Pubmed December 2011 Update

My favorites this week includes the first two - a paper from Serbia on post-mortem evaluations and a review of a LARGE dataset describing types of prescription opioid users and their overdose risk profiles.

1) Association of pulmonary histopathological findings with toxicological findings in forensic autopsies of illicit drug users.

Todorović MS, Mitrović S, Aleksandrić B, Mladjenović N, Matejić S.

Vojnosanit Pregl. 2011 Aug;68(8):639-42.

Comment: This is a really interesting paper out of Serbia. Pulmonary edema (water in the lungs) by far most common pathological finding in drug users who died suddenly, most of whom were opioid users. This makes sense and is not inconsistent with the known mechanism of death from opioids. Of note, pulmonary edema has been reported in people who were administered naloxone, but this is almost certainly due to the overdose itself rather than any toxicity from naloxone.

2) Typologies of prescription opioid use in a large sample of adults assessed for substance abuse treatment.

Green TC, Black R, Grimes Serrano JM, Budman SH, Butler SF.

PLoS One. 2011;6(11):e27244. Epub 2011 Nov 2.

Comment: This one takes a while to read through, but is intensely interesting. I highly recommend taking a close look at the article, the figures and tables, and even (!) digging through the entire text. Keep in mind this is a sample seeking substance abuse treatment - this is not an analysis of the general population of people who use prescription opioid.

3) HIV infection and risk of overdose: a systematic review and meta-analysis.

Green TC, McGowan SK, Yokell MA, Pouget ER, Rich JD.

AIDS. 2011 Nov 22.

Comment: In many areas of the world, overdose is the most common cause of death among those at risk for (or infected with) HIV. This study found that HIV-seropositivity was associated with a 74% increased risk overdose death (I can't access the article to provide more detail about this).

__________________________________

The next two are directed at those prescribing opioids ...

4) Canadian guideline for safe and effective use of opioids for chronic noncancer pain: Clinical summary for family physicians. Part 2: special populations.

Kahan M, Wilson L, Mailis-Gagnon A, Srivastava A.

Can Fam Physician. 2011 Nov;57(11):1269-76.

Comment: Title is really self-explanatory - recommendations for managing opioids in adolescents.

5) Management of chronic noncancer pain in depressed patients.

Barkin RL, Barkin SJ, Irving GA, Gordon A.

Postgrad Med. 2011 Sep;123(5):143-54. Review.

Comments: Another review for physicians of how to not rely so much on opioids for chronic pain.

Initial results from evaluation of Washington State's "911 Good Samaritan Law"

Washington State passed an overdose bill granting immunity from drug possession charges for those who witness or experience an overdose if help is sought AND granting legal and professional immunity to those who prescribe, dispense, purchase, possess, administer, or use naloxone with the intent to reverse opioid overdose.

Dr Caleb Banta-Green, of the University of Washington Alcohol and Drug Abuse Institute, headed up an evaluation of this law, with an emphasis on the "Good Samaritan" component that protects from drug charges. The study is funded by a grant from the Robert Wood Johnson Foundation to look at the law's legal intent, implementation, and outcomes. This is the first such evaluation of this type of law in the United States.

The study will ultimately include evaluations of behavior change among drug users, police, and paramedics during heroin overdoses, the legal intent of the law through document reviews and interviews with legislators and other stakeholders, and changes in the rates of opioid overdose (fatal and non-fatal), 911 overdose call volume and severity, and naloxone administration by lay persons and medical professionals.

Dr Banta-Green has released a preliminary report including legal intent and baseline beliefs, knowledge, and behaviors.

Disclaimer: I am one of the co-investigators on this study.

Pubmed November 2011 Update

Some good stuff this month...

1) Vital signs: overdoses of prescription opioid pain relievers --- United States, 1999--2008

MMWR Morb Mortal Wkly Rep. 2011 Nov 4;60:1487-92.

Comment: This report summarizes the impressive outbreak of death from opioid analgesics (around 15,000 in 2008) in the United States - providing a helpful state-by-state breakdown.

2) Influence of war on quantitative and qualitative changes in drug-induced mortality in Split-Dalmatia County, Croatia

Marasovic Susnjara I, Definis Gojanovic M, Vodopija D, Capkun V, Smoljanovic A.

Croat Med J. 2011 Oct 15;52(5):629-36.

Comment: Authors developed an interesting association of war and post-war periods with increased overdose deaths, the majority of which were due to heroin and half of which involved multiple drugs. Authors hypothesize that the reason for this increase is due to social instability and increased drug supply.

3) Pilot scheme shows that giving naloxone to families of drug users would save lives

Hurley R.

BMJ. 2011 Aug 25;343:d5445. doi: 10.1136/bmj.d5445. No abstract available.

Comment: A brief summary of the pilot program at drug treatment programs in England. 495 "carers" (generally family members) were trained and a subgroup (number not in the text) were also given naloxone in 2009 and 2010. Twenty ODs were witnessed and naloxone was given in 18 of those; all survived. These are important results, particularly in two settings: 1) regions where drug users frequently live with family, and 2) settings such as abstinence-based treatment or youth programs where there might be reluctance to provide a drug user with naloxone.

4) Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats.

Wallisch M, El Rody NM, Huang B, Koop DR, Baker JR Jr, Olsen GD.

Respir Physiol Neurobiol. 2011 Oct 19.

Comment: I don't usually include animal studies, but this was intriguing. Authors developed a depot pro-drug of naloxone that is released in the setting of hypoxemia - that is, when there's a low-level of oxygen in the blood naloxone is released, reversing the (presumed) opiate effect.

5) A History of Being Prescribed Controlled Substances and Risk of Drug Overdose Death.

Paulozzi LJ, Kilbourne EM, Shah NG, Nolte KB, Desai HA, Landen MG, Harvey W, Loring LD.

Pain Med. 2011 Oct 25. doi: 10.1111/j.1526-4637.2011.01260.x.

Comment: Our understanding of opioid analgesic deaths is so poor for many reasons - most notably it is hard to study this population because they are hidden. The authors here used a case-control design (I can't access the full article and their methods are not so well-described in the abstract) to identify risk factors for death. They found receipt of prescriptions for selected opioids and >40mg morphine equivalents daily to be substantial risk factors for overdose death. This is consistent with earlier studies.

News: Toronto now distributing naloxone kits (with bad instructions?)

A Toronto overdose kit

Good news from the great city of Toronto, where the city launched an overdose education and naloxone distribution program in October. Here's the full story from the CBC. As Toronto harm reduction pioneer Raffi Balian says in the article, "to have this product, which can reverse an overdose right away, is an amazing thing. I know it works because I have brought people back from overdoses at least three times and one person twice."

A couple things stuck out from the article though. First, have a look at the photo, which appears to show the contents of kits distributed by the city. The instructions on the pocket card are a little questionable, including direction to do chest compressions and no mention of airway management or rescue breathing. Second, the article has Shaun Hopkins, a Toronto needle exchange manager, saying that naloxone costs the city $8 a dose. Producers have been jacking up prices far and wide over the past couple years, but is Toronto getting ripped off? Comments and clarification from OPA's Toronto readers will be very welcome.

Overdose in Eastern Europe and Central Asia

The Eurasian Harm Reduction Network, which represents harm reduction groups in Central and Eastern Europe and Central Asia, recently launched a newsletter, and the first issue covers overdose in the region. You can download the English edition here, and the Russian here.


The whole issue is worth reading. It starts off with an article by OPA's own Dan Bigg on overdose as a fundamental, uniting issue in harm reduction. Other pieces present an overview of what we know about overdose in a region that stretches from the Afghan border to the heart of Europe, stories by people who have been saved from overdose by naloxone or used it on others, a story about a great overdose project in Tomsk, Russia, and much more.

www.take-homenaloxone.org relaunched!

From: Hill Duncan (NHS LANARKSHIRE)

Dear all

We are pleased to announce that the take-home naloxone website has successfully relaunched.

Please note the website address has slightly changed from .com to .org, see below:

http://www.take-homenaloxone.org/

Please update your records and links accordingly.

I hope you will find the site useful. We are still keen to add as many services as possible to populate the maps and provide website visitors with as much information to naloxone services as possible. We would be grateful if you could pass this information to others who are delivering or interested in delivering take-home naloxone services and encourage them to provide details of their service if not already included on the website. Suggestions are also welcome on how we can improve the website as we move forward.

Best wishes

Duncan

Duncan Hill

Specialist Pharmacist in Substance Misuse

NHS Lanarkshire

Torrance House

504 Windmillhill Street

Motherwell

ML1 2AF

T: 01698 210068

M: 0792 0711131

New VOCAL report on methadone in NY State highlights need for overdose education

The great organization VOCAL, which is led by and represents people who use drugs, people living with HIV and people affected by mass incarceration in New York, has just released a report called "Beyond Methadone: Improving the Health of Patients in Opioid Treatment Programs." The information in the report is relevant well beyond New York - issues related to patient rights, access to harm reduction services, hepatitis care and treatment, policing, and other areas will be familiar to anyone working on opioid substitution therapy anywhere in the world.


So the whole thing is worth a read, but on OPA we'd like to highlight the report's findings related to overdose. Among people interviewed for the report - all current methadone patients - 10% had experienced overdose themselves in the past 2 years, 20% had been with someone who had overdosed, but 70% of them had no overdose education or naloxone access through their methadone program.


This is changing. Not long ago I spoke with some folks from the Beth Israel Medical Center methadone program (New York's largest methadone provider), who had recently started ramping up overdose education and prescribing naloxone. But VOCAL's report is an important reminder that programs need to move, and now.

NIH/CDC solicits development of automated naloxone delivery device

The NIH and CDC have issued a solicitation for small businesses to develop an automated device to administer naloxone in the case of an opioid overdose.

This may just fit in the department of weird - of much more interest would be an easy, concentrated intranasal delivery system - but here it is in the interest of an open mind.

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES PHS 2012-1

Feedback-regulated Naloxone Delivery Device to Prevent Opiate Overdose Deaths

(Fast-Track proposals will be accepted)

Number of Anticipated Awards: 1

Budget (total costs): Phase I: $150,000 for 6 months; Phase II: $1,000,000 for 2 years

It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.

Drug overdose is currently the second leading cause of unintentional death in the United States, second only to motor vehicles crashes. The population at risk for opioid overdose is diverse and includes, for example, more than 3% of U.S. adults currently receiving long-term opioid therapy for chronic noncancer pain, in addition to drug/substance abusing population. Opioids are now more often being prescribed for patients with moderate to severe pain.

Thus, effective measures that would prevent/avert opioid overdoses are needed as overdoses and death often occur inadvertently in private settings where no one is present to offer assistance. Furthermore, patients with opioid addiction are prone to overdose on injected opiates or on excessive oral doses of opioid medications. These overdoses also often happen when no help is available and patient’s lives are at risk.

The objective of this project is to develop an automated device that would administer standard doses of naloxone to a patient in overdose, thus reversing the effects of excess opiate. Naloxone has been used for decades in medical settings to avert opioid overdose, and recent pilot programs demonstrated the feasibility of proper use of naloxone by non-medical personnel. Patients expressing physiologic signals of opiate overdose (e.g. hypoxia, respiratory rate below a critical threshold for a critical period of time, etc.) could be administered an appropriate dose of naloxone even if unconscious. Due to the short duration of action of naloxone, the unit should be capable of repeating the injection after resetting itself and detecting another set of critical information.

There are more than 300,000 heroin users, nearly 5 million prescription opiate users, plus millions of chronic pain patients receiving end-of-life opiate analgesic pain care. The number of poisoning deaths and the percentage of these deaths involving opioid analgesics increase each year. From 1999 through 2006, the number of fatal poisonings involving opioid analgesics more than tripled from 4,000 to 13,800 deaths. Potentially, everyone who has been prescribed opioids, for pain or addiction, and heroin users, could be offered this device by their treatment provider who may be an addiction specialist, primary care physician or pain doctor. There is a crucial need to provide this device to these populations to prevent unintended overdose and deaths and to address public health need.

Phase I Activities and Expected Deliverables

Design the prediction algorithm for opioid overdose requiring the intervention and establish the endpoints for algorithm development

Design and assemble a prototype of detectors, injector and supporting hardware

Propose a strategy to prevent un-indicated use, such as in a person who is unresponsive due to the reasons other than an opioid overdose

Field-test the prototype with focus group participants.

Phase II Activities and Expected Deliverables

Conduct the initial clinical testing in appropriate user population which is sufficiently powered to adequately inform Phase II

Develop detailed plans for initial production model with cost projections

Plan regulatory approval strategy

Establish an FDA-compliant system

Conduct clinical testing necessary for FDA approval.

Pubmed October 2011 Update

My PubMed search was missing a lot of good papers, so here goes with a broader approach pulling 8 interesting papers ...

1) A procedure that differentiates unintentional from intentional overdose in opioid abusers.

Britton PC, Bohnert AS, Wines JD Jr, Conner KR.

Addict Behav. 2011 Sep 2.

*The intentionality of overdose is a recurrent issue. I read this article and frankly do not understand what the authors did.

2) The effectiveness of opioid maintenance treatment in prison settings: a systematic review.

Hedrich D, Alves P, Farrell M, Stöver H, Møller L, Mayet S.

Addiction. 2011 Sep 29. doi: 10.1111/j.1360-0443.2011.03676.x.

*Some data that agonist maintenance therapy in prison reduces post-release overdose mortality

3) Opioid overdose prevention and naloxone distribution in Rhode Island.

Yokell MA, Green TC, Bowman S, McKenzie M, Rich JD.

Med Health R I. 2011 Aug;94(8):240-2.

*A review of programmatic data from the Rhode Island naloxone distribution program

4) Prescription of opioid analgesics and related harms in Australia.

Roxburgh A, Bruno R, Larance B, Burns L.

Med J Aust. 2011 Sep 5;195(5):280-4.

*Oxycodone is becoming an issue in Australia, although not nearly as substantial as in the U.S.

5) The source of methadone in overdose deaths in Western virginia in 2004.

Weimer MB, Korthuis PT, Behonick GS, Wunsch MJ.

J Addict Med. 2011 Sep;5(3):188-202.

*Interesting data suggesting that two-thirds of methadone-related fatalities were from diverted drug (i.e. not prescribed to the person who died); 28% were prescribed methadone for analgesia. I can't access the full article, but regardless this suggests very few were agonist maintenance patients.

6) 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.

*A review of structural and individual factors related to opioid overdose increases in the U.S.

7) Characteristics of an Overdose Prevention, Response, and Naloxone Distribution Program in Pittsburgh and Allegheny County, Pennsylvania.

Bennett AS, Bell A, Tomedi L, Hulsey EG, Kral AH.

J Urban Health. 2011 Jul 20.

*A very useful review of the PA naloxone distribution program, including the rate of survival among those administered naloxone.

8) Treatment of opioid overdose in a physician-based prehospital EMS: Frequency and long-term prognosis.

Nielsen K, Nielsen SL, Siersma V, Rasmussen LS.

Resuscitation. 2011 Jun 15.

*These data from Denmark again demonstrate the increasing risk of mortality among those who have overdosed multiple times