Saturday, September 5, 2015

PubMed Update August 2015

Sixteen in August. Back on schedule (thanks to jetlag).

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.

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.

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.

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.

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?

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.

Wednesday, August 12, 2015

PubMed Update June - July 2015

Great stuff this time! 34 in two months.

Wheeler E, Jones TS, Gilbert MK, Davidson PJ.
MMWR Morb Mortal Wkly Rep. 2015 Jun 19;64(23):631-5.
Comment: The long-awaited sequel to 2010’s blockbuster naloxone MMWR report! 152,283 laypersons trained and 26,463 overdose reversals reported to naloxone programs through 2014.

Mars SG, Fessel JN, Bourgois P, Montero F, Karandinos G, Ciccarone D.
Soc Sci Med. 2015 Jun 30;140:44-53. doi: 10.1016/j.socscimed.2015.06.032. [Epub ahead of print]
Comment: Interesting use of qualitative data exploring the role of heroin markets on overdose risk, suggesting that factors such as open-air versus behind-closed-door markets can affect risk.

Cropsey KL, Stevens EN, Valera P, Brendan Clark C, Bulls HW, Nair P, Lane PS.
Drug Alcohol Depend. 2015 Jul 10. pii: S0376-8716(15)00352-X. doi: 10.1016/j.drugalcdep.2015.06.038. [Epub ahead of print]
Comment: There’s a movement toward not prescribing opioids with benzodiazepines at all. This makes some sense from an overdose prevention perspective, however the impact of such a policy is unknown. Those who require both opioids and benzodiazepines generally have far more complex and substantial mental health challenges. Just removing one or the other of the agents may results in worsening mental health or even increased rates of self-harm. Or not. Nobody knows.

Soukup-Baljak Y, Greer AM, Amlani A, Sampson O, Buxton JA.
Int J Drug Policy. 2015 Jul 2. pii: S0955-3959(15)00200-5. doi: 10.1016/j.drugpo.2015.06.006. [Epub ahead of print]
Comment: This is interesting, particularly in an era of frequent high-potency batches of heroin or even pure fentanyl derivatives. Subjects recommend using words like “dangerous” or “lethal” instead of “potent” which can be misconstrued as desirable. They also emphasized timeliness. As one of the first studies to really look at this issue, this paper is well worth the read.

Visconti AJ, Santos GM, Lemos NP, Burke C, Coffin PO.
J Urban Health. 2015 Jun 16. [Epub ahead of print]
Comment: Epidemiology of opioid overdose mortality in San Francisco – the first since Pete Davidson’s seminal geocoding paper in 2003 that led SF to refocus overdose prevention efforts to the hardest hit neighborhoods. This paper documents that heroin overdose is now remarkably rare in San Francisco, although for me it raises more questions than it answers.

Monday, July 27, 2015

PubMed Update March - May 2015

Three months. 46 papers. I’m already a month behind.

Dahlem CH, Horstman MJ, Williams BC.
J Am Assoc Nurse Pract. 2015 Mar 26. doi: 10.1002/2327-6924.12249. [Epub ahead of print]
Comments: Naloxone programs have been providing kits to settings where homeless people receive services for many years. This is a description of a program at a homeless health clinic.

Christoffersen DJ, Brasch-Andersen C, Thomsen JL, Worm-Leonhard M, Damkier P, Brøsen K.
Forensic Sci Med Pathol. 2015 Jun;11(2):193-201. doi: 10.1007/s12024-015-9673-9. Epub 2015 Mar 24.
Comments: It’s been awhile since we had a forensics paper here. I think this is a novel method of identifying enantiomers.

Spaulding AC, Sharma A, Messina LC, Zlotorzynska M, Miller L, Binswanger IA.
Am J Public Health. 2015 May;105(5):e51-7. doi: 10.2105/AJPH.2014.302546. Epub 2015 Mar 19.
Comments: Stunningly low rate of drug overdose mortality in this cohort of prisoners in Georgia. This is one of the first times I’ve seen a paper on opioid overdose find radically different results in a different setting. I can’t access for details.

Mueller SR, Walley AY, Calcaterra SL, Glanz JM, Binswanger IA.
Subst Abus. 2015 Mar 16:1-14. [Epub ahead of print]
Comments: A review toward the end of using community distribution data to build clinical care naloxone prescription.

Hser YI, Evans E, Grella C, Ling W, Anglin D.
Harv Rev Psychiatry. 2015 Mar-Apr;23(2):76-89. doi: 10.1097/HRP.0000000000000052.
Comments: This is a systematic review of long-term studies of opioid users. Among many fascinating data reported, the length of time not using a drug of choice increases the likelihood of continuing to not use that drug. This seems obvious to many, but I don’t believe it’s been documented before. Good read for anyone looking to understand some of the longitudinal outcome data.

Sunday, March 8, 2015

PubMed Update November 2014 - February 2015

Catching up on 51 papers in 4 months. Did you miss me?

Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E.
Pharmacotherapy. 2014 Dec 4. doi: 10.1002/phar.1522. [Epub ahead of print]
Comment: Review of management of drug toxicities among novel, synthetic compounds.

Ray B, O'Donnell D, Kahre K.
Drug Alcohol Depend. 2015 Jan 1;146:107-10. doi: 10.1016/j.drugalcdep.2014.10.026. Epub 2014 Nov 8.
Comment: Police officers like being trained to carry naloxone.

Robinson A, Wermeling DP.
Am J Health Syst Pharm. 2014 Dec 15;71(24):2129-35. doi: 10.2146/ajhp130798.
Comment: Review of intranasal naloxone for overdose reversal.

Dasgupta N, Creppage K, Austin A, Ringwalt C, Sanford C, Proescholdbell SK.
Drug Alcohol Depend. 2014 Dec 1;145:238-41. doi: 10.1016/j.drugalcdep.2014.10.005. Epub 2014 Oct 18.
Comment: Heroin overdoses are increasing.

Jones JD, Roux P, Stancliff S, Matthews W, Comer SD.
Int J Drug Policy. 2014 Jan;25(1):166-70. doi: 10.1016/j.drugpo.2013.05.006. Epub 2013 Jun 15.
Comment: Brief overdose training works for naloxone distribution. This is important because many places are requiring prolonged trainings that end up limiting access to those who are unable or unwilling to invest that degree of time.

Behar E, Santos GM, Wheeler E, Rowe C, Coffin PO.
Drug Alcohol Depend. 2015 Mar 1;148:209-12. doi: 10.1016/j.drugalcdep.2014.12.009. Epub 2014 Dec 19.
Comment: Again, brief overdose training works for naloxone distribution.

Sunday, November 16, 2014

PubMed Update August-October 2014

Three months. 32 articles. Enough said.

Darke S, Marel C, Mills KL, Ross J, Slade T, Burns L, Teesson M.
Drug Alcohol Depend. 2014 Sep 16. [Epub ahead of print]
Comment: This study (the ATOS) and the team of investigators have produced some of the most powerful and useful data in substance use research. Once again they have delved into heroin overdose by following treatment patients 11 years out. At least 10.2% of the cohort had died by that time and an additional 9.4% were unaccounted for. Among the 70.1% interviewed, 67.5% had overdosed, 24.4% had experienced five or more overdoses (again suggesting that there are “overdosers” out there who are at very elevated risk of the event). In the past year before the follow-up visit, 4.9% had overdosed (11.8% of those who had used heroin in that period), 95.2% of whom had overdosed previously. Those who overdosed were more likely to report higher levels of non-heroin opiate use, as well as benzodiazepine, cocaine, and methamphetamine use.

Simonson W.
Geriatr Nurs. 2014 Sep-Oct;35(5):381-2.
Comment: A review of the role of take-home naloxone in the form of the new autoinjector.

Rudd RA, Paulozzi LJ, Bauer MJ, Burleson RW, Carlson RE, Dao D, Davis JW, Dudek J, Eichler BA, Fernandes JC, Fondario A, Gabella B, Hume B, Huntamer T, Kariisa M, Largo TW, Miles J, Newmyer A, Nitcheva D, Perez BE, Proescholdbell SK, Sabel JC, Skiba J, Slavova S, Stone K, Tharp JM, Wendling T, Wright D, Zehner AM.
MMWR Morb Mortal Wkly Rep. 2014 Oct 3;63(39):849-54.
Comment: This report demonstrates declining prescription opioid deaths (-6.6%), but heroin deaths increased so much (+101.7%) that the data actually demonstrate an overall increase in opioid overdose mortality from 2010 to 2012 (+4.3%). There is disagreement as to what is driving the increase in heroin use and overdose. Is it an inevitable consequence of increased availability of opioids? Or is it the result of growing restrictions on access to those opioids? Clearly there are elements of both, leaving us with conflicting duties when it comes to managing those already reliant upon prescription opioids. Western medical ethics is clear on this point: our patient is the person we treat, who may have been harmed by the very same prescribing behavior we are now trying to change and who may be further harmed by those changes. If we truly believe that this epidemic is “iatrogenic” (i.e. caused by medical care, akin to a surgeon leaving scissors in an abdomen), then we have to be extremely cautious and thoughtful in fixing the problem and we can never abandon the patient.

Lenton S, Dietze P, Olsen A, Wiggins N, McDonald D, Fowlie C.
Drug Alcohol Rev. 2014 Oct 1. doi: 10.1111/dar.12198. [Epub ahead of print]
Comment: It's taken an incredibly long time for take-home naloxone to reach Australia, especially given how innovative that country has been with respect to managing drug policy and overdose.

Green TC, Bratberg J, Dauria EF, Rich JD.
R I Med J (2013). 2014 Oct 1;97(10):29-33.
Comment: The first of three articles in this post from Rhode Island, US, which has been facing a surge in opioid overdose deaths and has been responding with expanded naloxone treatment availability. This and the next two articles are free at:

Tuesday, August 19, 2014

PubMed Update July 2014

Hooray for a mere 7 paper reprieve this month.

Mertz KJ, Janssen JK, Williams KE.
J Forensic Sci. 2014 Jul 16. doi: 10.1111/1556-4029.12541. [Epub ahead of print]
Comments: This manuscript presents critical and very concerning results regarding interpretation of our prescription opioid overdose epidemic. Morphine and codeine are commonly present and without 6-MAM (a third heroin metabolite) present at sufficient levels those deaths are coded as morphine and codeine. On this review of 112 such deaths, 66% met criteria for heroin involvement based on a history of heroin use (which may not be sufficient given the frequent use of other opioids among heroin users), drug paraphernalia or stamp bags, track marks, and detection of 6-MAM (generally at very low levels). Good toxicologists always check for 6-MAM so that shouldn’t be a major issue, but it is conceivable that some of these morphine/codeine cases are in fact heroin – an important caveat as we respond to the epidemic.

Trafton JA, Oliva EM.
Addiction. 2014 Aug;109(8):1243-4. doi: 10.1111/add.12585. No abstract available.
Comments: Authors argue that Good Samaritan and naloxone legislation may be effective strategies to reduce overdose.

Yen YF, Yen MY, Lin T, Li LH, Jiang XR, Chou P, Deng CY.
BMC Public Health. 2014 Jul 4;14(1):682. doi: 10.1186/1471-2458-14-682.
Comments: Again, HIV infection is associated with a history of overdose among persons who inject drugs.

Taheri F, Yaraghi A, Sabzghabaee AM, Moudi M, Eizadi-Mood N, Gheshlaghi F, Farajzadegan Z.
J Res Pharm Pract. 2013 Jul;2(3):130-4. doi: 10.4103/2279-042X.122387.
Comments: an analysis of methadone poisonings in Iran. Among 385 patients, 57.7% of cases were “intentional” and demonstrated high rates of psychiatric disorders (25.8%). Among the full cohort, 40% had opioid use disorders and 25.5% were in a methadone program.

Tuesday, July 8, 2014

PubMed Update May/June 2014

25 papers in two months. Anyone want to help with this?

Sabzghabaee AM, Eizadi-Mood N, Yaraghi A, Zandifar S.
Arch Med Sci. 2014 May 12;10(2):309-14. doi: 10.5114/aoms.2014.42584. Epub 2014 May 13.
PMID: 24904666 [PubMed] Free PMC Article
Comments: More data to support the utility of intranasal naloxone for overdose reversal. There are, however, some odd findings that suggest caution in interpreting the paper. The authors used 0.4mg of naloxone for IV or IN administration, whereas most efforts utilize 2mg for IN administration given the lower bioavailability. Moreover, they had a higher level of consciousness in the IN group, which seems odd.

Rambod M, Elhanafi S, Mukherjee D.
Ann Noninvasive Electrocardiol. 2014 Jun 5. doi: 10.1111/anec.12171. [Epub ahead of print]
PMID: 24903622 [PubMed - as supplied by publisher]
Comments: There are cases in which opioids can result in unstable heart rhythms. Usually this is related to high dose methadone, prolongation of the QT interval and torsades de pointes. In this case, heroin plus alcohol may have resulted in electrical conduction similar to “Brugada syndrome” which, in the interest of having an image in this blog post, I’ve posted an image of here. This type of electrical conduction is usually genetic and can result in sudden death through lethal arrhythmias.

Clark AK, Wilder CM, Winstanley EL.
J Addict Med. 2014 May-Jun;8(3):153-63. doi: 10.1097/ADM.0000000000000034.
PMID: 24874759 [PubMed - in process]
Comments: An impressive review of existing data for naloxone programs. Big kudos to the authors.

Iwersen-Bergmann S, Jungen H, Andresen-Streichert H, Müller A, Elakkary S, Püschel K, Heinemann A.
Int J Legal Med. 2014 May 25. [Epub ahead of print]
PMID: 24859230 [PubMed - as supplied by publisher]
Comments: Interesting analysis of methadone-related deaths among methadone maintenance patients suggesting that, while overdose deaths are not common, many may have been related to IV use of methadone.

Liu X, Wang G, Pu H, Jing H.
Brain Res. 2014 Jul 14;1572:40-9. doi: 10.1016/j.brainres.2014.05.016. Epub 2014 May 20.
PMID: 24854119 [PubMed - in process]
Comments: Intriguing analysis of rat brains suggesting a key role of calcium in neurotoxicity related to heroin use. Do medications like verapamil, generally used to manage hypertension, have a role in preventing neurologic damage from opioids and perhaps even reducing overdose risk?

Wang KH, Fiellin DA, Becker WC.
Am J Drug Alcohol Abuse. 2014 Jul;40(4):292-303. doi: 10.3109/00952990.2014.907301. Epub 2014 May 22.
PMID: 24853143 [PubMed - in process]
Comments: Around a fifth of people using prescription opioids “non-medically” get them directly from a physician.

Tuesday, May 27, 2014

PubMed Update March/April 2014

Better late than never, right? 24 papers over two months.

Doe-Simkins M, Quinn E, Xuan Z, Sorensen-Alawad A, Hackman H, Ozonoff A, Walley AY.
BMC Public Health. 2014 Apr 1;14(1):297. [Epub ahead of print]
Comments: Sometimes naloxone is used by bystanders who have not been formally educated (or “trained”) in administering naloxone. This innovative analysis suggests that the untrained witness does a good job in lay naloxone administration.

Kuehn BM.
JAMA. 2014 Apr 23-30;311(16):1600. doi: 10.1001/jama.2014.4483. No abstract available.
Comments: The naloxone auto-injector – Evzio – has been approved and is expected to be available this summer.

3) Research gaps on methadone harms and comparative harms: findings from a review of the evidence for an american pain society and college on problems of drug dependence clinical practice guideline.
Weimer MB, Chou R.
J Pain. 2014 Apr;15(4):366-76. doi: 10.1016/j.jpain.2014.01.496.
Comments: Basic summary is that it’s not entirely clear why there was such a surge in methadone-related deaths in the early part of the 2000s. It’s important to remember that the surge came after a surge in oxycontin-related deaths, when many payers shifted their preferred agent from oxycontin to methadone. Mortality data seems to follow the trend of the most prescribed agent.

Moore C, Lloyd G, Oretti R, Russell I, Snooks H.
BMJ Open. 2014 Mar 20;4(3):e004712. doi: 10.1136/bmjopen-2013-004712.
Comments: Outstanding, innovative design to reach those at very high risk of future overdose events. I anxiously await results.

Monday, March 3, 2014

PubMed Update February 2014

8 papers today, essentially about naloxone and heroin.

Maurer U, Kager C, Fellinger C, Loader D, Pollesböck A, Spitzer B, Jarisch R.
Subst Abuse Treat Prev Policy. 2014 Feb 27;9(1):12. [Epub ahead of print]

Comment: Seeking alternative explanations for “overdose”, the authors explored histamine levels in heroin using individuals. They found that heroin users had greater spikes in histamine levels when exposed to IV heroin compared to oral morphine. They hypothesized that this may explain why so many cases of overdose have a sublethal concentration of opioids, but this seems an overreach based on their data.

Kan M, Gall JA, Latypov A, Gray R, Alisheva D, Rakhmatova K, Sadieva AS.
Int J Drug Policy. 2014 Jan 23. pii: S0955-3959(14)00008-5. doi: 10.1016/j.drugpo.2014.01.005. [Epub ahead of print]

Comment: 47 to 81% of naloxone kits given out in Kyrgyzstan and Tajikistan were used to reverse an overdose – remarkable numbers, from 3 to 5 times higher than seen in western states.

Hansen A.
BMJ. 2014 Feb 20;348:g1686. doi: 10.1136/bmj.g1686. No abstract available.

Comment: Naloxone in Norway.

Seo S, Kwon YS, Yu K, Kim SW, Kwon OY, Kang KH, Kwon K.
Mol Med Rep. 2014 Apr;9(4):1395-9. doi: 10.3892/mmr.2014.1935. Epub 2014 Feb 7.

Comment: I can only see the abstract for this one and the science is outside of my realm – I’m unable to identify anything of apparent clinical relevance.

Bailey AM, Wermeling DP.
Ann Pharmacother. 2014 Feb 12. [Epub ahead of print]

Comment: Very helpful and relevant summary of some pharmacists experience with dispensing naloxone.

Aulet RM, Flis D, Sillman J.
Case Rep Otolaryngol. 2014;2014:962759. doi: 10.1155/2014/962759. Epub 2014 Jan 6.

Comment: Another case of opioid overdose-related sensorineural hearing loss, which means hearing loss from the cochlea (inner ear). The authors kindly run through some theories, including hypotension (e.g. reduced blood flow to the inner ear), overstimulation of kappa opioid receptors present in the cochlea, or adulteration with an ototoxic substance such as quinine.

Sarasa-Renedo A, Espelt A, Folch C, Vecino C, Majó X, Castellano Y, Casabona J, Brugal MT; Redan Study Group.
Gac Sanit. 2014 Jan 10. pii: S0213-9111(13)00227-6. doi: 10.1016/j.gaceta.2013.10.012. [Epub ahead of print]

Comment: Substance use disorder treatment programs are increasingly engaging in overdose prevention efforts – a badly needed development.

Dietze P.
Addiction. 2013 Jul;108(7):1277-8.

Comment: Interesting remarks by the author, suggesting that rather than advertising the high potency heroin, simply noting a spike in deaths and advertising overdose prevention/response strategies may be safer and more relevant to the target population.