Pubmed March 2012 Update

A number of good papers this month! Most notable are the MMWR report and the intriguing Copenhagen data on opioid overdoses attended by emergency medical services.

Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds.

Whelan PJ, Remski K.

J Neurosci Rural Pract. 2012 Jan;3(1):45-50.

Comment: Includes a brief review of the lower overdose risk with buprenorphine.

Delayed leukoencephalopathy after alprazolam and methadone overdose: A case report and review of the literature.

Carroll I, Heritier Barras AC, Dirren E, Burkhard PR, Horvath J.

Clin Neurol Neurosurg. 2012 Feb 16. [Epub ahead of print] No abstract available.

Comment: The precipitating event in this case is a hypoxic event in a patient with an enzyme deficiency, not a direct opioid or benzodiazepine toxicity.

Community-based opioid overdose prevention programs providing naloxone - United States, 2010.

Centers for Disease Control and Prevention (CDC).

MMWR Morb Mortal Wkly Rep. 2012 Feb 17;61:101-5.

Comment: Hooray! Read this for a review of U.S. nationwide naloxone program data.

Chromatographic determination of drugs of abuse in vitreous humor using solid-phase extraction.

Fernández P, Seoane S, Vázquez C, Tabernero MJ, Carro AM, Lorenzo RA.

J Appl Toxicol. 2012 Feb 15. doi: 10.1002/jat.2722. [Epub ahead of print]

Comment: An interesting method for identifying several drugs of abuse simoultaneously.

Opioid-dependent error processing.

Fellows-Smith J.

J Opioid Manag. 2011 Nov-Dec;7(6):443-9.

Comment: The importance of this article is not reflected in the title. This is a data linkage study in Australia looking at mortality rates among those receiving methadone (0.7%) versus naltrexone (2.6%) for opioid therapy. Again this raises the major concerns about opioid overdose after naltrexone therapy, concerns that were clearly inadequately addressed prior to FDA approval of naltrexone for opioid dependence.

Attitudes and knowledge about naloxone and overdose prevention among detained drug users in Ningbo, China.

Liu Y, Bartlett N, Li L, Lv X, Zhang Y, Zhou W.

Subst Abuse Treat Prev Policy. 2012 Feb 8;7(1):6. [Epub ahead of print]

Comment: Incarcerated drug users would like to have naloxone.

Comparative analysis of pathological and toxicological features of opiate overdose and non-overdose fatalities.

Soravisut N, Rattanasalee P, Junkuy A, Thampitak S, Sribanditmongkol P.

J Med Assoc Thai. 2011 Dec;94(12):1540-6.

Comment: There's an error in this title - it should be opiate versus non-opiate overdose deaths. Basic epidemiology.

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 Nov;82(11):1410-3. Epub 2011 Jun 15.

Comment: Very useful review of opioid overdoses attended by emergency medical services in Copenhagen. Of 3245 cases, 69% were released at the scene without transport to the hospital, 11% had cardiac arrest at the scene, 21% were admitted to the hospital, and 10% died. These data seem pretty consistent with my current understanding of EMS attended overdoses. Nonetheless, I find these data intensely interesting because, notwithstanding many theories, we still don't really know what happens to the overdoses that occur in the community.

Prehospital treatment of opioid overdose in Copenhagen--is it safe to discharge on-scene?

Rudolph SS, Jehu G, Nielsen SL, Nielsen K, Siersma V, Rasmussen LS.

Resuscitation. 2011 Nov;82(11):1414-8. Epub 2011 Jul 2.

Comment: This is a sub-analysis of the prior study. They looked at the 69% of people that were released after naloxone was given and not transported to the hospital. They found that 3 of 2241 individuals died from a suspected "rebound overdose" after naloxone was given. Put in other words, 0.1% of overdose victims who were given naloxone at the scene and then released fell back into an opioid overdose and died. The authors looked pretty deeply into the circumstances post-release, so I think these data are reliable. While this figure is impressively low, it does reaffirm the need for bystanders to stay with overdose victims for several hours after reversing an overdose.

Potential role of safer injection facilities in reducing HIV and hepatitis C infections and overdose mortality in the United States.

Semaan S, Fleming P, Worrell C, Stolp H, Baack B, Miller M.

Drug Alcohol Depend. 2011 Nov 1;118(2-3):100-10. Epub 2011 Apr 23.

Comment: A review of data on supervised injection facilities, which have impressive data on reducing local overdose mortality in Vancouver.

Methadone, another cause of opioid-associated hearing loss: a case report.

Shaw KA, Babu KM, Hack JB.

J Emerg Med. 2011 Dec;41(6):635-9. Epub 2010 Dec 9.

Comment: An unusual toxicity to opioid overdose, but one that has been previously documented. Generally neurologic in origin and reversible with removal of the offending opioid agent.

Naloxone programs in MMWR

This is a really big deal. MMWR is one of the principal publications of the medical and public health community. Articles are rigorously vetted and anything published here is taken seriously. Nice job Harm Reduction Coalition, Eliza Wheeler, Pete Davidson, Steve Jones, and Kevin Irwin!!

Some of the text ...

Community-Based Opioid Overdose Prevention Programs Providing Naloxone — United States, 2010

Weekly

February 17, 2012 / 61(06);101-105

Drug overdose death rates have increased steadily in the United States since 1979. In 2008, a total of 36,450 drug overdose deaths (i.e., unintentional, intentional [suicide or homicide], or undetermined intent) were reported, with prescription opioid analgesics (e.g., oxycodone, hydrocodone, and methadone), cocaine, and heroin the drugs most commonly involved (1). Since the mid-1990s, community-based programs have offered opioid overdose prevention services to persons who use drugs, their families and friends, and service providers. Since 1996, an increasing number of these programs have provided the opioid antagonist naloxone hydrochloride, the treatment of choice to reverse the potentially fatal respiratory depression caused by overdose of heroin and other opioids (2). Naloxone has no effect on non-opioid overdoses (e.g., cocaine, benzodiazepines, or alcohol) (3). In October 2010, the Harm Reduction Coalition, a national advocacy and capacity-building organization, surveyed 50 programs known to distribute naloxone in the United States, to collect data on local program locations, naloxone distribution, and overdose reversals. This report summarizes the findings for the 48 programs that completed the survey and the 188 local programs represented by the responses. Since the first opioid overdose prevention program began distributing naloxone in 1996, the respondent programs reported training and distributing naloxone to 53,032 persons and receiving reports of 10,171 overdose reversals. Providing opioid overdose education and naloxone to persons who use drugs and to persons who might be present at an opioid overdose can help reduce opioid overdose mortality, a rapidly growing public health concern.

Overdose is common among persons who use opioids, including heroin users. In a 2002–2004 study of 329 drug users, 82% said they had used heroin, 64.6% had witnessed a drug overdose, and 34.6% had experienced an unintentional drug overdose (4). In 1996, community-based programs began offering naloxone and other opioid overdose prevention services to persons who use drugs, their families and friends, and service providers (e.g., health-care providers, homeless shelters, and substance abuse treatment programs). These services include education regarding overdose risk factors, recognition of signs of opioid overdose, appropriate responses to an overdose, and administration of naloxone.

To identify local program locations and assess the extent of naloxone distribution, in October 2010 the Harm Reduction Coalition e-mailed an online survey to staff members at the 50 programs then known to distribute naloxone. Follow-up e-mails and telephone calls were used to encourage participation, clarify responses, and obtain information on local, community-based programs. The survey included questions about the year the program began distributing naloxone, the number of persons trained in overdose prevention and naloxone administration, the number of overdose reversals reported, and whether the totals were estimates or based on program data. The survey also asked questions regarding the naloxone formulations currently distributed, any recent difficulties in obtaining naloxone, and the program's experience with naloxone distribution.

Staff members at 48 (96%) of the 50 programs completed the online survey. Since the first program began distributing naloxone in 1996, through June 2010, the 48 responding programs reported providing training and distributing naloxone to an estimated 53,032 persons (program range: zero to 16,220; median: 102.5; mean: 1,104.8).* From the first naloxone distribution in 1996 through June 2010, the programs received reports of 10,171 overdose reversals using naloxone (range: zero to 2,385; median: 32; mean: 211.9).† During a recent 12-month period, respondents distributed an estimated 38,860 naloxone vials (Table).§ Using data from the survey, the number of programs beginning naloxone distribution each year during 1996–2010 was compared with the annual crude rates of unintentional drug overdose deaths per 100,000 population from 1979 to 2008 (Figure 1) (1).

The 48 responding programs were located in 15 states and the District of Columbia. Four responding programs provided consolidated data for multiple local, community-based programs. Three state health departments, in New York, New Mexico, and Massachusetts, provided data for 129 local programs (65, 56, and eight, respectively); a nongovernmental organization in Wisconsin provided data on a statewide operation with 16 local programs. In all, the 48 responding programs provided data for 188 local opioid overdose prevention programs that distributed naloxone (Figure 2). Nineteen (76.0%) of the 25 states with 2008 drug overdose death rates higher than the median and nine (69.2%) of the 13 states in the highest quartile (1) did not have a community-based opioid overdose prevention program that distributed naloxone (Figure 2).

For a recent 12-month period, the 48 responding programs reported distributing 38,860 naloxone vials, including refills (range: zero to 12,070; median: 97; mean: 809.6).¶ Overdose prevention programs were characterized as small, medium, large, or very large, based on the number of naloxone vials distributed during that period. The six responding programs in the large and very large categories distributed 32,812 (84.4%) of the naloxone vials (Table).

Twenty-one (43.7%) responding programs reported problems obtaining naloxone in the "past few months" before the survey. The most frequently reported reasons for difficulties obtaining naloxone were the cost of naloxone relative to available funding and the inability of suppliers to fill orders.**

Starting new naloxone programs: 2 new how-to guides from Europe

Two great new resources out this week on starting your own naloxone program from colleagues in Europe.

• The UK's National Treatment Agency for Substance Misuse Overdose and Training Programme for Families and Carers provides a list of minimum training elements and the questions a group needs to ask as they are trying to set it up. Good, simple, practical advice.
• Janna Ataiants and Dasha Ocheret of EHRN put together an awesome step-by-step guide to setting up naloxone programs. Topics covered include choosing models for procurement, storage and distribution, staff training, determining how many kits are needed, and advocacy strategies. The Annexes have tools for quality assessment and case studies.

Pubmed December/January 2012 Update

Lots of papers over the past 8 weeks ...

Mortality Among Young Injection Drug Users in San Francisco: A 10-Year Follow-up of the UFO Study.

Evans JL, Tsui JI, Hahn JA, Davidson PJ, Lum PJ, Page K.

Am J Epidemiol. 2012 Jan 6.

Comments: Thought I'd start with the best one this time, an excellent and desperately needed analysis that includes some estimates on mortality rates in one of the few prospective cohorts left.

Comparative analysis of pathological and toxicological features of opiate overdose and non-overdose fatalities.

Soravisut N, Rattanasalee P, Junkuy A, Thampitak S, Sribanditmongkol P.

J Med Assoc Thai. 2011 Dec;94(12):1540-6.

Comment: An interesting analysis of medical examiner cases in Chiang Mai. Interesting that tourists represented a growing proportion of cases over time.

Overdose deaths and Vancouver's supervised injection facility.

Christian G, Pike G, Santamaria J, Reece S, DuPont R, Mangham C.

Lancet. 2012 Jan 14;379(9811):117; author reply 118-9. No abstract available.Comment: An interesting critique of the seminal paper on the overdose fatality reduction associated with Vancouver's supervised injection facility. The authors' response appears to effectively belie the critique.

"Foam Cone" exuding from the mouth and nostrils following heroin overdose.

Dinis-Oliveira RJ, Santos A, Magalhães T.

Toxicol Mech Methods. 2012 Feb;22(2):159-60.Comment: I'm not able to access. Anyone?

CDC Grand Rounds: Prescription Drug Overdoses - a U.S. Epidemic.

Centers for Disease Control and Prevention (CDC)

MMWR Morb Mortal Wkly Rep. 2012 Jan 13;61:10-3.Comment: This is so watered down I'm not sure of the message.

Offer of a quick fix.

Gould M.

Nurs Stand. 2011 Nov 16-22;26(11):24-5.

Comment: I was only able to access this through my university account, but it is a really interesting discussion of the British prison-release take-home naloxone trial. Scotland dropped out and began routine naloxone distribution for all released prisoners. The ethics around the trial are complex - many doubt the need for proof while others point to the frustrating history of treatments assumed to work and later proven to be harmful. While it is true that similar interventions for other populations would not require proof for wide dissemination, broad application of naloxone distribution will be limited by the lack of randomized trial data.

Correlates of non-medical prescription drug use among a cohort of injection drug users in Baltimore City.

Khosla N, Juon HS, Kirk GD, Astemborski J, Mehta SH.

Addict Behav. 2011 Dec;36(12):1282-7. Epub 2011 Aug 5.

Comment: Lots of prescription opioid use among injectors.

The increasing mortality burden of liver disease among opioid-dependent people: cohort study.

Gibson A, Randall D, Degenhardt L.Addiction. 2011 Dec;106(12):2186-92. doi: 10.1111/j.1360-0443.2011.03575.x. Epub 2011 Oct 17.

Comment: This paper discusses another major interest of mine - hepatitis C. Hep C-related deaths have doubled since I began medical practice and will double again over the next 10-15 years. Broadened screening and improved access to treatment are desperately needed and will more than double the impact of the improved treatments we are already seeing.

A qualitative study exploring the reason for low dosage of methadone prescribed in the MMT clinics in China

Lin C, Detels R.

Drug Alcohol Depend. 2011 Aug 1;117(1):45-9. Epub 2011 Feb 9.

Comments: Interesting discussion of problems with methadone dosing in China.

Drug related deaths in the Split-Dalmatia County 1997-2007.

Susnjara IM, Smoljanović A, Gojanović MD.

Coll Antropol. 2011 Sep;35(3):823-8.

Comments: Basic epidemiology of overdose deaths in Croatia that again emphasizes the role of polydrug use.

Suicide verdicts as opposed to accidental deaths in substance-related fatalities (UK, 2001-2007).

Vento AE, Schifano F, Corkery JM, Pompili M, Innamorati M, Girardi P, Ghodse H.

Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jul 1;35(5):1279-83.

Comments: Can't access full article and I'm unclear how the results tie to conclusions from the abstract.

Can Nebulized Naloxone Be Used Safely and Effectively by Emergency Medical Services for Suspected Opioid Overdose?

Weber JM, Tataris KL, Hoffman JD, Aks SE, Mycyk MB.

Prehosp Emerg Care. 2011 Dec 22.

Comments: Nebulized naloxone is an interesting option for emergency medical services, although not widely available as a means of lay administration.

Video: Mobile Injection Room in Copenhagen

Broadcast on Project Lazarus shows community-based OD prevention in action

Check out this 5 minute video on how Project Lazarus empowers community groups to take a non-judgmental and pragmatic approach to overdose prevention: doctors, cops, paramedics, faith community, schools are all included.

Our full description of Project Lazarus and results show the detailed steps we've taken to implement community-based overdose prevention.

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

A new article by Traci Green and colleagues summarizes what we know about why HIV seems to increase risk for overdose. According to their systematic review of the literature, people who use drugs and have HIV have a 74% greater risk of having an overdose than their HIV-negative counterparts. That's a pretty staggering figure.

You can read Green's article here: http://www.ncbi.nlm.nih.gov/pubmed/22112599.

I've also posted a blog on the Open Society Foundations website about why people who care about HIV should also care about overdose: http://blog.soros.org/2011/12/preventing-drug-overdose-is-key-in-fight-against-aids/.

With the funding situation the way it is, we need to invest in interventions we know work, like methadone and buprenorphine treatment, highly active antiretroviral therapy, and naloxone distribution.

Boston Globe Editorial - "In fighting heroin overdoses, a key ally is often overlooked"

Editorial

In Fighting Overdoses, A Key Ally is Often Overlooked

November 27, 2011

FEW DEATHS from heroin overdose happen alone. A friend or relative is often standing by helplessly as a victim’s skin turns blue, their pulse slows, and breathing stops. In 2008, 594 people died from accidental overdoses of heroin and other opioid drugs in Massachusetts.

That’s why a promising state pilot program that gets a life-saving overdose-reversal drug called naloxone into the hands of friends and relatives of opioid addicts should be expanded to more communities. At the same time, more first responders should carry the drug, often known by the brand name Narcan, and state and federal authorities should relax the restrictions preventing wider public access.

Since 2007, the naloxone pilot program at eight sites across the Commonwealth is credited with reversing more than 1,100 overdoses. The drug, which is squirted into the nose of overdose victims, revives them for 30 to 90 minutes, long enough to get them to an emergency room.

Naloxone is not a new drug, but had previously been confined mostly to hospitals. When the state’s program started, critics worried it would be difficult for nonprofessionals to administer naloxone - or worse, that providing it would be tantamount to official acceptance of drug abuse. But the results speak for themselves:

In Lynn, one of the pilot sites, the number of reported deaths from accidental opioid overdose fell from 22 in 2006 to only 8 in 2008. In four years, according to state statistics, naloxone distributed in Lynn was used to reverse 166 overdoses. Statewide, the program cost only $170,000 this year.

The success of a program that relies on non-professionals - and of similar programs launched in other states over the last decade - ought to prod state and federal authorities to ease some of the needless restrictions on access to the drug, which is not addictive and has no potential for abuse itself. A bill introduced this year in the Massachusetts Senate would allow doctors to write prescriptions to friends or family members of addicts; it deserves the Legislature’s support. On the federal level, the Food and Drug Administration should study whether naloxone could safely be sold over the counter, as it is in Italy.

Meanwhile, as the results of naloxone programs become clear, grass-roots pressure is growing to find other ways to get more of the drug on the streets. Last year, for instance, a group of mothers of opioid addicts pushed Quincy police to carry naloxone, leading to 45 overdose reversals since June 2010. But few other first responders carry naloxone. This makes little sense. Opioid overdoses rank with car crashes as the leading causes of accidental death in the state. There is no reason why front-line public safety officers shouldn’t be fully equipped for them.

Even if more first responders carry naloxone, the reality is that the person squirting naloxone will often be a fellow drug user. Too often, though, fellow users fear arrest and don’t take the critical next step after administering the dose - calling 911. (After the effects of naloxone wear off, a person can go back into overdose if they don’t get help.) New Mexico, New York, and Washington have all passed good Samaritan bills that would protect people who call 911 to report drug overdoses; similar legislation has been introduced in both the Massachusetts House and Senate, and should be approved.

The families of addicts often carry a heavy load, boxed in by stigma and shame, and shadowed by the constant fear that a loved one could die with the next stronger-than expected bag of heroin. Naloxone isn’t a miracle drug, and it doesn’t eliminate addiction. But greater access to naloxone would empower families, provide hope - and save lives.

http://bostonglobe.com/opinion/editorials/2011/11/27/fighting-heroin-overdoses-key-ally-often-overlooked/qo2LNWaAjvmoBWyvUCU48K/story.html