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.

Cocaine, Speed, and “Overdose”: What Should We Be Doing? Part 2

By Eliza Wheeler, DOPE Project, Harm Reduction Coalition, San Francisco

This is part 2 of a series about cocaine and stimulant-related deaths and what harm reductionists can start doing about it.  We published the first part last week, which was a collection of thoughts about how to move forward to address stimulant-related deaths. This second part deals specifically with stimulants and “overdose” (not the right word, but we’ll get to that). This is a draft of a manual for speed users created as a result of a meeting with some folks from the Speed Project here in San Francisco. We are looking for suggestions on how to improve this document and welcome any feedback on this draft. We’ve included some great quotes from our discussion.

OVERAMPING!

or speed “overdose”

“When I’m talking about overamping, to me when I’m on speed, right, I’m not happy until the second or third day. I’m trying to get there…the first one is just the preliminaries, the first time you’re not there yet, you’re not in the euphoria or where you wanna be. So I got my sack, the first one I’m snorting, now I’m gonna go look for my rigs, now I take my first shot, ok, now I’m gonna go look for who we’re gonna spend time with. It’s like a whole little adventure, I’m in Alice in Wonderland and all this shit’s happening, and then when you’re into your 3^rd or 4^th day and then you take that one shot, still a lot of dope around, still a lot of people around, whatever, it’s fun, it’s casual, everything’s happening cool, and you take that one shot all of a sudden you go damn, I shouldn’t have done that, you did one too many and you just crossed the line and I’m gonna tell you how that feels. It feels like if you’ve ever had an experience with crack and you’re takin a hit and you’re taking a hit and everything’s fine, and you take that one hit all of a sudden, paranoid, everybody’s looking at you, you’re in a fishbowl, but with crystal it’s different because it lasts 12 fucking hours…and the shadow people are watching, everyone’s just on that side of the door looking at you, the cops have binoculars three stories away…”—R

Cocaine, Speed, and “Overdose”: What Should We Be Doing?

By Eliza Wheeler, DOPE Project, Harm Reduction Coalition, San Francisco

This is going to be a two-part post about cocaine and stimulant-related deaths and what harm reductionists can start doing about it. The first part is a rant, the second part is some harm reduction information about stimulants and “overdose” (not the right word, but we’ll get to that), created from a meeting with some folks from the Speed Project here in San Francisco.

The Rant

So, the good news is that we have over 200 places in the U.S. where someone can get naloxone and overdose prevention education, and more are popping up every day. This is a great thing, because we know that opioid-related overdoses (pharmaceuticals and heroin) make up the bulk of overdose deaths in the US. However, according to the CDC’s most recent report, there were 27,658 unintentional drug overdose deaths in the US in 2007 and the second most common drug involved in those deaths, before heroin, was cocaine. According to this report, there were about 12,000 opioid-related deaths and 1,900 heroin deaths—making up the majority. However, there were 5,000 cocaine-related deaths.  I’m sorry, but that’s 5,000 people who died (at least), and I personally think that’s a lot of people.

According to the most recent DAWN report (PDF), here in San Francisco, there were 103 cocaine-related deaths in 2008 and 65 stimulant-related deaths. There were 221 opioid-related deaths. The San Francisco Medical Examiner’s report shows the same thing—the majority of deaths are opioid-related, but following in close second is cocaine. However, cocaine is the most frequently found drug (after alcohol) in people’s system when the Medical Examiner does post-mortem toxicology.  Deaths are not the only issue, however. Stimulants like amphetamine and methamphetamine don’t contribute to a very high number of fatalities on their own, but are mentioned frequently in emergency room admissions and other types of deaths, including homicides, suicides, traumas, vehicular deaths. According to DAWN data, in 2008, cocaine was involved in 482,000 Emergency Department visits—48% of all visits involving illicit drugs. Stimulants, including amphetamines and methamphetamine, were involved in 91,939 ED visits, or 9.3 percent.

My point with the data (and believe me, I know data is flawed and incomplete and never tells the whole story) is that although opioids surely cause the majority of deaths, we have systematically ignored the fact that the second largest number of deaths is attributed to cocaine, not to mention other harms that come from cocaine and stimulant use that land people in the emergency room. By we, I mean harm reduction programs, overdose prevention projects, public health departments—you name it, we’ve done a bad job at addressing cocaine and stimulant-related death and injury.

I have many thoughts on why this is. Part of it is because it’s a more complex issue than opioid overdoses, and there’s no magic bullet like naloxone so people avoid talking about it. Also, cocaine and speed are different, and have different effects on the body, so even within the stimulant category, you need different messages. So are we lazy? Do we not care about cocaine and speed users? What’s our excuse? In my decade of harm reduction work, the most I usually hear in an overdose training is “for stimulants and coke, if they’re having a heart attack do CPR if you know how and call 911, sorry.” Is the harm reduction community (with some wonderful exceptions), shamefully heroin-centric? Is there deeply embedded racism, classism and…drugism (I made that up) effecting how much effort we put into certain aspects of harm reduction work? I think so, considering that in 2011, there are still only a handful of programs that even give out crack pipe covers, and inevitably when someone comes to the exchange tweaked on speed at least one person rolls their eyes and pretends to restock the condoms. The amount of shame and stigma still heaped onto coke and stimulant users is incredible—and I’m talking about just in the harm reduction world.

SO ANYWAY, what do we need? What do we do?

1.  First of all, we need a new word. Overdose is not the right word for what happens with cocaine or speed. Even if it was, it has too strong an association with heroin and other downers. I was talking with a group at the Speed Project in SF recently and I asked “what do you consider an overdose?” and they all said, “It’s what happens when you take too much heroin.” The word that group used to describe the uncomfortable or dangerous effects of taking speed was “overamping.” But what is it called if someone who has been smoking crack for 20 years and dies of a heart attack when they’re walking up the stairs at age 40? Is it an overdose? Not really. But there’s certainly a case to be made that a heart attack at age 40 was highly “influenced” by crack use which we know is very hard on the heart. With stimulants, the problem is not even necessarily dose-related at all. You could overamp on speed on your fourth day of a run because you are dehydrated, malnourished, haven’t slept and your body and mind are just telling you to knock it off. So long story short, like I said, overdose is the wrong word. It’s confusing and inaccurate.

2.  We need more data and research. Actually, we need better interventions and resources, but to get those, you need data and research. As Matt said in his post about “Missing Data,” we need more information on how co-morbidities or other behaviors like smoking affect risk of cocaine-related deaths. I’m curious about the speed-related deaths. What happened? I can never actually find any information on that. In the SF Medical Examiner’s report, it said that a few people died from aneurisms caused by speed. Really? I would like to know a bit more about that, thank you. I called the ME one day, and asked if all of the cocaine-related deaths were from cardiac arrest because I wondered if people also died from fatal seizures or strokes. He laughed at me and told me everyone dies from cardiac arrest. Smart ass. I guess it was a dumb question, but I didn’t know how to ask the question. This is where you researchers come in!

3.  We need to invest the same amount of effort into creating realistic messages around cocaine and speed-related harms that we did with heroin/opioid overdose. This means that drug user involvement in creating interventions for coke and speed users is an obvious necessity. We need to redefine overdose, talk to people about the amazing harm reduction strategies they already use (see part 2 of this post), and develop some real prevention strategies, not just “drink water and get some sleep.”  If we do a better job at treating co-morbidities like high blood pressure, COPD, or cardiovascular disease or offering smoking cessation, could cocaine-related heart attacks decrease?  So, is primary care the answer? Do we invest in educating physicians on how to not treat drug users like crap and to address stimulant-related harms by strengthening the rest of the body? Ah, so many questions.

So in the meantime, while you go figure all of this out, be on the lookout for part 2 of this article, which is a strategy we came up with here in SF to talk about overamping on speed. 

News: Overdose Trends in the USA: More Deaths by Overdose than Traffic Accidents?

The Los Angeles Times has a story up that looks at recent data on overdose deaths in the United States and concludes, among other things, that there are now more fatalities from overdose than form traffic accidents. The basic idea - that there are lots and lots of people dying from overdose and that prescription opioids are responsible for a lot of those deaths - is correct.


Some other aspects of the piece deserve to be read with with a few grains of salt. It's a little unclear how the Times used "preliminary data" from the U.S. Centers for Disease Control and Prevention (CDC) to come up with a purported 37% increase in overdose deaths between 2007 (the year for which CDC most recently reported, at 27,658 deaths) and 2010 (for which the Times estimates 37,485 deaths). Yes the trend has been upward, but I'm going to go out on a limb and say that the figure produced in the article sounds a little wrong.  The article also tends to lean too heavily on scary quotes from law enforcement warning of dire consequences from our "insatiable appetite" for Vicodin and so on, and misses some very interesting data showing major regional differences in overdose mortality. Still, not a terrible article and there's some important information in there.


For a more dispassionate take on recent trends in U.S. drug overdose, it's worth looking at CDC's 2010 issue briefing on "Unintentional Drug Poisoning in the United States." The whole thing is worth reading (and it's only 4 pages), but there are a couple nuggets that strike me as especially interesting. 


One is that while prescription drugs (largely opioids and benzodiazepines, but also other medications used in psychiatry) are now involved in about half of deaths, among illegal drugs cocaine was involved in more than twice as many deaths as heroin, and cocaine deaths have trended upward for the last 10 years. So where's the media attention to cocaine? More importantly, where are good cocaine overdose prevention programs?  Stay tuned, because we'll be looking more into that issue in an upcoming two-part series from the Harm Reduction Coalition's Eliza Wheeler, who runs the DOPE Project in San Francisco. 


Second, there's wide variation among the states. Part of that is due to some big differences in prescribing, but one of the most interesting things is where we see the lowest overdose mortality. For example, in New York and California we see about half the death rate of the states with the highest rates. These also happen to be places that have invested in harm reduction programming, including overdose prevention programs and drug treatment with methadone and buprenorphine. Coincidence? It's probably related to a lot of things, but there sure are a lot of these kinds of coincidences around overdose prevention.