23 papers for the last pre-pandemic month on PubMed! Thanks again to Nicola Gerbino, Rebecca Martinez, Cathleen Beliveau, and Irene Liu at www.csuhsf.org for working on these summaries!
Katzman JG, Takeda MY, Greenberg N, Moya Balasch M, Alchbli A, Katzman WG, Salvador JG, Bhatt SR.
JAMA Netw Open. 2020 Feb 5;3(2):e200117. doi: 10.1001/jamanetworkopen.2020.0117.
Comment:
Naloxone and opioid overdose education were provided to 395 participants in an outpatient clinic in New Mexico. 73 participants from the study performed 114 overdose reversals in the community, all of which were heroin related. Most of the reversals were performed on someone the participant knew personally. 73 out of the 395 participants (18%) performed overdose reversals in one year of follow-up – this is remarkably high.
2) Buprenorphine initiation to treat opioid use disorder in emergency rooms.
Jaeger S Jr, Fuehrlein B.
J Neurol Sci. 2020 Feb 6;411:116716. doi: 10.1016/j.jns.2020.116716. [Epub ahead of print] Review.
Comment:
The Veteran’s Administration in Connecticut has overcome some of the challenges associated with initiating buprenorphine in the emergency room (such as needing a waivered provider). The model the VA in Connecticut established and how success was measured is unclear because the full text is not available.
3) Opioid agonist treatment and fatal overdose risk in a state-wide US population receiving opioid use disorder services.
Krawczyk N, Mojtabai R, Stuart EA, Fingerhood M, Agus D, Lyons BC, Weiner JP, Saloner B.
Addiction. 2020 Feb 24. doi: 10.1111/add.14991. [Epub ahead of print]
Comment:
A retrospective cohort study comparing outcomes of 48,274 adults during periods of opioid agonist treatment and non-medication treatment in a specialty out-patient clinic in Maryland. There was a significant reduction in the hazard of opioid overdose deaths during medication treatment compared to non-medication treatment periods. The time after discharge for both medication and non-medication treatment was associated with an increased risk of overdose compared to non-medication treatment periods. In some contrast to other, larger cohorts from other countries, this study found a marked reduction on overdose death in medication versus abstinence-based opioid use disorder treatment, but no differential once treatment was discontinued. Either way, it remains the case that treating opioid use disorder with medications results in a significantly lower risk of death than other approaches.
4) The impact of chronic liver disease in patients receiving active pharmacological therapy for opioid use disorder: One-year findings from a prospective cohort study.
Dennis BB, Akhtar D, Cholankeril G, Kim D, Sanger N, Hillmer A, Chawar C, D’Elia A, Panesar B, Worster A, Marsh DC, Thabane L, Samaan Z, Ahmed A.
Drug Alcohol Depend. 2020 Feb 20;209:107917. doi: 10.1016/j.drugalcdep.2020.107917. [Epub ahead of print]
Comment:
Full paper not accessible to us, but looked at the impact of chronic liver disease (CLD) on methadone treatment outcomes through a prospective cohort study of 1234 patients with opioid use disorder and receiving methadone treatment. 25% (314 patients) had CLD, which included any liver disorder present for at least 6 months. Authors discuss “dangerous opioid consumption” but not defined in abstract.
5) A pilot study to compare virtual reality to hybrid simulation for opioid-related overdose and naloxone training.
Giordano NA, Whitney CE, Axson SA, Cassidy K, Rosado E, Hoyt-Brennan AM.
Nurse Educ Today. 2020 Feb 10;88:104365. doi: 10.1016/j.nedt.2020.104365. [Epub ahead of print]
Comment:
A quasi-experimental study evaluating nursing student knowledge about opioid overdose identification and response. Students either participated in a hybrid simulation or a virtual reality in which they had to identify the signs of an opioid overdose, administer intranasal naloxone, and provide recovery care. A pretest-posttest comparison of knowledge and attitude of nursing students found no significant difference in training type, suggesting virtual reality training is a feasible option for training nursing students about opioid-related overdose response.
6) Structure of heroin in a solution revealed by chiroptical spectroscopy.
Králík F, Fagan P, Kuchař M, Setnička V.
Chirality. 2020 Feb 20. doi: 10.1002/chir.23196. [Epub ahead of print]
Comment:
An in-depth look at the 3D structure of heroin.
7) The Opioid Epidemic: Challenge to Military Medicine and National Security.
Dembek ZF, Chekol T, Wu A.
Mil Med. 2020 Feb 20. pii: usz487. doi: 10.1093/milmed/usz487. [Epub ahead of print]
Comment:
This was a literature review looked at the landscape of opioid use in the military and veteran populations in the last five years. Battlefield pain management, opioid use among military and veterans, public health implications, and implemented solutions were included in the findings. While opioid overdose mortality continued to increase over the five years, there has also been several behavioral interventions and treatment programs introduced. Identifying the common issues, use behaviors, and solutions already in place is important for further addressing the high morbidity and mortality related to substance use in the military and veteran population.
8) Commentary on Park et al. (2020): Buprenorphine and benzodiazepine co-prescribing- key considerations and future directions.
Oliva EM.
Addiction. 2020 Feb 20. doi: 10.1111/add.14990. [Epub ahead of print] No abstract available.
Comment:
Commentary on the utility of including both potentials harms and benefits when discussing buprenorphine and benzodiazepine co-prescribing as discussed in Park et al., which examined associations between prescribed benzodiazepines, overdose death, and buprenorphine discontinuation among people receiving buprenorphine.
9) Degree of Bystander-Patient Relationship and Prehospital Care for Opioid Overdose.
McCann MK, Jusko TA, Jones CMC, Seplaki CL, Cushman JT.
Prehosp Emerg Care. 2020 Feb 19:1-14. doi: 10.1080/10903127.2020.1731029. [Epub ahead of print]
Comment:
A retrospective cohort study looking at bystander administration of pre-hospital naloxone to 545 unique individuals. Data only included patients who had prehospital naloxone delivered and had available EMS and medical record data. Spouses/family and close friends responded with naloxone more quickly and more often indicated an overdose event in 911 dispatch codes, compared to strangers or others not close to the victim.
10) Carfentanil toxicity in the African green monkey: Therapeutic efficacy of naloxone.
Langston JL, Moffett MC, Makar JR, Burgan BM, Myers TM.
Toxicol Lett. 2020 Feb 15;325:34-42. doi: 10.1016/j.toxlet.2020.02.008. [Epub ahead of print]
Comment:
Three experiments were performed on African green monkeys to determine the toxicity of carfentanil, the amount of naloxone required to restore respiration, and the time and dosage required to completely or partially reverse the effects of carfentanil. Naloxone was effective in immediately reversing respiratory depression but a higher dose of naloxone was required for complete behavioral recovery.
11) Dihydrocodeine for detoxification and maintenance treatment in individuals with opiate use disorders.
Carney T, Van Hout MC, Norman I, Dada S, Siegfried N, Parry CD.
Cochrane Database Syst Rev. 2020 Feb 18;2:CD012254. doi: 10.1002/14651858.CD012254.pub2. Review.
Comment:
A systematic review of randomized control trials evaluating the effectiveness of dihydrocodeine (DHC) treatment for detoxification and maintenance therapy for patients 15+ years who used illicit opioids. A total of 3 studies were included with the primary outcome being abstinence from illicit opioids post-detoxification or maintenance therapy. There was no significant difference in abstinence 6-months post detoxification for DHC compared to methadone or buprenorphine. DHC may be a low-barrier treatment but no conclusive statements can be made about its effectiveness. DHC is not an FDA approved medication for opioid use disorder, thus this study has little immediate significance for OUD treatment in the United States but may be an option in places where buprenorphine and methadone aren’t available.
12) Understanding the increase in opioid overdoses in New Hampshire: A rapid epidemiologic assessment.
Meier A, Moore SK, Saunders EC, McLeman B, Metcalf SA, Auty S, Walsh O, Marsch LA.
Drug Alcohol Depend. 2020 Feb 7;209:107893. doi: 10.1016/j.drugalcdep.2020.107893. [Epub ahead of print]
Comment:
Using demographic surveys and semi-structured interviews, this article describes possible factors contributing to New Hampshire’s high rates of fentanyl-related overdose. The majority of participants noted they knowingly sought out fentanyl and knew that the variability of fentanyl content increased overdose risk. As fentanyl becomes more popular, additional harm reduction services, treatment efforts, and education are needed to reduce fentanyl mortality.
13) Legal requirements and recommendations to prescribe naloxone.
Haffajee RL, Cherney S, Smart R.
Drug Alcohol Depend. 2020 Feb 6;209:107896. doi: 10.1016/j.drugalcdep.2020.107896. [Epub ahead of print]
Comment:
This review provides an overview of the adoption of state laws and policies for naloxone co-prescribing as of September 2019.
14) Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction.
Tas B, Jolley CJ, Kalk NJ, Van der Waal R, Bell J, Strang J.
Addiction. 2020 Feb 14. doi: 10.1111/add.15014. [Epub ahead of print]
Comment:
A single-participant study, spanning five years, that examined the effect of different maintenance doses of pharmaceutical heroin on respiratory depression. Oxygen saturation, end-tidal carbon dioxide, and respiratory rate were used as indicators of respiratory depression. The inter-session variability in respiratory response support the inconsistent relationship between opioid dose and overdose risk, although this is an n of 1.
15) Is the Gender Gap in Overdose Deaths (Still) Decreasing? An Examination of Opioid Deaths in Delaware, 2013-2017.
Eeckhaut MCW, Wagner J, Neitzke-Spruill L, Walker R, Anderson TL.
J Stud Alcohol Drugs. 2020 Jan;81(1):68-73.
Comment:
Examines if the overdose gender gap has narrowed or grown in the third wave of the opioid epidemic using toxicology reports from Delaware in 2013-2017. Overdose deaths rates increased for both men and women, but the rate increased 56% more for men than women, meaning the gender gap in overdose deaths has grown since the beginning of the opioid epidemic. Higher male-to-female opioid overdose deaths rates were found among older (45-64 years) individuals compared to younger individuals (15-44 years).
16) Severe Hypoxemia Prevents Spontaneous and Naloxone-induced Breathing Recovery after Fentanyl Overdose in Awake and Sedated Rats.
Haouzi P, Guck D, McCann M, Sternick M, Sonobe T, Tubbs N.
Anesthesiology. 2020 Feb 7. doi: 10.1097/ALN.0000000000003156. [Epub ahead of print]
Comment:
Hauozi et al. investigated the effects of hypoxemia after fentanyl overdose-induced apnea on sedated and unsedated rats. Outcomes were the ability to recover spontaneous breathing and the effects of naloxone. Among unsedated rats with fentanyl-induced apnea, the level of hypoxemia reached affected the ability to recover spontaneous breathing and respond to naloxone. Authors conclude that hypoxemia due to fentanyl-induced apnea can directly inhibit naloxone response and autoresuscitation. Not sure we agree with that assessment though – simple stimulation is often effective. One potential approach could be to recommend a sternal rub to confirm unresponsiveness prior to naloxone, and repeat it after naloxone.
17) Development and Clinical Validation of a Sensitive Lateral Flow Assay for Rapid Urine Fentanyl Screening in the Emergency Department.
Li Z, Chen H, Feng S, Liu K, Wang P.
Clin Chem. 2020 Feb 1;66(2):324-332. doi: 10.1093/clinchem/hvz023.
Comment:
The Lateral Flow Assay tested in this study is able to rapidly identify fentanyl and its major metabolite, norfentanyl, with specificity and sensitivity.
18) Buprenorphine to reverse respiratory depression from methadone overdose in opioid-dependent patients: a prospective randomized trial.
Zamani N, Buckley NA, Hassanian-Moghaddam H.
Crit Care. 2020 Feb 7;24(1):44. doi: 10.1186/s13054-020-2740-y.
Comment:
An Iranian clinical trial in which 85 patients who had a methadone overdose were randomized to receive either titrated naloxone doses or a low or high dose of buprenorphine to reverse their overdose. Patients were enrolled when they presented to the hospital with acute respiratory depression defined as cyanosis, less than 90% oxygen saturation, and respiratory rate less than 12 breaths per minute. Patients were believed to have overdosed on methadone, and urine testing was performed for confirmation. Buprenorphine and naloxone were both administered intravenously, and both reduced respiratory depression. Intubation and withdrawal were less common among patients who received buprenorphine. Naloxone required high titrated doses for reversal of respiratory depression. This use of buprenorphine is not uncommon in the community, and potentially aligned with current efforts to start patients on buprenorphine in the emergency department.
19) Association between state Medicaid expansion status and naloxone prescription dispensing.
Sohn M, Talbert JC, Delcher C, Hankosky ER, Lofwall MR, Freeman PR.
Health Serv Res. 2020 Feb 7. doi: 10.1111/1475-6773.13266. [Epub ahead of print]
Comment:
Medicaid expansion was associated with 38 additional naloxone prescriptions per state per quarter compared to states where Medicaid was not expanded. Expansion was also associated with an increase in the amount of naloxone prescriptions covered by Medicaid.
20) Protocol for a multi-site study of the effects of overdose prevention education with naloxone distribution program in Skåne County, Sweden.
Troberg K, Isendahl P, Blomé MA, Dahlman D, Håkansson A.
BMC Psychiatry. 2020 Feb 7;20(1):49. doi: 10.1186/s12888-020-2470-3.
Comment:
This is a protocol paper. In June 2018, Sweden launched its first take home naloxone program in Skåne County in response to high rates of overdose deaths. The take home program consisted of a multi-site train-the-trainer model including treatment units, needle exchanges, and in-patients units that provided training, naloxone, and study recruitment. Primary outcomes include the effect of overdose education and naloxone distribution on overdose mortality.
21) Carfentanil Outbreak – Florida, 2016-2017.
Delcher C, Wang Y, Vega RS, Halpin J, Gladden RM, O’Donnell JK, Hvozdovich JA, Goldberger BA.
MMWR Morb Mortal Wkly Rep. 2020 Feb 7;69(5):125-129. doi: 10.15585/mmwr.mm6905a2.
Comment:
Carfentanil is extremely potent. Outbreaks of carfentanil overdoses first reported in Ohio, Michigan, and Florida in 2016, and continued in Florida through 2017. Since then, overdoses due to fentanyl and fentanyl analogs have only continued to contribute to the spike in overdose deaths on both the east and west coasts of the U.S. Interestingly, carfentanil outbreaks tend to end quickly – the drug is just too potent.
22) Comparative Effectiveness of Different Treatment Pathways for Opioid Use Disorder.
Wakeman SE, Larochelle MR, Ameli O, Chaisson CE, McPheeters JT, Crown WH, Azocar F, Sanghavi DM.
JAMA Netw Open. 2020 Feb 5;3(2):e1920622. doi: 10.1001/jamanetworkopen.2019.20622.
Comment:
Wakeman et al. is an important study that clearly demonstrates the effectiveness of medication for opioid use disorder compared to nonpharmacologic treatment in treatment pathways outside of clinical trials. This is a retrospective study using data from over 40,000 patients with opioid use disorder from 2015-2017. Patients received one of six mutually exclusive treatment pathways (no treatment, inpatient detoxification or residential services, intensive behavioral health, buprenorphine or methadone, naltrexone, and nonintensive behavioral health), and outcomes included opioid-related overdose or serious acute care use 3 and 12 months after initial treatment. Only buprenorphine or methadone treatment was significantly associated with a 76% reduction in overdose risk after 3 months and 59% reduction in overdose risk at 12 months. Buprenorphine or methadone treatment was also associated with reduced risk of serious opioid-related acute care use at both 3 and 12 months. Notably, there was no reduction in overdose or acute care use associated with detoxification, intensive behavioral health, or naltrexone. This reaffirms the superiority of these medications for OUD.
23) Association of Opioid Overdose Risk Factors and Naloxone Prescribing in US Adults.
Lin LA, Brummett CM, Waljee JF, Englesbe MJ, Gunaseelan V, Bohnert ASB. J Gen Intern Med. 2020 Feb;35(2):420-427. doi: 10.1007/s11606-019-05423-7.
Comment:
Naloxone co-prescribing (with opioids) increased and was more often provided to patients with risks factors of opioid overdose (prescription of benzodiazepines, high daily opioid dosage, etc.) between 2014-2017.