:123-31. doi: 10.1016/j.comppsych.2015.07.004. Epub 2015 Jul 14.

Comment: Methadone patients with HCV are at *way* higher risk for suicide. Increasingly, studies suggest that there are real mental health costs to HCV and corresponding benefits to HCV treatment.

11) Opioid poisonings in Washington State Medicaid: trends, dosing, and guidelines.

Fulton-Kehoe D, Sullivan MD, Turner JA, Garg RK, Bauer AM, Wickizer TM, Franklin GM.

Med Care. 2015 Aug;53(8):679-85. doi: 10.1097/MLR.0000000000000384.

Comment: The increasing risk of overdose with opioid dose is likely about linear and just knowing dose or dosing frequency/duration doesn’t tell you the whole picture. Unfortunately big data just doesn’t answer the deep questions about substance use.

12) Use of naloxone for clonidine intoxication in the pediatric age group: case report and review of the literature.

Ahmad SA, Scolnik D, Snehal V, Glatstein M.

Am J Ther. 2015 Jan-Feb;22(1):e14-6. doi: 10.1097/MJT.0b013e318293b0e8. Review.

Comment: I can’t access the full article, but am not surprised that naloxone doesn’t reverse clonidine toxicity.

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) Buprenorphineinfrequently found in fatal overdosein 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.

7) Capsule Commentary on Binswanger et al., OverdoseEducation and Naloxone for Patients Prescribed Opioids in Primary Care: A Qualitative Study of Primary Care Staff.

Jackson JL.

J Gen Intern Med. 2015 Aug 19. [Epub ahead of print] No abstract available.

Comment: Summarizes the Bingswanger paper and that’s about it.

8) Factors associated with illicit methadoneinjecting in a Canadian setting.

Tucker D, Milloy MJ, Hayashi K, Nguyen P, Kerr T, Wood E.

Am J Addict. 2015 Sep;24(6):532-7. doi: 10.1111/ajad.12257. Epub 2015 Aug 18.

Comment: Really high-risk people inject methadone.

9) Gender differences in mortality among treated opioid dependent patients.

Evans E, Kelleghan A, Li L, Min J, Huang D, Urada D, Hser YI, Nosyk B.

Drug Alcohol Depend. 2015 Jul 17. pii: S0376-8716(15)00381-6. doi: 10.1016/j.drugalcdep.2015.07.010. [Epub ahead of print]

Comment: Some findings from a longitudinal study that I find hard to interpret and potentially specious.

10) Clinical and Forensic Diagnosis of Very Recent HeroinIntake by 6-acetylmorphine Immunoassay Test and LC-MS/MS Analysis in Urine and Blood.

Borriello R, Carfora A, Cassandro P, Petrella R.

Ann Clin Lab Sci. 2015 Jul;45(4):414-8.

Comment: The 6-MAM assay is pretty good.

11) Intravenous Heroin-Associated Delayed Spongiform Leukoencephalopathy: Case Report and Reviews of the Literature.

Pirompanich P, Chankrachang S.

J Med Assoc Thai. 2015 Jul;98(7):703-8.

Comment: We’ve reviewed heroin-associated spongiform leukoencephalopathy before on this blog. This is another case identified in a heroin injector – instead of smoker – and review of the literature. Interestingly, this case was identified after an overdose.

12) Intermittent versus Persistent Wolff-Parkinson-White Syndrome in Children: Electrophysiologic Properties and Clinical Outcomes.

Kiger ME, McCanta AC, Tong S, Schaffer M, Runciman M, Collins KK.

Pacing Clin Electrophysiol. 2015 Aug 8. doi: 10.1111/pace.12732. [Epub ahead of print]

Comment: There are some questions about the role of cardiac disease on overdose risk – this is pretty clearly the case for cocaine but not well understood for opioids. This report on WPW patients (WPW is an electrical conduction disease of the heart that affects repolarization of cardiac tissue and can result in potentially fatal arrhythmias in otherwise healthy people) refers briefly to a WPW patient who had to be resuscitated after methadone overdose. No further details unfortunately.

13) Orienting patients to greater opioid safety: models of community pharmacy-based naloxone.

Green TC, Dauria EF, Bratberg J, Davis CS, Walley AY.

Harm Reduct J. 2015 Aug 6;12:25. doi: 10.1186/s12954-015-0058-x.

Comment: Two models of pharmacy provision of naloxone. Exciting work in New England.

14) Office-Based Opioid Treatment with Buprenorphine(OBOT-B): Statewide Implementation of the Massachusetts Collaborative Care Model in Community Health Centers.

LaBelle CT, Han SC, Bergeron A, Samet JH.

J Subst Abuse Treat. 2015 Jun 26. pii: S0740-5472(15)00146-4. doi: 10.1016/j.jsat.2015.06.010. [Epub ahead of print]

Comment: Describes an effort to expand buprenorphine treatment availability in Massachusetts.

15) Acute adult and adolescent poisoning in Tehran, Iran; the epidemiologic trend between 2006 and 2011.

Hassanian-Moghaddam H, Zamani N, Rahimi M, Shadnia S, Pajoumand A, Sarjami S.

Arch Iran Med. 2014 Aug;17(8):534-8. doi: 014178/AIM.003.

Comment: Interesting that pesticides match opioids as the two leading causes of poisoning death.

16) DOH issues emergency regulations on expanding use of Narcan to prevent opioid overdose deaths.

[No authors listed]

R I Med J (2013). 2014 Apr;97(4):49. No abstract available.

Comment: We should exercise caution in our use of the term “Narcan” in the future as the brand was purchased by the manufacturers of a nasal device that is likely to be approved in the near future. Promoting one brand over another is poor form in public health and academic venues.