Pubmed Update April 2013

10 papers this time. Good stuff.

1. Take-Home Emergency Naloxone to Prevent Heroin Overdose Deaths after Prison Release: Rationale and Practicalities for the N-ALIVE Randomized Trial.

Strang J, Bird SM, Parmar MK.

J Urban Health. 2013 May 1. [Epub ahead of print]

Comment: Really interesting article on the design of the N-ALIVE trial of naloxone provision to prisoners pre-release.

2. Determination of dextromethorphan and levomethorphan in seized heroin samples by enantioselective HPLC and electronic CD.

Tedesco D, Di Pietra AM, Rossi F, Garagnani M, Del Borrello E, Bertucci C, Andrisano V.

J Pharm Biomed Anal. 2013 Apr 6;81-82C:76-79. doi: 10.1016/j.jpba.2013.03.024. [Epub ahead of print]

Comment: Methods paper demonstrating methorphan in some heroin samples involved in overdose death.

3. All-cause mortality in criminal justice clients with substance use problems-A prospective follow-up study.

Hakansson A, Berglund M.

Drug Alcohol Depend. 2013 Apr 24. doi:pii: S0376-8716(13)00109-9. 10.1016/j.drugalcdep.2013.03.014. [Epub ahead of print]

Comments: Another analysis of post-release mortality among prisoners, in which the largest group (39%) of deaths were due to accidental or undetermined intent poisoning.

4. Changing law from barrier to facilitator of opioid overdose prevention.

Davis C, Webb D, Burris S.

J Law Med Ethics. 2013 Mar;41 Suppl 1:33-6. doi: 10.1111/jlme.12035.

Comments: Excellent analysis of naloxone and Good Samaritan legislation.

Naloxone: Keep it with your lipstick

Excellent "Here and Now" radio story on naloxone in Massachusetts and administration by parents!

 

Mother Saves Her Son From Overdose Thanks To Pilot Program

PubMed Update February/March 2013

Another 8 papers on opioid overdose issues.

1) 'It's more about the heroin': injection drug users' response to an overdose warning campaign in a Canadian setting.

Kerr T, Small W, Hyshka E, Maher L, Shannon K.

Addiction. 2013 Mar 28. doi: 10.1111/add.12151. [Epub ahead of print]

Comment: Interesting qualitative analysis of warnings issued regarding high-potency heroin. Respondents instead sought out the suspect drug.

2) Opioid Agonist Treatments and Heroin Overdose Deaths in Baltimore, Maryland, 1995-2009.

Schwartz RP, Gryczynski J, O'Grady KE, Sharfstein JM, Warren G, Olsen Y, Mitchell SG, Jaffe JH.

Am J Public Health. 2013 Mar 14. [Epub ahead of print]

Comment: This analysis failed to consider heroin overdose prevention programming – i.e. naloxone distribution – that was scaled up over the exact same period that buprenorphine treatment expanded and heroin overdoses declined. While not all variables can be considered in the interrupted time series approach, not considering the impact of a naloxone-based “overdose prevention program” seems to be a major flaw in the presentation. Disappointing that this was not rigorously addressed.

3) Determination of substance overdose in two Iranian centers: Comparison between opioids and non-opioids.

Taghaddosinejad F, Arefi M, Fayaz AF, Tanhaeivash R.

J Forensic Leg Med. 2013 Apr;20(3):155-7.

Comment: Interesting exploration of overdose in Iran – opioids still predominate (1782) compared to other drugs (94).

4) Opioid overdose fatality prevention.

Leece P, Orkin A.

JAMA. 2013 Mar 6;309(9):873-4.

Comment: This reply to Beletsky, et al’s, November 2012 commentary Prevention of fatal opioid overdose is followed by the authors’ response.

5) Development of Opioid Overdose Knowledge (OOKS) and Attitudes (OOAS) Scales for take-home naloxone training evaluation.

Williams AV, Strang J, Marsden J.

Drug Alcohol Depend. 2013 Feb 28.

Comment: We are in desperate need of standardized and validated measures for overdose and naloxone distribution. These scales may be useful, although as a word of caution several elements are specific to UK programming.

News: Police host naloxone training for community

In response to a run of opioid overdoses, the Yarmouth police are co-sponsoring a training of lay persons in the community, so that there will be more naloxone in the community should future overdoses occur. 

This rapid response is made possible by the naloxone program supported by and run through the State health department, and raises the very intriguing concept that naloxone may have stark benefit in settings of overdose "outbreaks."

The Scottish Highland Overdose Prevention Programme Goes to Prison

Lisa Ross

NHS Highland Clinical Harm Reduction Nurse Specialist / Naloxone Lead

In July 2009, I started the Highland programme in Inverness, in the north of Scotland, to deliver overdose prevention services to those at risk of opiate overdose, their friends and family members, and staff working with those at risk. The program is part of the Scottish National Health Service, our universal public health care system. 

Trainees were given a supply of naloxone for intramuscular administration to take home and use in the event of witnessing an opiate overdose. The programme also included Inverness prison; those who were identified as at risk were trained whilst in prison and given a naloxone pack on their liberation date.

The Programme was rolled out after the first year throughout the Highland area. To date over 900 kits have been supplied and there have been over 200 recorded uses of naloxone with successful reversal of the overdose state. In 2012, the programme was developed to include supply of naloxone for intranasal administration.

Last year I also started to develop a network of peer trainers; one of the aims of this was to increase uptake to those at risk, particularly those who had not previously engaged with the programme. Peer trainers are ideally placed to deliver this training; after all they hold the most experience and are far more likely to engage with the identified target group.

This again included Inverness Prison; I trained a peer trainer as a trainer and he now delivers the training in prison to those at risk. The results of this have been hugely positive so far. In a short space of time he has managed to engage with more individuals and deliver the training to them than the health and addictions staff have managed throughout the year. This is even more impressive when we consider the prison is in its fourth year of delivering this intervention and supplies of naloxone were starting to decrease given that the majority of people had already been trained. Or so we thought!

There will be the opportunity for the peer trainer to continue delivering the programme upon his own liberation, working in the community with the Harm Reduction Service and the community peer trainers.

My ongoing intention for the programme is to increase the number of peer trainers throughout Highland; there is no doubt that when it comes to overdose prevention and Naloxone training; peer trainers can have the maximum impact.

Naloxone laws to prevent overdose

There have been a slew of recent bills introduced or passed to improve naloxone access around the United States. Most of these are similar to previous U.S. models, although some are quite innovative. 

First, here's a summary from the Network for Public Health Law of naloxone (and Good Samaritan) laws as of October 2012, when 8 U.S. states had naloxone access laws (CA, CT, MA, NM, NY, IL, WA, RI).

Now, below are some links to recently approved or newly considered bill/law text. Please let us know if there are others and offer comments on any of these. It's getting hard to keep track, so I've added a simple map - black areas have naloxone laws and orange areas have pending laws (black states with an orange mark have existing laws with pending modifications).

New laws:

Virginia

Washington DC

Bills:

California (builds on existing law that is to sunset)
Colorado

Kentucky

Maryland

Massachusetts (not sure in what ways this expands on existing law Act 192)

New Jersey

New Mexico (appropriations to support naloxone distribution)

North Carolina

Oregon (SB 384, passage appears likely, bill with amendments here)

Vermont (bill appears to require only consideration of a law change to encourage naloxone prescription)

West Virginia (requires naloxone be offered to all patients receiving chronic opioid therapy)

News: FDA denies Reckitt's request to block generic buprenorphine/naloxone tablets

The U.S. Food and Drug Administration has roundly denied all requests from Reckitt-Benckiser to block approval of generic buprenorphine/naloxone tablets. This request was made at the time when the monopoly on the product was ending and was based on risks of pediatric exposures that the company claimed were higher with the tablet than their new film product. The FDA provided an excellent review of the issues and rejected all components of the request.

This is an enormous relief for public health agencies providing buprenorphine services, many of which would have dropped buprenorphine services altogether or would have ceased to provide the buprenorphine/naloxone formulation due to cost.

PubMed Update December 2012 - January 2013

This is a really exciting time for research into overdose in general and naloxone in particular. 15 papers this time.

1. Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.

Walley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A.

BMJ. 2013 Jan 30;346:f174. doi: 10.1136/bmj.f174.

Comments: A long-awaited paper for which the authors deserve high praise, as they have produced the first real evidence of naloxone effectiveness and arguably the most important contribution to naloxone literature to-date. Although not randomized, the interrupted time series analysis is respectable and the results are impressive.

2. Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal.

Coffin PO, Sullivan SD.

Ann Intern Med. 2013 Jan 1;158(1):1-9. doi: 10.7326/0003-4819-158-1-201301010-00003.

Comments: I’ve wanted to write this paper for about a decade, when I thought about cost-effectiveness as three to four calculations on the back of a napkin, rather than years of work and RAM-straining matrices. There’s a long way to go with overdose research that will certainly contribute to future iterations of the model. In the meantime, this is probably a fair, if quite conservative, initial estimate. There is one sensitivity analysis – in which naloxone results in behavior change such that overdose risk is lower – which I suspect may be closer to the actual truth.

3. Naloxone for heroin overdose reversal.

Ann Intern Med. 2013 Jan 1;158(1):I-30. doi: 10.7326/0003-4819-158-1-201301010-00001. No abstract available.

Comments: An excellent editorial from our colleagues at NIDA and the FDA.

4. Prescription opioid use among addictions treatment patients: Nonmedical use for pain relief vs. other forms of nonmedical use.

Bohnert AS, Eisenberg A, Whiteside L, Price A, McCabe SE, Ilgen MA.

Addict Behav. 2012 Nov 23;38(3):1776-1781. doi: 10.1016/j.addbeh.2012.11.005. [Epub ahead of print]

Comments: Survey of prescription opioid use among treatment program patients. Use for reasons other than pain relief was associated with overdose as well as use of several other agents that increase the risk of overdose.

Naloxone reduces community-level opioid overdose mortality

Alex Walley and colleagues have published their analysis of the Massachusetts naloxone program, which shows what I'm going to call a per capita dose-dependent reduction in opioid overdose death (rate ratio of 0.73 [95%CI 0.57-0.91] if naloxone was given to 1-100 people per 100,000 population and 0.54 [0.39-0.76] for naloxone to >100/100,000). This provides the first real community-level effectiveness data to-date.

The finding that naloxone was more effective the more people per population were given kits suggests that aggressive distribution may be the optimal approach for naloxone programs. This study doesn't answer the question as to why there was a dose-dependent response - was it simply because more is better? were there social network effects where naloxone became substantially more effective if it reached into certain social networks, which was more likely if it was more widely distributed? Social network issues have yet to be explored in overdose prevention research.

Scotland's Stephen Malloy talks about why naloxone is important

Press release: Naloxone cost-effective

City and County of San Francisco Edwin M. Lee Mayor

San Francisco Department of Public Health Barbara A. Garcia, MPA Director of Health

Embargoed until 5p.m. Eastern Time	Eileen Shields, Public Information Officer
December 31, 2012	415/554-2507 (o) 415/370-3377 (cell) Eileen.Shields@sfdph.org

Study Shows Naloxone Cost-Effective in Preventing Overdose Deaths

San Francisco, CA, January 1, 2013 - The Annals of Internal Medicine released a study this week demonstrating that giving heroin users the overdose antidote naloxone is a cost-effective way to prevent overdose death and save lives. Phillip Coffin, MD, Director of Substance Use Research at the San Francisco Department of Public Health and Assistant Clinical Professor at the University of California San Francisco, and Sean Sullivan, PhD, Professor and Director of the Pharmaceutical Outcomes Research and Policy Program at the University of Washington, co-authored the study.

Drug overdose is now the leading cause of injury death in the United States with opioids, such as heroin, accounting for about 80% of those deaths. Naloxone is a safe and effective antidote that works by temporarily blocking opioid receptors. As of 2010, 183 public health programs around the country, including those supported by the San Francisco Department of Public Health, had trained over 53,000 individuals in how to use naloxone. These programs had documented more than 10,000 cases of successful overdose reversals.

The authors of this study developed a mathematical model to estimate the impact of distributing naloxone in this way. Their model was based on conservative estimates of the number of overdoses that occur each year. It accounted for people who overdose repeatedly, and it acknowledged that most people who overdose will survive whether or not they get naloxone.

In their basic model, Coffin and Sullivan estimated that reaching 20% of a million heroin users with naloxone would prevent about 9,000 overdose deaths over their lifetime. One life would be saved for every 164 naloxone kits given out. Based on optimistic assumptions, naloxone could prevent as many as 43,000 deaths – one life for every 36 kits given out.

Naloxone distribution would cost about $400 for every quality-adjusted year of life gained. This value is well below the customary $50,000 cutoff for medical interventions. It is also cheaper than most well-accepted prevention programs in medicine – most similar to the cost-effectiveness of smoking cessation or checking blood pressure. All reasonable assumptions produced costs that were well within traditional guidelines for cost-effectiveness.

“Naloxone is a highly cost-effective way to prevent overdose deaths,” said Dr Coffin. “And, as a researcher at the Department of Public Health, my priority is maximizing our resources to help improve the health of the community.”

Naloxone distribution has existed in San Francisco since the late 1990s, with SFDPH support since 2004. During that time, heroin overdose fatalities slowly decreased from a peak of 155 in 1995 to 10 in 2010. Opioid analgesic deaths (e.g., oxycodone, methadone, or hydrocodone) remain elevated, with 121 deaths in 2010. Efforts are currently underway to expand access to this lifesaving medication for patients receiving prescription opioids as well.

Contact Information and Follow-up

To obtain a copy of this study, see Annals of Internal Medicine

To discuss the paper, contact Dr. Coffin, pcoffin@gmail.com

###

More OD videos - Cops, reentry, and Spanish OD training!

It seems like there are a bunch of good overdose advocacy and training videos coming out these days. 

Here's a new video from the San Francisco Police Department and Department of Public Health instructing police not to interfere with syringe access sites or naloxone distribution. (Nice narration Emalie Huriaux!)




And here's a new Spanish-language video from Boston about how to recognize overdose and respond properly. The video highlights the fact that those just released from prison or other lock-up facilities are at higher risk of OD, especially in those first two weeks.

And while we're at it, we realized that OPA didn't mention the great video, "Staying Alive on the Outside" from our friends in Rhode Island that came out a few months back. It's and English-language video that focuses on OD risk and response after prison release. 



We hope you find these useful in your work!

Quote of the Day

"The naloxone shortage is going to hurt us. It is hurting us. People are dying now because of the shortage. More people are going to die because of it. Whatever your story is, you shouldn't have to die for how you choose to navigate your life and what's happened to you. We need naloxone everywhere. Opioid users didn't just appear out of nowhere -- everybody has someone that loves them, a father, a mother, a grandparent, a friend, niece, nephew, brother sister ... and you're important to that person. Naloxone can keep them from dying. It's harm reduction on a really intimate, yet grand scale because every OD death that is prevented means hundreds if not thousands of people prevented from losing and grieving."

                ---------- Lee Hertel, Minneapolis USA

A North Carolina family talks about overdose

Shelly's Story from North Carolina Harm Reduction on Vimeo.

PubMed Update October/November 2012

My apologies for tardiness. I'll try to be on time next month. 13 papers described below.

1. Prevention of fatal opioid overdose.

Beletsky L, Rich JD, Walley AY.

JAMA. 2012 Nov 14;308(18):1863-4. doi: 10.1001/jama.2012.14205.

Comment: An excellent summary of key issues in overdose prevention and increasing naloxone availability for lay overdose reversal. Read it.

2. Management of opioid analgesic overdose.

Picetti E, Rossi I, Caspani ML.

N Engl J Med. 2012 Oct 4;367(14):1371-3

Comment: Multiple letters in response to the recent review article.

3. Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence.

Krupitsky E, Zvartau E, Blokhina E, Verbitskaya E, Wahlgren V, Tsoy-Podosenin M, Bushara N, Burakov A, Masalov D, Romanova T, Tyurina A, Palatkin V, Slavina T, Pecoraro A, Woody GE.

Arch Gen Psychiatry. 2012 Sep;69(9):973-81.

Comment: This was a randomized, placebo-controlled trial comparing naltrexone implant to oral naltrexone to nothing for preventing relapse to opioid dependence among detoxified patients in Russia. Participants were followed for six months and then followed up a year later to see if there was more death from overdose. The implant was more effective in retaining participants through the six months although by 3 months off therapy there was no difference between the groups. Authors only report “no evidence of increased risk of death due to overdose after  naltrexone treatment” and cite the initial paper showing injectable naltrexone as effective for opioid dependence in Russia (I’m unclear as to why this citation was present). I find this radically insufficient. Naltrexone has lab evidence (animal evidence shows that exposing opioid receptors to naltrexone makes them more sensitive to opioids than mere abstinence) and clinical evidence (high death rates after oral naltrexone treatment) suggesting that it increases risk of overdose and overdose death. The authors of this paper provide no details as to how they showed no evidence of increased overdose. How many people were they able to follow-up with at 18 months (their numbers were really small to begin with)? Did they inquire as to non-fatal overdose? How did they collect information about overdose death (coroners in Russia rarely identify overdose as a cause of death due to stigma and payment issues)? While extended-release naltrexone formulations *might* have less of an association with overdose, the concerns about oral naltrexone are well-established - how did the investigators get approval for oral naltrexone for opioid users from a U.S. government funded study? This is a vulnerable population for whom greater attention to toxicities should be demanded. A high level of attention to overdose outcomes might put to rest these concerns, but I have not seen that as of yet.