Опиоиды

1. Br J Clin Pharmacol. 2019 Jun 7. doi: 10.1111/bcp.14019. [Epub ahead of print]

The relative lethal toxicity of pharmaceutical and illicit substances; A 16-year

study of the Greater Newcastle Hunter Area, Australia.

Brett J(1)(2), Wylie CE(2), Raubenheimer J(2), Isbister GK(3)(4), Buckley

NA(2)(5).

Author information:

(1)St. Vincent's Hospital, Sydney & New South Wales Poison Information Centre,

Sydney, Australia.

(2)Translational Australian Clinical Toxicology Program, School of Medical

Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney,

Australia.

(3)School of Medicine and Public Health, University of Newcastle, Callaghan,

Australia.

(4)Clinical Toxicologist and Emergency Medicine Specialist, New South Wales

Poison Information Centre & Hunter New England Toxicology Service, Sydney,

Australia.

(5)Clinical Toxicologist, New South Wales Poison Information Centre and Royal

Prince Alfred Hospital, Sydney, Australia.

AIMS: We aim to calculate two metrics of relative lethal toxicity; the fatal

toxicity index (FTI) (number of deaths per year of a daily dose) and the case

fatality (CF) (number of deaths per overdose) with a focus on opioids,

antidepressants, antipsychotics, benzodiazepines and illicit drugs.

METHODS: This descriptive cohort study used the Australian National Coronial

Information System (NCIS) to identify a population of individuals with

drug-associated deaths in the Greater Newcastle Hunter Region between January

2002 and December 2016. This was combined with Australian medicine dispensing

data and corresponding data from the Hunter Area Toxicology Service to calculate

FTI and CF.

RESULTS: There were 444 drug related deaths and 21,296 overdoses during the study

period. FTI and CF were well correlated (Spearman's rho 0.64, P<0.001). Of the

classes of interest, opioids had the highest FTI (40.3 95%CI 35.2-45.4 deaths per

100 years of use at the defined daily dose or deaths/DDD/100y) and CF (12.4%

95%CI 11.0-13.9). Fentanyl, methadone and morphine had the highest relative fatal

toxicity within this class. Tricyclic antidepressants had the highest relative

fatal toxicity of all antidepressants (FTI 14.5 95%CI 9.7-19.3 deaths/DDD/100y

and CF 7.1% (95%CI 4.8-9.3)) and benzodiazepines appeared to be more associated

with multiple agent deaths than single. Of the illicit drugs, heroin had the

highest CF (26.4%, 95%CI 19.1-33.7).

CONCLUSION: Knowledge of relative lethal toxicity is useful to prescribers and

medicines and public health policy makers in restricting access to more toxic

drugs and may also assist coroners in determining cause of death.

This article is protected by copyright. All rights reserved.

DOI: 10.1111/bcp.14019

PMID: 31173392

2. Natl Vital Stat Rep. 2019 Mar;68(3):1-19.

Drug Overdose Deaths Involving Fentanyl, 2011-2016.

Spencer MR, Warner M, Bastian BA, Trinidad JP, Hedegaard H.

Objectives-Fentanyl, a synthetic opioid, has been increasingly identified in drug

overdose deaths. This report describes trends in drug overdose deaths involving

fentanyl by demographic characteristics and geographic regions from 2011 through

2016. Methods-Drug overdose deaths were identified from the National Vital

Statistics System-Mortality (NVSS-M) multiple cause-of-death files (2011-2016)

using International Classification of Diseases, 10th Revision underlying causes

of death (codes X40-X44, X60-X64, X85, or Y10-Y14). NVSS-M records for drug

overdose deaths were linked with literal text from death certificates. Drug

overdose deaths involving fentanyl were identified using a methodology

established collaboratively by the National Center for Health Statistics and U.S.

Food and Drug Administration-referred to as the Drugs Mentioned with Involvement

(DMI) methodology-supplemented with search terms identified using text analytics

software. Fentanyl involvement was determined by the presence of any string term

or phrase listing fentanyl, or any fentanyl metabolite, precursor, analog, or

misspelling identified in the death certificate literal text fields (i.e., the

causes of death from Part I, significant conditions contributing to death from

Part II, and a description of how the injury occurred). Trends were evaluated

using the National Cancer Institute's Joinpoint Regression Program. Results-The

number of drug overdose deaths involving fentanyl was stable in 2011 (1,663) and

2012 (1,615), and began to increase in 2013, rising to 18,335 deaths in 2016. The

ageadjusted rate increased from 0.5 per 100,000 standard population in 2011 to

5.9 per 100,000 in 2016, with the increase starting in 2013 (0.6 in 2013 to 1.3

in 2014 and 2.6 in 2015). Numbers and rates increased for all sex, age, and

racial and ethnic subgroups, and most public health regions. Adjustment for

improved drug reporting over the study period did not change the trend patterns

observed.

All material appearing in this report is in the public domain and may be

reproduced or copied without permission; citation as to source, however, is

appreciated.

PMID: 31112123 [Indexed for MEDLINE]

3. J Investig Med. 2019 May 19. pii: jim-2019-001035. doi: 10.1136/jim-2019-001035.

[Epub ahead of print]

Characteristics of opioid prescriptions for discharged pediatric emergency

department patients with acute injuries.

Kahl LK(1), Stevens MW(1), Gielen AC(2), McDonald EM(2), Ryan L(1).

Author information:

(1)Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland,

USA.

(2)Johns Hopkins Center for Injury Research and Policy, Johns Hopkins University

Bloomberg School of Public Health, Baltimore, Maryland, USA.

This study describes the characteristics of opioid prescriptions for pediatric

patients discharged from the emergency department (ED) with acute injuries,

including type, formulation, quantity dispensed, and associations with patient

age group and prescriber level of training. This retrospective cohort study

enrolled all acutely injured patients receiving opioid prescriptions at discharge

from an urban academic pediatric ED in a 1-year period. Electronic medical

records were reviewed to abstract clinical and prescription data and prescriber

level of training. Descriptive statistics were used for analysis. We identified

254 patients with injuries who received opioid prescriptions at ED discharge

during the study period (mean age 9.5 years, 65% male). The most common injury

was fracture (71%). Oxycodone was the opioid most frequently prescribed (96.1%).

Liquid formulations were prescribed in 51.6% of cases. The median number of doses

prescribed per prescription was 12 (SD±9.1), with a range of 1-50. Residents

wrote 72.9% of prescriptions and prescribed more doses than non-residents (15.5

vs 12.2, p=0.01). Post-graduate year 2 (PGY2) residents prescribed more doses

than PGY1 or PGY3+ residents. Our data show wide variation in the number of

opioid doses prescribed to acutely injured pediatric patients at ED discharge and

frequent use of liquid formulation; both factors may place this population at

risk for accidental ingestion. These findings also support the development of

pediatric clinical guidelines to define appropriate quantities of opioids to

prescribe, promote poisoning prevention strategies, and design post-graduate

education for medical trainees about safe prescribing practices.

© American Federation for Medical Research 2019. No commercial re-use. See rights

and permissions. Published by BMJ.

DOI: 10.1136/jim-2019-001035

PMID: 31109930

Conflict of interest statement: Competing interests: None declared.

4. Forensic Sci Int. 2019 Jul;300:85-88. doi: 10.1016/j.forsciint.2019.04.030. Epub

2019 May 1.

Toxic lifespan of the synthetic opioid U-47,700 in Finland verified by

re-analysis of UPLC-TOF-MS data.

Kriikku P(1), Pelander A(2), Rasanen I(2), Ojanperä I(3).

Author information:

(1)Forensic Toxicology Unit, National Institute for Health and Welfare, Helsinki,

Finland; Department of Forensic Medicine, University of Helsinki, Helsinki,

Finland. Electronic address: pirkko.kriikku@thl.fi.

(2)Forensic Toxicology Unit, National Institute for Health and Welfare, Helsinki,

Finland.

(3)Forensic Toxicology Unit, National Institute for Health and Welfare, Helsinki,

Finland; Department of Forensic Medicine, University of Helsinki, Helsinki,

Finland.

U-47,700 is a synthetic opioid that emerged on the novel psychoactive substance

market a few years ago. After incorporating the substance into the urine

UPLC-TOF-MS screening used in post-mortem toxicology, the drug was detected in 10

autopsy cases within routine case work. In all cases, the cause of death was

accidental poisoning by U-47,700 alone or in combination with other psychoactive

substances. The concentration of U-47,700 in the blood samples ranged between

0.15-2.0 mg/L with a median of 0.30 mg/L. In one of the cases with a U-47,700

concentration of 0.27 mg/L, no other psychoactive substances were detected. The

stored TOF-MS analytical data from the year preceding the incorporation of

U-47,700 into the screening was reprocessed in order to search for more positive

cases. The data-independent acquisition of the original screening allowed for

retrospective re-analysis of the full-scan data without additional experiments on

the actual sample. The retrospective data-analysis revealed two additional cases

positive for U-47,700. The first mention of U-47,700 on a Finnish internet

discussion forum was in March 2015. After having been detected in several death

cases, the drug was put under national control in November 2016 and the last

fatality occurred in 2017. The toxic lifespan of U-47,700 thus lasted for

approximately 2 years in Finland. Forensic and clinical laboratories need to

rapidly adjust their screening procedures in order to adapt to the continuously

expanding field of novel psychoactive substances. Retrospective data-analysis is

a practical tool for monitoring the emergence of new substances onto the market.

Copyright © 2019 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2019.04.030

PMID: 31082566 [Indexed for MEDLINE]

5. J Subst Abuse Treat. 2019 May 1. pii: S0740-5472(19)30062-5. doi:

10.1016/j.jsat.2019.04.011. [Epub ahead of print]

"Another tool for the tool box? I'll take it!": Feasibility and acceptability of

mobile recovery outreach teams (MROT) for opioid overdose patients in the

emergency room.

Wagner KD(1), Oman RF(2), Smith KP(3), Harding RW(4), Dawkins AD(5), Lu M(6),

Woodard S(7), Berry MN(8), Roget NA(9).

Author information:

(1)School of Community Health Sciences, University of Nevada, Reno, 1664 N.

Virginia St., MC 0274, Reno, NV 89557, United States of America. Electronic

address: karlawagner@unr.edu.

(2)School of Community Health Sciences, University of Nevada, Reno, 1664 N.

Virginia St., MC 0274, Reno, NV 89557, United States of America. Electronic

address: roman@unr.edu.

(3)School of Community Health Sciences, University of Nevada, Reno, 1664 N.

Virginia St., MC 0274, Reno, NV 89557, United States of America. Electronic

address: smith167@unr.edu.

(4)School of Community Health Sciences, University of Nevada, Reno, 1664 N.

Virginia St., MC 0274, Reno, NV 89557, United States of America. Electronic

address: rharding@unr.edu.

(5)School of Community Health Sciences, University of Nevada, Reno, 1664 N.

Virginia St., MC 0274, Reno, NV 89557, United States of America. Electronic

address: adawkins@unr.edu.

(6)School of Community Health Sciences, University of Nevada, Reno, 1664 N.

Virginia St., MC 0274, Reno, NV 89557, United States of America. Electronic

address: minggenl@unr.edu.

(7)State of Nevada, Division of Public and Behavioral Health, Bureau of

Behavioral Health, Prevention, and Wellness, 4126 Technology Way, 2nd Floor,

Carson City, NV 89706, United States of America. Electronic address:

swoodard@health.nv.gov.

(8)Center for the Application of Substance Abuse Technologies (CASAT), School of

Community Health Sciences, University of Nevada, Reno, 1664 N. Virginia Street,

MC 279, Reno, NV 89557, United States of America. Electronic address:

mberry@casat.org.

(9)Center for the Application of Substance Abuse Technologies (CASAT), School of

Community Health Sciences, University of Nevada, Reno, 1664 N. Virginia Street,

MC 279, Reno, NV 89557, United States of America. Electronic address:

nroget@casat.org.

Drug poisoning deaths involving opioids have increased exponentially in the

United States. Post-overdose outreach to patients in the emergency room (ER) is a

promising strategy for increasing uptake of medication assisted treatment and

reducing subsequent overdose. We conducted a mixed methods study to investigate

the feasibility and acceptability of a mobile recovery outreach team (MROT)

program for opioid overdose patients presenting in Nevada's ERs, which was funded

by the SAMHSA Opioid State Targeted Response (STR) grant. We interviewed 25 ER

staff using quantitative questions informed by Diffusion of Innovation (DOI)

theory and qualitative questions regarding their experiences caring for overdose

patients, perceived benefits, and concerns about the MROT program. Respondents

expressed strong support and enthusiasm for the program, identified advantages of

the program relative to standard of care, highlighted logistical issues that must

be addressed prior to implementation, and illustrated how the MROT program is

compatible with their personal and professional values. Our results suggest that

the STR-funded MROT program could reduce burden and stress among ER staff and

improve patient outcomes, but must be informed by formative research that

addresses issues of logistical complexity and cultural compatibility.

Copyright © 2019 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jsat.2019.04.011

PMID: 31079951

6. J Subst Abuse Treat. 2019 Aug;103:58-63. doi: 10.1016/j.jsat.2019.05.001. Epub

2019 May 5.

Opioid medication discontinuation and risk of adverse opioid-related health care

events.

Mark TL(1), Parish W(2).

Author information:

(1)RTI International, United States of America. Electronic address:

tmark@rti.org.

(2)RTI International, United States of America.

BACKGROUND: Between 2012 and 2017, the United States dramatically reduced opioid

prescribing rates. While this may be appropriate given the opioid epidemic, there

has been little research to guide the clinical practice of discontinuing patients

from opioid medications and opioid death rates have continued to increase.

OBJECTIVE: To determine the relationship between time to opioid discontinuation

and the risk of an opioid-related emergency department visit or hospitalization

among high dose opioid users.

DESIGN: We applied Cox proportional hazard models to 2013-2017 Medicaid claims

data to research this relationship.

PARTICIPANTS: Medicaid beneficiaries in Vermont who filled prescription opioids

at high daily doses (at least 120 morphine milligram equivalents) for 90 or more

consecutive days and who subsequently discontinued opioid prescriptions

(n = 494).

MAIN MEASURES: The outcome was an opioid-related adverse event defined as an

emergency department visit or hospitalization with a primary or secondary

diagnosis of opioid poisoning or substance use disorder.

KEY RESULTS: The median length of time to discontinuation was 1 day indicating

that half of patients had no dose reduction prior to discontinuation. 86% of

patients discontinued within 21 days (considered rapid tapering in recent

clinical guidelines). 49% of members had an opioid-related hospitalization or

emergency department visit. After controlling for sociodemographic and clinical

factors, each additional week of discontinuation time was associated with a 7%

reduction in the probability of having opioid related adverse event (p < 0.01).

Although 60% of members had a diagnosed substance use disorder prior to tapering,

<1% of beneficiaries were transitioned onto an opioid use disorder medication.

CONCLUSIONS: Faster rates of opioid tapering were associated with a greater

probability of adverse events and many patients discontinued opioids suddenly,

with no dose reduction. Additional clinical guidance, research, and interventions

are needed to ensure that patients' opioid prescriptions are discontinued safely.

Copyright © 2019 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jsat.2019.05.001

PMID: 31079950

7. Forensic Sci Int. 2019 Jul;300:13-18. doi: 10.1016/j.forsciint.2019.04.008. Epub

2019 Apr 17.

Detection of fentanyl and fentanyl analogues in biological samples using liquid

chromatography-high resolution mass spectrometry.

Rab E(1), Flanagan RJ(2), Hudson S(3).

Author information:

(1)Specialised Clinical Chemistry, Sheffield Teaching Hospitals NHS Foundation

Trust, United Kingdom. Electronic address: edmund.rab@sth.nhs.uk.

(2)Specialised Clinical Chemistry, Sheffield Teaching Hospitals NHS Foundation

Trust, United Kingdom.

(3)LGC Sport and Specialised Analytical Services, Fordham, Cambridgeshire, United

Kingdom.

BACKGROUND: Fentanyl and analogues such as butyrylfentanyl, carfentanil,

4-fluorobutyrylfentanyl, and furanylfentanyl may be either added to, or sold as,

heroin. Fentanyl and carfentanil have approximately 100 and 10,000 times the

potency of morphine, respectively, and there is thus a high risk of death with

the use of these drugs.

METHODS: We looked for fentanyl/fentanyl analogues using liquid

chromatography-high resolution mass spectrometry (LC-HRMS) in selected biological

samples obtained post-mortem February 2017-end January 2018. Suspicion of

fentanyl poisoning arose from the circumstances of death, a history of heroin

use, and the geographical area in which the deceased was discovered, supplemented

by drugs intelligence data.

RESULTS: Of the 84 deaths investigated, fentanyl and/or a fentanyl analogue were

detected in 40 (48%). The fentanyls encountered were carfentanil (N = 17),

fentanyl (9), carfentanil and fentanyl together (12), and fentanyl, carfentanil,

4-fluorobutyrylfentanyl, and butyrylfentanyl together (2). The median (range)

post-mortem blood fentanyl concentration was 2.66 (0.21-107) μg/L and the median

(range) carfentanil concentration was 0.24 (0.03-1.66) μg/L. The most prevalent

compounds present together with fentanyls were ethanol [N = 28, median (range)

post-mortem blood concentration: 44 (<10-249) mg/dL)], benzoylecgonine [N = 22,

0.64 (<0.05-3.17) mg/L] and free morphine [N = 20, 0.05 (<0.05-0.34) mg/L].

Deaths in hospital excluded, median blood free morphine, and ethanol

concentrations were significantly lower in deaths where fentanyl/fentanyl

analogues were present, but there was much overlap with the blood concentrations

of these analytes in the non-fentanyl related deaths. A routine drugs of abuse

assay using LC-HRMS identified fentanyl with 100% sensitivity and carfentanil

with 89% sensitivity.

CONCLUSIONS: Given their potency, misuse of fentanyl and its analogues is likely

to cause severe toxicity. A simple LC-HRMS method detected all cases in which

fentanyl was identified post-mortem and most of the cases in which carfentanil

was detected.

Copyright © 2019 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2019.04.008

PMID: 31063883 [Indexed for MEDLINE]

8. MMWR Morb Mortal Wkly Rep. 2019 May 3;68(17):388-395. doi:

10.15585/mmwr.mm6817a3.

Drug Overdose Deaths Involving Cocaine and Psychostimulants with Abuse Potential

- United States, 2003-2017.

Kariisa M(1), Scholl L(1), Wilson N(1), Seth P(1), Hoots B(1).

Author information:

(1)Division of Unintentional Injury Prevention, National Center for Injury

Prevention and Control, CDC.

In 2016, a total of 63,632 persons died from drug overdoses in the United States

(1). Drug overdose deaths involving cocaine, psychostimulants with abuse

potential (psychostimulants), or both substances combined increased 42.4% from

12,122 in 2015 to 17,258 in 2016.* Psychostimulants with abuse potential include

drugs such as methamphetamine, 3,4-methylenedioxy-methamphetamine (MDMA),

dextroamphetamine, levoamphetamine, methylphenidate (Ritalin), and caffeine. From

2015 to 2016, cocaine-involved and psychostimulant-involved death rates increased

52.4% and 33.3%, respectively (1). A total of 70,237 persons died from drug

overdoses in the United States in 2017; approximately two thirds of these deaths

involved an opioid (2). CDC analyzed 2016-2017 changes in age-adjusted death

rates involving cocaine and psychostimulants by demographic characteristics,

urbanization levels, U.S. Census region, 34 states, and the District of Columbia

(DC). CDC also examined trends in age-adjusted cocaine-involved and

psychostimulant-involved death rates from 2003 to 2017 overall, as well as with

and without co-involvement of opioids. Among all 2017 drug overdose deaths,

13,942 (19.8%) involved cocaine, and 10,333 (14.7%) involved psychostimulants.

Death rates increased from 2016 to 2017 for both drug categories across

demographic characteristics, urbanization levels, Census regions, and states. In

2017, opioids were involved in 72.7% and 50.4% of cocaine-involved and

psychostimulant-involved overdoses, respectively, and the data suggest that

increases in cocaine-involved overdose deaths from 2012 to 2017 were driven

primarily by synthetic opioids. Conversely, increases in psychostimulant-involved

deaths from 2010 to 2017 occurred largely independent of opioids, with increased

co-involvement of synthetic opioids in recent years. Provisional data from 2018

indicate that deaths involving cocaine and psychostimulants are continuing to

increase.† Increases in stimulant-involved deaths are part of a growing

polysubstance landscape. Increased surveillance and evidence-based multisectoral

prevention and response strategies are needed to address deaths involving cocaine

and psychostimulants and opioids. Enhancing linkage to care, building state and

local capacity, and public health/public safety collaborations are critical

components of prevention efforts.

DOI: 10.15585/mmwr.mm6817a3

PMCID: PMC6541315

PMID: 31048676 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed.

9. BMC Emerg Med. 2019 Apr 29;19(1):29. doi: 10.1186/s12873-019-0244-3.

Gender differences in acute recreational drug toxicity: a case series from Oslo,

Norway.

Syse VL(1)(2), Brekke M(3), Grimsrud MM(1)(4), Persett PS(1)(5), Heyerdahl

F(6)(7), Hovda KE(8), Vallersnes OM(9)(10).

Author information:

(1)Faculty of Medicine, University of Oslo, Oslo, Norway.

(2)Oslo Accident and Emergency Outpatient Clinic, Department of Emergency General

Practice, City of Oslo Health Agency, Oslo, Norway.

(3)General Practice Research Unit, University of Oslo, Oslo, Norway.

(4)The Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway.

(5)Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

(6)Department of Prehospital Medicine, Oslo University Hospital, Oslo, Norway.

(7)Norwegian Air Ambulance Foundation, Oslo, Norway.

(8)The Norwegian CBRNe Centre of Medicine, Department of Acute Medicine, Oslo

University Hospital, Oslo, Norway.

(9)Oslo Accident and Emergency Outpatient Clinic, Department of Emergency General

Practice, City of Oslo Health Agency, Oslo, Norway.

o.m.vallersnes@medisin.uio.no.

(10)Department of General Practice, University of Oslo, Oslo, Norway.

o.m.vallersnes@medisin.uio.no.

BACKGROUND: Female drug users report poorer physical and mental health than male

drug users. We describe female and male patients treated for acute recreational

drug toxicity, and look for gender differences in clinical state, treatment, and

toxic agents taken.

METHODS: Retrospective case series from a primary care emergency outpatient

clinic and a hospital emergency department in Oslo, Norway. All patients treated

for acute recreational drug toxicity from October 2013 through March 2015 were

included, except patients with lone alcohol intoxication. Patients were grouped

according to whether they had taken opioids or not, as a proxy differentiation

between heavy drug users and party drug users. Data from the two clinical

settings were analysed separately.

RESULTS: In total, 2495 cases were included, 567 (22.7%) were women. Female

patients were younger than males, median 31 vs 34 years (p < 0.001). On most

comparisons of clinical variables there were no significant differences between

genders. A larger proportion of females in the outpatient opioid group were

hypotensive, 10.9% vs 3.9% (p < 0.001). Fewer females were intubated, none vs

21.1% (p = 0.019) in the hospital opioid group, and 6.4% vs 21.0% (p = 0.039) in

the hospital non-opioid group. The proportion of gamma-hydroxybutyrate (GHB)

poisoning was larger among females both at the outpatient clinic (14.4% vs 8.6%,

p < 0.001) and at the hospital (60.3% vs 36.4%, p = 0.001), while the proportion

of heroin poisoning was smaller among females at the outpatient clinic (37.1% vs

47.0%, p < 0.001).

CONCLUSION: One in four patients treated for acute recreational drug toxicity

were women. Female patients were younger, had more frequently taken GHB and were

less frequently intubated. Otherwise, the gender differences regarding clinical

state and treatment were small. Although female drug users are known to report

poorer health than males, we did not find that women had a more severe clinical

course than men when presenting with overdose.

DOI: 10.1186/s12873-019-0244-3

PMCID: PMC6489220

PMID: 31035940

10. Expert Opin Drug Saf. 2019 Jun;18(6):465-475. doi: 10.1080/14740338.2019.1613372.

Epub 2019 May 16.

The role of take-home naloxone in the epidemic of opioid overdose involving

illicitly manufactured fentanyl and its analogs.

Kim HK(1), Connors NJ(2), Mazer-Amirshahi ME(3)(4).

Author information:

(1)a Department of Emergency Medicine , University of Maryland School of Medicine

, Baltimore , MD , USA.

(2)b Department of Emergency Medicine , Medical University of South Carolina ,

Charleston , SC , USA.

(3)c Department of Emergency Medicine , MedStar Washington Hospital Center ,

Washington , DC , USA.

(4)d School of Medicine , Georgetown University , Washington , DC , USA.

Introduction: There has been an exponential increase in overdose fatalities as

illicitly manufactured fentanyl and its analogs (IMF) are becoming more prevalent

in the illicit drug supply. In response, overdose education and naloxone

distribution (OEND) programs have been implemented throughout the United States

as a harm reduction strategy. However, there are increasing reports that higher

naloxone doses or repeat administration might be required for overdose victims

involving IMF. Areas covered: In this article, we provide a comprehensive review

of the epidemiology, public health impact, and pharmacologic properties of IMF.

The pharmacokinetic properties of currently available take-home naloxone (THN)

kits, the role of THN as a harm reduction strategy and available data on its

clinical use are discussed. Implications of occupational IMF exposure for first

responders are also described. Expert opinion: THN administration by a bystander

is an effective harm reduction intervention. However, there is growing evidence

that higher dose or multiple administrations of naloxone are required to fully

reverse IMF related toxicity. Recently, the US Food and Drug Administration

approved THN kits with a concentrated naloxone dose that produce high

bioavailability. However, limited presence of OEND programs and cost of these new

devices impede their accessibility to the general public.

DOI: 10.1080/14740338.2019.1613372

PMID: 31033357 [Indexed for MEDLINE]

11. J Stud Alcohol Drugs. 2019 Mar;80(2):201-210.

Trends in Drug Poisoning Deaths Among Adolescents and Young Adults in the United

States, 2006-2015.

Ali B(1), Fisher DA(1), Miller TR(1), Lawrence BA(1), Spicer RS(2), Swedler

DI(1), Allison J(3).

Author information:

(1)Pacific Institute for Research and Evaluation, Calverton, Maryland.

(2)Impact Research, LLC, Columbia, Maryland.

(3)Health Imperatives, Brockton, Massachusetts.

OBJECTIVE: Despite the rising toll of drug poisoning deaths in the United States,

the extent of the problem among adolescents and young adults ages 15-24 years has

received relatively little attention. We examined sociodemographic

characteristics and state trends in drug poisoning deaths among adolescents and

young adults from 2006 to 2015 and estimated the costs of drug poisoning

mortality in this population.

METHOD: We used the National Vital Statistics System's Multiple Cause of Death

files from 2006 to 2015. We analyzed trends using Joinpoint regression analysis

and calculated total costs of drug poisoning deaths, including medical costs,

work loss costs, and quality of life loss, based on widely used cost estimates.

RESULTS: Drug poisoning death rates (per 100,000 population) in adolescents and

young adults increased from 8.1 in 2006 to 9.7 in 2015. The rates increased

significantly for Whites (1.7% per year) and Asian/Pacific Islanders (4.3% per

year) from 2006 to 2015 and for Blacks (11.8% per year) from 2009 to 2015. By

U.S. region, the rates increased significantly in the Midwest (4.4% per year)

from 2006 to 2015 and in the Northeast (11.0% per year) from 2009 to 2015. Trends

varied by age group, intent for drug poisoning, drug category (i.e., opioids,

pharmaceutical drugs excluding opioids, illicit drugs excluding opioids, and

unspecified drugs), urbanization level, and state. The estimated costs of drug

poisoning deaths among adolescents and young adults totaled approximately $35

billion in 2015.

CONCLUSIONS: Trends in drug poisoning deaths and estimated costs inform

state-specific prevention and intervention efforts.

PMCID: PMC6489543 [Available on 2020-03-01]

PMID: 31014465

12. Sultan Qaboos Univ Med J. 2018 Nov;18(4):e529-e532. doi:

10.18295/squmj.2018.18.04.017. Epub 2019 Mar 28.

Lead Toxicity due to Ingestion of Lead-Contaminated Opium in a Patient Presenting

with Motor Neuropathy and Upper Limb Paresis: A case report.

Mirzaei SMM(1), Akbari A(2), Mehrpour O(3), Zamani N(4).

Author information:

(1)Department of Neurology, Birjand University of Medical Sciences, Birjand,

Iran.

(2)Department of Medical Toxicology and Drug Abuse Research Center, Birjand

University of Medical Sciences, Birjand, Iran.

(3)Rocky Mountain Poison and Drug Center, Denver Health Medical Center, Denver,

Colorado, USA.

(4)Department of Clinical Toxicology, Loghman Hakim Hospital, Tehran, Iran.

Opium users may present with central or peripheral nervous system-related

symptoms, gastrointestinal complications and anaemia; in such cases, lead

poisoning should be suspected and chelation therapy initiated as soon as

possible. We report a 64-year-old male patient with a 20-year history of opium

addiction who was referred to the Imam Reza Hospital, Birjand, Iran, in 2017 with

severe motor neuropathy and paresis in both upper limbs. His primary symptoms

were generalised weakness, abdominal and bone pain, constipation and lower limb

paraesthesia that had started several months prior. In addition, he reported

severe progressive bilateral paresis of the upper limbs of one month's duration.

A diagnosis of lead poisoning was confirmed by a blood lead level of 140 μg/dL.

The patient underwent chelation therapy after which he improved significantly. At

a one-year follow-up visit, he was neurologically intact and symptom-free.

DOI: 10.18295/squmj.2018.18.04.017

PMCID: PMC6443289

PMID: 30988975 [Indexed for MEDLINE]

13. Sr Care Pharm. 2019 Apr 1;34(4):258-267. doi: 10.4140/TCP.n.2019.258..

The Effects of the Opioid Epidemic on Prescribing Practices in Long-Term Care

Residents.

Yamagishi L, Erickson O, Mazzei K, O'Neil C, Kamal KM.

OBJECTIVE: Evaluate opioid prescribing practices for older adults since the

opioid crisis in the United States.<br/> DESIGN: Interrupted time-series analysis

on retrospective observational cohort study.<br/> SETTING: 176-bed

skilled-nursing facility (SNF).<br/> PARTICIPANTS: Patients admitted to a

long-term care facility with pain-related diagnoses between October 1, 2015, and

March 31, 2017, were included. Residents discharged prior to 14 days were

excluded. Of 392 residents, 258 met inclusion criteria with 313 admissions.<br/>

MAIN OUTCOME MEASURE: Changes in opioid prescribing frequency between two

periods: Q1 to Q3 (Spring 2016) and Q4 to Q6 for pre- and postgovernment

countermeasure, respectively.<br/> RESULTS: Opioid prescriptions for patients

with pain-related diagnoses decreased during period one at -0.10% per quarter

(95% confidence interval [CI] -0.85-0.85; P = 0.99), with the rate of decline

increasing at -3.8% per quarter from period 1 and 2 (95% CI -0.23-0.15; P =

0.64). Opioid prescribing from top International Classification of Diseases,

Ninth Revision category, "Injury and Poisoning" decreased in prescribing

frequency by -3.0% per quarter from Q1 to Q6 (95% CI -0.16-0.10; P = 0.54).

Appropriateness of pain-control was obtained from the Minimum Data Set version

3.0 "Percent of Residents Who Self-Report Moderate to Severe Pain (Short Stay)"

measure; these results showed a significant increase in inadequacy of pain relief

by 0.28% per quarter (95% CI 0.12-0.44; P = 0.009).<br/> CONCLUSION: Residents

who self-report moderate- to severe pain have significantly increased since

October 2015. Opioid prescriptions may have decreased for elderly patients in

SNFs since Spring 2016. Further investigation with a larger population and wider

time frame is warranted to further evaluate significance.

DOI: 10.4140/TCP.n.2019.258.

PMID: 30935448 [Indexed for MEDLINE]

14. Forensic Sci Int. 2019 May;298:186-267. doi: 10.1016/j.forsciint.2019.02.021.

Epub 2019 Feb 25.

Death cases involving certain new psychoactive substances: A review of the

literature.

Kraemer M(1), Boehmer A(2), Madea B(3), Maas A(4).

Author information:

(1)University of Bonn, Institute of Forensic Medicine, Stiftsplatz 12, 53111

Bonn, Germany. Electronic address: michael.kraemer@uni-bonn.de.

(2)University of Bonn, Institute of Forensic Medicine, Stiftsplatz 12, 53111

Bonn, Germany. Electronic address: anna-maria.boehmer@web.de.

(3)University of Bonn, Institute of Forensic Medicine, Stiftsplatz 12, 53111

Bonn, Germany. Electronic address: b.madea@uni-bonn.de.

(4)University of Bonn, Institute of Forensic Medicine, Stiftsplatz 12, 53111

Bonn, Germany. Electronic address: alexandramaas@uni-bonn.de.

In the last decades, more and more new psychoactive substances (NPS) were

introduced on the drug market which were sold as "legal" alternatives for classic

drugs and misused medications. Due to an increased number of available substances

and a growing utilization by users of common drugs but also by inexperienced

users because of the supposed "legal" status, also undesired adverse effects of

these NPS, at worst leading to death, became apparent. This review summarizes

fatalities previously described in scientific literature which were attributed to

the use of NPS or such cases, in which intake of NPS was proven or even assumed

to contribute to death. This summary includes an overview of substances involved

(particularly synthetic cannabinoids ("spice"), novel opioids and synthetic

cathinones ("bath salts")) as well as of postmortem concentrations determined in

various biological matrices. The compiled data assist forensic toxicologists with

the interpretation of death cases involving NPS.

Copyright © 2019 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2019.02.021

PMID: 30925344 [Indexed for MEDLINE]

15. Prehosp Emerg Care. 2019 Mar 29:1-15. doi: 10.1080/10903127.2019.1597955. [Epub

ahead of print]

Evidence-Based Guidelines for EMS Administration of Naloxone.

Williams K, Lang ES, Panchal AR, Gasper JJ, Taillac P, Gouda J, Lyng JW, Goodloe

JM, Hedges M.

The opioid crisis is a growing concern for Americans, and it has become the

leading cause of injury-related death in the United States. An adjunct to

respiratory support that can reduce this high mortality rate is the

administration of naloxone by Emergency Medical Services (EMS) practitioners for

patients with suspected opioid overdose. However, clear evidence-based guidelines

to direct EMS use of naloxone for opioid overdose have not been developed.

Leveraging the recent Agency for Healthcare Research and Quality (AHRQ)

systematic review on the EMS administration of naloxone for opioid poisonings,

federal partners determined the need for a clinical practice guideline for EMS

practitioners faced with suspected opioid poisoning. Project funding was provided

by the National Highway Traffic Safety Administration, Office of EMS, (NHTSA

OEMS), and the Health Resources and Services Administration, Maternal and Child

Health Bureau's EMS for Children Program (EMSC). The objectives of this project

were to develop and disseminate an evidence-based guideline and model protocol

for administration of naloxone by EMS practitioners to persons with suspected

opioid overdose. We have four recommendations relating to route of

administration, all conditional, and all supported by low or very low certainty

of evidence. We recommend the intravenous route of administration to facilitate

titration of dose, and disfavor the intramuscular route due to difficulty with

titration, slower time to clinical effect, and potential exposure to needles. We

equally recommend the intranasal and intravenous routes of administration, while

noting there are variables which will determine which route is best for each

patient. Where we are unable to make recommendations due to evidence limitations

(dosing, titration, timing, and transport) we offer technical remarks.

Limitations of our work include the introduction of novel synthetic opioids after

many of the reviewed papers were produced, which may affect the dose of naloxone

required for effect, high risk of bias and imprecision in the reviewed papers,

and the introduction of new naloxone administration devices since many of the

reviewed papers were published. Future research should be conducted to evaluate

new devices and address the introduction of synthetic opioids.

DOI: 10.1080/10903127.2019.1597955

PMID: 30924736

16. Lancet. 2019 Mar 23;393(10177):e35. doi: 10.1016/S0140-6736(19)30502-1.

Heroin body-packing and naloxone.

Vahabzadeh M(1), Banagozar Mohammadi A(2).

Author information:

(1)Medical Toxicology Research Centre, Mashhad University of Medical Sciences,

Mashhad, Iran. Electronic address: vahabzadehm@mums.ac.ir.

(2)Internal Medicine Department, Faculty of Medicine, Tabriz University of

Medical Sciences, Tabriz, Iran.

DOI: 10.1016/S0140-6736(19)30502-1

PMID: 30910307 [Indexed for MEDLINE]

17. Drug Alcohol Depend. 2019 May 1;198:121-125. doi:

10.1016/j.drugalcdep.2019.01.042. Epub 2019 Mar 14.

Unintentional drug overdose deaths involving cocaine among middle-aged and older

adults in New York City.

Han BH(1), Tuazon E(2), Kunins HV(2), Mantha S(2), Paone D(2).

Author information:

(1)Division of Geriatric Medicine and Palliative Care, New York University School

of Medicine, United States. Electronic address: Benjamin.Han@nyumc.org.

(2)New York City Department of Health and Mental Hygiene, United States.

BACKGROUND: Cocaine is commonly involved in unintentional drug poisoning

(overdose) deaths, accounting for 46% of overdose deaths in New York City (NYC)

in 2016. However, little research exists regarding cocaine use by middle-aged and

older adults, who are more likely than younger individuals to have underlying

cardiovascular disease (CVD) and therefore, may be at increased risk for the

adverse health consequences of cocaine.

METHODS: We conducted a retrospective analysis of unintentional drug overdose

deaths of middle-aged and older NYC residents age 45-84 from 2000 to 2016 using

two linked sources, NYC death certificates and toxicology results from the Office

of the Chief Medical Examiner.

RESULTS: From 2000 to 2016, there were 6061 unintentional drug overdose deaths

among New Yorkers age 45-84. Of those, cocaine was involved in 53% (n = 3183).

Co-occurring opioid involvement (fentanyl, heroin, methadone, or opioid

analgesics) among deaths involving cocaine was common (58%). Compared to

decedents of non-cocaine involved overdose, decedents of cocaine-involved

overdose were more likely to be male and non-Latino Black. Multivariable analysis

showed that adults age 45-54 (adjusted odds ratio [AOR] = 1.34, 95% 1.05, 1.70),

males (AOR = 1.30, 95% CI 1.15, 1.46), Bronx residence (AOR = 1.29, 95% CI 1.08,

1.54), and non-Latino black race/ethnicity (AOR = 2.37, 95% CI 2.07, 2.72) were

independently associated with cocaine-involved overdose.

CONCLUSION: Characteristics of decedents of cocaine-involved overdose overlap

with populations with high CVD burden in NYC. Studies are needed to better

understand the risks of cocaine among adults with underlying CVD.

Copyright © 2019 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2019.01.042

PMCID: PMC6467745 [Available on 2020-05-01]

PMID: 30909019

18. Can J Psychiatry. 2019 Mar 24:706743719838777. doi: 10.1177/0706743719838777.

[Epub ahead of print]

An Observational Study of Suicide Deaths by Self-Poisoning with Opioids in

Toronto (1998-2015).

Sinyor M(1)(2), Williams M(1)(2), Gulati S(3), Schaffer A(1)(2).

Author information:

(1)1 Department of Psychiatry, University of Toronto, Sunnybrook Health Sciences

Centre, Toronto, Ontario, Canada.

(2)2 Mood and Anxiety Disorders Program, Department of Psychiatry, Sunnybrook

Health Sciences Centre, Ontario, Canada.

(3)3 Department of Family Medicine, Medical College of Wisconsin, Milwaukee, WI,

USA.

OBJECTIVE:: Opioid self-poisoning is a common suicide method in North America.

However, there is limited information about who dies by this method and whether

legislation on opioid access has resulted in lower suicide rates by

self-poisoning. The primary research question was whether the rate of suicide

involving opioids has diminished since the implementation of Ontario's Narcotics

Safety and Awareness Act (NSAA) (1998-2011 vs. 2012-2015).

METHODS:: This study examined all suicides by intentional self-poisoning with or

without an opioid in Toronto (1998-2015), and tested the mean change after NSAA

by one-way ANOVA. Demographic and clinical characteristics as well as details

surrounding the suicide were also compared for suicides by opioid and by

non-opioid self-poisoning.

RESULTS:: There were 773 suicides in Toronto by self-poisoning where the

substance used was known (19.0% of all suicides). Of these, 289 (37.4%) had an

opioid present and, in 249 (32.2%) suicides, the opioid was deemed to have been

lethal. The mean number of yearly suicides involving opioids was 15.6 before and

17.5 after NSAA implementation (F 1.16, df 1, p = 0.30). Neither the rate per

population nor the proportion of suicides by this method has changed between the

2 periods. People who died by suicide using an opioid had higher rates of pain,

musculoskeletal, gastrointestinal/liver disorders, and cancer.

CONCLUSIONS:: This study confirms that opioids are a major contributor to suicide

in Toronto, with no change in the rates after implementation of the NSAA.

Physicians who prescribe opioids should monitor patients for elevated suicide

risk and intervene where appropriate.

DOI: 10.1177/0706743719838777

PMID: 30905165

19. Lancet. 2019 Apr 27;393(10182):1760-1772. doi: 10.1016/S0140-6736(18)33078-2.

Epub 2019 Mar 14.

Management of opioid use disorder in the USA: present status and future

directions.

Blanco C(1), Volkow ND(2).

Author information:

(1)National Institute on Drug Abuse, Bethesda, MD, USA. Electronic address:

carlos.blanco2@nih.gov.

(2)National Institute on Drug Abuse, Bethesda, MD, USA.

Opioid use disorder is characterised by the persistent use of opioids despite the

adverse consequences of its use. The disorder is associated with a range of

mental and general medical comorbid disorders, and with increased mortality.

Although genetics are important in opioid use disorder, younger age, male sex,

and lower educational attainment level and income, increase the risk of opioid

use disorder, as do certain psychiatric disorders (eg, other substance use

disorders and mood disorders). The medications for opioid use disorder, which

include methadone, buprenorphine, and extended-release naltrexone, significantly

improve opioid use disorder outcomes. However, the effectiveness of medications

for opioid use disorder is limited by problems at all levels of the care cascade,

including diagnosis, entry into treatment, and retention in treatment. There is

an urgent need for expanding the use of medications for opioid use disorder,

including training of health-care professionals in the treatment and prevention

of opioid use disorder, and for development of alternative medications and new

models of care to expand capabilities for personalised interventions.

Copyright © 2019 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(18)33078-2

PMID: 30878228 [Indexed for MEDLINE]

20. Pain Med. 2019 Mar 16. pii: pnz031. doi: 10.1093/pm/pnz031. [Epub ahead of print]

Changes in Mortality Involving Extended-Release and Long-Acting Opioids After

Implementation of a Risk Evaluation and Mitigation Strategy.

Black JC(1), Bau GE(1), Rosen T(1), Cepeda MS(2), Wedin GP(3), Green JL(1)(4),

Dart RC(1).

Author information:

(1)Rocky Mountain Poison & Drug Center, Denver Health and Hospital Authority,

Denver, Colorado.

(2)Janssen Pharmaceutical Research & Development LLC, Titusville, New Jersey.

(3)Upsher-Smith Laboratories, LLC, Maple Grove, Minnesota.

(4)Inflexxion, Inc., Waltham, Massachusetts, USA.

OBJECTIVE: To assess changes in mortality rates in extended-release and

long-acting (ER/LA) opioid analgesics after the implementation of the Risk

Evaluation and Mitigation Strategy (REMS).

SETTING: All drug poisoning deaths in three states: Florida, Oregon, and

Washington. Data were obtained through state vital records offices and the

Researched Abuse, Diversion and Addiction-Related Surveillance System Medical

Examiner Program.

METHODS: Using cause-of-death literal text from death certificates, individual

opioid active pharmaceutical ingredients (APIs) involved in each death were

identified using rules-based natural language processing. Population-adjusted and

prescriptions dispensed-adjusted mortality rates were calculated for all ER/LA

opioid analgesic and individual opioid APIs. Rates before and after

implementation of the REMS were compared. Rate changes were compared with rates

from two APIs with little or no inclusion in the REMS: benzodiazepines and

hydrocodone.

RESULTS: The mean ER/LA opioid analgesic population-adjusted mortality rate

significantly decreased in all three states (FL: P = 0.003; OR: P = 0.003; WA:

P < 0.001). Mortality rates for benzodiazepines and hydrocodone also decreased

and were not statistically different. Significant heterogeneity in mortality

rates of individual opioids was observed between the three states. When adjusted

for prescription volume, the ER/LA opioid analgesic mortality rate decreased in

all three states, but was significant only for Washington (P < 0.001).

CONCLUSIONS: The population-adjusted mortality rate of ER/LA opioid analgesics

has decreased in three states. Notably, the contributions to mortality rates by

individual opioid analgesics were not uniform across the three states in this

study. However, these changes were not generally distinct from changes in

mortality rates where comparator substances were involved.

© 2019 American Academy of Pain Medicine.

DOI: 10.1093/pm/pnz031

PMID: 30877807

21. Subst Abus. 2019;40(1):71-79. doi: 10.1080/08897077.2018.1546263. Epub 2019 Mar

15.

Development and evaluation of a standardized research definition for opioid

overdose outcomes.

Binswanger IA(1)(2)(3), Narwaney KJ(1), Gardner EM(3)(4), Gabella BA(5),

Calcaterra SL(2)(3), Glanz JM(1)(6).

Author information:

(1)a Institute for Health Research , Kaiser Permanente Colorado , Denver ,

Colorado , USA.

(2)b Division of General Internal Medicine, Department of Medicine , University

of Colorado School of Medicine , Aurora , Colorado , USA.

(3)c Denver Health and Hospital Authority , Denver , Colorado , USA.

(4)d Denver Public Health , Denver , Colorado , USA.

(5)e Colorado Department of Public Health and Environment , Denver , Colorado ,

USA.

(6)f Department of Epidemiology , Colorado School of Public Health , Aurora ,

Colorado , USA.

Background: Increasing epidemiologic and intervention research is being conducted

on opioid overdose, a serious and potentially fatal outcome. However, there is

little consensus on how to verify opioid overdose outcomes for research purposes.

To ensure reproducibility, minimize misclassification, and permit data

harmonization across studies, standardized and consistent overdose definitions

are needed. The aims were to develop a case criteria classification scheme based

on information commonly available in medical records and to compare it with

reviewing physician clinical impression and simple encounter documentation.

Methods: In 2 large health systems, we developed a case criteria classification

scheme for opioid overdose based on prior literature, expert opinion, and pilot

testing with sample medical records. We then identified emergency department and

hospital encounters (n = 259) with at least 1 International Classification of

Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code representing a

broad range of opioid and non-opioid related poisonings. Physicians conducted

structured medical record reviews to identify the proposed case criteria and

generate a clinical impression, and trained abstractors verified documentation.

We then compared the case criteria classification scheme with clinical impression

and encounter documentation. Results: We developed a quantitative opioid overdose

case criteria classification scheme that included 3 sets of major criteria and 9

minor criteria (supporting documentation). For the encounters identified using

poisoning codes, the proportion verified as opioid overdoses using the case

criteria classification scheme, clinical impression, and encounter documentation

ranged from 50.4% to 52.7% at one site and 55.5% to 67.2% at the second site.

Discrepancies across approaches and sites related to differences in available

records and documentation of clinical signs of overdose. Conclusions: We propose

a novel case criteria classification scheme for opioid overdose that could be

used to rigorously and consistently define overdose across multiple research

settings. However, prior to widespread use, further refinement and validation are

needed.

DOI: 10.1080/08897077.2018.1546263

PMCID: PMC6579660 [Available on 2020-03-15]

PMID: 30875477

22. Expert Opin Drug Metab Toxicol. 2019 Apr;15(4):259-260. doi:

10.1080/17425255.2019.1588250. Epub 2019 Mar 8.

The transition of lead and microbial contamination from adulterated opium to the

human body.

Nakhaee S(1), Mehrpour O(2).

Author information:

(1)a Medical Toxicology and Drug Abuse Research Center (MTDRC) , Birjand

University of Medical Sciences , Birjand , Iran.

(2)b Rocky Mountain Poison and Drug Center, Denver Health , Denver, CO , USA.

DOI: 10.1080/17425255.2019.1588250

PMID: 30849246 [Indexed for MEDLINE]

23. Drug Metab Pers Ther. 2019 Feb 28;34(1). pii:

/j/dmdi.2019.34.issue-1/dmpt-2018-0025/dmpt-2018-0025.xml. doi:

10.1515/dmpt-2018-0025.

Seizures induced by tramadol overdose: what is the respective contribution of

tramadol and each of its metabolites?

Vodovar D(1)(2), Mégarbane B(1)(2).

Author information:

(1)Department of Medical and Toxicological Critical Care, Lariboisière Hospital,

Paris-Diderot University, Paris, France.

(2)INSERM UMRS-1144, Paris-Descartes University, Paris, France.

Comment on

Drug Metab Pers Ther. 2018 Jun 27;33(2):75-83.

DOI: 10.1515/dmpt-2018-0025

PMID: 30817297 [Indexed for MEDLINE]

24. Health Promot Chronic Dis Prev Can. 2019 Feb;39(2):56-60. doi:

10.24095/hpcdp.39.2.03.

At-a-glance - The impact of poisoning-related mortality on life expectancy at

birth in Canada, 2000 to 2016.

[Article in English, French; Abstract available in French from the publisher]

Orpana HM(1)(2), Lang JJ(1), George D(1), Halverson J(1).

Author information:

(1)Public Health Agency of Canada, Ottawa, Ontario, Canada.

(2)School of Epidemiology and Public Health, University of Ottawa, Ottawa,

Ontario, Canada.

Increases in opioid-related mortality have contributed to declines in life

expectancy at birth in the United States and British Columbia. Canadian national

mortality data from 2000 to 2016 were analyzed to determine the contribution of

poisoning-related mortality to changes in life expectancy at birth by age group

and sex. From 2000 to 2016, life expectancy at birth increased by almost three

years; however, mortality due to unintentional poisonings, including those

involving opioids, curbed this increase by 0.16 years. Although a national

decrease in life expectancy at birth has not been observed in Canada during this

period, current trends suggest that the national opioid overdose crisis will

continue to attenuate gains to life expectancy.

Publisher: L’augmentation de la mortalité liée aux opioïdes a contribué à des

baisses de l’espérance de vie à la naissance aux États-Unis et en

Colombie-Britannique. Nous avons analysé les données nationales sur la mortalité

au Canada entre 2000 et 2016 afin de déterminer dans quelle mesure les décès liés

aux intoxications avaient influencé l’espérance de vie à la naissance selon le

groupe d’âge et le sexe. Entre 2000 et 2016, l’espérance de vie à la naissance a

augmenté de presque trois ans, mais la mortalité attribuable aux intoxications

accidentelles, dont celles par opioïdes, a réduit cette hausse de 0,16 an. Même

si l’espérance de vie à la naissance n’a pas globalement diminué au Canada

pendant cette période, les tendances actuelles laissent présager que la crise

nationale des surdoses d’opioïdes va continuer à amoindrir les gains relatifs à

l’espérance de vie.

DOI: 10.24095/hpcdp.39.2.03

PMCID: PMC6394823

PMID: 30767855 [Indexed for MEDLINE]

Conflict of interest statement: There are no conflicts of interest to report.

25. Health Serv Res. 2019 Apr;54(2):407-416. doi: 10.1111/1475-6773.13119. Epub 2019

Feb 11.

Good Samaritan harm reduction policy and drug overdose deaths.

Atkins DN(1), Durrance CP(2), Kim Y(3).

Author information:

(1)College of Community Innovation and Education, University of Central Florida,

Orlando, Florida.

(2)Department of Public Policy, University of North Carolina at Chapel Hill,

Chapel Hill, North Carolina.

(3)Employment and Social Services, City of Toronto, Toronto, Ontario, Canada.

OBJECTIVE: To examine the effects of a harm reduction policy, specifically Good

Samaritan (GS) policy, on overdose deaths.

DATA SOURCES/STUDY SETTING: Secondary data from multiple cause of death,

mortality records paired with state harm reduction and substance use prevention

policy.

STUDY DESIGN: We estimate fixed effects Poisson count models to model the effect

of GS policy on overdose deaths for all, prescription, and illicit drugs,

controlled substances, and opioids, while controlling for other harm reduction

and substance use prevention policies.

DATA COLLECTION/EXTRACTION METHODS: We merge secondary data sources by state and

year between 1999 and 2016.

PRINCIPAL FINDINGS: We fail to identify a statistically significant effect of GS

policy in reducing overdose deaths broadly.

CONCLUSIONS: While we are unable to identify an effect of GS policy on overdose

deaths, GS policy may have important effects on first-stage outcomes not

investigated in this paper. Given recent state policy changes and rapid increase

in many categories of overdose deaths, additional research should continue to

examine the implementation and effects of harm reduction policy specifically and

substance use prevention policy broadly.

© Health Research and Educational Trust.

DOI: 10.1111/1475-6773.13119

PMCID: PMC6407344 [Available on 2020-04-01]

PMID: 30740691

26. Nat Med. 2019 Feb;25(2):197. doi: 10.1038/s41591-019-0362-1.

Detecting opioid overdoses with smartphones.

Stower H(1).

Author information:

(1)Nature Medicine, . h.stower@us.nature.com.

Comment on

Sci Transl Med. 2019 Jan 9;11(474):null.

DOI: 10.1038/s41591-019-0362-1

PMID: 30728530 [Indexed for MEDLINE]

27. Natl Vital Stat Rep. 2018 Dec;67(9):1-14.

Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011-2016.

Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M.

Objective-This report identifies the specific drugs involved most frequently in

drug overdose deaths in the United States from 2011 through 2016.

Methods-Record-level data from the 2011-2016 National Vital Statistics

System-Mortality files were linked to electronic files containing literal text

information from death certificates. Drug overdose deaths were identified using

the International Classification of Diseases, Tenth Revision underlying causeof-

death codes X40-X44, X60-X64, X85, and Y10-Y14. Drug mentions were identified by

searching the literal text in three fields of the death certificate: the causes

of death from Part I, significant conditions contributing to death from Part II,

and a description of how the injury occurred. Contextual information was used to

determine drug involvement in the death. Descriptive statistics were calculated

for drug overdose deaths involving the 10 most frequently mentioned drugs. Deaths

involving more than one drug (e.g., a death involving both heroin and cocaine)

were counted in all relevant drug categories (e.g., the same death was included

in counts of heroin deaths and in counts of cocaine deaths). Results-Among drug

overdose deaths that mentioned at least one specific drug, the 10 most frequently

mentioned drugs during 2011-2016 included fentanyl, heroin, hydrocodone,

methadone, morphine, oxycodone, alprazolam, diazepam, cocaine, and

methamphetamine. Oxycodone ranked first in 2011, heroin during 2012-2015, and

fentanyl in 2016. During the study period, cocaine consistently ranked second or

third. From 2011 through 2016, the age-adjusted rate of drug overdose deaths

involving heroin more than tripled, as did the rate of drug overdose deaths

involving methamphetamine. The rate of drug overdose deaths involving fentanyl

and fentanyl analogs doubled each year from 2013 through 2016, from 0.6 per

100,000 in 2013 to 1.3 in 2014, 2.6 in 2015, and 5.9 in 2016. The rate of

overdose deaths involving methadone decreased from 1.4 per 100,000 in 2011 to 1.1

in 2016. The 10 most frequently mentioned drugs often were found in combination

with each other. The drugs most frequently mentioned varied by the intent of the

drug overdose death. In 2016, the drugs most frequently mentioned in

unintentional drug overdose deaths were fentanyl, heroin, and cocaine, while the

drugs most frequently mentioned in suicides by drug overdose were oxycodone,

diphenhydramine, hydrocodone, and alprazolam.

All material appearing in this report is in the public domain and may be

reproduced or copied without permission; citation as to source, however, is

appreciated.

PMID: 30707673 [Indexed for MEDLINE]

28. Drug Alcohol Depend. 2019 Mar 1;196:46-50. doi: 10.1016/j.drugalcdep.2018.12.016.

Epub 2019 Jan 15.

Changing risk and presentation of overdose associated with consumption of street

drugs at a supervised injection site in Vancouver, Canada.

Notta D(1), Black B(2), Chu T(3), Joe R(3), Lysyshyn M(4).

Author information:

(1)Goldcorp Addiction Medicine Fellowship, St. Paul's Hospital, Vancouver,

British Columbia, Canada.

(2)Public Health and Preventive Medicine Residency Program, University of British

Columbia, Vancouver, British Columbia, Canada.

(3)Vancouver Coastal Health, Vancouver, British Columbia, Canada.

(4)Vancouver Coastal Health, Vancouver, British Columbia, Canada; School of

Population and Public Health, University of British Columbia, Vancouver, British

Columbia, Canada. Electronic address: Mark.Lysyshyn@vch.ca.

BACKGROUND: British Columbia is experiencing a public health emergency due to

overdoses resulting from consumption of street drugs contaminated with fentanyl.

While the risk of overdoses appears to be increasing, the overdose rate and

severity of overdose presentations have yet to be quantified.

METHODS: Insite is a supervised injection site in Vancouver. Data from Insite's

client database from January 2010 to June 2017 were used to calculate overdose

rates as well as the proportion of overdoses involving rigidity and naloxone

administration over time in order to estimate changes in the risk and severity of

overdose resulting from changes in the local drug supply.

RESULTS: The overdose rate increased significantly for all drug categories.

Heroin used alone or with other drugs continues to be associated with the highest

overdose rate. The overdose rate associated with heroin increased from 2.7/1000

visits to 13/1000 visits over the study period, meaning that clients were 4.8

times more likely to overdose in the most recent period as in the baseline

period. The proportion of overdose events involving rigidity, a known

complication of intravenous fentanyl use, increased significantly from 10.4% to

18.9%. The proportion of overdoses requiring naloxone administration increased

significantly from 48.4% to 57.1% and is now similar across all drug categories.

CONCLUSIONS: The risk and severity of overdoses at Insite have increased since

the emergence of illicit fentanyl. This information derived from supervised

injection site data can be used to inform local harm reduction efforts and the

response to the overdose emergency.

Copyright © 2019 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2018.12.016

PMID: 30665151 [Indexed for MEDLINE]

29. BMC Psychiatry. 2019 Jan 18;19(1):33. doi: 10.1186/s12888-019-2015-9.

Psychoactive substances in natural and unnatural deaths in Norway and Sweden - a

study on victims of suicide and accidents compared with natural deaths in

psychiatric patients.

Gravensteen IK(1), Ekeberg Ø(2)(3), Thiblin I(4), Helweg-Larsen K(5), Hem

E(2)(3), Rogde S(1)(6), Tøllefsen IM(7).

Author information:

(1)Department of Forensic Sciences, Oslo University Hospital, Box 4950 Nydalen,

N-0424, Oslo, Norway.

(2)Department of Behavioural Sciences in Medicine, Institute of Basic Medical

Sciences, Faculty of Medicine, University of Oslo, Box 1111 Blindern, N-0317,

Oslo, Norway.

(3)Division of Mental Health and Addiction, Oslo University Hospital Ullevaal,

Box 4956 Nydalen, N-0424, Oslo, Norway.

(4)Department of Surgical Sciences, Uppsala University, Box 256, 751 05, Uppsala,

Sweden.

(5)Department of Social Medicine, University of Copenhagen, Copenhagen, Denmark.

(6)Institute of Clinical Medicine, University of Oslo, Box 1072 Blindern, N-

0316, Oslo, Norway.

(7)Division of Medicine, Department of Acute Medicine, Oslo University Hospital

Ullevaal, Box 4950 Nydalen, N-0424, Oslo, Norway. uxtlli@ous-hf.no.

BACKGROUND: The extent of post-mortem detection of specific psychoactive drugs

may differ between countries, and may greatly influence the national death

register's classification of manner and cause of death. The main objective of the

present study was to analyse the magnitude and pattern of post-mortem detection

of various psychoactive substances by the manner of death (suicide, accidental,

undetermined and natural death with a psychiatric diagnosis) in Norway and

Sweden.

METHODS: The Cause of Death Registers in Norway and Sweden provided data on 600

deaths in 2008 from each country, of which 200 were registered as suicides, 200

as accidents or undetermined manner of death and 200 as natural deaths in

individuals with a diagnosis of mental disorder as the underlying cause of death.

We examined death certificates and forensic reports including toxicological

analyses.

RESULTS: The detection of psychoactive substances was commonly reported in

suicides (66 and 74% in Norway and Sweden respectively), accidents (85 and 66%),

undetermined manner of deaths (80% in the Swedish dataset) and in natural deaths

with a psychiatric diagnosis (50 and 53%). Ethanol was the most commonly reported

substance in the three manners of death, except from opioids being more common in

accidental deaths in the Norwegian dataset. In cases of suicide by poisoning,

benzodiazepines and z-drugs were the most common substances in both countries.

Heroin or morphine was the most commonly reported substance in cases of

accidental death by poisoning in the Norwegian dataset, while other opioids

dominated the Swedish dataset. Anti-depressants were found in 22% of the suicide

cases in the Norwegian dataset and in 29% of suicide cases in the Swedish

dataset.

CONCLUSIONS: Psychoactive substances were detected in 66 and 74% of suicides and

in 85 and 66% of accidental deaths in the Norwegian and Swedish datasets,

respectively. Apart from a higher detection rate of heroin in deaths by accident

in Norway than in Sweden, the pattern of detected psychoactive substances was

similar in the two countries. Assessment of a suicidal motive may be hampered by

the common use of psychoactive substances in suicide victims.

DOI: 10.1186/s12888-019-2015-9

PMCID: PMC6339417

PMID: 30658618

30. Drug Alcohol Depend. 2019 Mar 1;196:1-8. doi: 10.1016/j.drugalcdep.2018.12.004.

Epub 2019 Jan 9.

Fentanyl and fentanyl-analog involvement in drug-related deaths.

Dai Z(1), Abate MA(2), Smith GS(3), Kraner JC(4), Mock AR(5).

Author information:

(1)School of Public Health, West Virginia University, One Medical Center Drive,

Morgantown, WV 26506, United States. Electronic address: zd0001@hsc.wvu.edu.

(2)School of Pharmacy, West Virginia University, 1124 Health Sciences North,

Morgantown, WV 26506, United States. Electronic address: mabate@hsc.wvu.edu.

(3)School of Public Health, West Virginia University, One Medical Center Drive,

Morgantown, WV 26506, United States. Electronic address:

gordon.smith@hsc.wvu.edu.

(4)West Virginia Office of the Chief Medical Examiner, West Virginia Department

of Health and Human Resources, 619 Virginia Street West, Charleston, WV 25302,

United States. Electronic address: james.c.kraner@wv.gov.

(5)West Virginia Office of the Chief Medical Examiner, West Virginia Department

of Health and Human Resources, 619 Virginia Street West, Charleston, WV 25302,

United States. Electronic address: allen.r.mock@wv.gov.

BACKGROUND: To describe and analyze the involvement of fentanyl and fentanyl

analogs (FAs) in drug-related deaths in West Virginia (WV), United States.

METHODS: Retrospective analyses of all WV drug-related deaths from 2005 to 2017

were performed, including comparisons of demographic and toxicological

characteristics among total deaths, deaths in which fentanyl/FAs were present,

deaths in which they were absent, heroin-related deaths, and prescription

opioid-related deaths.

RESULTS: Most of the 8813 drug-related deaths were overdoses, with about 11%

resulting from transportation/other injuries in which drugs were contributors.

Prescription opioid presence (without fentanyl) decreased by 75% from 2005-14 to

2015-17 (3545 deaths to 859 deaths, respectively), while fentanyl involvement in

the deaths increased by 122% between these periods (487 to 1082 deaths). Ten FAs

were identified (427 instances) after 2015. Alprazolam and ethanol were among the

top five most frequently identified substances across years. Fentanyl, heroin and

cocaine replaced oxycodone, diazepam and hydrocodone in the top five beginning in

2015. Few decedents had a prescription for fentanyl after 2015, with fewer

prescriptions also present for other controlled substances identified.

CONCLUSIONS: Fentanyl, rapidly emerging FAs, and other illicit drugs in recent

years pose a serious health threat even though prescription opioid-related deaths

decreased over the same time period.

Copyright © 2019 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2018.12.004

PMCID: PMC6447047 [Available on 2020-03-01]

PMID: 30658219 [Indexed for MEDLINE]

31. MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):41-43. doi: 10.15585/mmwr.mm6802a4.

Notes from the Field: Fentanyl Drug Submissions - United States, 2010-2017.

Springer YP(1), Gladden RM(1), O'Donnell J(1), Seth P(1).

Author information:

(1)Division of Unintentional Injury Prevention, National Center for Injury

Prevention and Control, CDC.

DOI: 10.15585/mmwr.mm6802a4

PMID: 30653486 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed.

32. MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):37-40. doi: 10.15585/mmwr.mm6802a3.

Overdose Deaths Involving Fentanyl and Fentanyl Analogs - New York City,

2000-2017.

Colon-Berezin C(1), Nolan ML(1), Blachman-Forshay J(1), Paone D(1).

Author information:

(1)Bureau of Alcohol and Drug Use Prevention, Care, and Treatment, New York City

Department of Health and Mental Hygiene, New York City, New York.

Unintentional drug overdose deaths have climbed to record high levels, claiming

approximately 70,000 lives in the United States in 2017 alone (1). The emergence

of illicitly manufactured fentanyl* (a synthetic, short-acting opioid with 50-100

times the potency of morphine) mixed into heroin, cocaine, and counterfeit pills,

with or without the users' knowledge, has increased the risk for fatal overdose

(2,3). The New York City (NYC) Department of Health and Mental Hygiene (DOHMH)

conducts routine overdose mortality surveillance by linking death certificates

with toxicology findings from the NYC Office of the Chief Medical Examiner

(OCME). A 55% increase in the rate of fatal drug overdose in NYC was observed

from 2015 to 2017, resulting in the highest number of overdose deaths recorded

since systematic reporting began in 2000. Toxicology data indicate that this

unprecedented increase in overdose deaths is attributable to fentanyl. Early

identification of increased fentanyl involvement enabled DOHMH to respond rapidly

to the opioid overdose epidemic by increasing awareness of the risks associated

with fentanyl and developing effective risk reduction messaging. These results

strongly suggest that, wherever possible, jurisdictions should consider

integrating toxicology findings into routine overdose surveillance and work with

local medical examiners or coroners to include fentanyl in the literal text on

death certificates.

DOI: 10.15585/mmwr.mm6802a3

PMCID: PMC6336189

PMID: 30653482 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed.

33. Clin Toxicol (Phila). 2019 Jul;57(7):628-631. doi: 10.1080/15563650.2018.1546009.

Epub 2019 Jan 14.

Poisoning with malicious or criminal intent: characteristics and outcome of

patients presenting for emergency care.

Gauthey M(1), Capua M(2), Brent J(3)(4), Finkelstein Y(1)(5).

Author information:

(1)a Division of Pediatric Emergency Medicine , Hospital for Sick Children ,

Toronto , ON , Canada.

(2)b Division of Pediatric Emergency Medicine , Cohen Children's Medical Center ,

New Hyde Park , NY , USA.

(3)c Department of Medicine , University of Colorado, School of Medicine , Aurora

, CO , USA.

(4)d Department of Pediatrics , University of Colorado, School of Medicine ,

Aurora , CO , USA.

(5)e Division of Clinical Pharmacology and Toxicology , Hospital for Sick

Children , Toronto , ON , Canada.

Background: Poisoning is the leading cause of injury-related death in the USA.

Poisoning with malicious or criminal intent is uncommon, and poorly

characterized. Objectives: To explore substances, patients' demographics,

clinical presentation, management and outcome in victims of malicious poisoning

in the USA. Methods: Using the 47 participating sites of the Toxicology

Investigators Consortium (ToxIC) Registry, a North American research consortium,

we conducted an observational study of a prospectively collected cohort. We

identified all patients exposed to malicious poisoning who had received medical

toxicology consultation between January 2014 and June 2017. Clinical and

demographic data were collected including age, sex, agents of exposure, clinical

manifestations, treatment, disposition and outcome. Results: We identified 60

patients who presented to the emergency department with malicious poisoning, of

whom 21 (35%) were children. Among 21 children, 17 (81%) were younger than 2

years. There was no sex dominance among patients. The main substances involved in

pediatric patients were sympathomimetics (35%) and opioids (19%). In adults, a

more varied panel of offending substances was used, with no specific dominant

toxidrome. Children received more treatment interventions compared to adults

(overall treatment 81% versus 46% [p = 0.0132]; mechanical ventilation: 29%

versus 5% [p = 0.0176], respectively). Three (5%) patients died (two children,

one adult). Conclusions: Poisonings with malicious intent are uncommon; they are

disproportionally directed towards infants, frequently resulting in severe injury

and carry relatively high mortality.

DOI: 10.1080/15563650.2018.1546009

PMID: 30640550

34. Emerg Med Australas. 2019 Feb;31(1):144-145. doi: 10.1111/1742-6723.13224. Epub

2019 Jan 12.

Two cases of lead poisoning from inhaled opium in Victoria.

Law S(1), Ackerly I(2), Scott-Rimmington B(1), Nallaratnam K(1).

Author information:

(1)Department of Emergency Medicine, Western Health, Melbourne, Victoria,

Australia.

(2)Department of Surgery, Western Health, Melbourne, Victoria, Australia.

DOI: 10.1111/1742-6723.13224

PMID: 30635973 [Indexed for MEDLINE]

35. BMC Emerg Med. 2019 Jan 11;19(1):5. doi: 10.1186/s12873-018-0219-9.

Mortality and repeated poisoning after self-discharge during treatment for acute

poisoning by substances of abuse: a prospective observational cohort study.

Vallersnes OM(1)(2), Jacobsen D(3)(4), Ekeberg Ø(5)(6), Brekke M(7).

Author information:

(1)Department of General Practice, University of Oslo, Oslo, Norway.

o.m.vallersnes@medisin.uio.no.

(2)Department of Emergency General Practice, City of Oslo Health Agency, Oslo

Accident and Emergency Outpatient Clinic, Oslo, Norway.

o.m.vallersnes@medisin.uio.no.

(3)Department of Acute Medicine, Oslo University Hospital, Oslo, Norway.

(4)Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

(5)Division of Mental Health and Addiction, Oslo University Hospital, Oslo,

Norway.

(6)Department of Behavioural Sciences in Medicine, University of Oslo, Oslo,

Norway.

(7)General Practice Research Unit (AFE), University of Oslo, Oslo, Norway.

BACKGROUND: Though substance use is a known risk factor for self-discharge,

patients self-discharging during treatment for acute poisoning have not

previously been described. We charted characteristics of patients

self-discharging during treatment for acute poisoning by substances of abuse

looking for associations between self-discharge, repeated poisoning, and death.

METHODS: All patients 12 years and older treated for acute poisoning by

substances of abuse at an emergency outpatient clinic in Oslo, Norway, were

included consecutively from October 2011 through September 2012. We collected

data on gender, age, main toxic agent, suicidal intention, homelessness, history

of severe mental illness, and self-discharge. Information on deaths was retrieved

from the National Cause of Death Register. We did a multiple logistic regression

analysis to look for associations between self-discharge and repeated poisoning

and a Cox regression analysis for associations between self-discharge and death.

RESULTS: During one year, 1731 patients were treated for 2343 episodes of acute

poisoning by substances of abuse. Two-hundred-and-sixty-six (15%) patients

self-discharged during at least one poisoning episode. Self-discharging patients

were older, median age 39 years vs 32 years (p < 0.001), more frequently

homeless, 20/266 (8%) vs 63/1465 (4%) (p = 0.035), and the main toxic agent more

frequently was an opioid, 82/266 (31%) vs 282/1465 (19%) (p < 0.001).

Self-discharge was an independent risk factor for repeated poisoning. The

adjusted odds ratio for two or more poisoning episodes during one year among

self-dischargers was 3.0 (95% CI 2.2-4.1). The association was even stronger for

three or more poisoning episodes, adjusted odds ratio 5.0 (3.3-7.5). In total,

there were 34 deaths, 9/266 (3.4%) among self-discharging patients and 25/1465

(1.7%) among patients not self-discharging (p = 0.12). The adjusted hazard ratio

for death among self-discharging patients was 1.6 (0.75-3.6).

CONCLUSIONS: Self-discharge was associated with frequent poisonings by substances

of abuse. Short-term mortality was doubled among self-discharging patients,

though this increase was not statistically significant. Still, the increased risk

of repeated poisoning marks self-discharging patients as a vulnerable group who

might benefit from targeted post-discharge follow-up measures.

DOI: 10.1186/s12873-018-0219-9

PMCID: PMC6329053

PMID: 30634924 [Indexed for MEDLINE]

36. Int J Environ Res Public Health. 2019 Jan 9;16(2). pii: E177. doi:

10.3390/ijerph16020177.

Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health.

Lovrecic B(1), Lovrecic M(2)(3), Gabrovec B(4), Carli M(5), Pacini M(6),

Maremmani AGI(7)(8), Maremmani I(9)(10)(11).

Author information:

(1)National Institute of Public Health, 1000 Ljubljana, Slovenia.

barbara.lovrecic@nijz.si.

(2)National Institute of Public Health, 1000 Ljubljana, Slovenia.

mercedes.lovrecic@nijz.si.

(3)Centre for Psychiatry and Addiction Medicine, Izola Health Centre, 6310 Izola,

Slovenia. mercedes.lovrecic@nijz.si.

(4)National Institute of Public Health, 1000 Ljubljana, Slovenia.

branko.gabrovec@nijz.si.

(5)Department of Translational Research and New Technologies, University of Pisa,

56100 Pisa, Italy. carlimarco@outlook.it.

(6)G. De Lisio Institute of Behavioral Sciences, 56100 Pisa, Italy.

paciland@virgilio.it.

(7)Department of Psychiatry, North-Western Tuscany Region NHS Local Health Unit,

Versilia Zone, 55049 Viareggio, Italy. angelo.maremmani@uslnordovest.toscana.it.

(8)Association for the Application of Neuroscientific Knowledge to Social Aims

(AU-CNS), Pietrasanta, 55045 Lucca, Italy.

angelo.maremmani@uslnordovest.toscana.it.

(9)G. De Lisio Institute of Behavioral Sciences, 56100 Pisa, Italy.

maremman@med.unipi.it.

(10)Association for the Application of Neuroscientific Knowledge to Social Aims

(AU-CNS), Pietrasanta, 55045 Lucca, Italy. maremman@med.unipi.it.

(11)Vincent P. Dole Dual Disorder Unit, Santa Chiara University Hospital,

University of Pisa, 56100 Pisa, Italy. maremman@med.unipi.it.

Background: In the last decade there has been a progressive increase in the use

of new psychoactive substances (NPSs) that are not yet under international

control. In particular, novel synthetic opioids (NSOs) have reappeared on the

recreational drug market in the last few years. As a result, the use of NSOs has

increased rapidly. This poses an emerging and demanding challenge to public

health. Aim: To raise awareness among clinicians and other professionals about

NPSs, especially NSOs, to summarize current knowledge about pharmacological

properties, forms of NSO on the market, pattern of use, effects and consequences

of use. Methods: An electronic search was carried out on the Medline/PubMed and

Google Scholar databases to find selected search terms. Results: Some NPSs are

already controlled, while others can be legally sold directly on the drug market

(mainly via internet, less so by drug dealers) or be used as precursors for the

synthesis of other designer drugs that mimic the psychoactive effects of

controlled substances. Potential side-effects of NSOs include miosis, sedation,

respiratory depression, hypothermia, inhibition of gastrointestinal propulsion,

death (from opioid overdose). Conclusions: The severity of the opioid crisis has

intensified with the introduction of highly potent NSOs on the drug market. As

long as addicts are dying from overdose or similar causes, there is something

more constructive to do than waiting for addicts to overdose on heroin at a place

located near a remedy, as if to say, within reach of naloxone.

DOI: 10.3390/ijerph16020177

PMCID: PMC6352208

PMID: 30634521 [Indexed for MEDLINE]

37. J Affect Disord. 2019 Mar 1;246:814-819. doi: 10.1016/j.jad.2019.01.002. Epub

2019 Jan 4.

Relative toxicity of analgesics commonly used for intentional self-poisoning: A

study of case fatality based on fatal and non-fatal overdoses.

Hawton K(1), Ferrey A(2), Casey D(2), Wells C(3), Fuller A(4), Bankhead C(4),

Clements C(5), Ness J(6), Gunnell D(7), Kapur N(8), Geulayov G(2).

Author information:

(1)Department of Psychiatry, University of Oxford, UK; Oxford Health NHS

Foundation Trust, Oxford, UK. Electronic address: keith.hawton@psych.ox.ac.uk.

(2)Department of Psychiatry, University of Oxford, UK.

(3)Office for National Statistics, UK.

(4)Nuffield Department of Primary Care Health Sciences, University of Oxford, UK.

(5)Manchester Academic Health Sciences Centre, University of Manchester, UK.

(6)Centre for Self-harm and Suicide Prevention Research, Derbyshire Healthcare

NHS Foundation Trust, UK.

(7)School of Social and Community Medicine, University of Bristol, UK.

(8)Manchester Academic Health Sciences Centre, University of Manchester, UK;

Greater Manchester Mental Health NHS Foundation Trust, UK.

BACKGROUND: Analgesics are used most frequently in fatal and non-fatal medicinal

self-poisonings. Knowledge about their relative toxicity in overdose is important

for clinicians and regulatory agencies.

METHODS: Using data for 2005-2012 we investigated case fatality (number of

suicides relative to number of non-fatal self-poisonings) of paracetamol,

aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine

(co-codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and

co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due

to high toxicity). Data on suicides obtained from the Office for National

Statistics and on non-fatal self-poisonings from the Multicentre Study of

Self-harm in England. Case fatality was estimated for each drug, using

paracetamol as the reference category.

RESULTS: Compared to paracetamol and based on single drug deaths the case

fatality index of dihydrocodeine was considerably elevated (odds ratio (OR)

12.81, 95% Confidence Interval (CI) 10.19-16.12). Case fatality indices for

tramadol (OR 4.05, 95% CI 3.38-4.85) and codeine (OR 2.21, 95% CI 1.81-2.70) were

also significantly higher than for paracetamol. The results when multiple drug

deaths were included produced similar results. The relative toxicity of

co-proxamol far exceeded that of the other analgesics.

LIMITATIONS: Data on fatal self-poisonings were based on national data, whereas

those for non-fatal poisonings were based on local data.

CONCLUSIONS: Dihydrocodeine and tramadol are particularly toxic in overdose and

codeine is also relatively toxic. They should be prescribed with caution,

particularly to individuals at risk of self-harm.

Copyright © 2019. Published by Elsevier B.V.

DOI: 10.1016/j.jad.2019.01.002

PMID: 30634113 [Indexed for MEDLINE]

38. J Res Pharm Pract. 2018 Oct-Dec;7(4):200-204. doi: 10.4103/jrpp.JRPP_16_141.

Predictive Factors of Treatment Outcomes for Hospital Care in Children with Acute

Methadone Poisoning.

Atighi Y(1), Eizadi-Mood N(2), Mansourian M(3), Zamani A(4), Saffaei A(1),

Sabzghabaee AM(2).

Author information:

(1)Pharmacy Students' Research Committee, Isfahan University of Medical Sciences,

Isfahan, Iran.

(2)Isfahan Clinical Toxicology Research Center, Isfahan University of Medical

Sciences, Isfahan, Iran.

(3)Department of Epidemiology and Biostatistics, Isfahan University of Medical

Sciences, Isfahan, Iran.

(4)Medical Students' Research Committee, Isfahan University of Medical Sciences,

Isfahan, Iran.

Objective: The trend of methadone toxicity in children and adolescents seems to

be increasing in Iran since it is used as a legal measure of the treatment for

opioids addiction in methadone maintenance therapy clinics. In the present study,

we describe the clinical and demographical characteristics of acute methadone

toxicity in a cohort of pediatric poisoned patients in Isfahan, Iran and

discussed the predictive factors for their treatment outcomes.

Methods: In this 4-year cross-sectional study which was performed from 2013 to

2016 in a referral university hospital (Isfahan, Iran), medical records of the

demographic and admission time clinical characteristics of all in-patients aged

<18 years with acute methadone poisoning were abstracted and analyzed. According

to the outcomes of hospital care and treatment, patients were divided as survived

without medical complication and patients survived with at least one medical

complication or death.

Findings: A total number of 157 (79 male) children and adolescents with a mean

age of 105.4 ± 6.1 months were hospitalized and included in the study. A total of

145 (92.4%) patients survived and discharged from the hospital without any

medical complication. Pupil size, respiratory rate, and level of consciousness

were predictive factors for the outcome of death or medical complications.

Conclusion: It seems that methadone poisoning in children and adolescents is more

commonly accidental in school-aged boys (6-12 years old) and it occurs mostly

with the syrup dosage form, especially when one of the parents or people who live

with the child has an addiction history and if the patients' house located in

lower socioeconomic class area of Isfahan city (Iran).

DOI: 10.4103/jrpp.JRPP_16_141

PMCID: PMC6298138

PMID: 30622988

Conflict of interest statement: There are no conflicts of interest.

39. Eur J Pain. 2019 May;23(5):908-922. doi: 10.1002/ejp.1357. Epub 2019 Jan 31.

Risk of adverse events in patients prescribed long-term opioids: A cohort study

in the UK Clinical Practice Research Datalink.

Bedson J(1), Chen Y(1), Ashworth J(1), Hayward RA(1), Dunn KM(1), Jordan KP(1).

Author information:

(1)Arthritis Research UK Primary Care Centre, Research Institute for Primary Care

& Health Sciences, Keele University, Staffordshire, UK.

BACKGROUND: Long-term opioid prescribing for musculoskeletal pain is

controversial due to uncertainty regarding effectiveness and safety. This study

examined the risks of a range of adverse events in a large cohort of patients

prescribed long-term opioids using the UK Clinical Practice Research Datalink.

METHODS: Patients with musculoskeletal conditions starting a new long-term opioid

episode (defined as ≥3 opioid prescriptions within 90 days) between 2002 and 2012

were included. Primary outcomes: major trauma and intentional overdose (any).

SECONDARY OUTCOMES: addiction (any), falls, accidental poisoning, attempted

suicide/self-harm, gastrointestinal pathology and bleeding, and iron deficiency

anaemia. "Control" outcomes (unrelated to opioid use): incident eczema and

psoriasis.

RESULTS: A total of 98,140 new long-term opioids users (median age 61, 41% male)

were followed for (median) 3.4 years. Major trauma risk increased from 285 per

10,000 person-years without long-term opioids to 369/10,000 for a long-term

opioid episode (<20 mg MED), 382/10,000 (20-50 mg MED), and 424/10,000 (≥50 mg

MED). Adjusted hazard ratios were 1.09 (95% CI; 1.04, 1.14 for <20 mg MED vs. not

being in an episode of long-term prescribing), 1.24 (95% CI; 1.16, 1.32: 20-50 mg

MED) and 1.34 (95% CI; 1.20, 1.50: ≥50 mg MED). Significant dose-dependent

increases in the risk of overdose (any type), addiction, falls, accidental

poisoning, gastrointestinal pathology, and iron deficiency anaemia were also

found.

CONCLUSIONS: Patients prescribed long-term opioids are vulnerable to

dose-dependent serious adverse events. Opioid prescribing should be reviewed

before long-term use becomes established, and periodically thereafter to ensure

that patients are not being exposed to increased risk of harm, which is not

balanced by therapeutic benefit.

SIGNIFICANCE: Long-term opioid use is associated with serious adverse events such

as major trauma, addiction and overdose. The risk increases with higher opioid

doses. Opioid prescribing should be reviewed before long-term use becomes

established, and periodically thereafter to assess ongoing effectiveness.

© 2019 European Pain Federation - EFIC®.

DOI: 10.1002/ejp.1357

PMID: 30620116

40. Health Aff (Millwood). 2019 Jan;38(1):29-35. doi: 10.1377/hlthaff.2018.05186.

Divergence In Recent Trends In Deaths From Intentional And Unintentional

Poisoning.

Hempstead K(1), Phillips J(2).

Author information:

(1)Katherine Hempstead ( khempstead@rwjf.org ) is a senior policy adviser at the

Robert Wood Johnson Foundation, in Princeton, New Jersey.

(2)Julie Phillips is a professor of sociology at Rutgers, the State University of

New Jersey, in New Brunswick.

There have been massive increases in the supply of prescription and

nonprescription opioids, the prevalence of opioid use disorder, and rates of

fatal and nonfatal unintentional poisonings or overdoses in the US. We examined

the relationship between rates of unintentional overdoses and intentional

overdoses (poisoning suicides), using data for the period 2005-16 from the

Centers for Disease Control and Prevention. Contrary to expectations, we found no

evidence of positive associations in their trends. While unintentional opioid

overdoses have increased dramatically, rates of poisoning suicides have scarcely

changed. Furthermore, while unintentional overdoses have increased the most among

younger males, poisoning suicides have risen the most among older females. We

found that the prevalence of opioids in poisoning suicides was high but did not

change notably, nor did we find the large shift to heroin or fentanyl that has

occurred in unintentional poisonings. There is growing interest in the potential

links between suicide and opioid overdose deaths, yet these results suggest that

the relationship between them is not straightforward.

DOI: 10.1377/hlthaff.2018.05186

PMID: 30615524

41. Drug Alcohol Depend. 2019 Feb 1;195:94-100. doi:

10.1016/j.drugalcdep.2018.11.027. Epub 2018 Dec 30.

Geographic patterns of prescription opioids and opioid overdose deaths in New

York State, 2013-2015.

Romeiser JL(1), Labriola J(2), Meliker JR(2).

Author information:

(1)Program in Public Health, Department of Family, Population, and Preventive

Medicine, Stony Brook University, Stony Brook, NY 11794, USA; Department of

Anesthesiology, Stony Brook University, Stony Brook, NY 11794, USA. Electronic

address: Jamie.Romeiser@stonybrookmedicine.edu.

(2)Program in Public Health, Department of Family, Population, and Preventive

Medicine, Stony Brook University, Stony Brook, NY 11794, USA.

OBJECTIVES: To examine the relationship between prescription opioid rates and

prescription opioid overdose deaths using spatial cluster and regression

analyses.

METHODS: Publicly available county-level data were obtained from the New York

State Health Department and the Centers for Disease Control and Prevention,

2013-2015. Kulldorff's spatial scan statistic was used to investigate spatial

clustering of New York State opioid prescription overdose death rates, as well as

opioid prescription rates. A Poisson regression was used to analyze opioid

prescriptions as a predictor of mortality accounting for spatial autocorrelation

in the residuals.

RESULTS: We report 1440 overdose mortalities and 26.8 million opioid

prescriptions throughout New York State in 2013-2015. Multiple significant

clusters were found for both opioid prescription mortalities as well as

prescriptions, although the locations of the elevated rates did not strongly

overlap. Poisson regression showed a significant, small, negative relationship

between prescriptions and opioid mortalities, wherein for every 10,000

prescriptions increased, the number of opioid mortalities decreased approximately

0.12%; therefore, essentially a null relationship.

CONCLUSIONS: Simply reducing the number of prescriptions may not be effective in

reducing prescription related mortality; although opioid prescription dosing

information should be made available to engender a better evaluation of the

epidemic. Geographical differences in opioid mortalities exist above and beyond

what can be explained by prescription rate data; identifying these locations may

help inform and guide public health interventions. Despite the recent reduction

in opioid prescription rates, the overall population is still inundated with

prescriptions.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2018.11.027

PMID: 30605866 [Indexed for MEDLINE]

42. MMWR Morb Mortal Wkly Rep. 2018 Jan 4;67(5152):1419-1427. doi:

10.15585/mmwr.mm675152e1.

Drug and Opioid-Involved Overdose Deaths - United States, 2013-2017.

Scholl L(1), Seth P(1), Kariisa M(1), Wilson N(1), Baldwin G(1).

Author information:

(1)Division of Unintentional Injury Prevention, National Center for Injury

Prevention and Control, CDC.

The 63,632 drug overdose deaths in the United States in 2016 represented a 21.4%

increase from 2015; two thirds of these deaths involved an opioid (1). From 2015

to 2016, drug overdose deaths increased in all drug categories examined; the

largest increase occurred among deaths involving synthetic opioids other than

methadone (synthetic opioids), which includes illicitly manufactured fentanyl

(IMF) (1). Since 2013, driven largely by IMF, including fentanyl analogs (2-4),

the current wave of the opioid overdose epidemic has been marked by increases in

deaths involving synthetic opioids. IMF has contributed to increases in overdose

deaths, with geographic differences reported (1). CDC examined state-level

changes in death rates involving all drug overdoses in 50 states and the District

of Columbia (DC) and those involving synthetic opioids in 20 states, during

2013-2017. In addition, changes in death rates from 2016 to 2017 involving all

opioids and opioid subcategories,* were examined by demographics, county

urbanization levels, and by 34 states and DC. Among 70,237 drug overdose deaths

in 2017, 47,600 (67.8%) involved an opioid.† From 2013 to 2017, drug overdose

death rates increased in 35 of 50 states and DC, and significant increases in

death rates involving synthetic opioids occurred in 15 of 20 states, likely

driven by IMF (2,3). From 2016 to 2017, overdose deaths involving all opioids and

synthetic opioids increased, but deaths involving prescription opioids and heroin

remained stable. The opioid overdose epidemic continues to worsen and evolve

because of the continuing increase in deaths involving synthetic opioids.

Provisional data from 2018 indicate potential improvements in some drug overdose

indicators;§ however, analysis of final data from 2018 is necessary for

confirmation. More timely and comprehensive surveillance data are essential to

inform efforts to prevent and respond to opioid overdoses; intensified prevention

and response measures are urgently needed to curb deaths involving prescription

and illicit opioids, specifically IMF.

DOI: 10.15585/mmwr.mm675152e1

PMCID: PMC6334822

PMID: 30605448 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed.

43. Drug Alcohol Depend. 2019 Feb 1;195:66-73. doi: 10.1016/j.drugalcdep.2018.11.024.

Epub 2018 Dec 21.

Urban-rural variation in the socioeconomic determinants of opioid overdose.

Pear VA(1), Ponicki WR(2), Gaidus A(2), Keyes KM(3), Martins SS(3), Fink DS(3),

Rivera-Aguirre A(4), Gruenewald PJ(2), Cerdá M(4).

Author information:

(1)Violence Prevention Research Program, Department of Emergency Medicine,

University of California Davis School of Medicine, 2315 Stockton Blvd.,

Sacramento, CA 95817, USA. Electronic address: vapear@ucdavis.edu.

(2)Prevention Research Center, Pacific Institute for Research and Evaluation,

2150 Shattuck Ave., Suite 601, Berkeley, CA 94704, USA.

(3)Department of Epidemiology, Mailman School of Public Health, Columbia

University, 722 W. 168th St., New York, NY 10032, USA.

(4)Violence Prevention Research Program, Department of Emergency Medicine,

University of California Davis School of Medicine, 2315 Stockton Blvd.,

Sacramento, CA 95817, USA; Division of Epidemiology, Department of Population

Health, New York University School of Medicine, 650 First Ave., New York, NY

10016, USA.

BACKGROUND: Prescription opioid overdose (POD) and heroin overdose (HOD) rates

have quadrupled since 1999. Community-level socioeconomic characteristics are

associated with opioid overdoses, but whether this varies by urbanicity is

unknown.

METHODS: In this serial cross-sectional study of zip codes in 17 states,

2002-2014 (n = 145,241 space-time units), we used hierarchical Bayesian Poisson

space-time models to analyze the association between zip code-level socioeconomic

features (poverty, unemployment, educational attainment, and income) and counts

of POD or HOD hospital discharges. We tested multiplicative interactions between

each socioeconomic feature and zip code urbanicity measured with Rural-Urban

Commuting Area codes.

RESULTS: Percent in poverty and of adults with ≤ high school education were

associated with higher POD rates (Rate Ratio [RR], 5% poverty: 1.07 [95% credible

interval: 1.06-1.07]; 5% low education: 1.02 [1.02-1.03]), while median household

income was associated with lower rates (RR, $10,000: 0.88 [0.87-0.89]).

Urbanicity modified the association between socioeconomic features and HOD.

Poverty and unemployment were associated with increased HOD in metropolitan areas

(RR, 5% poverty: 1.12 [1.11-1.13]; 5% unemployment: 1.04 [1.02-1.05]), and median

household income was associated with decreased HOD (RR, $10,000: 0.88

[0.87-0.90]). In rural areas, low educational attainment alone was associated

with HOD (RR, 5%: 1.09 [1.02-1.16]).

CONCLUSIONS: Regardless of urbanicity, elevated rates of POD were found in more

economically disadvantaged zip codes. Economic disadvantage played a larger role

in HOD in urban than rural areas, suggesting rural HOD rates may have alternative

drivers. Identifying social determinants of opioid overdoses is particularly

important for creating effective population-level interventions.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2018.11.024

PMCID: PMC6375680 [Available on 2020-02-01]

PMID: 30592998 [Indexed for MEDLINE]

44. J Manag Care Spec Pharm. 2019 Jan;25(1):18-27. doi: 10.18553/jmcp.2019.25.1.018.

The Prevalence and Cost of Medicare Beneficiaries Diagnosed and At Risk for

Opioid Abuse, Dependence, and Poisoning.

Roland CL(1), Ye X(2), Stevens V(3), Oderda GM(2).

Author information:

(1)1 Pfizer, Durham, North Carolina.

(2)2 Pharmacotherapy Outcomes Research Center, University of Utah College of

Pharmacy, Salt Lake City.

(3)3 Division of Epidemiology, Department of Internal Medicine, University of

Utah School of Medicine, Salt Lake City.

BACKGROUND: Reliance on prescription opioids to manage pain has been associated

with increases in diversion, overdose, and addiction. Prevalence of misuse and

abuse has been shown to be higher among government-insured populations than

commercially insured populations. However, the prevalence and costs of

misuse/abuse among the Medicare fee-for-service (FFS) population has not been

studied.

OBJECTIVES: To (a) determine the prevalence and costs of prescription opioid

misuse/abuse and (b) evaluate the prevalence and costs associated with those

identified as at risk for opioid misuse/abuse in Medicare FFS beneficiaries.

METHODS: This retrospective case-control study used Medicare claims data for the

calendar years of 2010 and 2011 and included Medicare beneficiaries aged at least

18 years. The index date was the date of first diagnosed misuse/abuse or at risk

for abuse and had to occur between July 1, 2010, and June 30, 2011, and

beneficiaries had to have at least 6 months continuous eligibility before and

after the index date. Matching (1:1) was used for comparing opioid

misusers/abusers with nonabuser controls, as well as comparing patients at risk

for opioid abuse with controls not at risk for abuse. Controls were matched to

cases by gender, age, disability, and geographic region. The index date of the

control patient was set equal to the index date of the matched case.

RESULTS: Prevalence of misuse/abuse in the Medicare FFS population was 13.1 per

1,000 persons, with the majority among patients receiving Medicare based on

disability (76.2%). The prevalence of at risk for misuse/abuse was 117.4 per

1,000 persons. Approximately half of the Medicare FFS patients used an opioid.

Overall total annual unadjusted mean costs of health care resources were

significantly greater for abusers than for matched controls ($46,194 vs. $21,964;

P < 0.0001), with a mean annual excess cost of $24,230. The overall total

adjusted 6-month post-index mean costs of health care resources for abusers was

significantly greater than that of matched controls ($33,942 vs. $10,754; P <

0.0001), with a mean excess cost of $23,188.

CONCLUSIONS: The prevalence of diagnosed abuse among Medicare FFS population

(13.1 per 1,000 persons) was higher than other payer groups studied using similar

ICD-9-CM codes, and the majority of abuse was among those receiving Medicare

based on disability (76.2%). The prevalence of at-risk abuse was 9 times higher

than the prevalence of diagnosed abuse. As with other studies, health care

resource utilization and costs were significantly greater for diagnosed abuse

than matched controls.

DISCLOSURES: This study was sponsored by Pfizer. Roland is a Pfizer employee and

stockholder and was involved in all aspects of the study as part of a mid-career

fellowship in pharmacoeconomics with the University of Utah. Ye and Stevens are

employees of University of Utah, and Oderda was an employee of University of

Utah, which received financial support from Pfizer in connection with the

development of this manuscript. Oderda also reports consulting fees from Pfizer,

Trevena, and Pacira, unrelated to this study. The results of this study were

presented at the Academy of Managed Care Pharmacy Nexus 2015; October 26-29,

2015; Orlando, FL, and the AMCP Managed Care & Specialty Pharmacy Annual Meeting

2016; April 19-22, 2016; San Francisco, CA.

DOI: 10.18553/jmcp.2019.25.1.018

PMID: 30589633 [Indexed for MEDLINE]

45. Emerg Med J. 2019 Apr;36(4):219-224. doi: 10.1136/emermed-2018-207534. Epub 2018

Dec 22.

Incidence of mortality due to rebound toxicity after 'treat and release'

practices in prehospital opioid overdose care: a systematic review.

Greene JA(1)(2), Deveau BJ(1)(3), Dol JS(1), Butler MB(1).

Author information:

(1)Dalhousie University, Halifax, Canada.

(2)Emergency Health Services, Halifax, Canada.

(3)Canadian Armed Forces, Halifax, Canada.

INTRODUCTION: Death due to opioid overdose was declared a public health crisis in

Canada in 2015. Traditionally, patients who have overdosed on opioids that are

managed by emergency medical services (EMS) are treated with the opioid

antagonist naloxone, provided ventilatory support and subsequently transported to

hospital. However, certain EMS agencies have permitted patients who have been

reversed from opioid overdose to refuse transport, if the patient exhibits

capacity to do so. Evidence on the safety of this practice is limited. Therefore,

our intent was to examine the available literature to determine mortality and

serious adverse events within 48 hours of EMS treat and release due to suspected

rebound opioid toxicity after naloxone administration.

METHODS: A systematic search was performed on 11 May 2017 in PubMed, Cochrane

Central, Embase and CINHAL. Studies that reported on the outcome of patients

treated with prehospital naloxone and released at the scene were included.

Analyses for incidence of mortality and adverse events at the scene were

conducted. Risk of bias and assessment of publication bias was also done.

RESULTS: 1401 records were screened after duplicate removal. Eighteen full-text

studies were reviewed with seven selected for inclusion. None were found to be

high risk of bias. In most studies, heroin was the source of the overdose.

Mortality within 48 hours was infrequent with only four deaths among 4912

patients ﴾0.081%﴿ in the seven studies. Only one study reported on adverse events

and found no incidence of adverse events from their sample of 71 released

patients.

CONCLUSION: Mortality or serious adverse events due to suspected rebound toxicity

in patients released on scene post-EMS treatment with naloxone were rare.

However, studies involving longer-acting opioids were rare and no study involved

fentanyl.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and

permissions. Published by BMJ.

DOI: 10.1136/emermed-2018-207534

PMID: 30580317 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: None declared.

46. Harm Reduct J. 2018 Dec 22;15(1):64. doi: 10.1186/s12954-018-0271-5.

Rigidity, dyskinesia and other atypical overdose presentations observed at a

supervised injection site, Vancouver, Canada.

Kinshella MW(1), Gauthier T(1), Lysyshyn M(2)(3)(4).

Author information:

(1)Vancouver Coastal Health, Vancouver, Canada.

(2)Vancouver Coastal Health, Vancouver, Canada. mark.lysyshyn@vch.ca.

(3)School of Population and Public Health, University of British Columbia,

Vancouver, Canada. mark.lysyshyn@vch.ca.

(4)Office of the Medical Health Officer, 5th Floor, 132 West Esplanade, North

Vancouver, Canada. mark.lysyshyn@vch.ca.

OBJECTIVE: In midst of the overdose crisis, the clinical features of opioid

overdoses seem to be changing. Understanding of the adverse effects of synthetic

opioids such as fentanyl is currently limited to clinical settings. Insite, a

supervised injection site in Vancouver, Canada, provides an opportunity to better

understand illicit drug overdose presentations.

METHODS: A review of clinical records at Insite for October 2016 to April 2017

was undertaken to quantify atypical overdose presentations. Overdose reports were

reviewed for the number of atypical opioid overdose presentations, temporal

trends over the study period, concurrent symptoms, and interventions employed by

staff.

RESULTS: Insite staff responded to 1581 overdoses during the study period,

including 497 (31.4%) that did not fit a typical presentation for opioid

overdoses. Of these, 485 fit into five categories of atypical features: muscle

rigidity, dyskinesia, slow or irregular heart rate, confusion, and anisocoria.

Muscle rigidity was the most common atypical presentation, observed in 240

(15.2%) of the overdose cases, followed by dyskinesia, observed in 150 (9.2%).

Slow or irregular heart rate was observed in 69 (4.4%) cases, confusion in 24

(1.5%), and anisocoria in 2 (0.1%) of overall overdose cases.

DISCUSSION: The similarity of atypical overdose cases at Insite with

anesthesiology case reports supports the understanding that the illicit drug

supply is contaminated by fentanyl and other synthetic opioids. Atypical overdose

presentations can affect clinical overdose response. The experience at Insite

highlights the potential for supervised consumption sites to be innovative spaces

for community learning and knowledge translation.

DOI: 10.1186/s12954-018-0271-5

PMCID: PMC6303894

PMID: 30577844 [Indexed for MEDLINE]

47. J Stud Alcohol Drugs. 2018 Nov;79(6):893-898.

Prescription-, Illicit-, and Self-Harm Opioid Overdose Cases Treated in Hospital.

Conner KR(1)(2), Wiegand TJ(1), Kaukeinen K(3), Gorodetsky R(1)(4), Schult R(1),

Heavey SC(2).

Author information:

(1)Department of Emergency Medicine, University of Rochester Medical Center,

Rochester, New York.

(2)Department of Psychiatry, University of Rochester Medical Center, Rochester,

New York.

(3)Department of Biostatistics, University of Rochester Medical Center,

Rochester, New York.

(4)D'Youville College School of Pharmacy, Buffalo, New York.

OBJECTIVE: Research suggests unintentional overdose on prescription drugs and

intentional self-harm cases differ fundamentally from unintentional illicit drug

overdoses, but there are few data on opioid overdose per se.

METHOD: We analyzed consecutive opioid overdose patients age 13 and over (N =

435) treated by a toxicology consult service to compare three poisoning groups:

unintentional illicit drug (illicit, n = 128), unintentional prescription drug

(prescription, n = 217), and intentional self-harm (self-harm, n = 90). The

groups were compared on key characteristics of the poisoning events (severity,

co-ingestion of non-opioid) and the hospital-based treatments required to manage

the poisonings (use of antidote, provision of pharmacological support). Logistic

regressions yielded incident rate ratios (IRRs) and 95% confidence intervals (CI)

adjusted for age and sex.

RESULTS: Compared to the illicit group, the prescription group was more likely to

co-ingest a non-opioid drug (IRR [95% CI] = 1.594 [1.077, 2.358], p = .020.

Compared to illicit cases, self-harm cases were more likely to co-ingest a

non-opioid drug (IRR = 3.181 [1.620, 6.245], p = .001) and had a lower poisoning

severity score (IRR = 0.750 [0.564, 0.997], p = .048). There were no

statistically significant differences between the self-harm and prescription

groups.

CONCLUSIONS: The similarities between the self-harm and prescription poisoning

groups suggest that they may benefit from common interventions including

appropriate restriction on prescription of opioids and other medications that may

be misused (e.g., sedative-hypnotic/muscle relaxants). The characteristics of the

illicit poisoning group (use of heroin; more severe overdose events) suggest the

need for initiation of intensive substance use treatment interventions during

hospitalization.

PMID: 30573020

48. MMWR Morb Mortal Wkly Rep. 2018 Dec 21;67(50):1384-1387. doi:

10.15585/mmwr.mm6750a2.

Drug, Opioid-Involved, and Heroin-Involved Overdose Deaths Among American Indians

and Alaska Natives - Washington, 1999-2015.

Joshi S, Weiser T, Warren-Mears V.

The opioid epidemic has resulted in a threefold increase in drug overdose deaths

in the United States during 1999-2015 (1). Whereas American Indians/Alaska

Natives (AI/AN) have experienced larger increases in drug overdose mortality than

have other racial/ethnic groups in the United States (2), little is known about

the regional impact of opioids in tribal and urban AI/AN communities. To address

this data gap, death records from the Washington State Center for Health

Statistics, corrected for misclassification of AI/AN race, were examined to

identify trends and disparities in drug, opioid-involved, and heroin-involved

overdose mortality rates for AI/AN and non-Hispanic whites (whites) in

Washington. Although AI/AN and whites had similar overdose mortality rates during

1999-2001, subsequent overdose rates among AI/AN increased at a faster rate than

did those among whites. During 2013-2015, mortality rates among AI/AN were 2.7

and 4.1 times higher than rates among whites for total drug and opioid-involved

overdoses and heroin-involved overdoses, respectively. Washington death

certificates that were not corrected for misclassification of AI/AN race

underestimated drug overdose mortality rates among AI/AN by approximately 40%.

National statistics on the opioid epidemic, which report that overdose mortality

rates are significantly higher among whites than among AI/AN, are not reflective

of regional prevalences, disparities, and trends. Comprehensive efforts to

address the opioid epidemic in AI/AN communities rely on strong partnerships

between tribal governments and local, state, and federal entities. Additional

measures are needed for community-based surveillance, treatment, and prevention

to effectively respond to the epidemic across diverse tribal and urban AI/AN

communities.

DOI: 10.15585/mmwr.mm6750a2

PMCID: PMC6342552

PMID: 30571673 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. Sujata Joshi

reports travel support from the Council of State and Territorial Epidemiologists

during the conduct of the study. No other potential conflicts of interest were

disclosed.

49. Medicine (Baltimore). 2018 Nov;97(48):e13449. doi: 10.1097/MD.0000000000013449.

Human deaths from drug overdoses with carfentanyl involvement-new rising problem

in forensic medicine: A STROBE-compliant retrospective study.

Fomin D(1)(2), Baranauskaite V(2), Usaviciene E(2), Sumkovskaja A(2), Laima

S(1)(2), Jasulaitis A(1), Minkuviene ZN(1)(2), Chmieliauskas S(1)(2), Stasiuniene

J(1).

Author information:

(1)Department of Pathology, Forensic Medicine and Pharmacology, Institute of

Biomedical Sciences of the Faculty of Medicine of Vilnius University.

(2)State Forensic Medicine Service, Vilnius, Lithuania.

Carfentanyl, an ultra-potent synthetic opioid, is approved for use only in

veterinary medicine as a tranquilizing agent. However, many cases of human

poisoning with carfentanyl have recently appeared in the news with limited

information given and scientific literature provides only 1 case of documented

human exposure to carfentanyl.Fifteen cases of death from drug overdoses with

carfentanyl involvement are being presented. Fifteen blood and urine samples have

been taken for alcohol and drug testing. Headspace gas chromatography was used

for alcohol detection. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)

and liquid chromatography-time-of-flight mass spectrometry (LC/MS TOF) system was

used for drug detection.Sixty-three cases of death from poisoning with drugs have

been tested for carfentanyl in the State Forensic Medicine Service. Fifteen of

them were positive for carfentanyl.The cases mentioned above show that

carfentanyl exposure causes signs and symptoms similar to other opioid toxicity.

Carfentanyl intoxication may even be fatal if appropriate treatment is not

available. Therefore, nowadays it is very important to draw forensic medicine

expert's attention to new substances in drug trade.

DOI: 10.1097/MD.0000000000013449

PMCID: PMC6283219

PMID: 30508965 [Indexed for MEDLINE]

50. Forensic Sci Int. 2019 Jan;294:80-85. doi: 10.1016/j.forsciint.2018.11.007. Epub

2018 Nov 16.

Fatal poisoning involving cyclopropylfentanyl - Investigation of time-dependent

postmortem redistribution.

Brockbals L(1), Staeheli SN(1), Gentile S(2), Schlaepfer M(3), Bissig C(3),

Bolliger SA(2), Kraemer T(1), Steuer AE(4).

Author information:

(1)Department of Forensic Pharmacology and Toxicology, Zurich Institute of

Forensic Medicine, University of Zurich, Switzerland.

(2)Department of Forensic Medicine & Imaging, Zurich Institute of Forensic

Medicine, University of Zurich, Switzerland.

(3)Zurich Forensic Science Institute, Zurich, Switzerland.

(4)Department of Forensic Pharmacology and Toxicology, Zurich Institute of

Forensic Medicine, University of Zurich, Switzerland. Electronic address:

andrea.steuer@irm.uzh.ch.

A growing number of fatal overdoses involving opioid drugs, in particular

involving fentanyl and its analogues, pose an immense threat to public health.

Postmortem casework of forensic toxicologists in such cases is challenging, as

data on pharmacodynamic and pharmacokinetic properties as well as reference

values for acute toxicities and data on potential postmortem redistribution (PMR)

mechanisms often do not exist. A fatal case involving cyclopropylfentanyl was

investigated at the Zurich Institute of Forensic Medicine and the Zurich Forensic

Science Institute; an unknown powder found at the scene was reliably identified

as cyclopropylfentanyl by gas chromatography-infrared spectroscopy (GC-IR).

Femoral blood samples were collected at two time points after death; 11h

postmortem (t1) and during the medico-legal autopsy 29h after death (t2). At the

autopsy, additional samples from the heart blood, urine and gastric content were

collected. Cyclopropylfentanyl was quantified using a validated liquid

chromatography-tandem mass spectrometric (LC-MS/MS) method. Femoral blood

concentration of cyclopropylfentanyl at autopsy was 19.8ng/mL (t1=15.7ng/mL;

heart blood concentration at autopsy=52.4ng/mL). In the light of the current

literature and under the exclusion that no other morphological findings could

explain the cause of death, contribution of cyclopropylfentanyl to death was

proposed (polydrug use). Significant postmortem concentration increases of

cyclopropylfentanyl in femoral blood during 18h after the first sampling were

observed, thus indicating a relevant potential to undergo PMR. A

central-to-peripheral blood concentration ratio of 2.6 supports this.

Consequently, the current case suggests that postmortem cyclopropylfentanyl

concentration should always be interpreted with care.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2018.11.007

PMID: 30497048 [Indexed for MEDLINE]

51. Harm Reduct J. 2018 Nov 16;15(1):57. doi: 10.1186/s12954-018-0262-6.

Assessing pharmacy student experience with, knowledge of and attitudes towards

harm reduction: illuminating barriers to pharmacist-led harm reduction.

Mahon LR(1), Hawthorne AN(1), Lee J(1), Blue H(1), Palombi L(2).

Author information:

(1)Department of Pharmacy Practice and Pharmaceutical Sciences, University of

Minnesota, College of Pharmacy, 232 Life Science, 1110 Kirby Drive, Duluth, MN,

55812-3003, USA.

(2)Department of Pharmacy Practice and Pharmaceutical Sciences, University of

Minnesota, College of Pharmacy, 232 Life Science, 1110 Kirby Drive, Duluth, MN,

55812-3003, USA. lpalombi@d.umn.edu.

BACKGROUND: As the burden from the opioid epidemic continues to increase in the

state of Minnesota and across the nation, the University of Minnesota College of

Pharmacy seeks to design an innovative, comprehensive harm reduction curriculum

in order to better train student pharmacists to serve the varied needs of the

greater community. This study examines incoming individuals' baseline knowledge

of and attitudes toward harm reduction in order to better inform curriculum

planning and to ultimately produce pharmacists capable of impacting the

devastating effects of the opioid crisis.

METHODS: Incoming first-year pharmacy students took a survey focused on their

knowledge of opioid overdose and the drug naloxone and also provided written

reflections on their perceptions of harm reduction. Data was coded using

consensual qualitative research (CQR) into appropriate domains.

RESULTS: Pharmacy students beginning their professional education revealed a lack

of knowledge of proper response to an overdose situation, with 18.56% unfamiliar

with the opioid antagonist drug naloxone. Close to 10% (9.58%) of students

expressed unwillingness to do anything other than call an ambulance during an

overdose event, while 8.98% were either unsure or felt that they would not feel

compelled to do something to help. Qualitative coding revealed many barriers to

students' becoming capable harm reductionists, including lack of knowledge of

substance use, addiction, and harm reduction, in addition to the presence of bias

and stigma.

CONCLUSION: In order to interrupt the cycle of misinformation and stigma within

the larger community and the subgroup of medical providers, gaps in student

knowledge must be addressed in meaningful, specific ways over the course of their

pharmacy education. Evaluating baseline knowledge and beliefs informs the design

of a flexible, action-oriented curriculum to produce well-trained pharmacists

ready to engage in finding solutions to the opioid crisis.

DOI: 10.1186/s12954-018-0262-6

PMCID: PMC6240215

PMID: 30445958 [Indexed for MEDLINE]

52. Rev Med Interne. 2019 Jun;40(6):389-394. doi: 10.1016/j.revmed.2018.10.389. Epub

2018 Nov 11.

[The American opioid overdose crisis: A threat for France?]

[Article in French]

Vodovar D(1), Langrand J(2), Tournier N(3), Mégarbane B(4).

Author information:

(1)Centre antipoison et de toxicovigilance de Paris, hôpital Fernand-Widal, 200,

rue du Faubourg-Saint-Denis, 75010 Paris, France; Fédération de toxicologie

FeTox, hôpital Lariboisière/Fernand-Widal, AP-HP, 75010 Paris, France; Inserm

UMRS 1144, 4, avenue de l'Observatoire, 75006 Paris, France; Service hospitalier

Fréderic Joliot/CEA, laboratoire IMIV, boulevard Dubreuil, 91400 Orsay, France;

Université Paris-Diderot, 75013 Paris, France. Electronic address:

dominique.vodovar@aphp.fr.

(2)Centre antipoison et de toxicovigilance de Paris, hôpital Fernand-Widal, 200,

rue du Faubourg-Saint-Denis, 75010 Paris, France; Fédération de toxicologie

FeTox, hôpital Lariboisière/Fernand-Widal, AP-HP, 75010 Paris, France; Inserm

UMRS 1144, 4, avenue de l'Observatoire, 75006 Paris, France.

(3)Service hospitalier Fréderic Joliot/CEA, laboratoire IMIV, boulevard Dubreuil,

91400 Orsay, France.

(4)Fédération de toxicologie FeTox, hôpital Lariboisière/Fernand-Widal, AP-HP,

75010 Paris, France; Inserm UMRS 1144, 4, avenue de l'Observatoire, 75006 Paris,

France; Université Paris-Diderot, 75013 Paris, France; Réanimation médicale et

toxicologique, hôpital Lariboisière, 2, rue Ambroise-Paré, Paris, France.

Since the 2000s, a concerning increase in opioid-analgesic-related overdoses and

deaths has been reported in the United States. In contrast with opioid overdoses

reported in the 80-90s mostly involving heroin, currently it is the misuse of

opioid analgesics that is mainly responsible for opioid overdoses. This crisis is

related to factors (not limited to the US) which occurred during the 90s and

which have led to a broad prescription of opioids in non-cancer pain. In Europe

and France, there is (but to a much lesser extent) an increase in strong opioid

consumption and in opioid prescription related morbi-mortality. This situation,

which can be described as "worrying" today, requires awareness among the French

medical community, both upstream (rational prescription of opioids) and

downstream (optimal management of opioid poisoning) from the opioid prescription.

Copyright © 2018 Société Nationale Française de Médecine Interne (SNFMI).

Published by Elsevier Masson SAS. All rights reserved.

DOI: 10.1016/j.revmed.2018.10.389

PMID: 30429046

53. Res Social Adm Pharm. 2018 Oct 17. pii: S1551-7411(18)30282-1. doi:

10.1016/j.sapharm.2018.10.023. [Epub ahead of print]

Patterns of opioid prescriptions received prior to unintentional prescription

opioid overdose death among Veterans.

Moyo P(1), Zhao X(2), Thorpe CT(3), Thorpe JM(3), Sileanu FE(2), Cashy JP(2),

Hale JA(2), Mor MK(4), Radomski TR(5), Donohue JM(6), Hausmann LRM(7), Hanlon

JT(8), Good CB(9), Fine MJ(7), Gellad WF(10).

Author information:

(1)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Center for Pharmaceutical Policy and Prescribing,

University of Pittsburgh Health Policy Institute, Pittsburgh, PA, USA; Department

of Health Services, Policy and Practice, Brown University School of Public

Health, Providence, RI, USA.

(2)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA.

(3)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Center for Pharmaceutical Policy and Prescribing,

University of Pittsburgh Health Policy Institute, Pittsburgh, PA, USA; Department

of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy,

Pittsburgh, PA, USA.

(4)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Department of Biostatistics, Graduate School of

Public Health, University of Pittsburgh, Pittsburgh, PA, USA.

(5)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Center for Pharmaceutical Policy and Prescribing,

University of Pittsburgh Health Policy Institute, Pittsburgh, PA, USA; Division

of General Internal Medicine, University of Pittsburgh School of Medicine,

Pittsburgh, PA, USA.

(6)Center for Pharmaceutical Policy and Prescribing, University of Pittsburgh

Health Policy Institute, Pittsburgh, PA, USA; Department of Health Policy &

Management, Graduate School of Public Health, University of Pittsburgh,

Pittsburgh, PA, USA.

(7)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Division of General Internal Medicine, University of

Pittsburgh School of Medicine, Pittsburgh, PA, USA.

(8)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Center for Pharmaceutical Policy and Prescribing,

University of Pittsburgh Health Policy Institute, Pittsburgh, PA, USA; Department

of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy,

Pittsburgh, PA, USA; Division of Geriatric Medicine, University of Pittsburgh

School of Medicine, Pittsburgh, PA, USA.

(9)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Center for Pharmaceutical Policy and Prescribing,

University of Pittsburgh Health Policy Institute, Pittsburgh, PA, USA; Department

of Pharmacy and Therapeutics, University of Pittsburgh School of Pharmacy,

Pittsburgh, PA, USA; Division of Geriatric Medicine, University of Pittsburgh

School of Medicine, Pittsburgh, PA, USA; Center for Value Based Pharmaceutical

Initiatives, UPMC Health Plan, Pittsburgh, PA, USA.

(10)Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare

System, Pittsburgh, PA, USA; Center for Pharmaceutical Policy and Prescribing,

University of Pittsburgh Health Policy Institute, Pittsburgh, PA, USA; Division

of General Internal Medicine, University of Pittsburgh School of Medicine,

Pittsburgh, PA, USA. Electronic address: walid.gellad@va.gov.

BACKGROUND: Few studies have assessed prescription opioid supply preceding death

in individuals dying from unintentional prescription opioid overdoses, or

described the characteristics of these individuals, particularly among Veterans.

OBJECTIVES: To describe the history of prescription opioid supply preceding

prescription opioid overdose death among Veterans.

METHODS: In a national cohort of Veterans who filled ≥1 opioid prescriptions from

the Veterans Health Administration (VA) or Medicare Part D during 2008-2013, we

identified deaths from unintentional or undetermined-intent prescription opioid

overdoses in 2012-2013. We captured opioid prescriptions using both linked VA and

Part D data, and VA data only.

RESULTS: Among 1181 decedents, 643 (54.4%) had prescription opioid supply on the

day of death, and 735 (62.2%) within 30 days based on linked data, compared to

40.1% and 46.7%, respectively, using VA data alone. Decedents with prescription

opioid supply were significantly older and less likely to have alcohol or illicit

drugs as co-occurring substances involved in the overdose. Using linked data, 241

(20.4%) decedents lacked prescription opioid supply within a year of death.

CONCLUSIONS: Many VA patients who die from prescription opioid overdose receive

opioid prescriptions outside VA or not at all. It is important to supplement VA

with non-VA data to more accurately measure prescription opioid exposure and

improve opioid medication safety.

Published by Elsevier Inc.

DOI: 10.1016/j.sapharm.2018.10.023

PMCID: PMC6470039 [Available on 2020-04-17]

PMID: 30385111

54. Drug Alcohol Depend. 2018 Dec 1;193:169-176. doi:

10.1016/j.drugalcdep.2018.09.009. Epub 2018 Oct 18.

Trends and correlates of perceived access to heroin among young adults in the

United States, 2002-2016.

Salas-Wright CP(1), Oh S(2), Vaughn MG(3), Muroff J(4), Amodeo M(4), Delva J(4).

Author information:

(1)School of Social Work, Boston University, 264 Bay State Rd., Boston, MA 02215,

USA. Electronic address: cpsw@bu.edu.

(2)Steve Hick's School of Social Work, The University of Texas at Austin, 1925

San Jacinto Blvd., Austin, TX, 78712, USA.

(3)School of Social Work, College for Public Health and Social Justice, Saint

Louis University, 1 N. Grand Blvd., St. Louis, MO 63103, USA.

(4)School of Social Work, Boston University, 264 Bay State Rd., Boston, MA 02215,

USA.

BACKGROUND: We are at a unique moment in United States (US) history as heroin

overdose rates are higher than at any time in recent memory. Based on prior

research and the developmental risks faced by young adults (ages 18-25), we

examine the trends and correlates of perceived access to heroin among this group

over a 15-year period.

METHODS: We analyzed national trend data from the National Survey on Drug Use and

Health (2002-2016) on young adults' (N = 247,679; ages 18-25) perceived access to

heroin. We conducted logistic regression analyses with survey year specified as

an independent variable and heroin access specified as the dependent variable

while controlling for sociodemographic factors.

RESULTS: A majority of respondents reported that it would be difficult or

impossible to obtain heroin, if desired. Young adult reports that it would be

"probably impossible" to access heroin increased significantly from 31% in 2002

to 41% in 2016. The upward trend in the perceived lack of access was most robust

among African Americans and Hispanics as well as those reporting no past-year

substance use or drug/criminal justice system involvement.

CONCLUSIONS: In the midst of a very serious opioid epidemic, the present study

found that most young adults in the US consider that it would be "probably

impossible" to obtain heroin. This trend was observed across young adulthood and

across gender, racial/ethnic, and family income differences. However, we found

that these trends are largely driven by those at relatively low risk of drug

misuse and deviant behaviors generally.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2018.09.009

PMCID: PMC6239938 [Available on 2019-12-01]

PMID: 30384325 [Indexed for MEDLINE]

55. N Engl J Med. 2018 Nov 1;379(18):1782. doi: 10.1056/NEJMc1809521.

Lethal Fentanyl and Cocaine Intoxication.

Khatri UG(1), Viner K(2), Perrone J(3).

Author information:

(1)Hospital of the University of Pennsylvania, Philadelphia, PA.

(2)Philadelphia Department of Public Health, Philadelphia, PA.

(3)Perelman School of Medicine at the University of Pennsylvania, Philadelphia,

PA.

DOI: 10.1056/NEJMc1809521

PMID: 30380395 [Indexed for MEDLINE]

56. Eur J Pediatr. 2019 Feb;178(2):161-172. doi: 10.1007/s00431-018-3281-0. Epub 2018

Oct 29.

Central nervous system-active drug abused and overdose in children: a worldwide

exploratory study using the WHO pharmacovigilance database.

Carnovale C(1), Mahzar F(2), Scibelli S(2), Gentili M(2), Arzenton E(3), Moretti

U(3), Leoni O(4), Pozzi M(5), Peeters GGAM(2), Clementi E(2)(5), Medaglia M(4),

Radice S(2).

Author information:

(1)Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences

L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan,

Italy. carla.carnovale@unimi.it.

(2)Unit of Clinical Pharmacology Department of Biomedical and Clinical Sciences

L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, 20157, Milan,

Italy.

(3)Department of Diagnostics and Public Health, Section of Pharmacology,

University of Verona, Verona, Italy.

(4)Regional Pharmacovigilance Center of Lombardy, Milan, Italy.

(5)Scientific Institute, IRCCS E. Medea, Bosisio Parini, Lecco, Italy.

Recent epidemiological studies have reported an increase in central nervous

system (CNS)-active drug abuse rates in paediatric settings, raising several

public health concerns. No study to date has explored this issue worldwide. We

performed an extensive analysis of drugs abuse/overdose reported for children in

the last decade by using the largest pharmacovigilance database, i.e. the

VigiBase, collecting adverse drug reaction reports that involved at least one

suspect drug belonging to the Anatomical Therapeutic Chemical code "Nervous

System" through the Standardised Medical Dictionary for Drug Regulatory Affairs

Queries for Drug abuse. 8.682 reports matched our criteria. An increase in

reporting activity was observed, starting from 2014; an intentional overdose was

reported more frequently than an accidental one, with a difference between age

groups. We retrieved 997 reports with death outcome. These referred more to

adolescents (n = 538) than subjects of any other paediatric age group.

Paracetamol and opioid analgesics were the most common suspect drugs in deaths

across all age groups due to hypoxic-ischaemic encephalopathy, brain death, and

cardio-respiratory arrest.Conclusion: The number of reports associated with drug

abuse and overdose is increasing (for opioid and paracetamol-containing products)

and a considerable number of adverse drug reactions are serious. Data on the

patterns of use of such medicines from each country may help in implementing

strategies of risk-minimisation and renewing healthcare recommendations

worldwide. An increased clinical awareness of drug abuse and overdose is

warranted, while continuing to provide effective treatments. What is Known: • The

large increase in paediatric prescriptions for CNS-active drugs in the last

20 years has recently raised public health concerns about drug abuse and

overdose. • No study to date has examined this issue in paediatric patients

worldwide. What is New: • The number of paediatric reports associated with CNS

drug abuse and intentional overdose is increasing, including those with fatal

outcome; over 4 years; more than 35% of the reports was entered from European

countries. • Opioid and paracetamol were most frequently suspected for ADRs with

fatal outcome across all age groups, due to hypoxic-ischaemic encephalopathy and

cardio-respiratory arrest, suggesting the need to implement strategies of

risk-minimisation.

DOI: 10.1007/s00431-018-3281-0

PMID: 30374752 [Indexed for MEDLINE]

57. J Anal Toxicol. 2018 Oct 1;42(8):581-585. doi: 10.1093/jat/bky052.

Child Fatalities Due to Heroin/Fentanyl Exposure: What the Case History Missed.

DeRienz RT(1), Baker DD(1), Kelly NE(1), Mullins AM(1), Barnett RY(1), Hobbs

JM(1), Daniels JA(1), Harshbarger KE(1), Ortiz AM(1).

Author information:

(1)Franklin County Coroner's Office, 520 King Avenue, Columbus, OH, USA.

This case report presents three unrelated children found to have heroin and/or

fentanyl in their systems after general unknown systematic toxicological analysis

(STA). The first case involves an 11-month-old male found unresponsive at their

residence. The scene response suggested a potentially unsafe sleeping condition

or a sudden unexplained infant death. The second case is a 14-month-old female

found unresponsive after eating soft candies, suggesting that a choking related

death may have occurred. The third case is a 12-year-old male found unresponsive

in bed and foaming from the mouth. Gum was removed from the child's airway,

suggesting another choking related death. The STA included a 14-drug category

enzyme linked immunosorbant assay (ELISA) screening in whole blood. Cases 1 and 3

were presumptively positive for fentanyl, while Case 2 was presumptively positive

for opiates and fentanyl. Reflex confirmation was performed in blood, urine and

gastric contents, by solid-phase extraction (SPE) for 12 opiates including

morphine and 6-monoacetylmorphine (6MAM) by gas chromatography-mass spectrometry

(GC-MS) and for fentanyl, norfentanyl, and novel analogs, by liquid

chromatography tandem mass spectrometry (LC-MS-MS). High concentrations of

fentanyl and 6MAM in the gastric contents of Case 1, along with the presence of

diacetylmorphine, suggested probable enteral ingestion of heroin and fentanyl,

separately or in a combined formulation. Interpretation of the toxicology results

could not determine a probable route of exposure to heroin/fentanyl in Case 2,

however, the cause of death was clearly related to this drug mixture. In Case 3,

the presence of acetylfentanyl suggested an illicit fentanyl exposure. The

intention of this case report is to demonstrate the need for a STA approach for

all non-trauma postmortem cases regardless of case circumstances, age or

suspicion of drug use.

DOI: 10.1093/jat/bky052

PMID: 30371840 [Indexed for MEDLINE]

58. N Z Med J. 2018 Oct 26;131(1484):46-60.

Feasibility and reliability of clinical coding surveillance for the routine

monitoring of adverse drug events in New Zealand hospitals.

Ng J(1), Andrew P(2), Muir P(3), Greene M(4), Mohan S(5), Knight J(6), Hider

P(7), Davis P(8), Seddon M(9), Scahill S(10), Harrison J(11), Zhou L(12), Selak

V(13), Lawes C(14), Galgali G(15), Broad J(16), Crawley M(17), Pevreal W(18),

Houston N(19), Brott T(20), Ryan D(21), Peach J(22), Brant A(23), Bramley D(24).

Author information:

(1)Lead Advisor, Improvement, Research & Informatics, Institute for Innovation

and Improvement (i3), Waitemata DHB, Auckland.

(2)Director, Institute for Innovation and Improvement (i3), Waitemata DHB,

Auckland.

(3)Medical Fellow, Planning, Funding and Outcomes, Waitemata DHB, Auckland.

(4)Information Analyst, Institute for Innovation and Improvement (i3), Waitemata

DHB, Auckland.

(5)Clinical Coding Auditor, Health Information Group, Waitemata DHB, Auckland.

(6)Clinical Coding Team Leader, Health Information Group, Waitemata DHB,

Auckland.

(7)Senior Lecturer, Department of Population Health, University of Otago,

Christchurch.

(8)Professor, Centre of Methods and Policy Application in the Social Sciences

(COMPASS), University of Auckland, Auckland.

(9)Independent Consultant, Seddon Healthcare Quality, Auckland.

(10)Senior Lecturer, School of Management, Massey University, Auckland.

(11)Associate Professor, School of Pharmacy, University of Auckland, Auckland.

(12)Chief Advisor for Asian International Collaboration, Waitemata District

Health Board, Auckland.

(13)Senior Lecturer, School of Population Health, University of Auckland,

Auckland.

(14)Public Health Physician (Surgical), Institute for Innovation and Improvement

(i3), Waitemata DHB, Auckland.

(15)Public Health Physician (Maternity), Child, Women and Family, Waitemata DHB,

Auckland.

(16)Senior Research Fellow, Department of Geriatric Medicine, University of

Auckland, Auckland.

(17)Chief Pharmacist, Pharmacy Department, Waitemata DHB, Auckland.

(18)Medication Safety Pharmacist, Pharmacy Department, Waitemata DHB, Auckland

(Died 24 April 2018).

(19)Clinical Director for Safety and Quality in Primary Care, Waitemata DHB,

Auckland.

(20)Executive Director-Allied Health, Scientific & Technical Professions,

Waitemata DHB, Auckland.

(21)Information Systems Change Manager, Health Information Group, Waitemata DHB,

Auckland.

(22)Director of Nursing and Midwifery, Waitemata DHB, Auckland.

(23)Chief Medical Officer, Waitemata DHB, Auckland.

(24)Chief Executive Officer, Waitemata DHB, Auckland.

AIM: To explore the feasibility and reliability of Clinical Coding Surveillance

(CCS) for the routine monitoring of Adverse Drug Events (ADE) and describe the

characteristics of harm identified through this approach in a large district

health board (DHB).

METHOD: All hospital admissions at Waitemata DHB from 2015 to 2016 with an

ADE-related ICD10-AM code of Y40-Y59, X40-X49 or T36-T50 were extracted from

clinical coded data. The data was analysed using descriptive statistics,

statistical process control and Pareto charts. Two clinicians assessed a random

sample of 140 ADEs for their accuracy against what was clinically documented in

medical records.

RESULTS: A total of 11,999 ADEs were identified in 244,992 admissions (4.9 ADEs

per 100 admissions). ADEs were more prevalent in older adults and associated with

longer average length of stays and medicines such as analgesics, antibiotics,

anticoagulants and diuretics. Only 2,164 (18%) of ADEs were classified as

originating within hospital. Of ADEs originating outside of the hospital, the

main causes were poisoning by psychotropics, anti-epileptics and

anti-parkinsonism agents and non-opioid analgesics. Clinicians agreed that 91% of

ADE positive admissions were accurately classified as per clinical documentation.

CONCLUSION: CCS is a feasible and reliable approach for the routine monitoring of

ADEs in hospitals.

PMID: 30359356 [Indexed for MEDLINE]

Conflict of interest statement: Nil.

59. Am J Public Health. 2018 Dec;108(12):1682-1687. doi: 10.2105/AJPH.2018.304683.

Epub 2018 Oct 25.

Identifying Unreported Opioid Deaths Through Toxicology Data and Vital Records

Linkage: Case Study in Marion County, Indiana, 2011-2016.

Lowder EM(1), Ray BR(1), Huynh P(1), Ballew A(1), Watson DP(1).

Author information:

(1)Evan M. Lowder and Bradley R. Ray are with the School of Public and

Environmental Affairs, Indiana University-Purdue University Indianapolis,

Indianapolis. At the time of this study, Philip Huynh and Dennis P. Watson were

with the Center for Health Engagement and Equity Research, Department of Social

and Behavioral Sciences, Indiana University Richard M. Fairbanks School of Public

Health, Indiana University-Purdue University. Alfarena Ballew is with the Marion

County Coroner's Office, Indianapolis.

OBJECTIVES: To demonstrate the severity of undercounting opioid-involved deaths

in a local jurisdiction with a high proportion of unspecified accidental

poisoning deaths.

METHODS: We matched toxicology data to vital records for all accidental poisoning

deaths (n = 1238) in Marion County, Indiana, from January 2011 to December 2016.

From vital records, we coded cases as opioid involved, specified other substance,

or unspecified. We extracted toxicology data on opioid substances for unspecified

cases, and we have reported corrected estimates of opioid-involved deaths after

accounting for toxicology findings.

RESULTS: Over a 6-year period, 57.7% of accidental overdose deaths were

unspecified and 34.2% involved opioids. Toxicology data showed that 86.8% of

unspecified cases tested positive for an opioid. Inclusion of toxicology results

more than doubled the proportion of opioid-involved deaths, from 34.2% to 86.0%.

CONCLUSIONS: Local jurisdictions may be undercounting opioid-involved overdose

deaths to a considerable degree. Toxicology data can improve accuracy in

identifying opioid-involved overdose deaths. Public Health Implications.

Mandatory toxicology testing and enhanced training for local coroners on

standards for death certificate reporting are needed to improve the accuracy of

local monitoring of opioid-involved accidental overdose deaths.

DOI: 10.2105/AJPH.2018.304683

PMCID: PMC6236744 [Available on 2019-12-01]

PMID: 30359109

60. Drug Alcohol Depend. 2018 Dec 1;193:69-74. doi: 10.1016/j.drugalcdep.2018.09.006.

Epub 2018 Oct 12.

Characterizing fentanyl-related overdoses and implications for overdose response:

Findings from a rapid ethnographic study in Vancouver, Canada.

Mayer S(1), Boyd J(2), Collins A(3), Kennedy MC(4), Fairbairn N(5), McNeil R(6).

Author information:

(1)British Columbia Centre on Substance Use, Level 4, 1045 Howe Street,

Vancouver, BC, V6Z 2A9, Canada. Electronic address: samara.mayer@bccsu.ubc.ca.

(2)British Columbia Centre on Substance Use, Level 4, 1045 Howe Street,

Vancouver, BC, V6Z 2A9, Canada; Department of Medicine, University of British

Columbia, St. Paul's Hospital, 608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6,

Canada. Electronic address: jade.boyd@bccsu.ubc.ca.

(3)British Columbia Centre on Substance Use, Level 4, 1045 Howe Street,

Vancouver, BC, V6Z 2A9, Canada; Faculty of Health Sciences, Simon Fraser

University, 8888 University Drive, Burnaby, BC, V5A 1S6, Canada. Electronic

address: alex.collins@bccsu.ubc.ca.

(4)British Columbia Centre on Substance Use, Level 4, 1045 Howe Street,

Vancouver, BC, V6Z 2A9, Canada; School of Population and Public Health,

University of British Columbia, 2206 E Mall, Vancouver, BC V6T 1Z3 E Mall,

Vancouver, BC, V6T 1Z3, Canada. Electronic address:

maryclare.kennedy@bccsu.ubc.ca.

(5)British Columbia Centre on Substance Use, Level 4, 1045 Howe Street,

Vancouver, BC, V6Z 2A9, Canada; Department of Medicine, University of British

Columbia, St. Paul's Hospital, 608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6,

Canada. Electronic address: nadia.fairbairn@bccsu.ubc.ca.

(6)British Columbia Centre on Substance Use, Level 4, 1045 Howe Street,

Vancouver, BC, V6Z 2A9, Canada; Department of Medicine, University of British

Columbia, St. Paul's Hospital, 608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6,

Canada. Electronic address: ryan.mcneil@bccsu.ubc.ca.

BACKGROUND: North America is experiencing an opioid overdose epidemic, fuelled by

the proliferation of fentanyl, related analogues, and fentanyl-adulterated

opioids. British Columbia, Canada has similarly experienced a rapid increase in

the proportion of opioid overdose deaths associated with fentanyl. This study

builds off of research characterizing fentanyl exposure to further explore the

presentation of fentanyl use and related overdoses among people who use drugs.

METHODS: From December 2016 to April 2017, rapid ethnographic fieldwork was

conducted in Vancouver, Canada to examine the implementation of low-threshold

overdose prevention sites, where people use drugs under the supervision of staff

and peers trained to respond to overdose. Data collection included 185 h of

ethnographic observation and in-depth interviews with 72 people who inject drugs,

44 of whom reported experiencing an overdose in the year prior to the interviews.

RESULTS: While most participants had experienced previous opioid-related

overdose, they characterized how fentanyl was markedly distinct in terms of:

potency, and rapid onset. Ethnographic observations and participant narratives

highlighted how fentanyl use and related overdoses had implications for frontline

response, including: rapid onset, multiple concurrent overdoses, body and chest

rigidity, and the need to administer larger doses of naloxone.

CONCLUSIONS: Participant narratives and observational data documented distinct

symptoms for fentanyl-attributed overdoses compared to other opioid related

overdose events, which had implications for response. Findings may serve to

inform best practices in responding to fentanyl-related overdoses including; the

provision of oxygen and effective doses of naloxone, and also considerations

regarding overdose identification.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2018.09.006

PMCID: PMC6447427 [Available on 2019-12-01]

PMID: 30343236 [Indexed for MEDLINE]

61. CMAJ Open. 2018 Oct 18;6(4):E478-E485. doi: 10.9778/cmajo.20180084. Print 2018

Oct-Dec.

Relation between opioid-related harms and socioeconomic inequalities in Ontario:

a population-based descriptive study.

Cairncross ZF(1), Herring J(2), van Ingen T(2), Smith BT(2), Leece P(2), Schwartz

B(2), Hohenadel K(2).

Author information:

(1)Dalla Lana School of Public Health (Cairncross, Smith, Leece, Schwartz),

University of Toronto; Public Health Ontario (Cairncross, Herring, van Ingen,

Smith, Leece, Schwartz, Hohenadel), Toronto, Ont.

zoe.cairncross@mail.utoronto.ca.

(2)Dalla Lana School of Public Health (Cairncross, Smith, Leece, Schwartz),

University of Toronto; Public Health Ontario (Cairncross, Herring, van Ingen,

Smith, Leece, Schwartz, Hohenadel), Toronto, Ont.

BACKGROUND: Negative health outcomes associated with the use of both prescribed

and nonprescribed opioids are increasingly prevalent. We examined long-term

trends in opioid-related harms in Ontario across a set of 6 indicators and the

relation between harms and neighbourhood income in 2016.

METHODS: We examined rates of neonatal abstinence syndrome, opioid poisoning

(fatal and nonfatal) and nonpoisoning opioid-related events from 2003 to 2016 in

Ontario using population-based health administrative databases. We conducted

descriptive analyses for harm indicators across neighbourhood income quintiles in

2016 (2015 for death). We examined social inequalities in opioid-related harms on

both relative (prevalence ratio) and absolute (potential rate reduction) scales.

RESULTS: Rates of opioid-related harms increased dramatically between 2003 and

2016. In 2016, neonatal abstinence syndrome and opioid poisoning and nonpoisoning

events showed a strong social gradient, with harm rates being lowest in

higher-income neighbourhoods and highest in lower-income neighbourhoods.

Prevalence ratios for the lowest-income neighbourhoods compared to the

highest-income neighbourhoods ranged from 2.36 (95% confidence interval [CI]

2.15-2.58) for emergency department visits for opioid poisoning to 3.70 (95% CI

2.62-5.23) for neonatal abstinence syndrome. Potential rate reductions for

opioid-related harms ranged from 34.8% (95% CI 29.1-40.1) to 49.9% (95% CI

36.7-60.5), which suggests that at least one-third of all harmful events could be

prevented if all neighbourhoods had the same socioeconomic profile as the

highest-income neighbourhoods.

INTERPRETATION: Rates of opioid-related harms increased in Ontario between 2003

and 2016, and people in lower-income neighbourhoods experienced substantially

higher rates of opioid-related harms than those in higher-income neighbourhoods.

This finding can inform planning for opioid-related public health interventions

with consideration of health equity.

Copyright 2018, Joule Inc. or its licensors.

DOI: 10.9778/cmajo.20180084

PMCID: PMC6201733

PMID: 30337473

Conflict of interest statement: Competing interests: None declared.

62. BMC Res Notes. 2018 Oct 12;11(1):724. doi: 10.1186/s13104-018-3834-3.

Factors associated with rapidly repeated acute poisoning by substances of abuse:

a prospective observational cohort study.

Vallersnes OM(1)(2), Jacobsen D(3), Ekeberg Ø(4)(5), Brekke M(6).

Author information:

(1)Department of General Practice, University of Oslo, Oslo, Norway.

o.m.vallersnes@medisin.uio.no.

(2)Oslo Accident and Emergency Outpatient Clinic, City of Oslo Health Agency,

Oslo, Norway. o.m.vallersnes@medisin.uio.no.

(3)Department of Acute Medicine, Oslo University Hospital, University of Oslo,

Oslo, Norway.

(4)Division of Mental Health and Addiction, Oslo University Hospital, Oslo,

Norway.

(5)Department of Behavioural Sciences in Medicine, University of Oslo, Oslo,

Norway.

(6)General Practice Research Unit (AFE), University of Oslo, Oslo, Norway.

OBJECTIVE: We have previously found that 9% of patients treated for acute

poisoning by substances of abuse in a primary care emergency outpatient setting

presented with a new poisoning within a week. We now identify factors associated

with rapidly repeated acute poisoning by substances of abuse.

RESULTS: In 169/1952 (9%) cases of acute poisoning by substances of abuse

included consecutively from October 2011 through September 2012 at a primary care

emergency outpatient clinic in Oslo, Norway, the patient re-presented within a

week with a new poisoning. Homeless patients were more likely to re-present,

adjusted odds ratio (AOR) 2.0 (95% confidence interval (CI) 1.3-3.2, p = 0.003),

as were self-discharging patients, AOR 1.7 (95% CI 1.2-2.4, p = 0.007), and

patients with an opioid as main toxic agent, AOR 1.5 (95% CI 1.0-2.3, p = 0.028).

There was no statistically significant association between rapid re-presentation

and severe mental illness or suicidal intention.

DOI: 10.1186/s13104-018-3834-3

PMCID: PMC6186040

PMID: 30314502 [Indexed for MEDLINE]

63. Fam Med. 2018 Oct;50(9):698-701. doi: 10.22454/FamMed.2018.757385.

Opioid Overdose Prevention in Family Medicine Clerkships: A CERA Study.

Gano L(1), Renshaw SE(1), Hernandez RH(1), Cronholm PF(2).

Author information:

(1)Department of Family Medicine, Indiana University, Indianapolis, IN.

(2)Department of Family and Community Health, University of Pennsylvania School

of Medicine, Philadelphia, PA.

BACKGROUND AND OBJECTIVES: The national opioid crisis requires medical education

to develop a proactive response centering on prevention and treatment. Primary

care providers (PCPs)-many of whom are family medicine physicians-commonly treat

patients on opiates, and write nearly 50% of opioid prescriptions. Despite

linkages between PCP opioid prescribing patterns and the associated potential for

overdose, little is known about how family medicine clerkship students are

trained to prevent opioid overdose, including training on the use of naloxone.

This study describes the presence of opioid overdose education at the national

level and barriers to inclusion. It also discusses implementation strategies

along with instructional methodology and learner evaluation.

METHODS: Data were collected as part of a cross-sectional survey administered

electronically by the Council of Academic Family Medicine Educational Research

Alliance to 139 family medicine clerkship directors.

RESULTS: A total of 99 clerkship directors (71.2% response rate) responded to the

survey. A large majority (86.4%) agreed that it is important to offer opioid

overdose prevention education in the clerkship, yet only 25.8% include this

topic. Of these, only 50.0% address naloxone use. The most common barriers to

including opioid overdose prevention education were prioritization of educational

topics (82.1%) followed by lack of available faculty with sufficient

experience/expertise (67.7%).

CONCLUSIONS: Findings point to a disparity between perceived importance of opioid

overdose prevention education and inclusion of this topic in family medicine

clerkship-level medical education. Innovative use of online education and

partnering with community resources may address barriers related to curricular

prioritization while supporting interprofessional education principles.

DOI: 10.22454/FamMed.2018.757385

PMID: 30307589 [Indexed for MEDLINE]

64. Workplace Health Saf. 2019 Jan;67(1):36-45. doi: 10.1177/2165079918796242. Epub

2018 Oct 10.

The Opioid Epidemic and the Role of the Occupational Health Nurse.

Higgins SA(1), Simons J(2).

Author information:

(1)1 NC Division of Public Health.

(2)2 Procter & Gamble.

The opioid epidemic is a national public health crisis. It began with the misuse

of commonly used prescription opioid pain relievers and has led to the increased

use of heroin and illicit fentanyl. Large-scale initiatives have begun on the

federal and state level and place an emphasis on improved opioid prescribing,

which have important implications for the workplace. Treatment of work injury may

initiate the use of prescription opioids and result in misuse and possible

overdose. Prescription drug abuse affects all aspects of society so potentially

any workplace could be affected. A multifaceted approach is needed to reduce

opioid morbidity and mortality and the occupational health nurse should be

actively involved. The intent of this article is to provide an overview of the

epidemic and its impact on health, the challenges for the workplace, and

recommended strategies for the occupational health nurse to impact the problem.

DOI: 10.1177/2165079918796242

PMID: 30305006 [Indexed for MEDLINE]

65. J Forensic Leg Med. 2018 Nov;60:35-37. doi: 10.1016/j.jflm.2018.09.007. Epub 2018

Sep 21.

Commentary. Fentanyl-related death and the underreporting risk.

D'Errico S(1).

Author information:

(1)Department of Legal Medicine, Azienda USL Toscana Nordovest, Lucca, Italy.

Electronic address: stefano.derrico@uslnordovest.toscana.it.

Novel synthetic opioid overdose deaths have been rising largely worldwide as a

result of fentanyl adulteration in the illegal drug supply. Interpretation of

post mortem analytical results concerning fentanyl can be challenging in

particular due to redistribution phenomena. Lacking of resources, infrastructures

and expertise to perform forensic toxicological investigation when an unknown

drug or complex mixture of drugs is suspected can affect failure in exactly

reporting cause in drug related death. Public safety and public health entities

are called working together to enhance the timeliness and accuracy of the

analytical characterization and toxicology testing of novel synthetic opioids.

Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All

rights reserved.

DOI: 10.1016/j.jflm.2018.09.007

PMID: 30265903 [Indexed for MEDLINE]

66. J Emerg Med. 2018 Nov;55(5):666-669. doi: 10.1016/j.jemermed.2018.07.016. Epub

2018 Sep 24.

Mucosal Injury From Calcium Oxalate Crystals Resembling Anaphylaxis and

Angioedema.

Ceretto V(1), Nacca N(2).

Author information:

(1)Department of Emergency Medicine, University of Rochester Medical Center,

Rochester, New York.

(2)Department of Emergency Medicine, University of Rochester Medical Center,

Rochester, New York; Department of Medical Toxicology, University of Rochester

Medical Center, Rochester, New York.

BACKGROUND: There are 215 families of plants that contain insoluble needle-shaped

calcium oxalate crystals on the surface of their tissues. Upon mucosal contact,

injury can cause extreme pain, soft-tissue swelling, salivation, dysphagia, and

even aphonia. This presentation can resemble angioedema or anaphylaxis.

CASE REPORT: A 55-year-old Asian female presented to the emergency department

complaining of oral pain, swelling, and numbness. Her family reported that she

began to experience sharp pain of the tongue and lips immediately after eating

"elephant root." Physical examination revealed a patient sitting in an upright

position, leaning forward with pooling secretions. She had few lingual petechiae,

a subtle diffuse erythema, and mild edema of the lower lip. Due to pain, she was

unable to speak and swallow. Her vitals remained within normal limits. The

patient was taking lisinopril for hypertension. WHY SHOULD AN EMERGENCY PHYSICIAN

BE AWARE OF THIS?: Injury by calcium oxalate crystals is a relatively common

occurrence that will present to the emergency department. Although most exposures

are benign, patients can develop critical illness, requiring emergent therapies

and airway management. Due to the nature of presentation, exposure can easily be

misdiagnosed as anaphylaxis or hereditary and drug-induced angioedema. Severe

pain and the temporal relationship to plant ingestion distinguish insoluble

calcium oxalate crystal exposure from these alternative causes of angioedema.

There is minimal evidence-based data evaluating treatment of these injuries.

Standard treatment regimen includes a local anesthetic, corticosteroids, opioids,

and antihistaminergic agents. Given the relative low cost, ease of

administration, and benign adverse effect profile, sodium bicarbonate rinse may

have a role as an adjunct therapy, however, research is needed.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jemermed.2018.07.016

PMID: 30262249 [Indexed for MEDLINE]

67. Basic Clin Pharmacol Toxicol. 2019 Mar;124(3):341-347. doi: 10.1111/bcpt.13135.

Epub 2018 Oct 31.

Extracorporeal treatments in poisonings from four non-traditionally dialysed

toxins (acetaminophen, digoxin, opioids and tricyclic antidepressants): A

combined single-centre and national study.

Campion GH(1), Wang JJ(2), Hoffman RS(1)(3)(4), Cormier M(4), Lavergne V(5),

Mowry JB(6), Roberts DM(7), Ghannoum M(5), Su MK(1)(3), Gosselin S(2)(4)(8).

Author information:

(1)NYU School of Medicine, New York, New York.

(2)McGill University, Montréal, Quebec, Canada.

(3)New York City Poison Control Center, New York, New York.

(4)Montreal Medical Toxicology Initiative, Montréal, Quebec, Canada.

(5)University of Montreal, Montréal, Quebec, Canada.

(6)Indiana Poison Center, Indianapolis, Indiana.

(7)New South Wales Poisons Information Centre, Sydney Children's Hospital

Network, Randwick, New South Wales, Australia.

(8)McGill University Health Center, Montréal, Quebec, Canada.

The use of extracorporeal treatments (ECTRs) for poisonings with four

non-traditionally dialysed toxins (NTDTs) is increasing in the United States.

This study evaluated whether ECTRs are prescribed for toxin removal or the

treatment of other medical illnesses or complications. We performed a 2-Phase

retrospective analysis evaluating the main indication for ECTRs in patients with

poisoning from a NTDT (defined for this study as acetaminophen, opioids,

tricyclic antidepressants (TCAs) or digoxin) and ECTR. The first phase assessed

all cases from a single site (New York City Poison Control Center) between the

years 2000 and 2016, and the second phase surveyed all United States Poison

Control Centers (PCCs). In Phase 1, demographics, toxin ingested and main

indication for ECTR were extracted. In Phase 2, a query to the National Poison

Data System using the a pragmatic subset of inclusion criteria from Phase 1

restricted to single toxin ingestions over a narrower time frame (2014-2016)

provided the cases for study. A structured online questionnaire was sent to all

United States PCCs to request their database review regarding the indication for

ECTR for their cases. In Phase 1, 92 cases met inclusion criteria. In Phase 2,

519 cases were screened and 425 met inclusion criteria. In Phase 1 91/92 (98.9%)

and Phase 2 411/425 (96.7%), of extracorporeal treatments were used to treat

underlying medical conditions or poisoning-related complications rather than

accelerate toxin removal. The increasing number of ECTRs reported in patients who

ingested one of the four NTDTs thus appears to be for medical indications rather

than attempts at toxin removal, a distinction that is important.

© 2018 Nordic Association for the Publication of BCPT (former Nordic

Pharmacological Society).

DOI: 10.1111/bcpt.13135

PMID: 30248244

68. Science. 2018 Sep 21;361(6408). pii: eaau1184. doi: 10.1126/science.aau1184.

Changing dynamics of the drug overdose epidemic in the United States from 1979

through 2016.

Jalal H(1), Buchanich JM(2), Roberts MS(1), Balmert LC(2)(3), Zhang K(4), Burke

DS(5).

Author information:

(1)Department of Health Policy and Management, Graduate School of Public Health,

University of Pittsburgh, Pittsburgh, PA, USA.

(2)Department of Biostatistics, Graduate School of Public Health, University of

Pittsburgh, Pittsburgh, PA, USA.

(3)Department of Preventive Medicine (Biostatistics), Feinberg School of

Medicine, Northwestern University, Chicago, IL, USA.

(4)Division of Unintentional Injury Prevention, Centers for Disease Control and

Prevention, Atlanta, GA, USA.

(5)Department of Epidemiology, Graduate School of Public Health, University of

Pittsburgh, Pittsburgh, PA, USA. donburke@pitt.edu.

Comment in

Nat Med. 2018 Nov;24(11):1637.

Better understanding of the dynamics of the current U.S. overdose epidemic may

aid in the development of more effective prevention and control strategies. We

analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital

Statistics System in which accidental drug poisoning was identified as the main

cause of death. By examining all available data on accidental poisoning deaths

back to 1979 and showing that the overall 38-year curve is exponential, we

provide evidence that the current wave of opioid overdose deaths (due to

prescription opioids, heroin, and fentanyl) may just be the latest manifestation

of a more fundamental longer-term process. The 38+ year smooth exponential curve

of total U.S. annual accidental drug poisoning deaths is a composite of multiple

distinctive subepidemics of different drugs (primarily prescription opioids,

heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with

its own specific demographic and geographic characteristics.

Copyright © 2018 The Authors, some rights reserved; exclusive licensee American

Association for the Advancement of Science. No claim to original U.S. Government

Works.

DOI: 10.1126/science.aau1184

PMID: 30237320 [Indexed for MEDLINE]

69. BMC Emerg Med. 2018 Sep 19;18(1):30. doi: 10.1186/s12873-018-0181-6.

Epidemiological and clinical profiles of acute poisoning in patients admitted to

the intensive care unit in eastern Iran (2010 to 2017).

Mehrpour O(1)(2), Akbari A(3), Jahani F(3), Amirabadizadeh A(3), Allahyari E(4),

Mansouri B(3), Ng PC(5).

Author information:

(1)Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University

of Medical Sciences, Moallem Avenue, Birjand, 9717853577, Iran.

omid.mehrpour@yahoo.com.au.

(2)Rocky Mountain Poison and Drug Center, Denver, CO, USA.

omid.mehrpour@yahoo.com.au.

(3)Medical Toxicology and Drug Abuse Research Center (MTDRC), Birjand University

of Medical Sciences, Moallem Avenue, Birjand, 9717853577, Iran.

(4)Social Determinants of Health Research Center, Birjand University of Medical

Sciences, Birjand, Iran.

(5)Rocky Mountain Poison and Drug Center, Denver, CO, USA.

BACKGROUND: Acute poisoning is a common chief complaint leading to emergency

department visits and hospital admissions in developing countries such as Iran.

Data describing the epidemiology of different poisonings, characteristics of the

clinical presentations, and the predictors of outcome are lacking. Such data can

help develop more efficient preventative and management strategies to decrease

morbidity and mortality related to these poisonings. This manuscript describes

the epidemiology of acute poisoning among patients admitted to the intensive care

unit (ICU) in Birjand, Iran.

METHODS: This retrospective, cross-sectional study was conducted to characterize

acute poisonings managed in the ICU during a 7-year period from March 2010 to

March 2017 in a single center in Birjand, Iran. Patient characteristics,

suspected exposure, the route of exposure, and outcome data were collected from

hospital medical records.

RESULTS: During the study period, 267 (64% male and 36% female) patients met

inclusion criteria. Pharmaceutical medication (36.6%), opioids (26.2%) followed

by pesticides (13.9%) were the most common exposures 38.2% of these cases were

identified as suicide attempts. There were different frequencies in terms of

xenobiotic exposure in relation to gender (p = 0.04) and the survival

(p = 0.001). There was a significant difference between various xenobiotics

identified as the cause of poisoning (p = 0.001). Mortality rate in our study was

19.5%. The incidence of outcomes was significantly higher in patients poisoned

with opioids, pesticides, benzodiazepines, and tricyclic antidepressants

(p < 0.05). The median length of hospital stay was higher in pesticide-poisoned

patients (p = 0.04).

CONCLUSION: Opioids and pesticides were the most common exposures. The mortality

rate of the poisoned patients in the ICU was proportionately high. The mortality

rate due to opioid poisoning is a major concern and the most significant cause

death due to poisoning in the region. Further monitoring and characterization of

acute poisoning in Birjand, Iran is needed. These data can help develop

educational and preventative programs to reduce these exposures and improve

management of exposures in the prehospital and hospital settings.

DOI: 10.1186/s12873-018-0181-6

PMCID: PMC6146606

PMID: 30231863 [Indexed for MEDLINE]

70. Forensic Sci Med Pathol. 2018 Dec;14(4):531-535. doi: 10.1007/s12024-018-0018-3.

Epub 2018 Sep 18.

Another fatal case related to the recreational abuse of U-47700.

Strehmel N(1), Dümpelmann D(2), Vejmelka E(2), Strehmel V(3), Roscher S(2),

Scholtis S(2), Tsokos M(2).

Author information:

(1)Governmental Institute of Legal Medicine and Forensic Sciences, Turmstraße 21,

D-10559, Berlin, Germany. nadine.theofel@germed.berlin.de.

(2)Governmental Institute of Legal Medicine and Forensic Sciences, Turmstraße 21,

D-10559, Berlin, Germany.

(3)Faculty of Chemistry, Institute for Coatings and Surface Chemistry,

Niederrhein University of Applied Sciences, Adlerstrasse 32, D-47798, Krefeld,

Germany.

The abuse of synthetic opioids has become a major threat in recent years. Several

clinical reports and fatal case reports exist discussing life-threatening

hypoventilation and fatal respiratory depression following the abuse of

trans-3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)-N-methylbenzamide (U-47700).

The reported concentration of U-47700 in peripheral blood varies between

0.01 μg/mL and 1.46 μg/mL. These values depend on the mode of administration and

whether the drug was used in combination with other drugs and/or pharmaceuticals.

In the past, U-47700 was predominantly insufflated and not injected. The current

study presents a non-targeted liquid chromatography/mass spectrometry

(LC/MS)-based screening approach of urine and cerebrospinal fluid samples after

intravenous injection of U-47700. Furthermore, quantitative values on U-47700 as

obtained by liquid chromatography coupled to a linear ion trap (LC/ESI-QTRAPMS)

are presented concerning femoral blood (0.29 μg/mL), urine (0.24 μg/mL), gastric

contents (0.57 μg/mL), bile fluid (2.3 μg/mL), heart blood (1.25 μg/mL), liver

(9.9 μg/g), cerebrospinal fluid (0.4 μg/mL), and hair (0.14 ng/mg). Thereof,

concentrations in hair, gastric contents, bile fluid and cerebrospinal fluid have

never been reported before. Drug paraphernalia were also analyzed by liquid

chromatography coupled to a diode array detector (LC/DAD) and nuclear magnetic

resonance spectrometer (NMR). The analyses show that the powder had a relatively

high purity and was adulterated to a low degree. This is the first case report

which lists concentration distributions of various specimens after intravenous

injection. These findings as well as the U-47700 concentration are important to

evaluate autopsy cases of U-47700 intoxication in the future.

DOI: 10.1007/s12024-018-0018-3

PMID: 30229428 [Indexed for MEDLINE]

71. Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):343-347. doi:

10.24095/hpcdp.38.9.07.

At-a-glance - The role of opioid toxicity in suicide deaths in Alberta, 2000 to

2016.

[Article in English, French; Abstract available in French from the publisher]

Chan EYL(1)(2), McDonald BM(1), Brooks-Lim E(3), Jones GR(3), Klein KB(4),

Svenson LW(1)(5)(6)(7).

Author information:

(1)Analytics and Performance Reporting Branch, Alberta Ministry of Health,

Edmonton, Alberta, Canada.

(2)Public Health Agency of Canada, Ottawa, Ontario, Canada.

(3)Office of the Chief Medical Examiner, Alberta Ministry of Justice and

Solicitor General, Edmonton, Alberta, Canada.

(4)Office of the Chief Medical Officer of Health, Alberta Ministry of Health,

Edmonton, Alberta, Canada.

(5)Division of Preventive Medicine, Faculty of Medicine and Dentistry, University

of Alberta, Edmonton, Alberta, Canada.

(6)School of Public Health, University of Alberta, Edmonton, Alberta, Canada.

(7)Department of Community Health Sciences, Cumming School of Medicine,

University of Calgary, Calgary, Alberta, Canada.

Given the current opioid crisis in Canada, there is interest in the role of

opioid toxicity in suicide deaths, particularly in whether any observed patterns

are similar to those of unintentional deaths. The present analysis examined

characteristics of opioid-toxicity suicide, and its role in relation to other

suicide methods, from 2000 to 2016 in Alberta. It does not appear that the opioid

crisis has resulted in a disproportionately higher number of suicides in Alberta.

Individuals who die from unintentional opioid toxicity and those who die by

opioid-toxicity suicide are likely distinct populations, requiring nuanced public

health responses for prevention.

Publisher: Dans le cadre de la crise actuelle des opioïdes au Canada, il est

important de s'intéresser au rôle joué par l’intoxication aux opioïdes dans les

décès par suicide et, plus particulièrement, de déterminer si les tendances

observées à cet égard sont similaires aux tendances observées pour les décès

accidentels. Dans cette analyse, on examine les caractéristiques du suicide par

intoxication aux opioïdes et la corrélation entre cette méthode et d’autres

moyens de suicide entre 2000 et 2016 en Alberta. La crise des opioïdes ne semble

pas avoir causé un nombre disproportionnellement élevé de suicides en Alberta.

Les personnes qui décèdent des suites d’une intoxication accidentelle aux

opioïdes et celles qui se suicident en s’intoxiquant avec des opioïdes

constituent probablement des populations différentes, ce qui nécessite des

interventions préventives nuancées en matière de santé publique.

DOI: 10.24095/hpcdp.38.9.07

PMCID: PMC6169706

PMID: 30226729 [Indexed for MEDLINE]

Conflict of interest statement: The authors have no conflicts of interest to

report.

72. Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):339-342. doi:

10.24095/hpcdp.38.9.06.

At-a-glance - What can paramedic data tell us about the opioid crisis in Canada?

[Article in English, French; Abstract available in French from the publisher]

Do MT(1)(2)(3), Furlong G(4), Rietschlin M(4), Leyenaar M(5), Nolan M(6), Poirier

P(7), Field B(8), Thompson W(1).

Author information:

(1)Public Health Agency of Canada, Ottawa, Ontario, Canada.

(2)Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario,

Canada.

(3)Department of Health Science, Carleton University, Ottawa, Ontario, Canada.

(4)Ottawa Paramedic Service, Ottawa, Ontario, Canada.

(5)McMaster University, Hamilton, Ontario, Canada.

(6)Renfrew County Paramedic Service, Renfrew, Ontario, Canada.

(7)Paramedic Association of Canada, Ottawa, Ontario, Canada.

(8)Interdev Inc., Toronto, Ontario, Canada.

The nature of Canada's opioid crisis necessitates additional data sources that

can provide a more comprehensive picture of the epidemic, in order to provide

public health officials and decision-makers with a robust evidence base.

Paramedic data provide a conduit into the community where overdoses occur.

Prehospital events and circumstances surrounding opioid-related overdoses provide

unique opportunities to collect evidence that can contribute to prevention, harm

reduction and health promotion efforts. Using data extracted from the Ottawa

Paramedic Service (OPS), this proof-of-concept study demonstrated that paramedic

response data were useful in providing near real-time epidemiological information

(person, time and place) on the opioid epidemic and in assessing trends and

opportunities to develop alert triggers. Between January and June 2017, the OPS

responded to an average of four opioid-related calls each week. On average, 0.5

mg of naloxone was administered each time. For the study period, linear trends

show a small but insignificant increase in calls (p = 0.18). A higher volume of

calls occurred between April 16 and 29, 2017. According to local media reports,

this spike in paramedic responses was due to the arrival of high-grade fentanyl

in Ottawa. With further validation, paramedic data can potentially provide a

novel data source to monitor opioid-related overdoses.

Publisher: La nature de la crise des opioïdes au Canada nécessite des sources de

données supplémentaires aptes à dresser un portrait plus fidèle de l’épidémie,

afin de fournir aux responsables en santé publique et aux décideurs une base de

données probantes solide. Les données des ambulanciers paramédicaux sont un point

d’accès aux collectivités où les surdoses surviennent. Les événements

préhospitaliers et les circonstances entourant les surdoses d’opioïdes offrent

des occasions uniques de recueillir des données probantes pouvant contribuer à la

prévention, à la réduction des méfaits et aux efforts de promotion de la santé. À

l’aide de données extraites du Service paramédic d’Ottawa (SPO), cette étude de

validation de principe a démontré que les données d’intervention ambulancière

paramédicale étaient utiles pour obtenir des renseignements épidémiologiques en

temps quasi réel (personne, heure et lieu) sur l’épidémie d’opioïdes et pour

évaluer les tendances ainsi que les possibilités d’élaborer des déclencheurs

d’alerte. Entre janvier et juin 2017, le SPO a répondu à une moyenne de quatre

appels liés aux opioïdes par semaine. À chaque fois, 0,5 mg de naloxone ont en

moyenne été administrés. Pour la période à l’étude, les tendances linéaires

montrent une faible augmentation des appels, non significative (p = 0,18). Le

volume d’appels a augmenté entre le 16 et le 29 avril 2017. Selon les médias

locaux, ce pic dans les interventions ambulancières paramédicales est attribuable

à l’arrivée de fentanyl de qualité supérieure à Ottawa. Avec une validation plus

poussée, ces données paramédicales pourraient potentiellement constituer une

nouvelle source de données pour la surveillance des surdoses liées aux opioïdes.

DOI: 10.24095/hpcdp.38.9.06

PMCID: PMC6169701

PMID: 30226728 [Indexed for MEDLINE]

73. Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):334-338. doi:

10.24095/hpcdp.38.9.05.

At-a-glance - Concurrent monitoring of opioid prescribing practices and

opioid-related deaths: the context in Nova Scotia, Canada.

[Article in English, French; Abstract available in French from the publisher]

Schleihauf E(1), Crabtree K(2), Dohoo C(3), Fleming S(4), McPeake H(2), Bowes

M(5).

Author information:

(1)Public Health Agency of Canada, Halifax, Nova Scotia, Canada.

(2)Nova Scotia Prescription Monitoring Program, Dartmouth, Nova Scotia, Canada.

(3)Public Health Agency of Canada, Ottawa, Ontario, Canada.

(4)Nova Scotia Department of Health and Wellness, Halifax, Nova Scotia, Canada.

(5)Nova Scotia Medical Examiner Service, Dartmouth, Nova Scotia, Canada.

Timely public health surveillance is required to understand trends in opioid use

and harms. Here, opioid dispensing data from the Nova Scotia Prescription

Monitoring Program are presented alongside fatality data from the Nova Scotia

Medical Examiner Service. Concurrent monitoring of trends in these data sources

is essential to detect population-level effects (whether intended or unintended)

of interventions related to opioid prescribing.

Publisher: Une surveillance en santé publique en temps opportun est nécessaire

pour comprendre les tendances associées à la consommation d’opioïdes et à ses

méfaits connexes. Cet article met en correspondance les données sur la délivrance

d’opioïdes recueillies par le Nova Scotia Prescription Monitoring Program et les

données sur les décès compilées par le Service de médecin légiste de la

Nouvelle-Écosse. La surveillance simultanée des tendances au moyen de ces sources

de données est essentielle pour détecter les effets sur la population (qu’ils

soient intentionnels ou non) des interventions liées à la prescription

d’opioïdes.

DOI: 10.24095/hpcdp.38.9.05

PMCID: PMC6169707

PMID: 30226727 [Indexed for MEDLINE]

Conflict of interest statement: All authors have no conflicts of interest to

disclose.

74. Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):328-333. doi:

10.24095/hpcdp.38.9.04.

Patterns of health care utilization among people who overdosed from illegal

drugs: a descriptive analysis using the BC Provincial Overdose Cohort.

[Article in English, French; Abstract available in French from the publisher]

Otterstatter MC(1)(2), Crabtree A(1)(2), Dobrer S(1), Kinniburgh B(3), Klar S(3),

Leamon A(4)(5), May-Hadford J(6)(7), Mill C(1)(7), Park M(1)(5), Tu AW(8), Zheng

L(9).

Author information:

(1)BC Centre for Disease Control, Vancouver, British Columbia, Canada.

(2)School of Population and Public Health, University of British Columbia,

Vancouver, British Columbia, Canada.

(3)Fraser Health Authority, Surrey, British Columbia, Canada.

(4)Island Health Authority, Victoria, British Columbia, Canada.

(5)BC Observatory for Population and Public Health, BC Centre for Disease

Control, Vancouver, British Columbia, Canada.

(6)First Nations Health Authority, Vancouver, British Columbia, Canada.

(7)Public Health Agency of Canada, Ottawa, Ontario, Canada.

(8)BC Coroners Service, Burnaby, British Columbia, Canada.

(9)BC Emergency Health Services, Victoria, British Columbia, Canada.

INTRODUCTION: British Columbia (BC) declared a public health emergency in April

2016 in response to a rapid rise in overdose deaths. Further understanding of

health care utilization is needed to inform prevention strategies for individuals

who overdose from illegal drugs.

METHODS: The Provincial Overdose Cohort includes linked administrative data on

health care utilization by individuals who experienced an illegal drug overdose

event in BC between 1 January 2015 and 30 November 2016. Overdose cases were

identified using data from ambulance services, coroners' investigations, poison

control centre calls and hospital, emergency department and physician

administrative records. In total, 10 455 overdose cases were identified and

compared with 52 275 controls matched on age, sex and area of residence for a

descriptive analysis of health care utilization.

RESULTS: Two-thirds (66%) of overdose cases were male and about half (49%) were

20-39 years old. Over half of the cases (54%) visited the emergency department

and about one-quarter (26%) were admitted to hospital in the year before the

overdose event, compared with 17% and 9% of controls, respectively. Nevertheless,

nearly onefifth (19%) of cases were recorded leaving the emergency department

without being seen or against medical advice. High proportions of both cases

(75%) and controls (72%) visited community-based physicians. Substance use and

mental health-related concerns were the most common diagnoses among people who

went on to overdose.

CONCLUSION: People who overdosed frequently accessed the health care system in

the year before the overdose event. In light of the high rates of health care

use, there may be opportunities to identify at-risk individuals before they

overdose and connect them with targeted programs and evidence-based

interventions. Further work using the BC Provincial Overdose Cohort will focus on

identifying risk factors for overdose events and death by overdose.

Publisher: La Colombie-Britannique (C.-B.) a déclaré un état d'urgence en santé

publique en avril 2016 en réaction à une augmentation rapide du nombre de décès

par surdose. Une meilleure compréhension de l'utilisation des soins de santé est

nécessaire pour guider les stratégies de prévention pour les personnes qui font

une surdose de drogues illicites.La cohorte provinciale des victimes de surdoses

comprend des données administratives couplées sur l'utilisation des soins de

santé par les personnes qui ont été victimes d'une surdose de drogues illicites

en Colombie-Britannique entre le 1er janvier 2015 et le 30 novembre 2016. Les cas

de surdose ont été relevés à l'aide de données provenant des services

ambulanciers, des enquêtes des coroners, des appels aux centres antipoison et des

dossiers administratifs des hôpitaux, des services d'urgence et des médecins. Au

total, 10 455 cas de surdose ont été recensés et comparés à 52 275 témoins

appariés selon l'âge, le sexe et la zone de résidence en vue d'une analyse

descriptive de l'utilisation des soins de santé.Les deux tiers (66 %) des cas de

surdose concernaient des hommes, et environ la moitié (49 %) les 20 à 39 ans.

Plus de la moitié des cas (54 %) se sont rendus au service d'urgence, et environ

le quart (26 %) ont été admis à l'hôpital au cours de l'année précédant la

surdose, comparativement à respectivement 17 % et 9 % des témoins. Cependant,

près d'un cinquième (19 %) des cas ont été enregistrés comme ayant quitté le

service d'urgence sans avoir été vus par le médecin ou contre son avis. Des

proportions élevées de cas (75 %) et de témoins (72 %) ont consulté un médecin en

milieu communautaire. La consommation de substances et des problèmes en santé

mentale ont été les diagnostics les plus courants chez les personnes qui ont fait

une surdose.Les personnes qui ont fait une surdose ont souvent eu accès au

système de soins de santé au cours de l'année précédant la surdose. Compte tenu

de ces taux élevés d'utilisation des soins de santé, on pourrait peut-être

repérer les personnes à risque avant qu'elles ne fassent de surdose et les

aiguiller vers des programmes ciblés et des interventions fondées sur des données

probantes. Il est prévu d'utiliser la cohorte provinciale des victimes de

surdoses de la Colombie-Britannique pour déterminer les facteurs de risque

relatifs aux surdoses et aux décès par surdose.

DOI: 10.24095/hpcdp.38.9.04

PMCID: PMC6169704

PMID: 30226726 [Indexed for MEDLINE]

Conflict of interest statement: The authors have no conflicts of interest to

declare.

75. Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):317-327. doi:

10.24095/hpcdp.38.9.03.

Sentinel surveillance of suspected opioid-related poisonings and injuries: trends

and context derived from the electronic Canadian Hospitals Injury Reporting and

Prevention Program, March 2011 to June 2017.

[Article in English, French; Abstract available in French from the publisher]

Do MT(1)(2)(3), Chang VC(1)(2), Tibebu S(1)(2), Thompson W(1), Ugnat AM(1).

Author information:

(1)Public Health Agency of Canada, Ottawa, Ontario, Canada.

(2)Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario,

Canada.

(3)Department of Health Sciences, Carleton University, Ottawa, Ontario, Canada.

INTRODUCTION: The opioid epidemic is currently a major public health problem in

Canada. As such, knowledge of upstream risk factors associated with opioid use is

needed to inform injury prevention, health promotion and harm reduction efforts.

METHODS: We analyzed data extracted from 11 pediatric and 6 general hospital

emergency departments (EDs) as part of the electronic Canadian Hospitals Injury

Reporting and Prevention Program (eCHIRPP) from March 2011 to June 2017. We

identified suspected opioid-related injuries using search strings and manually

verified them. We computed age-adjusted and sex-stratified proportionate injury

ratios (PIRs) and 95% confidence intervals (CIs) to compare opioid-related

injuries to all injuries in eCHIRPP. Negative binomial regression was used to

determine trends over time. We conducted qualitative analyses of narratives to

identify common themes across life stages.

RESULTS: Between March 2011 and June 2017, 583 suspected opioid-related

poisoning/ injury cases were identified from eCHIRPP. Most of the cases were

females (55%). Many of the injuries occurred in patients' own homes (51%).

Forty-five percent of the injuries were intentional self-harm. Among children

(aged 1-9 years), most injuries were caused by inadvertent consumption of opioids

left unattended. Among youth (aged 10-19 years) and adults (aged 20-49 years),

opioid use was associated with underlying mental illness. Overall, the average

annual percent change (AAPC) in the rate of injuries (per 100 000 eCHIRPP cases)

has been increasing since 2012 (AAPC = 11.9%, p < .05). The increase is

particularly evident for males (AAPC = 16.3%, p < .05). Compared to other

injuries, people with suspected opioid-related injuries were more likely to be

admitted to hospital (PIR = 5.3, 95% CI: 4.6-6.2).

CONCLUSION: The upstream determinants of opioid-related injuries are complex and

likely vary by subpopulations. Therefore, continued monitoring of risk factors is

important in providing the evidence necessary to prevent future overdoses and

deaths.

Publisher: La crise actuelle des opioïdes est un problème de santé publique

majeur au Canada. Il est nécessaire de connaître les facteurs de risque en amont

associés à la consommation d’opioïdes pour éclairer les efforts de prévention des

blessures, de promotion de la santé et de réduction des méfaits.Nous avons

analysé les données sur les blessures subies par des personnes traitées dans les

services d’urgence (SU) de onze hôpitaux pédiatriques et de six hôpitaux généraux

au Canada et recueillies par le Système canadien hospitalier d’information et de

recherche en prévention des traumatismes en ligne (SCHIRPTe) entre mars 2011 et

juin 2017. Nous avons identifié les blessures apparemment liées aux opioïdes au

moyen de chaînes de recherche et nous les avons vérifiées manuellement. Nous

avons calculé des rapports proportionnels de blessures (RPB) en fonction de l’âge

et du sexe ainsi que des intervalles de confiance à 95 % pour comparer les

blessures liées à la consommation d’opioïdes à l'ensemble des blessures figurant

dans le SCHIRPTe. Une régression binomiale négative a été utilisée pour

déterminer les tendances au fil du temps. Nous avons effectué des analyses

qualitatives des informations descriptives afin d'en dégager les thèmes communs

spécifiques à chaque étape de vie.Nous avons identifié 583 cas d'intoxications ou

de blessures apparemment liées aux opioïdes dans le SCHIRPTe pour la période

allant de mars 2011 à juin 2017. La majorité concernaient des femmes (55 %) et

sont survenues au domicile des patients (51 %). Quarante-cinq pour cent des

blessures étaient des automutilations intentionnelles. Chez les enfants (1 à 9

ans), la plupart des blessures ont été causées par une consommation accidentelle

d’opioïdes laissés sans surveillance. Chez les jeunes (10 à 19 ans) et les

adultes (20 à 49 ans), la consommation d’opioïdes était associée à une maladie

mentale sous-jacente. Dans l’ensemble, on observe une augmentation de la

variation annuelle moyenne en pourcentage (VAMP) du taux de blessures (pour 100

000 cas dans le SCHIRPTe) depuis 2012 (VAMP = 11,9 %, p < 0,05), particulièrement

marquée chez les hommes (VAMP = 16,3 %, p < 0,05). Les personnes victimes de

blessures apparemment liées à la consommation d’opioïdes étaient plus

susceptibles d’être admises à l’hôpital que les personnes victimes d'autres types

de blessure (RPB = 5,3, IC à 95 % : 4,6 à 6,2).Les déterminants en amont des

blessures liées à l’utilisation d’opioïdes sont complexes et varient probablement

selon les sous-populations. La surveillance continue des facteurs de risque est

donc importante afin d'obtenir les données probantes nécessaires à la prévention

d’autres surdoses et décès.

DOI: 10.24095/hpcdp.38.9.03

PMCID: PMC6169700

PMID: 30226725 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflicts of interest.

76. Prev Med. 2018 Nov;116:112-118. doi: 10.1016/j.ypmed.2018.09.001. Epub 2018 Sep

11.

Correlations between population-levels of prescription opioid dispensing and

related deaths in Ontario (Canada), 2005-2016.

Fischer B(1), Jones W(2), Varatharajan T(3), Malta M(4), Kurdyak P(5).

Author information:

(1)Institute for Mental Health Policy Research, Centre for Addiction and Mental

Health (CAMH), Toronto, Canada; Department of Psychiatry, University of Toronto,

Toronto, Canada; Institute of Medical Science (IMS), University of Toronto,

Toronto, Canada; Centre for Criminology & Sociolegal Studies, University of

Toronto, Toronto, Canada; Department of Psychiatry, Federal University of São

Paulo, São Paulo, Brazil. Electronic address: benedikt.fischer@utoronto.ca.

(2)Centre for Applied Research in Mental Health and Addictions, Faculty of Health

Sciences, Simon Fraser University, Vancouver, Canada.

(3)Institute for Mental Health Policy Research, Centre for Addiction and Mental

Health (CAMH), Toronto, Canada.

(4)Institute for Mental Health Policy Research, Centre for Addiction and Mental

Health (CAMH), Toronto, Canada; Department of Psychiatry, University of Toronto,

Toronto, Canada.

(5)Institute for Mental Health Policy Research, Centre for Addiction and Mental

Health (CAMH), Toronto, Canada; Department of Psychiatry, University of Toronto,

Toronto, Canada; Mental Health & Addictions Research Program, Institute for

Clinical Evaluative Sciences, Toronto, Canada.

Canada is experiencing an ongoing opioid-related public health crisis, including

persistently rising opioid (e.g., poisoning) mortality. Previous research has

documented marked correlations between population-levels of opioid dispensing and

deaths. We examined possible correlations between annual population-level

dispensing of specific opioid formulations and related poisoning deaths in

Ontario (Canada), for the period 2005-2016. Annual coroner statistics-based

numbers of poisoning deaths associated with six main opioid formulations

(codeine, fentanyl, hydromorphone, methadone, morphine, and oxycodone) for

Ontario were converted into annual death rates (per 100,000 population). Annual

dispensing data for the opioid formulations under study were based on commercial

retail-sales data from a representative, stratified sample of community

pharmacies (IMSQuintiles/IQVIA CompuScript), converted into Defined Daily Doses

(DDD/1,000 population/day). Possible relationships between the annual death and

dispensing rates were assessed by Pearson's correlation coefficient analyses.

Death rates increased for almost all, while dispensing rates increased for half

of the opioid categories. A significant positive correlation between death and

dispensing rates was found for hydromorphone (r = 0.97, 95% CI: 0.88-0.99) and

oxycodone (r = 0.90, 95% CI: 0.68-0.97) formulations; a significant negative

correlation was found for codeine (r = -0.78, 95% CI: -0.93 to -0.37). No

significant correlations were detected for fentanyl, methadone, and morphine

related deaths. Strong correlations between levels of dispensing and deaths for

select opioid formulations were found. For select others, extrinsic factors -

e.g., increasing involvement of non-medical opioid products (e.g., fentanyl) in

overdose deaths - likely confounded underlying correlation effects. Opioid

dispensing levels continue to influence population-level mortality levels, and

need to be addressed by prevention strategies.

Copyright © 2018. Published by Elsevier Inc.

DOI: 10.1016/j.ypmed.2018.09.001

PMID: 30217407

77. Br J Gen Pract. 2018 Oct;68(675):e703-e710. doi: 10.3399/bjgp18X698897. Epub 2018

Sep 10.

Poisoning substances taken by young people: a population-based cohort study.

Tyrrell EG(1), Kendrick D(1), Sayal K(2), Orton E(3).

Author information:

(1)Division of Primary Care.

(2)Division of Psychiatry & Applied Psychiatry.

(3)Division of Primary Care, School of Medicine, University of Nottingham,

Nottingham.

BACKGROUND: Globally, poisonings account for most medically-attended self-harm.

Recent data on poisoning substances are lacking, but are needed to inform

self-harm prevention.

AIM: To assess poisoning substance patterns and trends among 10-24-year-olds

across England DESIGN AND SETTING: Open cohort study of 1 736 527 young people,

using linked Clinical Practice Research Datalink, Hospital Episode Statistics,

and Office for National Statistics mortality data, from 1998 to 2014.

METHOD: Poisoning substances were identified by ICD-10 or Read Codes. Incidence

rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning

substances by age, sex, index of multiple deprivation, and calendar year.

RESULTS: In total, 40 333 poisoning episodes were identified, with 57.8%

specifying the substances involved. The most common substances were paracetamol

(39.8%), alcohol (32.7%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.6%),

antidepressants (10.2%), and opioids (7.6%). Poisoning rates were highest at ages

16-18 years for females and 19-24 years for males. Opioid poisonings increased

fivefold from 1998-2014 (females: aIRR 5.30, 95% confidence interval (CI) = 4.08

to 6.89; males: aIRR 5.11, 95% CI = 3.37 to 7.76), antidepressant poisonings

three-to fourfold (females: aIRR 3.91, 95% CI = 3.18 to 4.80, males: aIRR 2.70,

95% CI = 2.04 to 3.58), aspirin/NSAID poisonings threefold (females: aIRR 2.84,

95% CI = 2.40 to 3.36, males: aIRR 2.76, 95% CI = 2.05 to 3.72) and paracetamol

poisonings threefold in females (aIRR 2.87, 95% CI = 2.58 to 3.20). Across all

substances poisoning incidence was higher in more disadvantaged groups, with the

strongest gradient for opioid poisonings among males (aIRR 3.46, 95% CI = 2.24 to

5.36).

CONCLUSION: It is important that GPs raise awareness with families of the

substances young people use to self-harm, especially the common use of

over-the-counter medications. Quantities of medication prescribed to young people

at risk of self-harm and their families should be limited, particularly

analgesics and antidepressants.

© British Journal of General Practice 2018.

DOI: 10.3399/bjgp18X698897

PMCID: PMC6145981

PMID: 30201829

78. Harm Reduct J. 2018 Sep 10;15(1):46. doi: 10.1186/s12954-018-0252-8.

Evaluation of a fentanyl drug checking service for clients of a supervised

injection facility, Vancouver, Canada.

Karamouzian M(1)(2)(3), Dohoo C(4), Forsting S(5), McNeil R(1)(6), Kerr T(1)(6),

Lysyshyn M(7)(8).

Author information:

(1)British Columbia Centre for Excellence in HIV/AIDS, St. Paul's Hospital,

608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.

(2)School of Population and Public Health, University of British Columbia, 5804

Fairview Avenue, Vancouver, BC, V6T 1Z3, Canada.

(3)HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV

Surveillance, Institute for Futures Studies in Health, Kerman University of

Medical Sciences, Kerman, 7616913555, Iran.

(4)Public Health Agency of Canada, Ottawa, ON, K1A 0K9, Canada.

(5)Vancouver Coastal Health Authority, Vancouver, BC, V5Z 4C2, Canada.

(6)Department of Medicine, University of British Columbia, St. Paul's Hospital,

608-1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada.

(7)School of Population and Public Health, University of British Columbia, 5804

Fairview Avenue, Vancouver, BC, V6T 1Z3, Canada. mark.lysyshyn@vch.ca.

(8)Vancouver Coastal Health Authority, Vancouver, BC, V5Z 4C2, Canada.

mark.lysyshyn@vch.ca.

BACKGROUND: British Columbia, Canada, is experiencing a public health emergency

related to opioid overdoses driven by consumption of street drugs contaminated

with illicitly manufactured fentanyl. This cross-sectional study evaluates a drug

checking intervention for the clients of a supervised injection facility (SIF) in

Vancouver.

METHODS: Insite is a facility offering supervised injection services in

Vancouver's Downtown East Side, a community with high levels of injection drug

use and associated harms, including overdose deaths. During July 7, 2016, to June

21, 2017, Insite clients were offered an opportunity to check their drugs for

fentanyl using a test strip designed to test urine for fentanyl. Results of the

drug check were recorded along with information including the substance checked,

whether the client intended to dispose of the drug or reduce the dose and whether

they experienced an overdose. Logistic regression models were constructed to

assess the associations between drug checking results and dose reduction or drug

disposal. Crude odds ratios (OR) and 95% confidence intervals (CI) were reported.

RESULTS: About 1% of the visits to Insite during the study resulted in a drug

check. Out of 1411 drug checks conducted by clients, 1121 (79.8%) were positive

for fentanyl. Although most tests were conducted post-consumption, following a

positive pre-consumption drug check, 36.3% (n = 142) of participants reported

planning to reduce their drug dose while only 11.4% (n = 50) planned to dispose

of their drug. While the odds of intended dose reduction among those with a

positive drug check was significantly higher than those with a negative result

(OR = 9.36; 95% CI 4.25-20.65), no association was observed between drug check

results and intended drug disposal (OR = 1.60; 95% CI 0.79-3.26). Among all

participants, intended dose reduction was associated with significantly lower

odds of overdose (OR = 0.41; 95% CI 0.18-0.89).

CONCLUSIONS: Although only a small proportion of visits resulted in a drug check,

a high proportion (~ 80%) of the drugs checked were contaminated with fentanyl.

Drug checking at harm reduction facilities such as SIFs might be a feasible

intervention that could contribute to preventing overdoses in the context of the

current overdose emergency.

DOI: 10.1186/s12954-018-0252-8

PMCID: PMC6131768

PMID: 30200991 [Indexed for MEDLINE]

79. Am J Forensic Med Pathol. 2018 Dec;39(4):364-366. doi:

10.1097/PAF.0000000000000431.

Postmortem Hyperthermia: Two Case Reports and a Review of the Literature.

Angélique F, Guillaume G, Nicolas G, Jean Sébastien R(1), Laurent M.

Author information:

(1)Institut de médecine légale de Strasbourg, Université de Strasbourg,

Strasbourg, France.

In this daily practice, the forensic pathologist is rarely confronted with

postmortem hyperthermia associated with the rapid onset of rigor mortis. We

report 2 similar cases where the rectal temperature value taken during the

on-scene investigations by the forensic pathologist was greater than 40°C (104°F)

in both cases, and rigor mortis was complete within less than 6 hours postmortem.

The first case was due to a deadly intoxication by ecstasy and the second one to

the deadly association of methadone and a possible neuroleptic malignant

syndrome. Infection-related deaths were eliminated. Thus, the association of

postmortem hyperthermia and rapid-onset rigor mortis would suggest in the first

hypothesis a toxic death, particularly 3,4-methylenedioxymethamphetamine.

However, an autopsy and toxicological analysis are necessary to confirm the cause

of death.

DOI: 10.1097/PAF.0000000000000431

PMID: 30198916 [Indexed for MEDLINE]

80. Handb Exp Pharmacol. 2018;252:3-49. doi: 10.1007/164_2018_160.

Responding to New Psychoactive Substances in the European Union: Early Warning,

Risk Assessment, and Control Measures.

Evans-Brown M(1), Sedefov R(2).

Author information:

(1)European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal.

michael.evans-brown@emcdda.europa.eu.

(2)European Monitoring Centre for Drugs and Drug Addiction, Lisbon, Portugal.

New psychoactive substances (NPS) are drugs that are not controlled by the United

Nations international drug control conventions of 1961 and 1971 but that may pose

similar threats to public health. Many of them are traded as "legal" replacements

to controlled drugs such as cannabis, heroin, benzodiazepines, cocaine,

amphetamines, and 3,4-methylenedioxymethamphetamine (MDMA). Driven by

globalization, there has been a large increase in the availability and,

subsequently, harms caused by these substances over the last decade in Europe.

The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is

monitoring more than 670 NPS that have appeared on Europe's drug market in the

last 20 years, of which almost 90% have appeared in the last decade. While some

recent policy responses have been successful in reducing availability and sales

of these substances in some settings - such as "legal highs" and "research

chemicals" sold openly in the high street and online - and there are signs that

growth in the market is slowing, new challenges have emerged. This includes

monitoring a growing number of highly potent substances - including 179 synthetic

cannabinoid receptor agonists and 28 fentanils - that can pose a high risk of

life-threatening poisoning to users and can cause explosive outbreaks. This

chapter briefly traces the origins of NPS, provides an overview of the situation

in Europe, and discusses the work of the EMCDDA as part of a legal framework of

early warning, risk assessment, and control measures that allows the European

Union to rapidly detect, assess, and respond to public health and social threats

caused by these substances.

DOI: 10.1007/164_2018_160

PMID: 30194542 [Indexed for MEDLINE]

81. R I Med J (2013). 2018 Sep 4;101(7):25-30.

State Unintentional Drug Overdose Reporting Surveillance: Opioid Overdose Deaths

and Characteristics in Rhode Island.

Jiang Y(1), McDonald JV(2), Goldschmidt A(3), Koziol J(4), McCormick M(5),

Viner-Brown S(6), Alexander-Scott N(7).

Author information:

(1)Senior Public Health Epidemiologist in the Center for Health Data and Analysis

at the Rhode Island Department of Health, and Assistant Professor of the Practice

of Epidemiology, School of Public Health, Brown University.

(2)Medical Director of the Division of Customer Services, Division of Policy,

Information and Communications, and of the Drug Overdose Prevention Program, as

well as Chief Administrative Officer of the Board of Medical Licensure and

Discipline, Board Certified Pediatrics and Preventive Medicine, at the Rhode

Island Department of Health.

(3)Assistant Medical Examiner of the Rhode Island Center for the Office of State

Medical Examiners at the Rhode Island Department of Health and Clinical Assistant

Professor of Pathology and Laboratory Medicine at Brown University.

(4)Program Manager of the Drug Overdose Prevention Program in the Center for

Health Promotion, Division of Community Health and Equity, Rhode Island

Department of Healt.

(5)Public Health Epidemiologist of the Drug Overdose Prevention Program in the

Center for Health Promotion, Division of Community Health and Equity, Rhode

Island Department of Health.

(6)Chief of the Center for Health Data and Analysis at the Rhode Island

Department of Health.

(7)Director of the Rhode Island Department of Health; Associate Professor of

Pediatrics and Medicine, Alpert Medical School of Brown University and Associate

Professor of Health Services, Policy and Practice, School of Public Health, Brown

University.

Unintentional opioid overdoses are a growing public health epidemic in the United

States. Rhode Island is also faced with a challenging crisis of drug overdose

deaths. The State Unintentional Drug Overdose Reporting Surveillance (SUDORS)

data from the second half of 2016 were used to present opioid overdose deaths and

characteristics in Rhode Island. During July-December 2016, 142 individuals died

of opioid overdose in Rhode Island. People who died by opioid overdose were more

likely to be 25-65 years old, male, and non-Hispanic white. The most common

precipitating circumstances were substance abuse (88%), current mental health

problems (43%), and physical health problems (27.5%). Over 83% of decedents had 2

or more substances attribute to causing their death, with fentanyl (71.1%) as the

most common substance. Only 36.6% of decedents had naloxone administered. Fatal

opioid overdose data are important for understanding this public health crisis

and can guide overdose intervention efforts.

PMID: 30189700 [Indexed for MEDLINE]

82. J Addict Nurs. 2018 Jul/Sep;29(3):188-195. doi: 10.1097/JAN.0000000000000235.

Evaluation of an Opiate Overdose Educational Intervention and Naloxone

Prescribing Program in Homeless Adults Who Use Opiates.

Pietrusza LM(1), Puskar KR, Ren D, Mitchell AM.

Author information:

(1)Lisa M. Pietrusza, BSN, RN, Kathryn R. Puskar, DrPH, RN, Dianxu Ren, MD, PhD,

and Ann M. Mitchell, PhD, RN, AHN-BC, FIANN, FAAN, University of Pittsburgh

School of Nursing, Pennsylvania.

Opiate overdose deaths are considered an epidemic by the Centers for Disease

Control and Prevention. Homeless adults are disproportionately affected by opioid

overdoses. The purpose of this project was to implement an opiate overdose

training and routine naloxone prescribing program for patients at a Health Care

for the Homeless clinic. Education consisted of overdose risk factors, signs of

overdose, how to respond to an opiate overdose, and how to administer naloxone.

Knowledge was measured with a pretest and a posttest. Intranasal naloxone was

prescribed for each person who received the education, and prescription fill

rates were tracked 1 week after the clinic visit. Patients had a significant

increase in knowledge, and the overall naloxone fill rate was 33%. Fill rates

varied by housing, insurance, and other prescription status. Opiate overdose

education can effectively be delivered in a homeless medical clinic, although

more research is needed regarding barriers to naloxone fill rates.

DOI: 10.1097/JAN.0000000000000235

PMID: 30180005 [Indexed for MEDLINE]

83. J Addict Nurs. 2018 Jul/Sep;29(3):157-162. doi: 10.1097/JAN.0000000000000231.

Opioid Overdose and Naloxone Kit Distribution: A Quality Assurance Educational

Program in the Primary Care Setting.

Lockett TL(1), Hickman KL, Fils-Guerrier BJ, Lomonaco M, Maye JP, Rossiter AG.

Author information:

(1)Tiffany L. Lockett, DNP, ARNP, AGNP-C, Kim L. Hickman, DNP, ARNP, PMHNP-BC,

Bernoune J. Fils-Guerrier, DNP, ARNP, FNP-BC, NP-C, Michael Lomonaco, DNP, FNP-C,

ARNP, CEN, John P. Maye, PhD, CRNA, and Alicia Gill Rossiter, DNP, ARNP, FNP,

PCPNP-BC, FAANP, College of Nursing, University of South Florida, Tampa.

PROBLEM: In 2014, there were approximately 200,000 incidents of an unintentional

opioid overdose nationwide. The 2016 Centers for Disease Control and Prevention

opioid prescription guidelines identified a knowledge deficit regarding opioid

prescribing among primary care providers as a contributing factor to this

epidemic.

PURPOSE: The purpose of this quality assurance project was to provide education

on opioid overdose and distribution of naloxone kits through a presentation to

primary care providers at Veterans Administration facilities in the southeast

region of the United States.

METHODS: A convenience sampling strategy was utilized for this project. Primary

care providers who prescribe opioids or care for patients at risk of an

opioid-related event or death were invited to participate. A Likert scale survey

was used to determine the effectiveness of the presentation.

RESULTS: The results of the survey showed a potential for improving medical

providers' perceptions and comfort with prescribing naloxone kits. The mean score

at pretest was 32 of 50 (64%) in contrast to 42 of 50 (84%) after attending the

presentation. Attending this quality assurance presentation was related to an

increased awareness of naloxone kit availability and Centers for Disease Control

and Prevention recommendations regarding the safe administration of opioids.

CONCLUSION: This educational presentation can assist providers in identifying

patients who are prescribed opioids and at risk for accidental overdose and

death.

DOI: 10.1097/JAN.0000000000000231

PMID: 30180000 [Indexed for MEDLINE]

84. Forensic Sci Int. 2018 Oct;291:76-82. doi: 10.1016/j.forsciint.2018.08.010. Epub

2018 Aug 17.

High buprenorphine-related mortality is persistent in Finland.

Kriikku P(1), Häkkinen M(2), Ojanperä I(3).

Author information:

(1)Forensic Toxicology Unit, National Institute for Health and Welfare, P.O.Box

30, 00271 Helsinki, Finland; Department of Forensic Medicine, University of

Helsinki, Finland. Electronic address: pirkko.kriikku@thl.fi.

(2)A-Clinic Foundation, Addiction Hospital, Finland.

(3)Forensic Toxicology Unit, National Institute for Health and Welfare, P.O.Box

30, 00271 Helsinki, Finland; Department of Forensic Medicine, University of

Helsinki, Finland.

Sublingual buprenorphine is used in opioid maintenance treatment but

buprenorphine is also widely abused and causes fatal poisonings. The aim of this

study was to investigate buprenorphine-positive fatalities in order to gain novel

information on the magnitude and nature of buprenorphine abuse. All post-mortem

toxicology cases positive for urinary buprenorphine, including fatal poisonings

caused by buprenorphine and fatalities in which the cause of death was unrelated

to buprenorphine, in the five year period of 2010-2014 in Finland were

characterized according to urine buprenorphine and naloxone concentrations

(n=775). Urine concentrations were used to assess which buprenorphine preparation

had been used; mono-buprenorphine or a buprenorphine-naloxone combination, and

whether they had been administered parenterally. In at least 28.8% of the

buprenorphine-positive cases the drug had been administered parenterally. The

majority of the parenteral users (68.6%) had taken mono-buprenorphine. Fatal

poisoning was significantly more common among the identified parenteral users

(65.5%) than among other users of buprenorphine products (45.3%). The proportion

of buprenorphine-related poisoning was similar in identified parenteral users of

mono-buprenorphine (68.6%) and buprenorphine-naloxone (64.1%). In nearly all of

the fatal poisoningss the deceased had used other drugs and/or alcohol along with

buprenorphine (98.7%). The median age of the deceased increased significantly

over the study period, from 32 to 38 years. Our results show that there is

ongoing parenteral abuse of both mono-buprenorphine and buprenorphine-naloxone

combination. Parenteral users of buprenorphine put themselves into a great risk

of fatal poisoning or other accidental injury death which is further exacerbated

by the frequent poly-drug use.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2018.08.010

PMID: 30170272 [Indexed for MEDLINE]

85. MMWR Morb Mortal Wkly Rep. 2018 Aug 31;67(34):945-951. doi:

10.15585/mmwr.mm6734a2.

Opportunities to Prevent Overdose Deaths Involving Prescription and Illicit

Opioids, 11 States, July 2016-June 2017.

Mattson CL, O'Donnell J, Kariisa M, Seth P, Scholl L, Gladden RM.

In 2016, 63,632 drug overdose deaths occurred in the United States, 42,249

(66.4%) of which involved opioids (1). The development of prevention programs are

hampered by a lack of timely data on specific substances contributing to and

circumstances associated with fatal overdoses. This report describes opioid

overdose deaths (referred to as opioid deaths) for decedents testing positive for

prescription opioids (e.g., oxycodone and hydrocodone), illicit opioids (e.g.,

heroin, illicitly manufactured fentanyl, and fentanyl analogs), or both

prescription and illicit opioids, and describes circumstances surrounding the

overdoses, in 11 states participating in CDC's Enhanced State Opioid Overdose

Surveillance (ESOOS) program.* During July 2016-June 2017, among 11,884 opioid

overdose deaths, 17.4% of decedents tested positive for prescription opioids

only, 58.7% for illicit opioids only, and 18.5% for both prescription and illicit

opioids (type of opioid could not be classified in 649 [5.5%] deaths).

Approximately one in 10 decedents had been released from an institutional setting

in the month preceding the fatal overdose. Bystanders were reportedly present in

approximately 40% of deaths; however, naloxone was rarely administered by a

layperson. Enhanced surveillance data from 11 states provided more complete

information on the substances involved in and circumstances surrounding opioid

overdose deaths. Consistent with other emerging evidence and recommendations,†

these data suggest prevention efforts should prioritize naloxone distribution to

persons misusing opioids or using high dosage prescription opioids and to their

family members and friends. In addition, these data suggest a need to expand

treatment and support for persons who have experienced a nonfatal overdose and to

expand treatment in detention facilities and upon release.

DOI: 10.15585/mmwr.mm6734a2

PMCID: PMC6124818

PMID: 30161105 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed

86. MMWR Morb Mortal Wkly Rep. 2018 Aug 24;67(33):925-930. doi:

10.15585/mmwr.mm6733a3.

Occupational Patterns in Unintentional and Undetermined Drug-Involved and

Opioid-Involved Overdose Deaths - United States, 2007-2012.

Harduar Morano L, Steege AL, Luckhaupt SE.

The opioid epidemic affects multiple segments of the U.S. population (1).

Occupational patterns might be critical to understanding the epidemic. Opioids

are often prescribed for specific types of work-related injuries, which vary by

occupation* (2). CDC used mortality data from the National Occupational Mortality

Surveillance (NOMS) system to examine unintentional or undetermined drug overdose

mortality within 26 occupation groups. This study included data from the 21 U.S.

states participating in NOMS during 2007-2012.† Drug overdose mortality was

compared with total mortality using proportional mortality ratios (PMRs)

indirectly standardized for age, sex, race, year, and state. Mortality patterns

specific to opioid-related overdose deaths were also assessed. Construction

occupations had the highest PMRs for drug overdose deaths and for both

heroin-related and prescription opioid-related overdose deaths. The occupation

groups with the highest PMRs from methadone, natural and semisynthetic opioids,

and synthetic opioids other than methadone were construction, extraction (e.g.,

mining, oil and gas extraction), and health care practitioners. The workplace is

an integral part of life for the majority of the adult U.S. population;

incorporating workplace research and interventions likely will benefit the opioid

epidemic response.

DOI: 10.15585/mmwr.mm6733a3

PMCID: PMC6107320

PMID: 30138306 [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed and submitted the

ICMJE form for disclosure of potential conflicts of interest. No potential

conflicts of interest were disclosed.

87. Handb Exp Pharmacol. 2018;252:461-473. doi: 10.1007/164_2018_134.

Epidemiology of NPS Based Confirmed Overdose Cases: The STRIDA Project.

Helander A(1), Bäckberg M(2).

Author information:

(1)Karolinska Institutet and Karolinska University Laboratory, Stockholm, Sweden.

anders.helander@ki.se.

(2)Swedish Poisons Information Centre, Stockholm, Sweden. mat.backberg@gmail.com.

The Swedish STRIDA project on new psychoactive substances (NPS) monitored the

occurrence and health hazards of novel recreational drugs in Sweden through

evaluation of analytically confirmed adverse events presenting in emergency

departments and intensive care units. During a ~6-year period from 2010 to early

2016, about 2,600 cases of suspected NPS intoxications were included in the

project. About 75% of patients were men and the total age range was 8-71 (median

24) years and 57% were 25 years or younger. A large number of NPS belonging to

many different drug classes were identified in project samples of urine and blood

(serum/plasma) submitted for free drug testing, including synthetic cannabinoid

receptor agonists, stimulants, cathinones, hallucinogens, dissociative drugs,

benzodiazepines, and opioids, and also in drug materials from the cases forwarded

to the laboratory along with the biological samples. The STRIDA project has been

shown to serve as an effective early warning system for NPS by collecting data on

incidence, distribution, and adverse effects and has supported healthcare

professionals in the knowledge and critical care of intoxications caused by a

wide range of novel substances. The results of the STRIDA project have also

illustrated how drug regulations can drive the NPS market.

DOI: 10.1007/164_2018_134

PMID: 30135990 [Indexed for MEDLINE]

88. Med Hypotheses. 2018 Oct;119:54-57. doi: 10.1016/j.mehy.2018.07.027. Epub 2018

Jul 29.

A plausible causal relationship between the increased use of fentanyl as an

obstetric analgesic and the current opioid epidemic in the US.

Brimdyr K(1), Cadwell K(2).

Author information:

(1)Healthy Children Project, Inc., 327 Quaker Meeting House Road, East Sandwich,

MA 02537, United States. Electronic address: kajsa@centerforbreastfeeding.org.

(2)Healthy Children Project, Inc., 327 Quaker Meeting House Road, East Sandwich,

MA 02537, United States.

Drug poisoning deaths have more than doubled in the United States since 2000 with

fentanyl and fentanyl analogues primarily responsible for the jump in opioid

deaths. Robust data indicate a convincing correlation between the exposure of the

fetus to other labor medications (morphine, pethidine hydrochloride,

barbiturates, phenobarbitone, meperidine, and secobarbital) and the later

addiction of young adults to the same category of drug. We present the hypothesis

that this effect is also true of the opioid, fentanyl: there is a causal

relationship between the increased popularity of fentanyl as a labor anesthetic

in the United States since the 1980's and the current epidemic of fentanyl abuse.

Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.mehy.2018.07.027

PMID: 30122491 [Indexed for MEDLINE]

89. Forensic Sci Int. 2018 Sep;290:310-317. doi: 10.1016/j.forsciint.2018.07.020.

Epub 2018 Jul 25.

Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and

in vitro metabolite profiling in pooled human hepatocytes.

Mardal M(1), Johansen SS(2), Davidsen AB(2), Telving R(3), Jornil JR(3),

Dalsgaard PW(2), Hasselstrøm JB(3), Øiestad ÅM(4), Linnet K(2), Andreasen MF(3).

Author information:

(1)Section of Forensic Chemistry, Department of Forensic Medicine, University of

Copenhagen, Copenhagen, Denmark. Electronic address: marie.mardal@sund.ku.dk.

(2)Section of Forensic Chemistry, Department of Forensic Medicine, University of

Copenhagen, Copenhagen, Denmark.

(3)Section of Forensic Chemistry, Department of Forensic Medicine, Aarhus

University, Aarhus, Denmark.

(4)Section of Forensic Toxicological Analysis, Department of Forensic Sciences,

Oslo University Hospital, Oslo, Norway.

Methoxyacetylfentanyl belongs to the group of fentanyl analogues and has been

associated with several deaths in recent years. We present three case reports of

deceased individuals that tested positive for methoxyacetylfentanyl consumption,

as well as in vitro and in vivo metabolite profiles. Methoxyacetylfentanyl was

quantified by ultra-high performance liquid chromatography-tandem mass

spectrometry (UHPLC-MS/MS) in femoral blood, as well as in urine and brain tissue

when these were available. Metabolite profiling was performed by incubating

methoxyacetylfentanyl with pooled human hepatocytes (pHH) in Leibovitz's L-15

medium supplemented with fetal bovine serum. Metabolites were identified in vivo

and in vitro using UHPLC-high resolution (HR)-MS/MS. The measured

methoxyacetylfentanyl concentration was 0.022-0.056mg/kg (N=3) in femoral blood,

0.12mg/kg (N=1) in urine, and 0.074mg/kg (N=1) in brain tissue homogenate. A

total of 10 metabolites were identified. The observed metabolic pathways were:

hydroxylation(s), N-dealkylation, O-demethylation, deamination, glucuronidation,

and combinations thereof. Major analytical targets in vitro and across measured

biological samples in vivo were methoxyacetylfentanyl, the O-demethyl-

metabolite, and the deamide-metabolite. Intoxication with methoxyacetylfentanyl

was judged as the cause of death or a major contributing factor in all three

presented cases.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2018.07.020

PMID: 30107329 [Indexed for MEDLINE]

90. Handb Exp Pharmacol. 2018;252:495-541. doi: 10.1007/164_2018_110.

Fatal Poisonings Associated with New Psychoactive Substances.

Kronstrand R(1)(2), Guerrieri D(3)(4), Vikingsson S(3)(4), Wohlfarth A(3)(4),

Gréen H(3)(4).

Author information:

(1)Department of Forensic Genetics and Forensic Toxicology, National Board of

Forensic Medicine, Linköping, Sweden. robert.kronstrand@rmv.se.

(2)Division of Drug Research, Linköping University, Linköping, Sweden.

robert.kronstrand@rmv.se.

(3)Department of Forensic Genetics and Forensic Toxicology, National Board of

Forensic Medicine, Linköping, Sweden.

(4)Division of Drug Research, Linköping University, Linköping, Sweden.

This chapter describes how new psychoactive substances (NPS) have been involved

in fatal intoxications from 2010 and onwards. It summarizes the circumstances,

antemortem symptoms, and adverse effects that have led to death after ingestion

of one or more NPS and tabulates concentrations, and postmortem findings from

these intoxications.Consumption of NPS exerts health problems and unknown risks

for the users. Data on toxicity of many NPS are scarce or nonexistent and

long-term toxicity and risks are still largely unknown. In addition, purity and

composition of products containing NPS are often inconsistent or not known, which

places users at high risk as evidenced by hospital emergency admissions and

deaths.The most serious threat to drug users are the synthetic opioids that with

strong central nervous depressant effects have caused numerous accidental deaths

spread over the entire globe. The synthetic cannabinoids seem to be the most

unpredictable with no clear toxidrome and unknown or poorly understood mechanisms

of toxicity, but with adverse effects pointing toward the cardiovascular system.

The toxidromes commonly encountered after ingestion of cathinones and

phenethylamines are of sympathomimetic and hallucinogenic character, which

includes risk of developing a serotonin syndrome, excited delirium, and

life-threatening cardiovascular effects. In comparison to their conventional

"parent" drug, i.e., heroin, cannabis, and amphetamine, most NPS appear to

exhibit more severe adverse effects. The deaths attributed to NPS have

dramatically increased in the last years. In our opinion, this is because of the

shift from synthetic cannabinoids and cathinones to the even more toxic and

dangerously potent fentanyl analogues.

DOI: 10.1007/164_2018_110

PMID: 30105471 [Indexed for MEDLINE]

91. Addiction. 2019 Jun;114(6):1026-1034. doi: 10.1111/add.14412. Epub 2018 Sep 5.

Rising pregabalin use and misuse in Australia: trends in utilization and

intentional poisonings.

Cairns R(1)(2), Schaffer AL(3), Ryan N(4), Pearson SA(3), Buckley NA(1)(2).

Author information:

(1)New South Wales Poisons Information Centre, The Children's Hospital at

Westmead, Westmead, NSW, Australia.

(2)Clinical Pharmacology and Toxicology Research Group, Discipline of

Pharmacology, School of Medical Sciences, Sydney Medical School, University of

Sydney, NSW, Australia.

(3)Centre for Big Data Research in Health, University of New South Wales, Sydney,

Australia.

(4)Clinical Toxicology Research Group, Faculty of Health and Medicine, University

of Newcastle, Australia.

BACKGROUND AND AIMS: Pregabalin is a gamma-aminobutyric acid (GABA) analogue,

used to treat neuropathic pain and epilepsy. Pregabalin was registered in

Australia in 2005, and subsidized publically in 2013. We aimed to describe

Australian patterns of pregabalin use and intentional poisoning, and identify

people potentially at high risk of misuse.

DESIGN AND SETTING: Population-based retrospective cohort study of dispensings in

the 10% sample of Australian Pharmaceutical Benefits Scheme (July 2012-February

2017); intentional poisoning calls to New South Wales Poisons Information Centre

(NSWPIC) (2004-2016); intentional poisonings in two Australian toxicology service

databases; and poisoning fatalities in NSW coronial records (2005-2016).

PARTICIPANTS: A total of 122 572 people dispensed pregabalin, people with

intentional pregabalin overdoses managed by NSWPIC and the toxicology services

and pregabalin-associated deaths referred to the NSW coroner.

MEASUREMENTS: Trends in dispensing, poisoning, death; demographics and patient

characteristics, proportion of users at high risk of misuse (latent class

analysis, LCA) and characteristics of high-risk users.

FINDINGS: Pregabalin dispensing increased by 73 424 per year [95% confidence

interval (CI) = 61726-85 121 P < 0.001] between 2013 and 2016. NSWPIC received

1158 reports of intentional pregabalin poisonings, with a 53.8% increase per

year, 2005-2016 (95% CI = 44.0-64.2%, P < 0.001). We identified 88

pregabalin-associated deaths, 57.8% yearly increase (95% CI = 30.0-91.6%,

P < 0.001). Patients overdosing on pregabalin commonly co-ingested opioids,

benzodiazepines and illicit drugs, and had high rates of psychiatric and

substance use comorbidities; 14.7% of pregabalin users were classed by the LCA as

at high risk of misuse, and were more likely to be younger, male, co-prescribed

benzodiazepines or opioids, have more individual prescribers and higher

pregabalin strengths dispensed.

CONCLUSIONS: There has been a dramatic increase in pregabalin use, poisonings and

deaths in Australia since it became subsidized publicly in 2013. One in seven

Australians dispensed pregabalin appears to be at high risk of misuse.

© 2018 Society for the Study of Addiction.

DOI: 10.1111/add.14412

PMID: 30098227

92. MMWR Morb Mortal Wkly Rep. 2018 Aug 10;67(31):850-853. doi:

10.15585/mmwr.mm6731a2.

Naloxone Administration Frequency During Emergency Medical Service Events -

United States, 2012-2016.

Cash RE, Kinsman J, Crowe RP, Rivard MK, Faul M, Panchal AR.

As the opioid epidemic in the United States has continued since the early 2000s

(1,2), most descriptions have focused on misuse and deaths. Increased cooperation

with state and local partners has enabled more rapid and comprehensive

surveillance of nonfatal opioid overdoses (3).* Naloxone administrations obtained

from emergency medical services (EMS) patient care records have served as a

useful proxy for overdose surveillance in individual communities and might be a

previously unused data source to describe the opioid epidemic, including fatal

and nonfatal events, on a national level (4-6). Using data from the National

Emergency Medical Services Information System (NEMSIS),† the trend in rate of EMS

naloxone administration events from 2012 to 2016 was compared with opioid

overdose mortality rates from National Vital Statistics System multiple

cause-of-death mortality files. During 2012-2016, the rate of EMS naloxone

administration events increased 75.1%, from 573.6 to 1004.4 administrations per

100,000 EMS events, mirroring the 79.7% increase in opioid overdose mortality

from 7.4 deaths per 100,000 persons to 13.3. A bimodal age distribution of

patients receiving naloxone from EMS parallels a similar age distribution of

deaths, with persons aged 25-34 years and 45-54 years most affected. However, an

accurate estimate of the complete injury burden of the opioid epidemic requires

assessing nonfatal overdoses in addition to deaths. Evaluating and monitoring

nonfatal overdose events via the novel approach of using EMS data might assist in

the development of timely interventions to address the evolving opioid crisis.

DOI: 10.15585/mmwr.mm6731a2

PMCID: PMC6089336

PMID: 30091966 [Indexed for MEDLINE]

Conflict of interest statement: No conflicts of interest were reported.

93. Drug Test Anal. 2019 Jan;11(1):173-177. doi: 10.1002/dta.2473. Epub 2018 Sep 3.

An ocfentanil-related death case: UHPLC-MS/MS analysis of the drug.

Casati S(1), Minoli M(1), Angeli I(1), Ravelli A(1), Crudele GDL(2), Orioli M(1).

Author information:

(1)Laboratory of Forensic Toxicology, Department of Biomedical, Surgical and

Dental Science, University of Milan, via Luigi Mangiagalli 37, 20133, Milan,

Italy.

(2)Department of Biomedical Sciences for Health, University of Milan, via Luigi

Mangiagalli 37, 20133, Milan, Italy.

DOI: 10.1002/dta.2473

PMID: 30091284 [Indexed for MEDLINE]

94. JAMA. 2018 Aug 7;320(5):502-504. doi: 10.1001/jama.2018.6933.

Opioid Overdose After Surgical Discharge.

Ladha KS(1), Gagne JJ(1), Patorno E(1), Huybrechts KF(1), Rathmell JP(2), Wang

SV(1), Bateman BT(1).

Author information:

(1)Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's

Hospital, Boston, Massachusetts.

(2)Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and

Women's Hospital, Boston, Massachusetts.

DOI: 10.1001/jama.2018.6933

PMCID: PMC6142985

PMID: 30087999 [Indexed for MEDLINE]

95. Food Chem Toxicol. 2018 Oct;120:571-577. doi: 10.1016/j.fct.2018.07.061. Epub

2018 Aug 3.

Oxidative stress in opium users after using lead-adulterated opium: The role of

genetic polymorphism.

Shojaeepour S(1), Fazeli M(2), Oghabian Z(3), Pourgholi L(4), Mandegary A(5).

Author information:

(1)Department of Pharmacology, School of Veterinary, Shiraz University, Iran;

Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University

of Medical Sciences, Kerman, Iran. Electronic address: drsaeideh@yahoo.com.

(2)Department of Pharmacology, School of Veterinary, Shiraz University, Iran.

Electronic address: mfazeli@shirazu.ac.ir.

(3)Gastroenterology and Hepatology Research Center, Institute of Basic and

Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman,

Iran; Department of Toxicology & Pharmacology, School of Pharmacy, Kerman

University of Medical Sciences, Kerman, Iran. Electronic address:

zoghabian@kmu.ac.ir.

(4)Department of Toxicology & Pharmacology, School of Pharmacy, Kerman University

of Medical Sciences, Kerman, Iran; Pharmaceutics Research Center, Institute of

Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Electronic address: leyla.pourgholi5@gmail.com.

(5)Department of Toxicology & Pharmacology, School of Pharmacy, Kerman University

of Medical Sciences, Kerman, Iran; Neuroscience Research Center, Institute of

Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

Electronic address: alimandegary@kmu.ac.ir.

Use of lead-adulterated opium has become one of the major sources of lead

poisoning in Iran. This study was designed to assess clinical effects and

oxidative stress and its association with GSTM1, GSTT1, NQO1, and ALAD genes

polymorphisms and blood lead level (BLL) in lead-adulterated opium users. The

oxidative stress status in 192 opium users with lead poisoning symptoms measured

and compared with 102 healthy individuals. Gluthatione S-transferase (GST)-M1 and

-T1 genes deletion, NQO1 rs1800566, and δ-aminolevulinic acid dehydratase (ALAD)

rs1800435 polymorphisms were determined using PCR and PCR-RFLP. The relation

between the polymorphisms, BLL, and oxidative stress parameters were analysed

using multivariate linear regressions. The common symptoms of lead toxicity were

gastrointestinal and neurologic complications. Oxidative stress was significantly

higher in opium addicts and lipid peroxidation significantly correlated with BLL.

There was significant association between ALAD rs1800435 and BLL, and the BLL was

significantly lower in the patients with ALAD 1-2 genotype. Use of

lead-adulterated opium causes high frequency of lead toxicity symptoms,

hematological and biochemical abnormalities, and oxidative stress which are

associated with BLL. Route of opioid use and the polymorphism of rs1800435 in

ALAD gene are the major determinants of BLL in lead-adulterated opium users.

Copyright © 2018 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.fct.2018.07.061

PMID: 30081045 [Indexed for MEDLINE]

96. Clin Ther. 2018 Aug;40(8):1366-1374.e8. doi: 10.1016/j.clinthera.2018.06.012.

Epub 2018 Jul 31.

Sex Differences in Poisonings Among Older Adults: An Analysis of the Toxicology

Investigators Consortium (ToxIC) Registry, 2010 to 2016.

Beauchamp GA(1), Carey JL(2), Adams T(3), Wier A(3), Colón MF(3), Cook M(4),

Cannon R(4), Katz KD(4), Greenberg MR(3); Toxicology Investigators Consortium

(ToxIC).

Author information:

(1)Lehigh Valley Health Network, Department of Emergency and Hospital

Medicine/USF Morsani College of Medicine, Allentown, Pennsylvania; Lehigh Valley

Health Network, Department of Emergency and Hospital Medicine, Section of Medical

Toxicology, Allentown, Pennsylvania. Electronic address:

beauchamp.gillian@gmail.com.

(2)University of Massachusetts Medical School, Department of Emergency Medicine,

Division of Medical Toxicology, Worcester, Massachusetts.

(3)Lehigh Valley Health Network, Department of Emergency and Hospital

Medicine/USF Morsani College of Medicine, Allentown, Pennsylvania.

(4)Lehigh Valley Health Network, Department of Emergency and Hospital

Medicine/USF Morsani College of Medicine, Allentown, Pennsylvania; Lehigh Valley

Health Network, Department of Emergency and Hospital Medicine, Section of Medical

Toxicology, Allentown, Pennsylvania.

PURPOSE: Adults aged >65 years are susceptible to intentional and unintentional

poisoning, with contributing factors that include polypharmacy, comorbidity,

susceptibility to medication error, and gaps in research. Although toxicologists

are often tasked with managing and preventing poisoning among older adults,

little is known about sex differences in these poisonings. The aim of this study

was to review sex differences in poisonings among older adults managed at the

bedside by medical toxicologists.

METHODS: All case subjects aged >65 years in the Toxicology Investigators

Consortium (ToxIC) registry between January 2010 and December 2016 were reviewed.

Data included reasons for exposure and consultation, exposure agents and routes,

presenting clinical findings, and treatment provided. Cases missing age, sex, or

primary reason for toxicology consultation data were excluded. We used χ2 tests

to assess differences in distribution of study variables according to participant

sex.

FINDINGS: Among 51,441 total registry cases, 542 (1.05%) were excluded because of

missing data. Among the remaining 50,899 cases, 2930 (5.8%) were included for age

>65 years; 52.3% of older adults were female. Race was missing or unknown for

49.2% of cases. Adverse drug reactions were more commonly encountered in female

subjects than in their male counterparts (9.6% vs 6.4%; P = 0.001). No

statistically significant sex differences were observed for total numbers of

intentional, unintentional pharmaceutical, and nonpharmaceutical exposures. The

most common medications involved were cardiovascular (16.8%) and

analgesics/opioids (14.8%). Female subjects were more likely than male subjects

to be evaluated by a toxicologist for cardiovascular medications (18.7% vs 14.7%;

P = 0.004) and analgesics/opioids (17.6% vs 11.8%; P < 0.001). Male subjects were

more likely than female subjects to be evaluated for ethanol toxicity (7.4% vs

1%; P < 0.001) and for envenomations (4.2% vs 1.8%; P < 0.001). The most common

route of exposure was oral ingestion (81.3%). Signs/symptoms were noted in 54.8%

of cases, with the most common abnormal vital sign being bradycardia (17.2%).

Pharmacologic support was the most common intervention and was more common in

male subjects than in female subjects (17.7% vs 12.3%; P < 0.001). Deaths were

reported in 38 female subjects (2.45%) and 46 male subjects (3.34%); there was no

statistically significant difference in death rate according to sex (P = 0.148).

IMPLICATIONS: Older female adults were more commonly evaluated by a medical

toxicologist for an adverse drug reaction than older male adults. Female patients

were more likely than male patients to be evaluated for poisoning related to

analgesic/opioids and cardiovascular medications, and older male patients more

frequently received pharmacologic support than older female patients. No

significant sex differences were observed in numbers of toxicology consultations

for intentional, unintentional pharmaceutical, and nonpharmaceutical exposures.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.clinthera.2018.06.012

PMID: 30072041

97. MMWR Morb Mortal Wkly Rep. 2018 Aug 3;67(30):815-818. doi:

10.15585/mmwr.mm6730a2.

Characteristics of Tianeptine Exposures Reported to the National Poison Data

System - United States, 2000-2017.

El Zahran T, Schier J, Glidden E, Kieszak S, Law R, Bottei E, Aaron C, King A,

Chang A.

Tianeptine (marketed as Coaxil or Stablon) is an atypical tricyclic drug used as

an antidepressant in Europe, Asia, and Latin America. In the United States,

tianeptine is not approved by the Food and Drug Administration (FDA) for medical

use and is an unscheduled pharmaceutical agent* (1). Animal and human studies

show that tianeptine is an opioid receptor agonist (2). Several case studies have

reported severe adverse effects and even death from recreational abuse of

tianeptine (3-5). To characterize tianeptine exposures in the United States, CDC

analyzed all exposure calls related to tianeptine reported by poison control

centers to the National Poison Data System (NPDS)† during 2000-2017. Tianeptine

exposure calls, including those for intentional abuse or misuse, increased across

the United States during 2014-2017, suggesting a possible emerging public health

risk. Most tianeptine exposures occurred among persons aged 21-40 years and

resulted in moderate outcomes. Neurologic, cardiovascular, and gastrointestinal

signs and symptoms were the most commonly reported health effects, with some

effects mimicking opioid toxicity. A substantial number of tianeptine exposure

calls also reported clinical effects of withdrawal. Among 83 tianeptine exposures

with noted coexposures, the most commonly reported coexposures were to phenibut,

ethanol, benzodiazepines, and opioids.

DOI: 10.15585/mmwr.mm6730a2

PMCID: PMC6072055

PMID: 30070980 [Indexed for MEDLINE]

Conflict of interest statement: No conflicts of interest were reported.

98. PLoS Med. 2018 Jul 31;15(7):e1002625. doi: 10.1371/journal.pmed.1002625.

eCollection 2018 Jul.

Methadone maintenance treatment and mortality in people with criminal

convictions: A population-based retrospective cohort study from Canada.

Russolillo A(1), Moniruzzaman A(1), Somers JM(1).

Author information:

(1)Somers Research Group, Faculty of Health Sciences, Simon Fraser University,

Burnaby, British Columbia, Canada.

Comment in

PLoS Med. 2018 Jul 31;15(7):e1002626.

BACKGROUND: Individuals with criminal histories have high rates of opioid

dependence and mortality. Excess mortality is largely attributable to overdose

deaths. Methadone maintenance treatment (MMT) is one of the best evidence-based

opioid substitution treatments (OSTs), but there is uncertainty about whether

methadone treatment reduces the risk of mortality among convicted offenders over

extended follow-up periods. The objective of this study was to investigate the

association between adherence to MMT and overdose fatality as well as other

causes of mortality.

METHODS AND FINDINGS: We conducted a retrospective cohort study involving linked

population-level administrative data among individuals in British Columbia (BC),

Canada with a history of conviction and who filled a methadone prescription

between January 1, 1998 and March 31, 2015. Participants were followed from the

date of first-dispensed methadone prescription until censoring (date of death or

March 31, 2015). Methadone was divided into medicated (methadone was dispensed)

and nonmedicated (methadone was not dispensed) periods and analysed as a

time-varying exposure. Hazard ratios (HRs) with 95% CIs were estimated using

multivariable Cox regression to examine mortality during the study period.

All-cause and cause-specific mortality rates were compared during medicated and

nonmedicated methadone periods. Participants (n = 14,530) had a mean age of 34.5

years, were 71.4% male, and had a median follow-up of 6.9 years. A total of 1,275

participants died during the observation period. The overall all-cause mortality

rate was 11.2 per 1,000 person-years (PYs). Participants were significantly less

likely to die from both nonexternal (adjusted HR [AHR] 0.27 [95% CI 0.23-0.33])

and external (AHR 0.41 [95% CI 0.33-0.51]) causes during medicated periods,

independent of sociodemographic, criminological, and health-related factors.

Death due to infectious diseases was 5 times lower (AHR 0.20 [95% CI 0.13-0.30]),

and accidental poisoning (overdose) deaths were nearly 3 times lower (AHR 0.39

[95% CI 0.30-0.50]) during medicated periods. A competing risk regression

demonstrated a similar pattern of results. The use of a Canadian offender

population may limit generalizability of results. Furthermore, our observation

period represents community-based methadone prescribing and may omit

prescriptions administered during hospital separations. Therefore, the magnitude

of the protective effects of methadone from nonexternal causes of death should be

interpreted with caution.

CONCLUSIONS: Adherence to methadone was associated with significantly lower rates

of death in a population-level cohort of Canadian convicted offenders. Achieving

higher rates of adherence may reduce overdose deaths and other causes of

mortality among offenders and similarly marginalized populations. Our findings

warrant examination in other study centres in response to the crisis of

opiate-involved deaths.

DOI: 10.1371/journal.pmed.1002625

PMCID: PMC6067717

PMID: 30063699 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that no competing interests

exist.

99. Clin Drug Investig. 2018 Oct;38(10):977-982. doi: 10.1007/s40261-018-0679-4.

Identification of Somatic Disorders Related to Psychoactive Drug Use from an

Inpatient Database in a French University Hospital.

Lafaurie M(1), Pochard L(1), Lotiron C(1), Molinier L(2)(3), Lapeyre-Mestre

M(1)(2), Jouanjus E(4)(5).

Author information:

(1)CEIP-Addictovigilance, Service de Pharmacologie Médicale et Clinique, CHU

Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.

(2)UMR1027 Inserm-Université Paul Sabatier Toulouse III, 37 allées Jules Guesde,

31000, Toulouse, France.

(3)Département d'Information Médicale, Hôtel-Dieu Saint-Jacques, CHU Toulouse, 2

rue Viguerie, 31059, Toulouse, France.

(4)CEIP-Addictovigilance, Service de Pharmacologie Médicale et Clinique, CHU

Toulouse, 37 allées Jules Guesde, 31000, Toulouse, France.

emilie.jouanjus@univ-tlse3.fr.

(5)UMR1027 Inserm-Université Paul Sabatier Toulouse III, 37 allées Jules Guesde,

31000, Toulouse, France. emilie.jouanjus@univ-tlse3.fr.

BACKGROUND AND OBJECTIVE: Studies have explored hospital records to identify

serious complications related to use of psychoactive drugs, but this approach is

time consuming with a high rate of false positives. We propose a method to

improve the detection of these somatic complications from an inpatient database.

METHODS: Hospitalisations in Toulouse University Hospital (France) between 1 July

and 31 December 2013 with at least one International Classification of Diseases,

Tenth Edition (ICD-10) code related to possible abuse/addiction (F11-F19: "mental

and behavioural disorder due to psychoactive substance use", T40-T43:

"poisoning", or X61-X62: "self-poisoning") and at least another ICD-10 code

unrelated to abuse/addiction were extracted. Hospital discharge summaries (HDS)

were reviewed using two strategies: in Strategy 1, all HDS were reviewed, whereas

in Strategy 2, associated ICD-10 codes unrelated to abuse/addiction were firstly

assessed to preselect some HDS. Positive predictive values (PPVs) were calculated

to evaluate their performance.

RESULTS: With Strategy 1, we found 58 psychoactive drug-related somatic

complications among the 578 hospitalisations extracted (PPV = 10.0%), including

three cases spontaneously reported to the French Addictovigilance Network.

Strategy 2 retained 94.8% of the hospitalisations identified with Strategy 1,

while the number of reviewed HDS was reduced by half (PPV = 20.1%). Cannabis

(56.9%), cocaine (27.6%) and prescription opioids (22.4%) were mainly involved.

Complications mainly corresponded to nervous (25.9%) and respiratory and

circulatory (22.4%) system disorders.

CONCLUSIONS: Combining extraction of ICD-10 codes and a focused review of a

preselection of relevant hospitalisations appears to be efficient and

time-saving. This method should be applied in other hospital settings before

considering the exploration of inpatient data on a wider scale.

DOI: 10.1007/s40261-018-0679-4

PMID: 30047105 [Indexed for MEDLINE]

100. J Subst Abuse Treat. 2018 Sep;92:35-39. doi: 10.1016/j.jsat.2018.06.008. Epub

2018 Jun 20.

US hospital discharges documenting patient opioid use disorder without opioid

overdose or treatment services, 2011-2015.

Peterson C(1), Xu L(2), Mikosz CA(2), Florence C(2), Mack KA(2).

Author information:

(1)National Center for Injury Prevention and Control, Centers for Disease Control

and Prevention (CDC), Atlanta, GA, USA. Electronic address:

cora.peterson@cdc.hhs.gov.

(2)National Center for Injury Prevention and Control, Centers for Disease Control

and Prevention (CDC), Atlanta, GA, USA.

BACKGROUND: Understanding more about circumstances in which patients receive an

opioid use disorder (OUD) diagnosis might illuminate opportunities for

intervention and ultimately prevent opioid overdoses. This study aimed to

describe patient and clinical characteristics of hospital discharges documenting

OUD among patients not being treated for opioid overdose, detoxification, or

rehabilitation.

METHODS: We assessed patient, payer, and clinical characteristics of

nationally-representative 2011-2015 National Inpatient Sample discharges

documenting OUD, excluding opioid overdose, detoxification, and rehabilitation.

Discharges were clinically classified by Diagnostic Related Group (DRG) for

analysis.

RESULTS: Annual discharges grew 38%, from 347,137 (2011) to 478,260 (2015),

totaling 2 million discharges during the study period. The annual discharge rate

increased among all racial/ethnic groups, but was highest among the non-Hispanic

black population until 2015, when non-Hispanic whites had a slightly higher rate

(164 versus 162 per 100,000 population). Female patients and Medicaid and

Medicare as primary payer accounted for an increasing annual proportion of

discharges. Just 14 DRGs accounted for nearly 50% of discharges over the study

period. The most prevalent primary treatment received during OUD inpatient stays

was for psychoses (DRG 885; 16% of discharges) and drug and alcohol abuse or

dependence symptoms (including withdrawal) or (non-opioid) poisoning (DRG 894,

897, 917, 918; 12% of discharges).

CONCLUSIONS: Now nearly half a million yearly US hospital discharges for a range

of primary treatment include patients' diagnosis of OUD without opioid overdose,

detoxification, or rehabilitation services. Inpatient stays present an important

opportunity to link OUD patients to treatment to reduce opioid-related morbidity

and mortality.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jsat.2018.06.008

PMCID: PMC6084454

PMID: 30032942

101. Appl Health Econ Health Policy. 2018 Oct;16(5):609-632. doi:

10.1007/s40258-018-0402-x.

The Economic Burden of Abuse of Prescription Opioids: A Systematic Literature

Review from 2012 to 2017.

Reinhart M(1), Scarpati LM(2), Kirson NY(3), Patton C(1), Shak N(1), Erensen

JG(4).

Author information:

(1)Analysis Group, Inc., 1010 El Camino Real, Suite 310, Menlo Park, CA, 94025,

USA.

(2)Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199,

USA.

(3)Analysis Group, Inc., 111 Huntington Avenue, 14th Floor, Boston, MA, 02199,

USA. noam.kirson@analysisgroup.com.

(4)Purdue Pharma L.P., One Stamford Forum, 201 Tresser Boulevard, Stamford, CT,

06901, USA.

BACKGROUND: Abuse of prescription opioids [opioid use disorder (OUD), poisoning,

and fatal and non-fatal overdose] is a public health and economic challenge that

is associated with considerable morbidity and mortality in the USA and globally.

OBJECTIVE: To systematically review and summarize the health economics literature

published over the last 5 years that describes the economic burden of abuse of

prescription opioids.

METHODS: Findings from searches of databases including MEDLINE, Embase, and

Cochrane CENTRAL as well as hand searches of multiple conference abstracts were

screened against predefined inclusion criteria to identify studies reporting cost

and healthcare resource utilization (HRU) data associated with abuse of

prescription opioids.

RESULTS: A total of 49 unique studies were identified. Most of the studies

examined direct costs and HRU, which were substantially higher for abusers of

prescription opioids than non-abuser controls in several matched cohort analyses

(US$20,343-US$28,718 vs US$9716-US$14,079 for mean direct combined annual

healthcare costs reported in 6 studies). Although only a small number of studies

reported indirect costs, these findings suggest a high societal burden related to

productivity losses, absenteeism, morbidity, and mortality among those who abuse

opioids. Studies of medication-assisted treatment demonstrated that factors such

as adherence, dose, formulation (film or tablet), and relapse during treatment,

were associated with direct costs and HRU among treated patients.

CONCLUSIONS: This systematic literature review shows that abuse of prescription

opioids is characterized by substantial direct healthcare costs, medical

utilization, and related societal costs. Future research should further

investigate the indirect costs of opioid abuse.

DOI: 10.1007/s40258-018-0402-x

PMCID: PMC6132448

PMID: 30027533

102. Cardiovasc Toxicol. 2019 Feb;19(1):62-71. doi: 10.1007/s12012-018-9474-y.

Electrocardiographic Findings in Mortalities Due to Pure Methadone Toxicity.

Sheibani M(1), Zamani N(2), Hassanian-Moghaddam H(3)(4).

Author information:

(1)Cardiovascular Research Center, Shahid Beheshti University of Medical

Sciences, Tehran, Islamic Republic of Iran.

(2)Department of Clinical Toxicology, School of Medicine, Shahid Beheshti

University of Medical Sciences, Arabi Ave, Daneshjoo Blvd, Velenjak, 19839-63113,

Tehran, Islamic Republic of Iran.

(3)Department of Clinical Toxicology, School of Medicine, Shahid Beheshti

University of Medical Sciences, Arabi Ave, Daneshjoo Blvd, Velenjak, 19839-63113,

Tehran, Islamic Republic of Iran. Hassanian@sbmu.ac.ir.

(4)Department of Clinical Toxicology, Loghman-Hakim Hospital, Kamali Street,

South Karegar Avenue, 1333431151, Tehran, Islamic Republic of Iran.

Hassanian@sbmu.ac.ir.

We aimed to evaluate electrocardiographic (ECG) abnormalities in mortalities due

to pure methadone toxicity in ICU patients since methadone-related mortality may

be due to cardiac complications even in acute toxicities. In a retrospective

single-center study, files of all patients who had died with confirmed diagnosis

of pure methadone toxicity between 2011 and 2016 were evaluated. Autopsy was

performed in all cases. A cardiologist measured all ECG quantitative and

qualitative indices. Fifty-one deaths were recorded. Forty-two dead patients were

males. Median [IQR] age of the patients was 44 [30, 60] years. Of them, 38 (69%)

were methadone-dependent and were significantly older than methadone-naïve

patients (p = 0.008 and p = 0.001, respectively). ECG abnormalities were detected

in all cases. ST-T abnormalities were found in 33 (64.7%) patients. Except longer

PR interval in dependent patients (p = 0.017) and specific ST elevation in naïve

cases (p = 0.008), other ECG indices were similar in two groups. No correlation

was found between ST-T abnormalities and coronary disease in autopsy. ECG

abnormalities irrelevant to coronary artery diseases are common in

methadone-related mortalities. Methadone toxicity may affect myocardium and play

a role in death. Further prospective studies to evaluate other cardiac indices in

methadone-poisoned patients are recommended.

DOI: 10.1007/s12012-018-9474-y

PMID: 30019098 [Indexed for MEDLINE]

103. Forensic Sci Int. 2018 Sep;290:e15-e18. doi: 10.1016/j.forsciint.2018.06.035.

Epub 2018 Jul 3.

Intentional heroin administration resulting in homicide in a 10-month old infant.

Paul ABM(1), Simms L(2), Mahesan AM(3).

Author information:

(1)Department of Pathology, University of Ottawa, Ottawa, ON, K1H 8M5, Canada;

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Oxford,

OX3 9DU, United Kingdom. Electronic address: abm.paul@hotmail.com.

(2)Office of the Medical Examiner, Clark County Coroner, 1704 Pinto Lane, Las

Vegas, NV, 89106, USA. Electronic address: LSI@ClarkCountyNV.gov.

(3)University of Southern California, Los Angeles, CA, 90007, USA. Electronic

address: mahesan@usc.edu.

Homicide occurs in approximately one in five injury-related deaths among infants

in the United States and studies suggest that male caretakers (fathers or

mothers' intimate partners) are the perpetrators of the majority of infant

homicides. Opioid abuse is common and it is estimated that between 26.4 million

and 36 million people abuse opioids worldwide. In this case report, we add to the

literature the first reported homicide by intentional heroin administration in a

10-month old infant. Toxicology revealed morphine 1092ng/L, codeine 74ng/mL, and

6-monoacetyl-morphine 359ng/L in cardiac blood. Morphine 803ng/g, codeine 54ng/g

in liver tissue, and morphine 181ng/mL was found in vitreous humor. With the

prevalence of opioid abuse on the rise accidental opioid ingestions in the

pediatric population have increased. However, forensic personnel must recognize

the possibility of intentional poisoning in this vulnerable population.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2018.06.035

PMID: 30017664 [Indexed for MEDLINE]

104. Forensic Sci Int. 2018 Sep;290:121-128. doi: 10.1016/j.forsciint.2018.06.041.

Epub 2018 Jul 5.

Can measurements of heroin metabolites in post-mortem matrices other than

peripheral blood indicate if death was rapid or delayed?

Thaulow CH(1), Øiestad ÅML(2), Rogde S(3), Andersen JM(2), Høiseth G(3), Handal

M(4), Mørland J(5), Vindenes V(3).

Author information:

(1)Department of Forensic Sciences, Oslo University Hospital, PO Box 4950,

Nydalen, N-0424 Oslo, Norway. Electronic address: cectha@ous-hf.no.

(2)Department of Forensic Sciences, Oslo University Hospital, PO Box 4950,

Nydalen, N-0424 Oslo, Norway.

(3)Department of Forensic Sciences, Oslo University Hospital, PO Box 4950,

Nydalen, N-0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo,

PO Box 1171, Blindern, N-0318 Oslo, Norway.

(4)Department of Mental Disorders, Norwegian Institute of Public Health, PO Box

4404, Nydalen, N-0403 Oslo, Norway.

(5)Institute of Clinical Medicine, University of Oslo, PO Box 1171, Blindern,

N-0318 Oslo, Norway; Division of Health Data and Digitalisation, Norwegian

Institute of Public Health, PO Box 4404, Nydalen, N-0403 Oslo, Norway.

BACKGROUND: In heroin-related deaths, it is often of interest to determine the

approximate time span between intake of heroin and death, and to decide whether

heroin or other opioids have been administered. In some autopsy cases, peripheral

blood cannot be sampled due to decomposition, injuries or burns. The aim of the

present study was to investigate whether measurements of heroin metabolites in

matrices other than peripheral blood can be used to differentiate between rapid

and delayed heroin deaths, and if morphine/codeine ratios measured in other

matrices can separate heroin from codeine intakes.

METHODS: In this study, we included 51 forensic autopsy cases where morphine was

detected in peripheral blood. Samples were collected from peripheral and cardiac

blood, pericardial fluid, psoas and lateral vastus muscles, vitreous humor and

urine. The opioid analysis included 6-acetylmorphine (6-AM), morphine,

morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G) and codeine. Urine was

only used for qualitative detection of 6-AM. 45 heroin-intake cases were divided

into rapid deaths (n=24), based on the detection of 6-AM in blood, or delayed

deaths (n=21), where 6-AM was detected in at least one other matrix but not in

blood. An additional 6 cases were classified as codeine-intake cases, based on a

morphine/codeine ratio below unity (<1) in peripheral blood, without detecting

6-AM in any matrix.

RESULTS: The median morphine concentrations were significantly higher in the

rapid compared with the delayed heroin deaths in all matrices (p=0.004 for

vitreous humor and p<0.001 for the other matrices). In the rapid heroin deaths,

the M3G/morphine concentration ratios were significantly lower than in the

delayed deaths both in peripheral and cardiac blood (p<0.001), as well as in

pericardial fluid (p<0.001) and vitreous humor (p=0.006), but not in muscle. The

morphine/codeine ratios measured in cardiac blood, pericardial fluid and the two

muscle samples resembled the ratios in peripheral blood, although codeine was

less often detected in other matrices than peripheral blood.

CONCLUSIONS: Measurements of heroin-metabolites in cardiac blood, pericardial

fluid and vitreous humor provide information comparable to that of peripheral

blood regarding rapid and delayed heroin deaths, e.g. M3G/morphine ratios <2

indicate a rapid death while ratios >3 indicate a delayed death. However,

considerable overlap in results from rapid and delayed deaths was observed, and

measurements in muscle appeared less useful. Furthermore, matrices other than

peripheral blood can be used to investigate morphine/codeine ratios, but vitreous

humor seems less suited.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2018.06.041

PMID: 30015276 [Indexed for MEDLINE]

105. MMWR Morb Mortal Wkly Rep. 2018 Jul 13;67(27):767-768. doi:

10.15585/mmwr.mm6727a4.

Notes from the Field: Overdose Deaths with Carfentanil and Other Fentanyl Analogs

Detected - 10 States, July 2016-June 2017.

O'Donnell J(1), Gladden RM(1), Mattson CL(1), Kariisa M(1).

Author information:

(1)Division of Unintentional Injury Prevention, National Center for Injury

Prevention and Control, CDC.

DOI: 10.15585/mmwr.mm6727a4

PMCID: PMC6047470

PMID: 30001560 [Indexed for MEDLINE]

Conflict of interest statement: No conflicts of interest were reported.

106. Harm Reduct J. 2018 Jul 11;15(1):36. doi: 10.1186/s12954-018-0243-9.

A pragmatic harm reduction approach to manage a large outbreak of wound botulism

in people who inject drugs, Scotland 2015.

Trayner KMA(1)(2), Weir A(3), McAuley A(3)(4), Godbole G(5), Amar C(5), Grant

K(5), Penrice G(6), Roy K(3).

Author information:

(1)Health Protection Scotland, NHS National Services Scotland, Meridian Court, 5

Cadogan Street, Glasgow, Scotland. kirsten.trayner@nhs.net.

(2)Glasgow Caledonian University, Cowcaddens Road, Glasgow, Scotland.

kirsten.trayner@nhs.net.

(3)Health Protection Scotland, NHS National Services Scotland, Meridian Court, 5

Cadogan Street, Glasgow, Scotland.

(4)Glasgow Caledonian University, Cowcaddens Road, Glasgow, Scotland.

(5)Gastrointestinal Bacteria Reference Unit (GBRU), National Infection Service,

Public Health England, London, England.

(6)Public Health Protection Unit, Gartnavel Royal Hospital, NHS Greater Glasgow

and Clyde, Glasgow, Scotland.

BACKGROUND: People who inject drugs (PWID) are at an increased risk of wound

botulism, a potentially fatal acute paralytic illness. During the first 6 months

of 2015, a large outbreak of wound botulism was confirmed among PWID in Scotland,

which resulted in the largest outbreak in Europe to date.

METHODS: A multidisciplinary Incident Management Team (IMT) was convened to

conduct an outbreak investigation, which consisted of enhanced surveillance of

cases in order to characterise risk factors and identify potential sources of

infection.

RESULTS: Between the 24th of December 2014 and the 30th of May 2015, a total of

40 cases were reported across six regions in Scotland. The majority of the cases

were male, over 30 and residents in Glasgow. All epidemiological evidence

suggested a contaminated batch of heroin or cutting agent as the source of the

outbreak. There are significant challenges associated with managing an outbreak

among PWID, given their vulnerability and complex addiction needs. Thus, a

pragmatic harm reduction approach was adopted which focused on reducing the risk

of infection for those who continued to inject and limited consequences for those

who got infected.

CONCLUSIONS: The management of this outbreak highlighted the importance and need

for pragmatic harm reduction interventions which support the addiction needs of

PWID during an outbreak of spore-forming bacteria. Given the scale of this

outbreak, the experimental learning gained during this and similar outbreaks

involving spore-forming bacteria in the UK was collated into national guidance to

improve the management and investigation of future outbreaks among PWID.

DOI: 10.1186/s12954-018-0243-9

PMCID: PMC6042261

PMID: 29996865 [Indexed for MEDLINE]

107. Med Care. 2018 Aug;56(8):727-735. doi: 10.1097/MLR.0000000000000944.

Overview of Prescription Opioid Deaths in the Oklahoma State Medicaid Population,

2012-2016.

Pham TT(1), Skrepnek GH(1), Bond C(2), Alfieri T(2), Cothran TJ(1), Keast SL(1).

Author information:

(1)Department of Pharmacy, Clinical and Administrative Sciences, University of

Oklahoma College of Pharmacy, Oklahoma City, OK.

(2)Purdue Pharma L.P., Stamford, CT.

BACKGROUND: Medicaid members are predisposed to unintentional prescription opioid

overdose. However, little is known about their individual risk factors.

OBJECTIVES: To describe demographic and clinical characteristics, medical

utilization, opioid use, concurrent use of benzodiazepines, risk factors, and

substances involved in death for Oklahoma's Medicaid members who died of

unintentional prescription opioid poisoning.

SUBJECTS: Decedents who were Medicaid eligible in Oklahoma during the year of

death, had an opioid recorded in cause of death, and had ≥1 opioid prescription

claim between January 1, 2011 and June 30, 2016 were cases. Controls were living

Medicaid members and were matched 3:1 to cases through propensity score matching.

MEASURES: Demographics, clinical characteristics, and medical/pharmacy

utilization were examined in the 12 months before the index date.

RESULTS: Of 639 members with fatal unintentional prescription opioid overdoses,

321 had ≥1 opioid prescription claim in the year before death; these were matched

to 963 controls. Compared with controls, decedents had significantly greater

proportions of nonopioid substance use disorders, opioid abuse/dependence,

hepatitis, gastrointestinal bleeding, trauma not involving motor vehicle

accidents, nonopioid poisonings, and mental illness disorders. Decedents had

significantly higher daily morphine milligram equivalent doses (67.2±74.4 vs.

47.2±50.9 mg) and greater opioid/benzodiazepine overlap (70.4% vs. 35.9%).

Benzodiazepines were involved in 29.3% of deaths.

CONCLUSIONS: Several comorbidities indicative of opioid use disorder and greater

exposure to opioids and concomitant benzodiazepines were associated with

unintentional prescription opioid overdose fatalities. Prescribers and state

agencies should be aware of these addressable patient-level factors among the

Medicaid population. Targeting these factors with appropriate policy

interventions and education may prevent future deaths.

DOI: 10.1097/MLR.0000000000000944

PMID: 29995696 [Indexed for MEDLINE]

108. Can J Public Health. 2018 Apr;109(2):231-232. doi: 10.17269/s41997-018-0044-7.

Epub 2018 Mar 5.

The synthetic opioid epidemic and the need for mental health support for first

responders who intervene in overdose cases.

Jozaghi E(1)(2), Maynard R(3), Dadakhah-Chimeh Z(4), Yake K(5)(6), Blyth S(7)(8).

Author information:

(1)The BC Centre for Disease Control, 655 W 12th Ave, Vancouver, BC, V5Z 4R4,

Canada. ehsan.jozaghi@ubc.ca.

(2)The School of Population and Public Health, Faculty of Medicine, University of

British Columbia, 2206 East Mall, Vancouver, BC, V6T 1Z3, Canada.

ehsan.jozaghi@ubc.ca.

(3)PHS Community Services Society, Vancouver, BC, Canada.

(4)Faculty of Health Sciences, The Psychiatrist Nursing Program, Douglas College,

1250 Pinetree Way, Coquitlam, BC, V3B 7X3, Canada.

(5)Vancouver Area Network of Drug Users, 380 E Hastings St, Vancouver, BC, V6A

1P4, Canada.

(6)The Western Aboriginal Harm Reduction Society, 380 E Hastings St, Vancouver,

BC, V6A 1P4, Canada.

(7)Overdose Prevention Society, Vancouver, BC, Canada.

(8)Downtown Eastside Street Market Society, Vancouver, BC, Canada.

DOI: 10.17269/s41997-018-0044-7

PMID: 29981029 [Indexed for MEDLINE]

109. Harm Reduct J. 2018 Jul 5;15(1):34. doi: 10.1186/s12954-018-0240-z.

Fentanyl-contaminated drugs and non-fatal overdose among people who inject drugs

in Baltimore, MD.

Park JN(1)(2), Weir BW(3), Allen ST(3), Chaulk P(4)(5)(6), Sherman SG(3)(7).

Author information:

(1)Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of

Public Health, Ju Nyeong Park, 624 N Broadway, HH163, Baltimore, MD, 21205, USA.

ju.park@jhu.edu.

(2)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,

615 N. Wolfe St, Baltimore, MD, 21205, USA. ju.park@jhu.edu.

(3)Department of Health, Behavior and Society, Johns Hopkins Bloomberg School of

Public Health, Ju Nyeong Park, 624 N Broadway, HH163, Baltimore, MD, 21205, USA.

(4)Baltimore City Health Department, 1001 E. Fayette St, Baltimore, MD, 21201,

USA.

(5)Department of Health, Policy and Management, Johns Hopkins Bloomberg School of

Public Health, 624 N. Broadway, Baltimore, MD, 21205, USA.

(6)Division of Infectious Diseases, School of Medicine, Johns Hopkins University,

Baltimore, MD, 21205, USA.

(7)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,

615 N. Wolfe St, Baltimore, MD, 21205, USA.

BACKGROUND: The opioid crisis remains a major public health issue in the US and

beyond. Despite rapid rises in fentanyl-related mortality nationally, little is

known about the role of fentanyl in the occurrence of non-fatal overdose among

people who use drugs. We examined the prevalence of non-fatal overdose and

perceived fentanyl exposure among syringe services program (SSP) clients and

modeled the correlates of non-fatal overdose.

METHODS: Data were drawn from a cross-sectional survey of 203 SSP clients in

Baltimore, MD recruited in 2016. Logistic regression models were used to identify

the correlates of experiencing non-fatal overdose in the past 12 months.

RESULTS: The majority (65%) was male, 52% were black, 41% were white, and 37%

were homeless. Almost all (97%) used heroin, 64% injected heroin with cocaine

(i.e., speedball), and many used other types of drugs. Half (53%) perceived

fentanyl presence in their drugs either half, most or all of the time. Lifetime

and past 12 month prevalence of non-fatal overdose were 58 and 31%, respectively.

Independent correlates of non-fatal overdose in the past 12 months were

perceiving fentanyl in drugs more than half the time (aOR = 2.79; 95%

CI = 1.00-4.68), speedball injection (aOR = 2.80, 95% CI = 1.26-6.23),

non-prescription buprenorphine use (aOR = 6.37; 95% CI = 2.86-14.17), and

homelessness (aOR = 3.07; 95% CI = 1.28-7.39).

CONCLUSIONS: These data demonstrate that SSP clients are at high-risk of

overdose, some of which is likely attributable to fentanyl exposure. Addressing

the rising fentanyl epidemic will require comprehensive and innovative strategies

that attend to drug use patterns and structural factors such as homelessness.

DOI: 10.1186/s12954-018-0240-z

PMCID: PMC6034235

PMID: 29976195 [Indexed for MEDLINE]

110. BMC Public Health. 2018 Jul 4;18(1):829. doi: 10.1186/s12889-018-5718-9.

"Taking away the chaos": a health needs assessment for people who inject drugs in

public places in Glasgow, Scotland.

Tweed EJ(1)(2), Rodgers M(3)(4), Priyadarshi S(5), Crighton E(6).

Author information:

(1)Directorate of Public Health, NHS Greater Glasgow and Clyde, West House,

Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G11 0SX, UK.

emily.tweed@nhs.net.

(2)MRC/CSO Social and Public Health Sciences Unit, University of Glasgow, 200

Renfield Street, Glasgow, G2 3QB, UK. emily.tweed@nhs.net.

(3)NHS Greater Glasgow and Clyde, JB Russell House, Gartnavel Royal Hospital,

1055 Great Western Road, Glasgow, G11 0SX, UK.

(4)School of Medicine, Dentistry, and Nursing, University of Glasgow, Glasgow,

G12 8QQ, UK.

(5)NHS Greater Glasgow and Clyde Addictions Services, Festival Business Centre,

150 Brand Street, Glasgow, G51 1DP, UK.

(6)Directorate of Public Health, NHS Greater Glasgow and Clyde, West House,

Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G11 0SX, UK.

BACKGROUND: Public injecting of recreational drugs has been documented in a

number of cities worldwide and was a key risk factor in a HIV outbreak in

Glasgow, Scotland during 2015. We investigated the characteristics and health

needs of people involved in this practice and explored stakeholder attitudes to

new harm reduction interventions.

METHODS: We used a tripartite health needs assessment framework, comprising

epidemiological, comparative, and corporate approaches. We undertook an analysis

of local and national secondary data sources on drug use; a series of rapid

literature reviews; and an engagement exercise with people currently injecting in

public places, people in recovery from injecting drug use, and staff from

relevant health and social services.

RESULTS: Between 400 and 500 individuals are estimated to regularly inject in

public places in Glasgow city centre: most experience a combination of profound

social vulnerabilities. Priority health needs comprise addictions care;

prevention and treatment of blood-borne viruses; other injecting-related

infections and injuries; and overdose and drug-related death. Among people with

lived experience and staff from relevant health and social care services, there

was widespread - though not unanimous - support for the introduction of safer

injecting facilities and heroin-assisted treatment services.

CONCLUSIONS: The environment and context in which drug consumption occurs is a

key determinant of harm, and is inextricably linked to upstream social factors.

Public injecting therefore requires a multifaceted response. Though

evidence-based interventions exist, their implementation internationally is

variable: understanding the attitudes of key stakeholders provides important

insights into local facilitators and barriers. Following this study, Glasgow

plans to establish the world's first co-located safer injecting facility and

heroin-assisted treatment service.

DOI: 10.1186/s12889-018-5718-9

PMCID: PMC6030790

PMID: 29973179 [Indexed for MEDLINE]

111. Public Health Rep. 2018 Jul/Aug;133(4):423-431. doi: 10.1177/0033354918774330.

Epub 2018 Jun 27.

The Effect of Incomplete Death Certificates on Estimates of Unintentional

Opioid-Related Overdose Deaths in the United States, 1999-2015.

Buchanich JM(1), Balmert LC(2), Williams KE(3), Burke DS(4).

Author information:

(1)1 Department of Biostatistics, Graduate School of Public Health, University of

Pittsburgh, Pittsburgh, PA, USA.

(2)2 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern

University, Chicago, IL, USA.

(3)3 Office of the Medical Examiner of Allegheny County, Pittsburgh, PA, USA.

(4)4 Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA,

USA.

OBJECTIVES: A complete and accurate count of the number of opioid-related

overdose deaths is essential to properly allocate resources. We determined the

rate of unintentional overdose deaths (non-opioid-related, opioid-related, or

unspecified) in the United States and by state from 1999 to 2015 and the possible

effects of underreporting on national estimates of opioid abuse.

METHODS: We abstracted unintentional drug overdose deaths ( International

Classification of Diseases, 10th Revision, codes X40-X44) with contributory

drug-specific T codes (T36.0-T50.9) from the Mortality Multiple Cause Micro-Data

Files. We assumed that the proportion of unspecified overdose deaths that might

be attributed to opioids would be the same as the proportion of opioid-related

overdose deaths among all overdose deaths and calculated the number of deaths

that could be reallocated as opioid-related for each state and year. We then

added these reallocated deaths to the reported deaths to determine their

potential effect on total opioid-related deaths.

RESULTS: From 1999 to 2015, a total of 438 607 people died from unintentional

drug overdoses. Opioid-related overdose deaths rose 401% (from 5868 to 29 383),

non-opioid-related overdose deaths rose 150% (from 3005 to 7505), and unspecified

overdose deaths rose 220% (from 2255 to 29 383). In 5 states (Alabama, Indiana,

Louisiana, Mississippi, and Pennsylvania), more than 35% of unintentional

overdose deaths were coded as unspecified. Our reallocation resulted in

classifying more than 70 000 unspecified overdose deaths as potential additional

opioid-related overdose deaths.

CONCLUSIONS: States may be greatly underestimating the effect of opioid-related

overdose deaths because of incomplete cause-of-death reporting, indicating that

the current opioid overdose epidemic may be worse than it appears.

DOI: 10.1177/0033354918774330

PMCID: PMC6055296 [Available on 2019-07-01]

PMID: 29945473 [Indexed for MEDLINE]

112. Pediatrics. 2018 Jul;142(1). pii: e20173652. doi: 10.1542/peds.2017-3652.

Buprenorphine Exposures Among Children and Adolescents Reported to US Poison

Control Centers.

Post S(1)(2), Spiller HA(3)(4), Casavant MJ(1)(3)(4), Chounthirath T(1), Smith

GA(5)(4)(6).

Author information:

(1)Center for Injury Research and Policy, The Research Institute at Nationwide

Children's Hospital, Columbus, Ohio.

(2)Northeast Ohio Medical University, Rootstown, Ohio.

(3)Central Ohio Poison Center, Columbus, Ohio.

(4)Department of Pediatrics, College of Medicine, The Ohio State University,

Columbus, Ohio; and.

(5)Center for Injury Research and Policy, The Research Institute at Nationwide

Children's Hospital, Columbus, Ohio; gary.smith@nationwidechildrens.org.

(6)Child Injury Prevention Alliance, Columbus, Ohio.

OBJECTIVE: To investigate buprenorphine exposures among children and adolescents

≤19 years old in the United States.

METHODS: Data were analyzed from calls to US poison control centers for 2007-2016

from the National Poison Data System.

RESULTS: From 2007 to 2016, there were 11 275 children and adolescents ≤19 years

old exposed to buprenorphine reported to US poison control centers. Most

exposures were among children <6 years old (86.1%), unintentional (89.2%), and to

a single substance (97.3%). For single-substance exposures, children <6 years old

had greater odds of hospital admission and of serious medical outcome than

adolescents 13 to 19 years old. Adolescents accounted for 11.1% of exposures;

77.1% were intentional (including 12.0% suspected suicide), and 27.7% involved

multiple substances. Among adolescents, the odds of hospital admission and a

serious medical outcome were higher for multiple-substance exposures than

single-substance exposures.

CONCLUSIONS: Buprenorphine is important for the treatment of opioid use disorder,

but pediatric exposure can result in serious adverse outcomes. Manufacturers

should use unit-dose packaging for all buprenorphine products to help prevent

unintentional exposure among young children. Health providers should inform

caregivers of young children about the dangers of buprenorphine exposure and

provide instructions on proper medication storage and disposal. Adolescents

should receive information regarding the risks of substance abuse and misuse.

Suspected suicide accounted for 12% of adolescent exposures, highlighting the

need for access to mental health services for this age group.

Copyright © 2018 by the American Academy of Pediatrics.

DOI: 10.1542/peds.2017-3652

PMID: 29941678 [Indexed for MEDLINE]

Conflict of interest statement: POTENTIAL CONFLICT OF INTEREST: Dr Casavant has

been retained to review and comment on a legal case involving buprenorphine; the

other authors have indicated they have no potential conflicts of interest to

disclose.

113. J Forensic Sci. 2019 Jan;64(1):149-153. doi: 10.1111/1556-4029.13840. Epub 2018

Jun 25.

Acetyl Fentanyl: Trends and Concentrations in Metro Detroit.

Avedschmidt S(1), Schmidt C(1), Isenschmid D(2), Kesha K(3), Moons D(1), Gupta

A(1).

Author information:

(1)Michigan Medicine Department of Pathology/Wayne County Medical Examiner's

Office, 1300 E Warren Ave, Detroit, MI, 48207.

(2)National Medical Services, 3701 Welsh Road, Willow Grove, PA, 19090.

(3)Department of Forensic Pathology, Auckland City Hospital, PO Box 110031,

Auckland, New Zealand, 1148.

Acetyl fentanyl (N-[1-phenethylpiperidin-4-yl]-N-phenylacetamide) is a potent

opioid analgesic with no medicinal uses. We report deaths between 2016 and 2017

at the Medical Examiner's Office in Detroit, MI where acetyl fentanyl was found

in the decedent's blood and compare them to previously published deaths between

2015 and 2016. The recent cases (cohort B) had a mean acetyl fentanyl

concentration of 0.9 ng/mL (range: 0.1-5.3 ng/mL) and an associated higher

concentration of fentanyl along with multiple other drugs present. The older

cases (cohort A) had higher concentrations of acetyl fentanyl (mean: 8.9 ng/mL;

range: 0.28-37 ng/mL) with lower, yet still toxic, concentrations of fentanyl. We

conclude that the cause of death in these recent cases was likely multiple drug

toxicity with fentanyl and that the consistently observed lower peripheral blood

concentrations of acetyl fentanyl are most likely an artifact in the manufacture

of the consumed illicit fentanyl.

© 2018 American Academy of Forensic Sciences.

DOI: 10.1111/1556-4029.13840

PMID: 29940698 [Indexed for MEDLINE]

114. Med Clin North Am. 2018 Jul;102(4):621-634. doi: 10.1016/j.mcna.2018.02.005.

Preventing Opioid Overdose in the Clinic and Hospital: Analgesia and Opioid

Antagonists.

Peglow SL(1), Binswanger IA(2).

Author information:

(1)Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical

School, 825 Fairfax Avenue Suite 710, Norfolk, VA 23507, USA. Electronic address:

Peglowsl@evms.edu.

(2)Institute for Health Research, Kaiser Permanente Colorado, 2550 South Parker

Road, Suite 200, Aurora, CO 80014, USA; Division of General Internal Medicine,

Department of Medicine, University of Colorado, 12631 East 17th Avenue, Academic

Office One, Campus Box B180, Aurora, CO 80045, USA.

Drawing from existing opioid prescribing guidelines, this article describes how

medical providers can reduce the risk of overdose. Through primary prevention,

providers can prevent initial exposure and associated risks by educating

patients, using risk stratification, minimizing opioid dose and duration, and

avoiding coprescribing with sedatives. Secondary prevention efforts include

monitoring patients with urine toxicology and prescription monitoring programs,

and screening for opioid use disorders. Tertiary prevention includes treating

opioid use disorders and providing naloxone to prevent overdose death. Specific

preventive strategies may be required for those with psychiatric disorders or

substance use disorders, adolescents, the elderly, and pregnant women.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.mcna.2018.02.005

PMCID: PMC6029888 [Available on 2019-07-01]

PMID: 29933819 [Indexed for MEDLINE]

115. Health Promot Chronic Dis Prev Can. 2018 Jun;38(6):252-255. doi:

10.24095/hpcdp.38.6.06.

At-a-glance - Lessons learned from launching the Manitoba Take-Home Naloxone

Program.

[Article in English, French; Abstract available in French from the publisher]

Bozat-Emre S(1)(2), Marshall SG(3), Zhong C(1)(4), Reimer J(1)(2)(3).

Author information:

(1)Manitoba Health, Seniors and Active Living, Winnipeg, Manitoba, Canada.

(2)Max Rady College of Medicine, Faculty of Health Sciences, University of

Manitoba, Winnipeg, Manitoba, Canada.

(3)Winnipeg Regional Health Authority, Winnipeg, Manitoba, Canada.

(4)Department of Statistics, Faculty of Science, University of Manitoba,

Winnipeg, Manitoba, Canada.

The Government of Manitoba launched the provincial Take-Home Naloxone Program in

January 2017. By the end of September 2017, there were over 60 sites operating in

Manitoba. These sites distributed 765 kits to people at risk of opioid overdose,

and 93 of these kits were replacement kits used in overdose events. Most of these

events occurred among males (60.2%) and in a private residence (72.0%). Fentanyl

and carfentanil were the most common substances reported during overdose events.

Take-Home Naloxone Program data provide important information about the unique

context of the opioid crisis in Manitoba.

Publisher: Le gouvernement du Manitoba a lancé son programme de naloxone à

emporter à domicile en janvier 2017. Fin septembre 2017, plus de 60 sites de

distribution fonctionnaient dans la province. Ces sites ont distribué 765

trousses aux personnes à risque de surdose d’opioïdes, dont 93 en remplacement

d'une trousse utilisée lors d’une surdose. La plupart de ces surdoses ont touché

des hommes (60,2 %) et ont eu lieu dans une résidence privée (72,0 %). Le

fentanyl et le carfentanil ont été les substances en cause les plus fréquemment

rapportées dans les cas de surdose. Les données du programme de naloxone à

emporter à domicile fournissent des renseignements importants sur le contexte

spécifique de la crise des opioïdes au Manitoba.

DOI: 10.24095/hpcdp.38.6.06

PMCID: PMC6034973

PMID: 29911822 [Indexed for MEDLINE]

Conflict of interest statement: The authors have no conflict of interest to

declare.

116. Health Promot Chronic Dis Prev Can. 2018 Jun;38(6):244-247. doi:

10.24095/hpcdp.38.6.04.

At-a-glance - Hospitalizations and emergency department visits due to opioid

poisoning in Canada.

[Article in English, French; Abstract available in French from the publisher]

O'Connor S(1), Grywacheski V(1), Louie K(1).

Author information:

(1)Canadian Institute for Health Information, Ottawa, Ontario, Canada.

The rise in opioid-related harms is an issue of increasing public health

importance in Canada. This analysis used data from the Hospital Morbidity

Database and the National Ambulatory Care Reporting System to determine the

number of opioid poisoning hospitalizations and emergency department visits in

Canada. Opioid poisoning hospitalizations have increased over the past 10 years,

reaching 15.6 per 100 000 population in 2016/17. Emergency department visits due

to opioid poisoning have also increased in Alberta and Ontario, the two provinces

that collect emergency department data at the level of detail required for this

analysis. These findings highlight the importance of pan- Canadian surveillance

of opioid-related harms, as well as the need for evidence-based policies to help

reduce these harms.

Publisher: L’augmentation des méfaits attribuables aux opioïdes constitue un

problème de plus en plus préoccupant en santé publique au Canada. Cette analyse a

utilisé les données de la Base de données sur la morbidité des hôpitaux et du

Système national de rapports sur les soins ambulatoires pour déterminer le nombre

d’hospitalisations et de visites aux services d’urgence en raison d’un

empoisonnement aux opioïdes au Canada. Le nombre d’hospitalisations pour

empoisonnement aux opioïdes a augmenté au cours des 10 dernières années,

atteignant 15,6 par tranche de 100 000 habitants en 2016-2017, et celui des

visites aux services d’urgence en raison d’un empoisonnement aux opioïdes a

également augmenté en Alberta et en Ontario, les deux provinces qui ont recueilli

des données des services d’urgence assez détaillées pour être analysées. Ces

résultats soulignent l’importance de la surveillance pancanadienne des méfaits

attribuables aux opioïdes, ainsi que la nécessité de politiques fondées sur des

données probantes pour aider à les réduire.

DOI: 10.24095/hpcdp.38.6.04

PMCID: PMC6034974

PMID: 29911820 [Indexed for MEDLINE]

Conflict of interest statement: CIHI has received five years of funding from

Health Canada for work related to the monitoring and surveillance of prescription

drug abuse in Canada. The authors have no other conflicts of interest to

disclose.

117. Health Promot Chronic Dis Prev Can. 2018 Jun;38(6):224-233. doi:

10.24095/hpcdp.38.6.02.

The opioid crisis in Canada: a national perspective.

[Article in English, French; Abstract available in French from the publisher]

Belzak L(1), Halverson J(1).

Author information:

(1)Public Health Agency of Canada, Ottawa, Ontario, Canada.

INTRODUCTION: This review provides a national summary of what is currently known

about the Canadian opioid crisis with respect to opioid-related deaths and harms

and potential risk factors as of December 2017.

METHODS: We reviewed all public-facing opioid-related surveillance or

epidemiological reports published by provincial and territorial ministries of

health and chief coroners' or medical examiners' offices. In addition, we

reviewed publications from federal partners and reports and articles published

prior to December 2017. We synthesized the evidence by comparing provincial and

territorial opioid-related mortality and morbidity rates with the national rates

to look for regional trends.

RESULTS: The opioid crisis has affected every region of the country, although

some jurisdictions have been impacted more than others. As of 2016, apparent

opioid-related deaths and hospitalization rates were highest in the western

provinces of British Columbia and Alberta and in both Yukon and the Northwest

Territories. Nationally, most apparent opioid-related deaths occurred among

males; individuals between 30 and 39 years of age accounted for the greatest

proportion. Current evidence suggests regional age and sex differences with

respect to health outcomes, especially when synthetic opioids are involved.

However, differences between data collection methods and reporting requirements

may impact the interpretation and comparability of reported data.

CONCLUSION: This report identifies gaps in evidence and areas for further

investigation to improve our understanding of the national opioid crisis. The

Public Health Agency of Canada will continue to work closely with the provinces,

territories and national partners to further refine and standardize national data

collection, conduct special studies and expand information-sharing to improve the

evidence needed to inform public health action and prevent opioid-related deaths

and harms.

Publisher: Cette recension offre un panorama à l'échelle nationale de ce que l’on

savait, en décembre 2017, au sujet de la crise des opioïdes au Canada, en matière

de décès et de méfaits liés à la consommation d’opioïdes et en matière de

facteurs de risque potentiels.Nous avons examiné tous les rapports de

surveillance et les rapports épidémiologiques sur les opioïdes destinés au public

ayant été publiés par les ministères de la Santé des provinces et des territoires

et les bureaux des coroners en chef ou des médecins légistes. Nous avons

également examiné les publications de nos partenaires fédéraux ainsi que les

rapports et les articles sur le sujet publiés jusqu'à décembre 2017. Nous avons

synthétisé les données en comparant les taux de mortalité et de morbidité liés à

la consommation d’opioïdes dans les provinces et les territoires aux taux

observés à l’échelle nationale afin de déceler d’éventuelles tendances à

l’échelle régionale.La crise des opioïdes touche toutes les régions du pays, mais

certaines sont plus durement atteintes que d’autres. En effet, depuis 2016, les

taux de décès et d’hospitalisations apparemment liés à la consommation d’opioïdes

sont plus élevés dans les provinces de l’Ouest que sont la Colombie‑Britannique

et l’Alberta, ainsi qu’au Yukon et dans les Territoires du Nord‑Ouest. À

l’échelle nationale, la plupart des décès apparemment liés à la consommation

d’opioïdes sont survenus chez des hommes et ils ont touché en plus grande

proportion les 30 à 39 ans. Les données disponibles laissent penser qu'il existe

des différences régionales en matière de résultats de santé en fonction de l'âge

et du sexe, en particulier lorsque des opioïdes synthétiques sont en cause.

Toutefois, des différences relevant des méthodes de collecte et des exigences

relatives à la déclaration des données peuvent jouer sur l’interprétation et la

comparabilité des résultats.Ce rapport relève des lacunes en ce qui concerne

certaines données et certains domaines, auxquelles il faudra remédier en menant

des études plus approfondies pour mieux comprendre la crise nationale des

opioïdes. L’Agence de la santé publique du Canada va continuer de travailler en

étroite collaboration avec les provinces, les territoires et ses partenaires

nationaux pour affiner et normaliser les processus de collecte de données à

l’échelle nationale, mener des études spécifiques et améliorer l’échange

d’information, afin que l’on dispose de meilleures données sur lesquelles se

fonder pour élaborer des mesures de santé publique et prévenir les décès et les

méfaits liés aux opioïdes.

DOI: 10.24095/hpcdp.38.6.02

PMCID: PMC6034966

PMID: 29911818 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflicts of interest.

118. Arch Phys Med Rehabil. 2018 Oct;99(10):1941-1948. doi:

10.1016/j.apmr.2018.05.013. Epub 2018 Jun 13.

Personality, High-Risk Behaviors, and Elevated Risk of Unintentional Deaths

Related to Drug Poisoning Among Individuals With Spinal Cord Injury.

Krause JS(1), Cao Y(2), DiPiro ND(2), Cuddy E(2).

Author information:

(1)College of Health Professions, Medical University of South Carolina,

Charleston, SC. Electronic address: krause@musc.edu.

(2)College of Health Professions, Medical University of South Carolina,

Charleston, SC.

OBJECTIVE: To identify risk and protective factors for unintentional death

related to drug poisoning from prescription medications, including opioid-related

deaths, and death due to all other causes among participants with spinal cord

injury (SCI).

DESIGN: Prospective cohort study.

SETTING: Large specialty hospital in the southeastern United States.

PARTICIPANTS: Two cohorts of SCI participants (N=3070) (>18y) with chronic (>1y)

traumatic SCI. Cohort 1 was enrolled in 1997-1998 (n=1386), and cohort 2 was

enrolled in 2007-2009 (n=1684).

INTERVENTIONS: N/A.

MAIN OUTCOME MEASURES: Participants completed self-report assessments including

multiple behavioral variables (alcohol, smoking, prescription medication), as

well as the Zuckerman-Kuhlman Personality Questionnaire (ZKPQ). The primary

outcome is unintentional death related to drug poisoning. Mortality status was

determined as of December 31, 2014, using the National Death Index. The Centers

for Disease Control guidelines were used for classifying participants into 3

groups: (1) unintentional death related to drug poisoning, (2) other death, and

(3) alive.

RESULTS: There were 690 deaths (23%), including 24 unintentional deaths related

to drug poisoning (11 from opioids). Binge drinking, medication usage total

score, and impulsive-sensation seeking were risk factors for unintentional death

related to drug poisoning, whereas the ZKPQ activity scale was protective. Risk

factors for other causes of death included older age, greater injury severity,

being nonambulatory, regular smoker, medication use total score, and greater

neuroticism-anxiety scale scores.

CONCLUSIONS: Unintentional deaths related to prescription drug overdose are

associated with a set of risk factors that differs in meaningful ways from risk

of death due to other causes after SCI, and these differences hold the key to

prevention strategies.

Copyright © 2018 American Congress of Rehabilitation Medicine. Published by

Elsevier Inc. All rights reserved.

DOI: 10.1016/j.apmr.2018.05.013

PMID: 29908137

119. Pharmacoepidemiol Drug Saf. 2019 Jan;28(1):39-47. doi: 10.1002/pds.4572. Epub

2018 Jun 11.

Opioid tolerance and clinically recognized opioid poisoning among patients

prescribed extended-release long-acting opioids.

Young JC(1), Lund JL(1), Dasgupta N(2), Jonsson Funk M(1).

Author information:

(1)Department of Epidemiology, Gillings School of Global Public Health,

University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

(2)Injury Prevention Research Center, University of North Carolina at Chapel

Hill, Chapel Hill, NC, USA.

BACKGROUND: In recognition of potential for increased overdose risk, drug labels

for extended-release and long-acting (ER/LA) opioids emphasize the need for

established opioid tolerance prior to initiating high dosages.

OBJECTIVES: Describe the proportion of patients with opioid tolerance prior to

initiation of 90 morphine milligram equivalents (MME) ER/LA opioids and examine

subsequent risk of opioid poisoning.

METHODS: We used Truven Health Analytics' MarketScan Databases (2006-2015) to

identify patients initiating ER/LA opioids ≥90 MME. We examined prescription

histories and describe the proportion of initiators with opioid tolerance

(defined as ≥7 days of 60 MME in the prior 14 days). We adjusted for age, sex,

year of initiation, and baseline comorbidities using inverse probability of

treatment weighted Cox proportional hazards models. We estimated adjusted hazard

ratios and 95% confidence intervals for the effect of opioid tolerance on the

risk of clinically recognized opioid poisoning (based on diagnosis codes) in

specific periods (0-7, 8-30, 31-90, and 91-365 days) following initiation.

RESULTS: Among 372 038 initiators, 38% did not meet opioid tolerance criteria.

The proportion of nontolerant initiators was highest among those initiating

methadone (44%) and fentanyl (42%). Nontolerant patients were 37% more likely to

be diagnosed with opioid poisoning (adjusted hazard ratios = 1.37 [1.07, 1.76])

in the week following ER/LA initiation.

CONCLUSIONS: Over one-third of patients initiating ≥90 MME ER/LA opioids did not

have evidence of opioid tolerance. The 7 days following high dose ER/LA

initiation may represent a high-risk period for clinically diagnosed opioid

poisoning in patients who do not have prior opioid tolerance.

© 2018 John Wiley & Sons, Ltd.

DOI: 10.1002/pds.4572

PMID: 29888409

120. Scand J Public Health. 2019 Jun;47(4):452-461. doi: 10.1177/1403494818779955.

Epub 2018 Jun 11.

Mortality, morbidity and follow-up after acute poisoning by substances of abuse:

A prospective observational cohort study.

Vallersnes OM(1)(2), Jacobsen D(3), Ekeberg Ø(4)(5), Brekke M(1).

Author information:

(1)1 Department of General Practice, University of Oslo, Norway.

(2)2 Oslo Accident and Emergency Outpatient Clinic, Department of Emergency

General Practice, City of Oslo Health Agency, Norway.

(3)3 Department of Acute Medicine, Oslo University Hospital, Norway.

(4)4 Division of Mental Health and Addiction, Oslo University Hospital, Norway.

(5)5 Department of Behavioural Sciences in Medicine, University of Oslo, Norway.

AIMS: Despite the excess mortality and morbidity associated with acute poisoning

by substances of abuse, follow-up is frequently not organised. We assessed

morbidity, including repeated poisoning, and follow-up after acute poisoning by

substances of abuse through charting contacts with health services. We also

charted short-term mortality.

METHODS: Patients 12 years and older treated for acute poisoning by substances of

abuse at a primary care emergency outpatient clinic in Oslo, Norway, were

included consecutively from October 2011 through September 2012. We retrieved

information from national registers on fatalities, hospital admissions, and

contacts at outpatient specialist health services and with general practitioners

(GPs), during the 90 days following a poisoning episode.

RESULTS: We included 1731 patients treated for 2343 poisoning episodes. During

the 90 days following the poisoning, 31% of the patients were treated at somatic

hospitals, 9% admitted to psychiatric hospitals, 37% in treatment at outpatient

psychiatric/addiction specialist health services, 55% saw their GP, while 34% had

no follow-up. The short-term mortality rate was 2.0%, eight times higher than

expected. Increasing age, suicidal intention, opioid poisoning, and severe mental

illness were associated with increased risk of death. Increasing age, male

gender, opioid poisoning, and severe mental illness were associated with repeated

poisoning. Patients with increased risk of repeated poisoning were more likely to

be in follow-up at outpatient specialist psychiatric/addiction services and in

contact with their GP.

CONCLUSIONS: Follow-up measures seem targeted to those most in need, though one

out of three had none. The mortality rate calls for concern.

DOI: 10.1177/1403494818779955

PMID: 29886813 [Indexed for MEDLINE]

121. AMIA Annu Symp Proc. 2018 Apr 16;2017:545-554. eCollection 2017.

Large-scale Analysis of Opioid Poisoning Related Hospital Visits in New York

State.

Chen X(1), Wang Y(1), Yu X(1), Schoenfeld E(1), Saltz M(1), Saltz J(1), Wang

F(1).

Author information:

(1)Stony Brook University, Stony Brook, NY.

Opioid related deaths are increasing dramatically in recent years, and opioid

epidemic is worsening in the United States. Combating opioid epidemic becomes a

high priority for both the U.S. government and local governments such as New York

State. Analyzing patient level opioid related hospital visits provides a data

driven approach to discover both spatial and temporal patterns and identity

potential causes of opioid related deaths, which provides essential knowledge for

governments on decision making. In this paper, we analyzed opioid poisoning

related hospital visits using New York State SPARCS data, which provides

diagnoses of patients in hospital visits. We identified all patients with primary

diagnosis as opioid poisoning from 2010-2014 for our main studies, and from

2003-2014 for temporal trend studies. We performed demographical based studies,

and summarized the historical trends of opioid poisoning. We used frequent item

mining to find co-occurrences of diagnoses for possible causes of poisoning or

effects from poisoning. We provided zip code level spatial analysis to detect

local spatial clusters, and studied potential correlations between opioid

poisoning and demographic and social-economic factors.

PMCID: PMC5977648

PMID: 29854119 [Indexed for MEDLINE]

122. Drug Test Anal. 2018 Sep;10(9):1483-1487. doi: 10.1002/dta.2417. Epub 2018 Jun

29.

The analytical challenges of cyclopropylfentanyl and crotonylfentanyl: An

approach for toxicological analysis.

Maher S(1), Elliott SP(1), George S(1).

Author information:

(1)Alere Forensics, Malvern Hills Science Park, Geraldine Road, Malvern, WR14

3SZ, UK.

New psychoactive substances (NPS) are increasingly being seen in forensic

casework globally and encompass a number of types of drugs including "designer

opioids", especially fentanyl analogues, which are of particular concern due to

their high potency and significant risk of toxicity. They are often sold as

heroin or mixed with other illicit drugs and therefore users may be unaware they

are taking such hazardous compounds. Two fentanyl analogues that have recently

been detected are cyclopropylfentanyl and crotonylfentanyl. In order to

accurately determine the prevalence of such compounds in clinical and forensic

casework, including potential toxicity, they need to be correctly identified

using definitive and defensible techniques. Cyclopropylfentanyl and

crotonylfentanyl are structural isomers, and it has previously been highlighted

that these 2 compounds are analytically difficult to specifically identify owing

to their similarity in structure and chromatographic behaviour. To further

investigate in an attempt to overcome this problem, analysis of certified

reference material using high performance liquid chromatography with diode array

UV detection (HPLC-DAD), liquid chromatography-tandem mass spectrometry

(LC-MS/MS), and liquid chromatography-quadrupole time-of-flight-mass spectrometry

(LC-QToF-MS) has been performed. Whilst the compounds were shown to have an

identical mass-spectral fragmentation pattern, they had different UV spectra.

This was coupled with a discernible difference in retention time with the HPLC

conditions applied, allowing differentiation of the 2 compounds. Using this

approach, cyclopropylfentanyl was positively identified and subsequently

quantified in 4 fatalities with the exclusion of crotonylfentanyl.

© 2018 John Wiley & Sons, Ltd.

DOI: 10.1002/dta.2417

PMID: 29803198 [Indexed for MEDLINE]

123. Drug Test Anal. 2018 Sep;10(9):1474-1482. doi: 10.1002/dta.2414. Epub 2018 Jun

29.

Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high

resolution mass spectrometry and findings in forensic toxicology casework.

Fogarty MF(1), Papsun DM(2), Logan BK(1)(2).

Author information:

(1)The Center for Forensic Science Research and Education (CFSRE) at the Fredric

Rieders Family Foundation, Willow Grove, Pennsylvania.

(2)NMS Labs, Willow Grove, 19090, Pennsylvania.

3-methylfentanyl (3-MF),

N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide, has reappeared on the

US illicit drug market since its disappearance after a series of overdose deaths

in 1988. 3-MF presents an analytical challenge, due to presence of cis and trans

stereoisomers, each with different potencies, and ultimately very low

concentrations in the blood after use. A method was developed using liquid

chromatography-time-of-flight-mass spectrometry for the analysis of (±)-cis-3-MF

and (±)-trans-3-MF in blood specimens after solid phase extraction. The linear

dynamic range of this method was 0.1-10 ng/mL. Blood samples from 25 postmortem

cases and 2 human performance case involving 3-MF were submitted for quantitative

analysis. The mean and median concentration for the (±)-cis-3-MF were 0.84 ng/mL

(±0.81) and 0.67 ng/mL, respectively, range 0.14-3.43 ng/mL. The resulting

(±)-trans-3-MF mean concentration was 0.46 ng/mL (±0.38) and the median

concentration was 0.37 ng/mL with a range of 0.11-1.90 ng/mL. The resulting

(±)-cis-3-MF and (±)-trans-3-MF concentrations were summed to give the total

amount of 3-MF present in the case with the resulting average concentration at

1.28 ng/mL (±1.16), median at 1.01 ng/mL and range 0.18-5.18. As the estimated

dose of this compound is approximately 0.1 mg-0.5 mg with the resulting

concentrations in the sub-nanogram range, it is necessary for forensic toxicology

laboratories to obtain instruments sensitive enough to detect these substances in

driving under the influence of drugs and postmortem cases. Quantitation of 3-MF

with separation of (±)-cis and (±)-trans-3-MF provides additional detail for more

specific toxicological interpretation.

© 2018 John Wiley & Sons, Ltd.

DOI: 10.1002/dta.2414

PMID: 29801193 [Indexed for MEDLINE]

124. JAMA. 2018 Jun 5;319(21):2158-2160. doi: 10.1001/jama.2018.4648.

As Overdoses Climb, Emergency Departments Begin Treating Opioid Use Disorder.

Rubin R.

DOI: 10.1001/jama.2018.4648

PMID: 29800009 [Indexed for MEDLINE]

125. J Clin Pharm Ther. 2018 Dec;43(6):784-789. doi: 10.1111/jcpt.12701. Epub 2018 May

23.

Risk factors for opioid overdose among hospitalized patients.

Vu Q(1), Beselman A(2), Monolakis J(2), Wang A(3), Rastegar D(2).

Author information:

(1)University of Maryland School of Pharmacy, Baltimore, MD, USA.

(2)Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.

(3)MedStar Union Memorial Hospital, Baltimore, MD, USA.

WHAT IS KNOWN AND OBJECTIVE: Hospitalized patients are at risk for opioid

overdose. Little is known about the risk factors for these events.

METHOD: Opioid overdose cases were identified by naloxone orders in computerized

order entry system from a single institution. For each case, two controls were

randomly selected. Data were collected on factors including age, gender, weight,

opioid dose, route of administration, concomitant CNS depressants, renal function

and comorbid conditions.

RESULTS AND DISCUSSION: Between 2010 and 2013, we identified 44 cases of opioid

overdose (OD), none of which were fatal, and matched these to 88 controls (no

OD). Patients with a history of substance use disorder were excluded from the

study. Factors associated with opioid overdose included age of 65 or older (40.9%

OD vs 29.5% no OD, P = .026), being in an ICU (MICU/CICU 27.3% OD vs. 3.4% no OD,

P < .001; SICU 18.1% OD vs 5.7% no OD, P = .031) and renal impairment (eGFR ≤60,

50.0% OD vs 28.4% no OD, P = .034). Total 24-hour opioid dose was lower in OD

group, but the difference was not statistically significant (71.9 vs 107.2 mg

morphine equivalent, P = .116). OD cases were more likely to have received

concomitant CNS depressants, but the difference was statistically significant

only for those who received 3 or more (15.9% OD vs 0% no OD, P = <.001). Heart

disease was the only comorbidity significantly associated with an increased risk

of opioid overdose (43.2% vs 20.5%, P = .025). Patient's BMI, duration of opioid

use, route of administration and history of COPD and/or psychiatry were not

associated with opioid overdoses.

WHAT IS NEW AND CONCLUSION: Among hospitalized patients, risk factors of opioid

overdose include age of 65 or greater, being in an ICU, renal impairment and

concomitant administration of CNS depressant medications. These findings may help

with the development and implementation of measures to prevent overdose.

© 2018 John Wiley & Sons Ltd.

DOI: 10.1111/jcpt.12701

PMID: 29797421 [Indexed for MEDLINE]

126. J Anal Toxicol. 2018 Nov 1;42(9):592-604. doi: 10.1093/jat/bky035.

Analysis of Fentanyl and 18 Novel Fentanyl Analogs and Metabolites by LC-MS-MS,

and report of Fatalities Associated with Methoxyacetylfentanyl and

Cyclopropylfentanyl.

Fogarty MF(1), Papsun DM(2), Logan BK(1)(2).

Author information:

(1)The Center for Forensic Science Research and Education (CFSRE), 2300 Stratford

Ave, Willow Grove, PA, USA.

(2)Toxicology, NMS Labs, 2300 Welsh Rd, Willow Grove, PA, USA.

Methoxyacetylfentanyl and cyclopropylfentanyl are two of the newest illicit

opioids that are infiltrating the heroin market. Methoxyacetylfentanyl and

cyclopropylfentanyl were reported by the Drug Enforcement Administration (DEA) in

their third quarter report of 2017 to have been chemically identified seven and

five times, respectively, from drug evidence analyzed by the DEA's lab system; Q3

was the first time cyclopropylfentanyl was identified by the DEA's lab system,

while methoxyacetylfentanyl was reported one time in Q2 2017. A method was

developed using liquid chromatography tandem mass spectrometry for the

quantitation of fentanyl, norfentanyl and 17 fentanyl analogs: furanylfentanyl,

butyrylfentanyl, despropionylfentanyl (4-ANPP), methoxyacetylfentanyl,

tetrahydrofuran fentanyl, fluoro-isobutyrylfentanyl, acrylfentanyl,

para-fluorofentanyl, ortho-fluorofentanyl, carfentanil, beta-methylfentanyl,

isobutyrylfentanyl, para-methylfentanyl, cyclopentylfentanyl,

cyclopropylfentanyl, beta-hydroxyfentanyl and alpha-methylfentanyl. The

calibration range for all compounds was 0.1-100 ng/mL. Blood samples from 42

postmortem cases involving cyclopropylfentanyl and methoxyacetylfentanyl from

Florida, Illinois, Michigan and Tennessee were submitted for toxicological

analysis. The mean and median concentration for the cases testing positive for

cyclopropylfentanyl (n = 32) was 15.3 (±11.9) ng/mL and 12.3 ng/mL, respectively,

with a range of 1.4-43.3 ng/mL. The mean (±SD) and median concentrations for the

11 cases quantitatively confirmed (3 cases were below the limit of quantitation)

for methoxyacetylfentanyl was 17.7 (±11.4) ng/mL and 15.1 ng/mL respectively,

with a range of 0.21-39.9 ng/mL. These novel illicit substances typically are

outside the scope of routine drug testing by hospitals and toxicology

laboratories or below the sensitivity levels for the detection of these

substances in biological specimens. These compounds have not previously been

studied in humans; therefore, it is significant to be able to associate the

pharmacological effects derived from case reports to the quantitative values

found in the postmortem specimens.

DOI: 10.1093/jat/bky035

PMID: 29750250 [Indexed for MEDLINE]

127. Toxicol Mech Methods. 2018 Oct;28(8):555-562. doi: 10.1080/15376516.2018.1475537.

Epub 2018 Jun 13.

Utilizing postmortem drug concentrations in mechanistic modeling and simulation

of cardiac effects: a proof of concept study with methadone.

Mikkelsen CR(1), Jornil JR(1), Andersen LV(1), Hasselstrøm JB(1), Polak S(2)(3).

Author information:

(1)a Section of Forensic Chemistry, Department of Forensic Medicine , Aarhus

University , Aarhus , Denmark.

(2)b Department of Social Pharmacy, Faculty of Pharmacy , Jagiellonian University

Medical College , Kraków , Poland.

(3)c Simcyp Division , Certara UK , Sheffield , UK.

Methadone-related poisoning has been found to be the leading and increasing cause

of death among intoxication cases in several countries. Aside from respiratory

depression, methadone is known to cause QT-prolongation, which may lead to sudden

cardiac death. Concentrations in heart tissue should be more accurate for

estimating cardiotoxic effects. The aim of this study was to investigate whether

the effect of methadone on the QT-interval could be simulated and whether the

concentrations in heart tissues allowed for better prediction of the Bazett

corrected QT-interval (QTcB). A predictive performance study was conducted using

the simulation platform Cardiac Safety Simulator to mimic five literature studies

using their described study conditions. Both free and total plasma and heart

concentrations were investigated using two different in silico models: the

O'Hara-Rudy (ORD) model and the 10 Tusscher (TNNP) model. The results showed that

the QTcB of methadone was best predicted either with total plasma using the TNNP

model or with free plasma using the ORD model. The ORD model was highly sensitive

to the total heart concentrations, resulting in overprediction of the QTcB. The

TNNP model also overpredicted the QTcB, but to a lesser degree than the ORD

model. Furthermore, due to a low baseline QTcB, the ORD model underpredicted the

QTcB for both the free plasma and free heart concentrations. In conclusion, it is

possible to simulate the cardiac effects of methadone, yet several elements

influence the approach uncertainty including but not limited to biophysically

details model of cardiac electrophysiology, exposure data, and input parameters.

DOI: 10.1080/15376516.2018.1475537

PMID: 29747546 [Indexed for MEDLINE]

128. N C Med J. 2018 May-Jun;79(3):195-200. doi: 10.18043/ncm.79.3.195.

Running the Numbers: County Level Dynamics of Heroin Mortality in North Carolina.

Gunn AH(1), Bartlett B(2), Feng G(3), Gayed M(3), Kanter K(3), Onuoha E(3),

Thornton M(3), Muzyk A(4), Schramm-Sapyta N(5).

Author information:

(1)project manager, Duke Institute for Brain Sciences; research assistant,

Duke-Margolis Center for Health Policy, Duke University, Durham, North Carolina.

(2)PhD candidate graduate student, Department of Sociology and Duke Population

Research Institute; fellow and statistical consultant, Program for Advanced

Research in Social Sciences, Duke University.

(3)undergraduate student, Duke Institute for Brain Sciences.

(4)clinical pharmacist, Department of Pharmacy, Duke University Hospital;

associate professor, Department of Pharmacy Practice, Campbell University College

of Pharmacy and Health Sciences, Campbell University, Buies Creek, North

Carolina.

(5)assistant professor of the Practice and chief operating officer, Duke

Institute for Brain Sciences; adjunct assistant professor, Department of

Psychiatry and Behavioral Sciences.

DOI: 10.18043/ncm.79.3.195

PMID: 29735630 [Indexed for MEDLINE]

129. N C Med J. 2018 May-Jun;79(3):192-194. doi: 10.18043/ncm.79.3.192.

Harm Reduction Strategies for the Opiod Crisis.

Castillo T(1).

Author information:

(1)advocacy and communications coordinator, North Carolina Harm Reduction

Coalition, Raleigh, North Carolina tswopecastillo@gmail.com.

In order to reduce disease transmission and overdose death resulting from the

opioid crisis, North Carolina has recently adopted several harm reduction

programs, including community based naloxone distribution and syringe exchange.

Additionally, discussions are taking place about safe injection facilities as a

way to further reduce the harm of opioids.

©2018 by the North Carolina Institute of Medicine and The Duke Endowment. All

rights reserved.

DOI: 10.18043/ncm.79.3.192

PMID: 29735629 [Indexed for MEDLINE]

130. N C Med J. 2018 May-Jun;79(3):172-173. doi: 10.18043/ncm.79.3.172.

Meeting Opioid Users Where They Are: A Service Referral Approach to Law

Enforcement.

Paul L(1).

Author information:

(1)captain, Fayetteville Police Department, Fayetteville, North Carolina

LPaul@ci.fay.nc.us.

DOI: 10.18043/ncm.79.3.172

PMID: 29735622 [Indexed for MEDLINE]

131. N C Med J. 2018 May-Jun;79(3):157-162. doi: 10.18043/ncm.79.3.157.

The Opioid Epidemic in NC: Progress, Challenges, and Opportunities.

Kansagra SM(1), Cohen MK(2).

Author information:

(1)chronic disease and injury section chief, NC Division of Public Health, NC

Department of Health and Human Services, Raleigh, North Carolina

susan.kansagra@dhhs.nc.gov.

(2)secretary, NC Department of Health and Human Services, Raleigh, North

Carolina.

Like many states, North Carolina faces an opioid crisis that has rapidly

intensified in recent years. Addressing this epidemic requires interventions such

as judicious prescribing of opioids, community based prevention efforts, broader

naloxone distribution, law enforcement efforts to curb drug trafficking, and harm

reduction efforts like safe syringe programs. Expanding access to treatment and

recovery services, as well as affordable health insurance for individuals with

substance use disorder or at risk for developing a disorder, is also critical.

North Carolina has made significant progress, but we have much more work to do.

©2018 by the North Carolina Institute of Medicine and The Duke Endowment. All

rights reserved.

DOI: 10.18043/ncm.79.3.157

PMID: 29735617 [Indexed for MEDLINE]

132. N C Med J. 2018 May-Jun;79(3):149-155. doi: 10.18043/ncm.79.3.149.

Facilitators and Barriers to Naloxone Kit Use Among Opioid-Dependent Patients

Enrolled in Medication Assisted Therapy Clinics in North Carolina.

Khatiwoda P(1), Proeschold-Bell RJ(2), Meade CS(3), Park LP(3), Proescholdbell

S(4).

Author information:

(1)Duke Global Health Institute, Durham, North Carolina.

(2)associate research professor, Duke Global Health Institute, Duke Center for

Health Policy & Inequalities Research, Durham, North Carolina Rae.jean@duke.edu.

(3)associate professor, Duke University School of Medicine, Duke Global Health

Institute, Durham, North Carolina.

(4)epidemiologist, Injury and Violence Prevention Branch, North Carolina Division

of Public Health, Raleigh, North Carolina.

BACKGROUND Naloxone-an opioid antagonist that reverses the effects of opioids-is

increasingly being distributed in non-medical settings. We sought to identify the

facilitators of, and barriers to, opioid users using naloxone kits in North

Carolina.METHODS In 2015, we administered a 15-item survey to a convenience

sample of 100 treatment seekers at 4 methadone/buprenorphine Medication Assisted

Therapy (MAT) clinics in North Carolina.RESULTS Seventy-four percent of

participants reported having ever gotten a naloxone kit; this percentage was

higher for females (81%) than males (63%) (P = .06). The primary reason given for

not having a kit was not knowing where to get one. Only 6% had heard of kits from

the media and only 5% received one from a medical provider. Among kit recipients,

56% of both females and males reported mostly or sometimes carrying the kit, with

additional participants reporting always. Reasons for not carrying a kit were no

longer being around drugs, forgetting it, and the kit being too large. Men

discussed the difficulties of carrying the naloxone kits, which are currently too

large to fit in a pocket. Ninety-four percent of naloxone users reported

intending to call emergency services in case of an overdose emergency.LIMITATIONS

Study limitations included a small sample, participants limited to MAT clinics,

and a predominantly white sample.CONCLUSIONS MAT treatment seekers reported a

willingness to carry and use naloxone kits. Education, outreach, media, and

medical providers need to promote naloxone kits. A smaller kit may increase the

likelihood of men carrying one.

©2018 by the North Carolina Institute of Medicine and The Duke Endowment. All

rights reserved.

DOI: 10.18043/ncm.79.3.149

PMID: 29735615 [Indexed for MEDLINE]

133. Drug Metab Pers Ther. 2018 Jun 27;33(2):75-83. doi: 10.1515/dmpt-2017-0040.

Correlation between plasma concentrations of tramadol and its metabolites and the

incidence of seizure in tramadol-intoxicated patients.

Ahmadimanesh M(1)(2), Shadnia S(3)(4), Rouini MR(2), Sheikholeslami B(5), Ahsani

Nasab S(6), Ghazi-Khansari M(7).

Author information:

(1)Department of Pharmacology, School of Medicine, Tehran University of Medical

Sciences, Tehran, Iran.

(2)Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics,

School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

(3)Department of Clinical Toxicology, Loghman-Hakim Hospital, School of Medicine,

Shahid Beheshti University of Medical Sciences, Tehran, Iran.

(4)Excellent Center of Clinical Toxicology, Ministry of Health and Medical

Education, Tehran, Iran.

(5)Faculty of Pharmacy, Lorestan University of Medical Sciences, Khorramabad,

Iran.

(6)Epidemiology and Biostatistics Department, School of Public Health, Tehran

University of Medical Sciences, Tehran, Iran.

(7)Department of Pharmacology, School of Medicine, Tehran University of Medical

Sciences, P.O. Box 1416753955, Tehran, Iran, Tel/Fax: +9821-6640-2569,

E-mail:khansagm@yahoo.com.

Comment in

Drug Metab Pers Ther. 2019 Feb 28;34(1):.

BACKGROUND: Seizure is one of the important symptoms of tramadol poisoning, but

its causes are still unknown. The aim of this study is to find a relationship

between tramadol and the concentrations of its metabolites versus the incidence

of seizures following the consumption of high doses of tramadol.

METHODS: For this purpose, the blood samples of 120 tramadol-intoxicated patients

were collected. The patients were divided in two groups (seizure and

non-seizure). The concentrations of tramadol and its metabolites (M1, M2 and M5)

were measured by using a high-performance liquid chromatography method. The

relationship between tramadol and the levels of its metabolites and seizure

incidences was also investigated.

RESULTS: In 72% of the patients, seizures occurred in the first 3 h after the

ingestion of tramadol. The seizure incidences were significantly correlated with

the patients' gender, concentrations of tramadol, M1 and M2 and the history of

previous seizures (p<0.001). The average concentration of M2 was significantly

higher in males (p=0.003). A previous history of the use of sedative-hypnotics

and the co-ingestion of benzodiazepines and other opioids were shown to

significantly decrease the rate of seizure. The rate of seizure was directly

related to the concentrations of tramadol and its metabolites. Higher M2

concentration in males can be considered a reason for increased incidences of

seizures in males. The plasma concentration of M1 affected the onset of seizure.

CONCLUSIONS: Therefore, it can be concluded that differences in the levels of the

metabolites can affect the threshold of seizure in tramadol-intoxicated patients.

DOI: 10.1515/dmpt-2017-0040

PMID: 29727299 [Indexed for MEDLINE]

134. Pediatrics. 2018 Jun;141(6). pii: e20174232. doi: 10.1542/peds.2017-4232. Epub

2018 May 3.

Unit-Dose Packaging and Unintentional Buprenorphine-Naloxone Exposures.

Wang GS(1)(2), Severtson SG(2), Bau GE(2), Dart RC(2)(3), Green JL(2)(4).

Author information:

(1)Department of Pediatrics, University of Colorado Anschutz Medical Campus,

Aurora, Colorado; george.wang@childrenscolorado.org.

(2)Rocky Mountain Poison and Drug Center, Denver Health and Hospital Authority,

Denver, Colorado.

(3)Department of Emergency Medicine, School of Medicine, University of Colorado,

Denver, Colorado; and.

(4)Inflexxion, Waltham, Massachusetts.

BACKGROUND AND OBJECTIVES: Buprenorphine accounts for the most opioid-related

pediatric hospital admissions when compared with other opioid analgesics. Since

2010, several manufacturers began distributing their buprenorphine products with

unit-dose packaging (UDP). Our main objective in this study is to evaluate the

impact of UDP on unintentional pediatric buprenorphine-naloxone poison center

exposures.

METHODS: This is an observational surveillance study in which the Researched

Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program

is used. The main outcome was cases of unintentional ingestions involving

children <6 years old and buprenorphine-naloxone (combination) products. The

study was split into 3 periods: pre-UDP (first quarter 2008 through fourth

quarter 2010), transition to UDP (first quarter 2011 through fourth quarter

2012), and post-UDP (first quarter 2013 through fourth quarter 2016).

RESULTS: Overall, there were 6217 exposures to combination products. In the

pre-UDP period, there were 20.57 pediatric unintentional exposures per 100 000

prescriptions dispensed; in the transition to UDP period, there were 8.77

pediatric unintentional exposures per 100 000 prescriptions dispensed; and in the

post-UDP period, there were 4.36 pediatric unintentional exposures per 100 000

prescriptions dispensed. This represents a 78.8% (95% confidence interval:

76.1%-81.3%; P < .001) relative decrease from the pre-UDP period.

CONCLUSIONS: The shift from non-UDP to UDP in over 80% of buprenorphine-naloxone

products was associated with a significant decrease in unintentional pediatric

exposures reported to poison centers. Packaging controls should be a mainstay in

the approach to the prevention of unintentional buprenorphine pediatric exposures

as well as exposures to other prescription opioids.

Copyright © 2018 by the American Academy of Pediatrics.

DOI: 10.1542/peds.2017-4232

PMID: 29724879 [Indexed for MEDLINE]

Conflict of interest statement: POTENTIAL CONFLICT OF INTEREST: The authors have

indicated they have no potential conflicts of interest to disclose.

135. JAMA. 2018 May 1;319(17):1819-1821. doi: 10.1001/jama.2018.2844.

Changes in Synthetic Opioid Involvement in Drug Overdose Deaths in the United

States, 2010-2016.

Jones CM(1), Einstein EB(2), Compton WM(2).

Author information:

(1)Substance Abuse and Mental Health Services Administration, Rockville,

Maryland.

(2)National Institute on Drug Abuse, Bethesda, Maryland.

DOI: 10.1001/jama.2018.2844

PMID: 29715347 [Indexed for MEDLINE]

136. N Engl J Med. 2018 Apr 26;378(17):1565-1567. doi: 10.1056/NEJMp1800216.

Strategies for Reducing Opioid-Overdose Deaths - Lessons from Canada.

Wood E(1).

Author information:

(1)From the Department of Medicine, University of British Columbia, and the

British Columbia Centre on Substance Use - both in Vancouver, Canada.

DOI: 10.1056/NEJMp1800216

PMID: 29694813 [Indexed for MEDLINE]

137. J Forensic Sci. 2019 Jan;64(1):144-148. doi: 10.1111/1556-4029.13808. Epub 2018

Apr 23.

Opioid Deaths in Milwaukee County, Wisconsin 2013-2017: The Primacy of Heroin and

Fentanyl.

Peterson BL(1)(2), Schreiber S(1), Fumo N(3), Brooke Lerner E(4).

Author information:

(1)Milwaukee County Medical Examiner's Office, 933 West Highland Avenue,

Milwaukee, WI, 53233.

(2)Department of Pathology, Medical College of Wisconsin, Froedert/Medical

College Lab Building FMCLB 239, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226.

(3)Comprehensive Injury Center, Medical College of Wisconsin, 8701 Watertown

Plank Road, Milwaukee, WI, 53226.

(4)Department of Emergency Medicine, Medical College of Wisconsin, Froedert

Hospital, Pavilion 1P, 9200 W. Wisconsin Avenue, Milwaukee, WI, 53226.

Heroin and fentanyl are the overwhelming and increasing cause of opioid deaths in

Milwaukee County, Wisconsin. We reviewed all drug and opioid deaths from 2013 to

2017 to delineate the specific opioid drugs involved and changes in their

incidence. From 2013 to 2017, 980 deaths were due to opioids, rising from 184 in

2013 to 337 in 2017. In 2017, opioid deaths exceeded combined non-natural deaths

from homicide and suicide. Illicit heroin and fentanyl/analogs caused 84% of

opioid deaths and 80% of drug deaths, with no increase in deaths due to oral

prescription drugs such as oxycodone and hydrocodone. Any approach to decreasing

this dramatic increase in opioid deaths should first focus on interdicting the

supply and cheap availability of these illicit opioids. Fentanyl and its analogs

represent the most deadly opioids and the greatest threat to human life in our

population.

© 2018 American Academy of Forensic Sciences.

DOI: 10.1111/1556-4029.13808

PMID: 29684941 [Indexed for MEDLINE]

138. Pharmacotherapy. 2018 Jun;38(6):e41-e45. doi: 10.1002/phar.2117. Epub 2018 May

22.

The Pharmacokinetics and Pharmacodynamics of Carfentanil After Recreational

Exposure: A Case Report.

Uddayasankar U(1), Lee C(2), Oleschuk C(2), Eschun G(3), Ariano RE(4)(5).

Author information:

(1)Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

(2)Diagnostic Services Manitoba, Winnipeg, Manitoba, Canada.

(3)Pulmonary Medicine and Critical Care, University of Manitoba, Winnipeg,

Manitoba, Canada.

(4)Department of Pharmacy, St. Boniface Hospital, Winnipeg, Manitoba, Canada.

(5)College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada.

Carfentanil and related fentanyl analogs have been linked to a number of overdose

deaths from drug users in several cities across North America. Diagnosis of

carfentanil exposure requires a very high index of clinical suspicion, especially

because available laboratory narcotic screens do not detect this agent. We

describe a 34-year-old man admitted with depressed level of consciousness and in

respiratory failure after recreational exposure to a white powder later inferred

to contain carfentanil. Urine and whole blood samples were obtained for

conventional preliminary drug screen immunoassays for unknown exposures, in

addition to utilizing a high-pressure liquid chromatography-tandem mass

spectrometry assay for quantification of carfentanil and its metabolite. The

patient was intubated and required mechanically assisted ventilation for 31 hours

until he was able to breathe safely on his own. Pharmacokinetic modeling of three

timed blood samples identified the elimination half-life as 5.7 hours for

carfentanil and 11.8 hours for the norcarfentanil metabolite. Awakening and

breathing spontaneously corresponded to an interpolated blood carfentanil

concentration of 0.52 ng/ml. This is the first pharmacokinetic and

pharmacodynamic case report on the recreational use of carfentanil. Critical care

clinicians should anticipate long periods of ventilatory support in the care of

patients exposed to carfentanil.

© 2018 Pharmacotherapy Publications, Inc.

DOI: 10.1002/phar.2117

PMID: 29679387 [Indexed for MEDLINE]

139. Lancet Public Health. 2018 May;3(5):e218-e225. doi:

10.1016/S2468-2667(18)30044-6. Epub 2018 Apr 18.

Distribution of take-home opioid antagonist kits during a synthetic opioid

epidemic in British Columbia, Canada: a modelling study.

Irvine MA(1), Buxton JA(2), Otterstatter M(2), Balshaw R(3), Gustafson R(4),

Tyndall M(2), Kendall P(5), Kerr T(6), Gilbert M(2), Coombs D(7).

Author information:

(1)Institute of Applied Mathematics, University of British Columbia, Vancouver,

BC, Canada; British Columbia Centre for Disease Control, Vancouver, BC, Canada.

(2)School of Population and Public Health, University of British Columbia,

Vancouver, BC, Canada; British Columbia Centre for Disease Control, Vancouver,

BC, Canada.

(3)British Columbia Centre for Disease Control, Vancouver, BC, Canada; George and

Fay Yee Centre for Healthcare Innovation, University of Manitoba, Winnipeg, MB,

Canada.

(4)Vancouver Coastal Health, Vancouver, BC, Canada.

(5)Ministry of Health, Victoria, BC, Canada.

(6)Department of Medicine, University of British Columbia, Vancouver, BC, Canada;

British Columbia Centre on Substance Use, Vancouver, BC, Canada.

(7)Institute of Applied Mathematics, University of British Columbia, Vancouver,

BC, Canada. Electronic address: Coombs@math.ubc.ca.

Comment in

Lancet Public Health. 2018 May;3(5):e204.

Lancet Public Health. 2018 May;3(5):e205-e206.

BACKGROUND: Illicit use of high-potency synthetic opioids has become a global

issue over the past decade. This misuse is particularly pronounced in British

Columbia, Canada, where a rapid increase in availability of fentanyl and other

synthetic opioids in the local illicit drug supply during 2016 led to a

substantial increase in overdoses and deaths. In response, distribution of

take-home naloxone (THN) overdose prevention kits was scaled up (6·4-fold

increase) throughout the province. The aim of this study was to estimate the

impact of the THN programme in terms of the number of deaths averted over the

study period.

METHODS: We estimated the impact of THN kits on the ongoing epidemic among people

who use illicit opioids in British Columbia and explored counterfactual scenarios

for the provincial response. A Markov chain model was constructed explicitly

including opioid-related deaths, fentanyl-related deaths, ambulance-attended

overdoses, and uses of THN kits. The model was calibrated in a Bayesian framework

incorporating population data between Jan 1, 2012, and Oct 31, 2016.

FINDINGS: 22 499 ambulance-attended overdoses and 2121 illicit drug-related

deaths (677 [32%] deaths related to fentanyl) were recorded in the study period,

mostly since January, 2016. In the same period, 19 074 THN kits were distributed.

We estimate that 298 deaths (95% credible interval [CrI] 91-474) were averted by

the THN programme. Of these deaths, 226 (95% CrI 125-340) were averted in 2016,

following a rapid scale-up in distribution of kits. We infer a rapid increase in

fentanyl adulterant at the beginning of 2016, with an estimated 2·3 times (95%

CrI 2·0-2·9) increase from 2015 to 2016. Counterfactual modelling indicated that

an earlier scale-up of the programme would have averted an additional 118 deaths

(95% CrI 64-207). Our model also indicated that the increase in deaths could

parsimoniously be explained through a change in the fentanyl-related overdose

rate alone.

INTERPRETATION: The THN programme substantially reduced the number of overdose

deaths during a period of rapid increase in the number of illicit drug overdoses

due to fentanyl in British Columbia. However, earlier adoption and distribution

of the THN intervention might have had an even greater impact on overdose deaths.

Our findings show the value of a fast and effective response at the start of a

synthetic opioid epidemic. We also believe that multiple interventions are needed

to achieve an optimal impact.

FUNDING: Canadian Institutes of Health Research Partnerships for Health Systems

Improvement programme (grant 318068) and Natural Science and Engineering Research

Council of Canada (grant 04611).

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access

article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights

reserved.

DOI: 10.1016/S2468-2667(18)30044-6

PMID: 29678561 [Indexed for MEDLINE]

140. Addiction. 2018 Aug;113(8):1461-1476. doi: 10.1111/add.14188. Epub 2018 Apr 19.

The impact of buprenorphine and methadone on mortality: a primary care cohort

study in the United Kingdom.

Hickman M(1), Steer C(1), Tilling K(1), Lim AG(1), Marsden J(2), Millar T(3),

Strang J(2), Telfer M(4), Vickerman P(1), Macleod J(1).

Author information:

(1)Population Health Sciences, Bristol Medical School, University of Bristol,

Bristol, UK.

(2)Addictions Department, Institute of Psychiatry, Psychiatry and Neuroscience,

King's College London, London, UK.

(3)Centre for Mental Health and Safety, School of Health Sciences, The University

of Manchester, Manchester, UK.

(4)Bristol Drug Project, Bristol, UK.

AIMS: To estimate whether opioid substitution treatment (OST) with buprenorphine

or methadone is associated with a greater reduction in the risk of all-cause

mortality (ACM) and opioid drug-related poisoning (DRP) mortality.

DESIGN: Cohort study with linkage between clinical records from Clinical Practice

Research Datalink and mortality register.

SETTING: UK primary care.

PARTICIPANTS: A total of 11 033 opioid-dependent patients who received OST from

1998 to 2014, followed-up for 30 410 person-years.

MEASUREMENTS: Exposure to methadone (17 373, 61%) OST episodes or buprenorphine

(9173, 39%) OST episodes. ACM was available for all patients; information on

cause of death and DRP was available for 5935 patients (54%) followed-up for

16 363 person-years. Poisson regression modelled mortality by treatment period

with an interaction between OST type and treatment period (first 4 weeks on OST,

rest of time off OST, first 4 weeks off OST, rest of time out of OST censored at

12 months) to test whether ACM or DRP differed between methadone and

buprenorphine. Inverse probability weights were included to adjust for

confounding and balance characteristics of patients prescribed methadone or

buprenorphine.

FINDINGS: ACM and DRP rates were 1.93 and 0.53 per 100 person-years,

respectively. DRP was elevated during the first 4 weeks of OST [incidence rate

ratio (IRR) = 1.93 95% confidence interval (CI) = 0.97-3.82], the first 4 weeks

off OST (IRR = 8.15, 95% CI = 5.45-12.19) and the rest of time out of OST

(IRR = 2.13, 95% CI = 1.47-3.09) compared with mortality risk from 4 weeks to end

of treatment. Patients on buprenorphine compared with methadone had lower ACM

rates in each treatment period. After adjustment, there was evidence of a lower

DRP risk for patients on buprenorphine compared with methadone at treatment

initiation (IRR = 0.08, 95% CI = 0.01-0.48) and rest of time on treatment

(IRR = 0.37, 95% CI = 0.17-0.79). Treatment duration (mean and median) was

shorter on buprenorphine than methadone (173 and 40 versus 363 and 111,

respectively). Model estimates suggest that there was a low probability that

methadone or buprenorphine reduced the number of DRP in the population: 28 and

21%, respectively.

CONCLUSIONS: In UK general medical practice, opioid substitution treatment with

buprenorphine is associated with a lower risk of all-cause and drug-related

poisoning mortality than methadone. In the population, buprenorphine is unlikely

to give greater overall protection because of the relatively shorter duration of

treatment.

© 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of

Society for the Study of Addiction.

DOI: 10.1111/add.14188

PMCID: PMC6282737

PMID: 29672985

141. Am J Ther. 2018 Nov/Dec;25(6):e752-e755. doi: 10.1097/MJT.0000000000000761.

Delayed Cerebral Edema Leading to Cerebral Hernia in a Patient With Heroin

Overdose.

Amjad W(1), Qureshi WT(2), Farooq AU(3).

Author information:

(1)Department of Internal Medicine, Northwell Health Long Island Jewish Forest

Hills Hospital, Forest Hills, NY.

(2)Department of Cardiology, Wake Forest School of Medicine, Winston Salem, NC.

(3)Department of Medicine, Charleston Area Medical Centre, Charleston, WV.

DOI: 10.1097/MJT.0000000000000761

PMID: 29668488 [Indexed for MEDLINE]

142. Am J Med Qual. 2018 Jul;33(4):345-347. doi: 10.1177/1062860618770032. Epub 2018

Apr 18.

Changing the Narrative: Refocusing the Efforts of Emergency Departments in the

Opioid Epidemic.

Voelker J(1), Maio V(1), Mammen P(1).

Author information:

(1)1 Thomas Jefferson University, Philadelphia, PA.

DOI: 10.1177/1062860618770032

PMID: 29667894 [Indexed for MEDLINE]

143. Drug Test Anal. 2018 Apr 10. doi: 10.1002/dta.2391. [Epub ahead of print]

Mixed intoxication by the synthetic opioid U-47700 and the benzodiazepine

flubromazepam with lethal outcome: Pharmacokinetic data.

Koch K(1), Auwärter V(2), Hermanns-Clausen M(3), Wilde M(2)(4), Neukamm MA(2).

Author information:

(1)ZLMT, MDI, Städtisches Klinikum Karlsruhe, Germany.

(2)Department of Forensic Toxicology, Institute of Forensic Medicine, Medical

Center - University of Freiburg, Faculty of Medicine, University of Freiburg,

Germany.

(3)Poisons Information Center, Departement of General Pediatrics, Adolescent

Medicine and Neonatology, Center for Pediatrics, Medical Center - University of

Freiburg, Faculty of Medicine, University of Freiburg, Germany.

(4)Hermann Staudinger Graduate School, University of Freiburg, Germany.

Novel synthetic opioids and benzodiazepines are an emerging trend on the narcotic

drugs market. We present a lethal case of U-47700 and flubromazepam poisoning. A

24-year-old man suffered apnoea after the consumption of the synthetic opioid

U-47700 in combination with the benzodiazepine flubromazepam. After reanimation

and hospital admission, hypoxic cerebral damage and severe brain oedema were

stated. Six days after admission, mechanical ventilation was discontinued, and

the patient died. Seven blood serum samples and one urine sample collected during

the hospitalisation were analysed by liquid chromatography-tandem mass

spectrometry. In the sample collected 42 minutes after admission, the

concentrations of U-47700 and flubromazepam were 370 and 830 ng/mL, respectively.

Three days later, the concentrations of U-47700 and flubromazepam dropped to 4.2

and 280 ng/mL, respectively. The resulting concentration-time-curves allowed

calculating a U-47700 elimination half-life of approximately six hours and

confirmed the previously reported flubromazepam elimination half-life of around

100 hours. In the presented case, intoxication by the synthetic opioid U-47700

with a contribution of flubromazepam can be assumed as the cause of death. The

concentration-time curves allow an estimation of the clinical course of similar

cases. Flubromazepam may lead to prolonged central-nervous depressant effects.

Copyright © 2018 John Wiley & Sons, Ltd.

DOI: 10.1002/dta.2391

PMID: 29637722

144. JAMA Neurol. 2018 Aug 1;75(8):929-938. doi: 10.1001/jamaneurol.2018.0333.

Risk of Unnatural Mortality in People With Epilepsy.

Gorton HC(1)(2), Webb RT(2)(3), Carr MJ(2)(3), DelPozo-Banos M(4), John A(4),

Ashcroft DM(1)(2).

Author information:

(1)Centre for Pharmacoepidemiology and Drug Safety, Division of Pharmacy and

Optometry, School of Health Sciences, Faculty of Biology, Medicine, and Health,

University of Manchester, MAHSC (Manchester Academic Health Sciences Centre),

Manchester, United Kingdom.

(2)National Institute for Health Research Greater Manchester Patient Safety

Translational Research Centre, University of Manchester, MAHSC, Manchester,

United Kingdom.

(3)Centre for Mental Health and Safety, Division of Psychology and Mental Health,

School of Health Sciences, Faculty of Biology, Medicine and Health, University of

Manchester, MAHSC, Manchester, United Kingdom.

(4)Farr Institute, Swansea University Medical School, Swansea, United Kingdom.

Comment in

Epilepsy Curr. 2018 Nov-Dec;18(6):365-366.

Importance: People with epilepsy are at increased risk of mortality, but, to

date, the cause-specific risks of all unnatural causes have not been reported.

Objective: To estimate cause-specific unnatural mortality risks in people with

epilepsy and to identify the medication types involved in poisoning deaths.

Design, Setting, and Participants: This population-based cohort study used 2

electronic primary care data sets linked to hospitalization and mortality

records, the Clinical Practice Research Datalink (CPRD) in England (from January

1, 1998, to March 31, 2014) and the Secure Anonymised Information Linkage (SAIL)

Databank in Wales (from January 1, 2001, to December 31, 2014). Each person with

epilepsy was matched on age (within 2 years), sex, and general practice with up

to 20 individuals without epilepsy. Unnatural mortality was determined using

International Statistical Classification of Diseases and Related Health Problems,

Tenth Revision codes V01 through Y98 in the Office for National Statistics

mortality records. Hazard ratios (HRs) were estimated in each data set using a

stratified Cox proportional hazards model, and meta-analyses were conducted using

DerSimonian and Laird random-effects models. The analysis was performed from

January 5, 2016, to November 16, 2017.

Exposures: People with epilepsy were identified using primary care epilepsy

diagnoses and associated antiepileptic drug prescriptions.

Main Outcomes and Measures: Hazard ratios (HRs) for unnatural mortality and the

frequency of each involved medication type estimated as a percentage of all

medication poisoning deaths.

Results: In total, 44 678 individuals in the CPRD and 14 051 individuals in the

SAIL Databank were identified in the prevalent epilepsy cohorts, and 891 429

(CPRD) and 279 365 (SAIL) individuals were identified in the comparison cohorts.

In both data sets, 51% of the epilepsy and comparison cohorts were male, and the

median age at entry was 40 years (interquartile range, 25-60 years) in the CPRD

cohorts and 43 years (interquartile range, 24-64 years) in the SAIL cohorts.

People with epilepsy were significantly more likely to die of any unnatural cause

(HR, 2.77; 95% CI, 2.43-3.16), unintentional injury or poisoning (HR, 2.97; 95%

CI, 2.54-3.48) or suicide (HR, 2.15; 95% CI, 1.51-3.07) than people in the

comparison cohort. Particularly large risk increases were observed in the

epilepsy cohorts for unintentional medication poisoning (HR, 4.99; 95% CI,

3.22-7.74) and intentional self-poisoning with medication (HR, 3.55; 95% CI,

1.01-12.53). Opioids (56.5% [95% CI, 43.3%-69.0%]) and psychotropic medication

(32.3% [95% CI, 20.9%-45.3%)] were more commonly involved than antiepileptic

drugs (9.7% [95% CI, 3.6%-19.9%]) in poisoning deaths in people with epilepsy.

Conclusions and Relevance: Compared with people without epilepsy, people with

epilepsy are at increased risk of unnatural death and thus should be adequately

advised about unintentional injury prevention and monitored for suicidal

ideation, thoughts, and behaviors. The suitability and toxicity of concomitant

medication should be considered when prescribing for comorbid conditions.

DOI: 10.1001/jamaneurol.2018.0333

PMCID: PMC6075702

PMID: 29630689

145. Ann Emerg Med. 2018 Jul;72(1):16-23. doi: 10.1016/j.annemergmed.2018.02.022. Epub

2018 Apr 6.

Prognostic Utility of Initial Lactate in Patients With Acute Drug Overdose: A

Validation Cohort.

Cheung R(1), Hoffman RS(2), Vlahov D(3), Manini AF(4).

Author information:

(1)Jacobs School of Medicine and Biomedical Sciences, State University of New

York at Buffalo, Buffalo, NY.

(2)Division of Medical Toxicology, Ronald O. Perelman Department of Emergency

Medicine, NYU School of Medicine, New York, NY.

(3)School of Nursing, University of California at San Francisco, San Francisco,

CA.

(4)Division of Medical Toxicology, Department of Emergency Medicine, the Icahn

School of Medicine at Mount Sinai, Elmhurst Hospital Center, New York, NY.

Electronic address: alex.manini@mssm.edu.

STUDY OBJECTIVE: Previous studies have suggested that the initial emergency

department (ED) lactate concentration may be an important prognostic indicator

for inhospital mortality from acute drug poisoning. We conduct this cohort study

to formally validate the prognostic utility of the initial lactate concentration

in a larger, distinct patient population with acute drug overdose.

METHODS: This observational, prospective, cohort study was conducted during 5

years at 2 urban teaching hospitals. Consecutive adult ED patients with acute

drug overdose had serum lactate levels tested as part of clinical care. The

primary outcome was inpatient fatality. Receiver operating characteristics were

plotted to determine optimal cut points, test characteristics, area under the

curve, odds ratios, and 95% confidence intervals (CIs).

RESULTS: Of 3,739 patients screened, 1,406 were analyzed (56% women; mean age

43.1 years) and 24 died (1.7%). The difference in mean initial lactate

concentration was 5.9 mmol/L (95% CI 3.4 to 8.1 mmol/L) higher in patients who

died compared with survivors. The area under the curve for prediction of fatality

was 0.85 (95% CI 0.73 to 0.95). The optimal lactate cut point for fatality was

greater than or equal to 5.0 (odds ratio 34.2; 95% CI 13.7 to 84.2; 94.7%

specificity). Drug classes for which lactate had the highest utility were

salicylates, sympathomimetics, acetaminophen, and opioids (all area under the

curve ≥0.97); lowest utility was for diuretics and angiotensin-converting enzyme

inhibitors.

CONCLUSION: Initial lactate concentration is a useful biomarker for early

clinical decisionmaking in ED patients with acute drug overdose. Studies of

lactate-tailored management for these patient populations are warranted.

Copyright © 2018 American College of Emergency Physicians. Published by Elsevier

Inc. All rights reserved.

DOI: 10.1016/j.annemergmed.2018.02.022

PMCID: PMC6014898 [Available on 2019-07-01]

PMID: 29628190

146. Forensic Sci Int. 2018 Jun;287:40-46. doi: 10.1016/j.forsciint.2018.03.032. Epub

2018 Mar 26.

Accurate identification of opioid overdose deaths using coronial data.

Roxburgh A(1), Pilgrim JL(2), Hall WD(3), Burns L(4), Degenhardt L(5).

Author information:

(1)National Drug and Alcohol Research Centre (NDARC), University of New South

Wales, NSW 2052, Australia. Electronic address: a.roxburgh@unsw.edu.au.

(2)Department of Forensic Medicine, Monash University, Australia.

(3)National Drug and Alcohol Research Centre (NDARC), University of New South

Wales, NSW 2052, Australia; University of Queensland Clinical Centre for

Research, University of Queensland, Brisbane, QLD 4072, Australia; University of

Queensland Centre for Youth Substance Abuse Research, University of Queensland,

Brisbane, QLD 4006, Australia; National Addiction Centre, Kings College London,

WC2R 2LS, United Kingdom.

(4)National Drug and Alcohol Research Centre (NDARC), University of New South

Wales, NSW 2052, Australia.

(5)National Drug and Alcohol Research Centre (NDARC), University of New South

Wales, NSW 2052, Australia; School of Population and Global Health, University of

Melbourne, VIC 3010, Australia.

INTRODUCTION: Defining drug-related mortality is complex as these deaths can

include a wide range of diseases and circumstances. This paper outlines a method

to identify deaths that are directly due to fatal opioid toxicity (i.e.

overdose), utilising coronial data.

MATERIALS AND METHODS: The National Coronial Information System (NCIS), an online

coronial database containing information on all deaths that are reported to a

coroner in Australia, is used to develop methods to more accurately identify

opioid overdose deaths. The NCIS contains demographic information, Medical Cause

of Death, and associated documentation on toxicology, clinical and police

investigations.

RESULTS: Identifying overdose deaths using the coroner determined Medical Cause

of Death provided greater capture, and specificity, of opioid overdose deaths.

Distinguishing morphine from heroin-related deaths presented challenges,

requiring analysis of clinical and investigative information in addition to

toxicology results. One-quarter of the deaths attributed to morphine were

recorded to heroin as a result of further investigation. There was also some

underestimation of codeine-related deaths. Access to clinical and investigative

information also yields important information in relation to comorbid conditions

among these decedents, such as history of chronic pain, substance use issues and

mental health problems.

CONCLUSIONS: Reliance on toxicology results alone leads to an underestimate of

heroin-related deaths. Differentiating between heroin and pharmaceutical opioid

(e.g. morphine) overdose deaths has important public health and policy

implications, particularly in relation to prescribing practices and development

of a strategic response. Understanding comorbidities among these decedents is

also important in efforts to reduce preventable causes of death such as opioid

overdose.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.forsciint.2018.03.032

PMID: 29627712 [Indexed for MEDLINE]

147. J Emerg Med. 2018 Jun;54(6):815-818. doi: 10.1016/j.jemermed.2018.01.044. Epub

2018 Apr 5.

Recurrent Ethylene Glycol Poisoning with Elevated Lactate Levels to Obtain Opioid

Medications.

Zuckerman M(1), Vo T(2).

Author information:

(1)Department of Emergency Medicine, University of Colorado School of Medicine,

Aurora, Colorado.

(2)Denver Health and Hospital Authority, Department of Emergency Medicine,

Denver, Colorado.

BACKGROUND: Malingering is when a patient feigns illness for secondary gain.

While most patients with malingering manufacture or exaggerate symptoms, some

patients may induce illness. Previous reports of malingering patients inducing

illness include sepsis, kidney pain, migraine, and chest pain. However, acute

poisoning as a manifestation of malingering appears to be rare.

CASE REPORT: We describe the case of a 39-year-old man who presented to the

emergency department complaining of diffuse body pain. The patient reported

multiple admission at outside hospitals for "lactate" and said, "it feels like it

is happening again because of how my body feels." Laboratory findings were

concerning for serum lactate of >20.0 mmol/L and ethylene glycol (EG) level of

19 mg/dL. A chart review found that the man had been admitted for elevated serum

lactate 8 times to area hospitals in several years, often in the setting of EG

poisoning. During these episodes he required intravenous fluids and frequent

intravenous pain medications. When confronted about concern regarding the

recurrent fallacious lactate levels in the setting of factitious EG ingestion,

the patient often became combative and left against medical advice. The primary

metabolite of EG, glycolic acid, can interfere with lactate assays, causing a

false elevation. Our patient apparently recognized this and took advantage of it

to be admitted and receive intravenous opioids. This is the only case known to us

of malingering via EG ingestion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF

THIS?: Emergency physicians should be aware that metabolites of EG may interfere

with serum lactate assay. In addition, they should be aware of possible

malingering-related poisoning and plausible association with requests for

intravenous opioid pain medications. This represents a risk to the patient and

others if undiagnosed.

Copyright © 2018 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jemermed.2018.01.044

PMID: 29627349 [Indexed for MEDLINE]

148. JAMA. 2018 May 22;319(20):2073-2074. doi: 10.1001/jama.2018.4867.

Increasing Naloxone Awareness and Use: The Role of Health Care Practitioners.

Adams JM(1).

Author information:

(1)US Public Health Service.

DOI: 10.1001/jama.2018.4867

PMID: 29621389 [Indexed for MEDLINE]

149. J Anal Toxicol. 2018 Sep 1;42(7):467-475. doi: 10.1093/jat/bky025.

N-Ethyl Pentylone (Ephylone) Intoxications: Quantitative Confirmation and

Metabolite Identification in Authentic Human Biological Specimens.

Krotulski AJ(1), Papsun DM(2), De Martinis BS(1)(3), Mohr ALA(1), Logan BK(1)(2).

Author information:

(1)Center for Forensic Science Research and Education, Fredric Rieders Family

Foundation, 2300 Stratford Ave, Willow Grove, PA, USA.

(2)NMS Labs, 3701 Welsh Rd, Willow Grove, PA, USA.

(3)Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, University of São

Paulo, Ribeirão Preto, SP, Brazil.

N-ethyl pentylone (ephylone) has been identified as the most recent novel

stimulant to emerge into the arena of evolving novel psychoactive substances

(NPS). Due to its novelty, information regarding case reports with associated

quantitative confirmations, biotransformation pathways, and identified unique

metabolites will assist the scientific community in understanding the

implications of the emergence and risks associated with N-ethyl pentylone use.

Authentic blood specimens (n = 26) submitted as part of toxicological death

investigations or drugged driving casework tested positive for N-ethyl pentylone,

and were quantitatively analyzed by liquid chromatography tandem mass

spectrometry (LC-MS-MS). N-ethyl pentylone concentrations ranged from 12 to 1,200

ng/mL, with mean (±standard deviation) and median concentrations of 313 (±366)

and 125 ng/mL, respectively, excluding one case measured at 50,000 ng/mL. N-ethyl

pentylone was often found in combination with other drugs of abuse and NPS,

include a variety of novel opioids including fentanyl analogs. Oral fluid

specimens (n = 5), collected from recreational drug users at a dance music

festival, were quantitatively analyzed using LC-MS-MS. Concentrations ranged from

12.6 to 1,377 ng/mL. Additional analysis was performed to characterize the

metabolic profile of N-ethyl pentylone using human liver microsomes (HLM),

followed by confirmation of the presence of the proposed metabolites in a subset

of the blood specimens and oral fluid specimens. Metabolomic analysis was

performed using a liquid chromatograph quadrupole time-of-flight mass

spectrometer (LC-QTOF), followed by data processing using MetabolitePilot™

software. In vivo verification of in vitro HLM-generated metabolites resulted in

the confirmation of four metabolites. Reduction of the beta-ketone to an alcohol

resulted in the most prominent metabolite found in the authentic specimens, and

its uniqueness to N-ethyl pentylone leads to this metabolite being an appropriate

biomarker to determine N-ethyl pentylone ingestion. This is the first study to

report N-ethyl pentylone concentrations and to characterize the metabolic profile

of N-ethyl pentylone.

DOI: 10.1093/jat/bky025

PMID: 29618077 [Indexed for MEDLINE]

150. MMWR Morb Mortal Wkly Rep. 2018 Mar 30;67(12):349-358. doi:

10.15585/mmwr.mm6712a1.

Overdose Deaths Involving Opioids, Cocaine, and Psychostimulants - United States,

2015-2016.

Seth P, Scholl L, Rudd RA, Bacon S.

During 1999‒2015, 568,699 persons died from drug overdoses in the United States.*

Drug overdose deaths in the United States increased 11.4% from 2014 to 2015

resulting in 52,404 deaths in 2015, including 33,091 (63.1%) that involved an

opioid. The largest rate increases from 2014 to 2015 occurred among deaths

involving synthetic opioids other than methadone (synthetic opioids) (72.2%) (1).

Because of demographic and geographic variations in overdose deaths involving

different drugs (2,3),† CDC examined age-adjusted death rates for overdoses

involving all opioids, opioid subcategories (i.e., prescription opioids, heroin,

and synthetic opioids),§ cocaine, and psychostimulants with abuse potential

(psychostimulants) by demographics, urbanization levels, and in 31 states and the

District of Columbia (DC). There were 63,632 drug overdose deaths in 2016; 42,249

(66.4%) involved an opioid.¶ From 2015 to 2016, deaths increased across all drug

categories examined. The largest overall rate increases occurred among deaths

involving cocaine (52.4%) and synthetic opioids (100%), likely driven by

illicitly manufactured fentanyl (IMF) (2,3). Increases were observed across

demographics, urbanization levels, and states and DC. The opioid overdose

epidemic in the United States continues to worsen. A multifaceted approach, with

faster and more comprehensive surveillance, is needed to track emerging threats

to prevent and respond to the overdose epidemic through naloxone availability,

safe prescribing practices, harm-reduction services, linkage into treatment, and

more collaboration between public health and public safety agencies.

DOI: 10.15585/mmwr.mm6712a1

PMCID: PMC5877356

PMID: 29596405 [Indexed for MEDLINE]

Conflict of interest statement: No conflicts of interest were reported.

151. Healthc Q. 2018 Jan;20(4):10-12. doi: 10.12927/hcq.2018.25430.

Opioid-Related Harms in Canada.

Grywacheski V(1), O'Connor S(2), Louie K(3).

Author information:

(1)Senior analyst with the PDA team at CIHI, Ottawa, Ontario. Vera can be reached

by e-mail at vgrywacheski@cihi.ca.

(2)Senior analyst with the PDA team at CIHI, Ottawa, Ontario. Shannon can be

reached by e-mail at soconnor@cihi.ca.

(3)Program lead with the PDA team at CIHI, Ottawa, Ontario. Krista can be reached

by e-mail at klouie@cihi.ca.

The rise in harms associated with opioids is an issue of increasing public health

importance in Canada. The Government of Canada recently reported 2,816 apparent

opioid-related deaths across the country in 2016. Recent 2017 data show that

deaths involving fentanyl-related opioids have doubled from January to March as

compared to the same time period in 2016 (Government of Canada 2017). Additional

measures that provide a better understanding of opioid-related harms, such as

hospitalizations and emergency department (ED) visits, are a high priority. The

objective of this study is to present pan-Canadian data on hospitalizations and

ED visits because of opioid poisoning.

© 2018 Longwoods Publishing.

DOI: 10.12927/hcq.2018.25430

PMID: 29595421 [Indexed for MEDLINE]

152. CMAJ. 2018 Mar 26;190(12):E355-E362. doi: 10.1503/cmaj.170666.

Person-level changes in oxycodone use after the introduction of a

tamper-resistant formulation in Australia.

Schaffer AL(1), Buckley NA(2), Degenhardt L(2), Larance B(2), Cairns R(2),

Dobbins TA(2), Pearson SA(2).

Author information:

(1)Centre for Big Data Research in Health (Schaffer, Pearson), University of New

South Wales; School of Medical Sciences (Buckley), University of Sydney; National

Drug and Alcohol Research Centre (Degenhardt, Larance, Dobbins), University of

New South Wales, Sydney, AU; New South Wales Poisons Information Centre (Cairns),

Children's Hospital at Westmead, Westmead, AU andrea.schaffer@unsw.edu.au.

(2)Centre for Big Data Research in Health (Schaffer, Pearson), University of New

South Wales; School of Medical Sciences (Buckley), University of Sydney; National

Drug and Alcohol Research Centre (Degenhardt, Larance, Dobbins), University of

New South Wales, Sydney, AU; New South Wales Poisons Information Centre (Cairns),

Children's Hospital at Westmead, Westmead, AU.

BACKGROUND: Australia introduced tamper-resistant controlled-release (CR)

oxycodone in April 2014. We quantified the impact of the reformulation on

dispensing, switching and poisonings.

METHODS: We performed interrupted time-series analyses using

population-representative national dispensing data from 2012 to 2016. We measured

dispensing of oxycodone CR (≥ 10 mg), discontinuation of use of strong opioids

and switching to other strong opioids after the reformulation compared with a

historical control period. Similarly, we compared calls about intentional opioid

poisoning using data from a regional poisons information centre.

RESULTS: After the reformulation, dispensing decreased for 10-30 mg (total level

shift -11.1%, 95% confidence interval [CI], -17.2% to -4.6%) and 40-80 mg

oxycodone CR (total level shift -31.5%, 95% CI -37.5% to -24.9%) in participants

less than 65 years of age but was unchanged in people 65 years of age or older.

Compared with the previous year, discontinuation of use of strong opioids did not

increase (adjusted hazard ratio [HR] 0.95, 95% CI 0.91 to 1.00), but switching to

oxycodone/naloxone did increase (adjusted HR 1.54, 95% CI 1.32 to 1.79).

Switching to morphine varied by age (p < 0.001), and the greatest increase was in

participants less than 45 years of age (adjusted HR 4.33, 95% CI 2.13 to 8.80).

Participants switching after the reformulation were more likely to be dispensed a

tablet strength of 40 mg or more (adjusted odds ratio [OR] 1.40, 95% CI 1.09 to

1.79). Calls for intentional poisoning that involved oxycodone taken orally

increased immediately after the reformulation (incidence rate ratio (IRR) 1.31,

95% CI 1.05-1.64), but there was no change for injected oxycodone.

INTERPRETATION: The reformulation had a greater impact on opioid access patterns

of people less than 65 years of age who were using higher strengths of oxycodone

CR. This group has been identified as having an increased risk of problematic

opioid use and warrants closer monitoring in clinical practice.

© 2018 Joule Inc. or its licensors.

DOI: 10.1503/cmaj.170666

PMCID: PMC5871439

PMID: 29581162

Conflict of interest statement: Competing interests: Briony Larance and Louisa

Degenhardt received untied investigator-driven educational grants from Reckitt

Benckiser for postmarketing surveillance studies of buprenorphine–naloxone

tablets and film, development of an opioid-related behaviour scale and a study

examining the uptake of opioid substitution therapy among chronic noncancer pain

patients; from Indivior for studies of buprenorphine depot in community treatment

and prison settings; and from Mundipharma for postmarketing surveillance studies

of Reformulated OxyContin. Briony Larance, Louisa Degenhardt and Rose Cairns

received an untied investigator-driven educational grant from Seqirus for

postmarketing surveillance studies of tapentadol. These funders played no role in

the design, conduct or interpretation of these studies’ findings, and there were

no restrictions placed on publication. No other competing interests were

declared.

153. BMJ Open. 2018 Mar 23;8(3):e020006. doi: 10.1136/bmjopen-2017-020006.

Opioid use and harms associated with a sustained-release tapentadol formulation:

a postmarketing study protocol.

Peacock A(1)(2), Larance B(1), Farrell M(1), Cairns R(3)(4), Buckley N(3)(4),

Degenhardt L(1)(5)(6)(7).

Author information:

(1)National Drug and Alcohol Research Centre, University of New South Wales,

Sydney, New South Wales, Australia.

(2)School of Medicine, University of Tasmania, Hobart, Tasmania, Australia.

(3)NSW Poisons Information Centre, The Children's Hospital at Westmead, Sydney,

New South Wales, Australia.

(4)School of Medical Sciences, University of Sydney, Sydney, New South Wales,

Australia.

(5)School of Population and Global Health, University of Melbourne, Melbourne,

Victoria, Australia.

(6)Murdoch Children's Research Institute, Parkville, Victoria, Australia.

(7)Department of Global Health, School of Public Health, University of

Washington, Seattle, Washington, USA.

INTRODUCTION: It has been argued that tapentadol may pharmacologically have lower

abuse potential than other pharmaceutical opioids currently available. However,

there has been no comprehensive triangulation of data regarding use and harms

associated with this formulation. A sustained-release formulation (SRF) of

tapentadol (Palexia) was released in Australia in 2011 and listed for public

subsidy in 2013. We summarise here the methods of a postmarketing study which

will measure postintroduction: (1) population level availability, (2)

extramedical use and diversion, (3) attractiveness for extramedical use and (4)

associated harms, of tapentadol compared against other pharmaceutical opioids.

METHODS AND ANALYSIS: We evaluated key sources on pharmaceutical use and harms in

Australia. This review indicateddata from four sources that disaggregate

pharmaceutical opioid formulations and capture tapentadol SRF could be

triangulated. These data sources comprised: (1) national pharmaceutical opioid

community sales data from 2011 to 2017, (2) national pharmaceutical opioid

poisonings reported to Poison Information Centres (PICs) from 2011 to 2017, (3)

number of vendors on online marketplaces listing pharmaceutical opioids for sale

and (4) data on pharmaceutical opioid extramedical use, attractiveness and harms

from interviews with people who regularly inject drugs in Australia.

ETHICS AND DISSEMINATION: Ethics approval is not required for use of

pharmaceutical sales data. Ethics approval has been obtained for use of national

pharmaceutical opioid poisonings reported to PICs (LNR/16/SCHN/44) and for use of

online marketplace data and interview data from people who inject drugs

(HC12086). Key findings will be published mid-2018 in a peer-reviewed academic

journal, and presented at various conferences and professional meetings.

© Article author(s) (or their employer(s) unless otherwise stated in the text of

the article) 2018. All rights reserved. No commercial use is permitted unless

otherwise expressly granted.

DOI: 10.1136/bmjopen-2017-020006

PMCID: PMC5875643

PMID: 29574444 [Indexed for MEDLINE]

Conflict of interest statement: Competing interests: Some of the investigators

have received investigator-initiated untied educational grants from Reckitt

Benckiser/Indivior for studies of buprenorphine-naloxone (BL, LD), buprenorphine

depot (BL, LD, MF), naloxone (LD, MF), the development of an opioid-related

behavior scale (BL, LD), the pharmacogenetic predictors of treatment success (RA)

and a study of opioid-substitution therapy uptake among patients with chronic

non-cancer pain (BL, LD). Some of the investigators have also received

investigator-initiated untied educational grants from Mundipharma for

postmarketing surveillance of a tamper-resistant opioid formulation (AP, BL, LD,

MF).

154. N Engl J Med. 2018 Mar 22;378(12):1157-1158. doi: 10.1056/NEJMc1716355.

Acute Amnestic Syndrome Associated with Fentanyl Overdose.

Barash JA(1), Ganetsky M(2), Boyle KL(2), Raman V(2), Toce MS(3), Kaplan S(4),

Lev MH(5), Worth JL(5), DeMaria A Jr(6).

Author information:

(1)Soldiers' Home, Chelsea, MA.

(2)Beth Israel Deaconess Medical Center, Boston, MA.

(3)Boston Children's Hospital, Boston, MA.

(4)Harvard Vanguard Medical Associates, Boston, MA.

(5)Massachusetts General Hospital, Boston, MA.

(6)Massachusetts Department of Public Health, Jamaica Plain, MA

alfred.demaria@massmail.state.ma.us.

Comment in

N Engl J Med. 2018 Jun 07;378(23):2247.

DOI: 10.1056/NEJMc1716355

PMID: 29562161 [Indexed for MEDLINE]

155. J Stud Alcohol Drugs. 2018 Mar;79(2):286-292.

Trends in Injector Deaths in Ireland, as Recorded by the National Drug-Related

Deaths Index, 1998-2014.

Lynn TM(1), Lynn E(1), Keenan E(2), Lyons S(1).

Author information:

(1)Health Research Board, Grattan House, Dublin, Ireland.

(2)Addiction Services, National Office for Social Inclusion, Health Service

Executive Primary Care Division, Palmerstown, Dublin, Ireland.

OBJECTIVE: The purpose of this study was to provide trend analysis on all deaths

among drug users who injected at or around the time of their death in Ireland

between 1998 and 2014.

METHOD: A review of the data recorded by the National Drug-Related Deaths Index

(NDRDI) was conducted to identify individuals who were known to be injecting at

or around the time of their death, from 1998 to 2014.

RESULTS: Between 1998 and 2014, 16,500 deaths were recorded by the NDRDI. Of

these, 792 (5%) people were known to be injecting at or around the time of death;

90% were poisoning deaths (n = 715) and 10% nonpoisoning deaths (n = 77). The

majority of those who died while injecting were male (n = 682; 86%). Most people

were living in Dublin city or county (n = 550; 69%). One fifth of those who died

were homeless (n = 149; 19%). Opioids, specifically heroin, were implicated in

the vast majority of injector poisoning deaths (n = 673; 94%), most commonly in

association with polydrug use (n = 417; 62%). Single opioid poisoning resulted in

256 deaths (38%), and two fifths of those who died by single opioid poisoning

were not alone at the time of death (n = 105; 41%).

CONCLUSIONS: This study is the first to describe the trends in all deaths among

drug users who injected at or around the time of their death in Ireland between

1998 and 2014. The analysis provides empirical evidence that can be used by

policy makers to support the ongoing improvement of drug treatment services, harm

reduction initiatives, and overdose prevention strategies for people who inject

drugs.

PMID: 29553358

156. J Emerg Nurs. 2018 Mar;44(2):207-209. doi: 10.1016/j.jen.2017.11.008.

Dantrolene for Treatment of Suspected Neuroleptic Malignant Syndrome.

Whyte CJ(1), Rosini JM(2).

Author information:

(1)Newark, DE. Electronic address: colleen.j.whyte@gmail.com.

(2)Newark, DE.

DOI: 10.1016/j.jen.2017.11.008

PMID: 29548378 [Indexed for MEDLINE]

157. Bull World Health Organ. 2018 Mar 1;96(3):165-172. doi: 10.2471/BLT.17.196287.

Epub 2018 Feb 5.

Lead poisoning outbreak among opium users in the Islamic Republic of Iran,

2016-2017.

Ghane T(1), Zamani N(2), Hassanian-Moghaddam H(3), Beyrami A(4), Noroozi A(5).

Author information:

(1)Drug and Poison Information Centre, Food and Drug Administration of the

Islamic Republic of Iran, Tehran, Iran.

(2)Social Determinants of Health Research Center, Shahid Beheshti University of

Medical Sciences, Teheran, Islamic Republic of Iran.

(3)Department of Clinical Toxicology, School of Medicine, Shahid Beheshti

University of Medical Sciences, Arabi Ave, Daneshjoo Blvd, Velenjak, Tehran

19839-63113, Islamic Republic of Iran.

(4)Office of Narcotics and Controlled Substances, Food and Drug Administration of

the Islamic Republic of Iran, Tehran, Islamic Republic of Iran.

(5)Iranian National Center for Addiction Studies, Tehran University of Medical

Sciences, Tehran, Islamic Republic of Iran.

Objective: To describe an outbreak of lead poisoning among opium users in the

Islamic Republic of Iran and estimate the number of affected people in the

country.

Methods: We used data from the country's largest poison treatment centre to

illustrate the epidemiology of an outbreak of lead poisoning in oral opium users.

We describe the government's referral and treatment guidelines in response to the

outbreak. Based on the number of individuals treated and previous studies on the

prevalence of oral opium use we estimated the total number of people at risk of

lead-contaminated opium nationwide.

Findings: In February 2016, we noticed a steep increase in the numbers of oral

opium users referred to our poison treatment centre with abdominal pain, anaemia

and constipation. Numbers peaked in June 2016 but the outbreak was ongoing in

August 2017. The mean blood lead level in a sample of 80 patients was 140.3 µg/dL

(standard deviation: 122.6). Analysis of an illegal opium sample showed 3.55 mg

lead in 1 g opium. Treatment was exposure reduction with opioid substitutes and

laxatives, or chelation therapy if indicated. Over 7 months, 4294 poison cases

were seen at main referral hospitals in Tehran out of an estimated 31 914 oral

opium users in the city. We estimate more than 260 000 out of 773 800 users

nationwide remain untreated and at risk of poisoning.

Conclusion: Lead-contaminated opium and heroin that has transited through the

Iranian markets is a global risk and highlights a need for better monitoring of

illegal drug supplies.

Publisher: Décrire la vague d'intoxications au plomb survenue chez les

consommateurs d'opium en République islamique d'Iran et estimer le nombre de

personnes concernées dans le pays.Nous avons utilisé les données du plus grand

centre antipoison du pays pour illustrer l'épidémiologie d'une vague

d'intoxications au plomb survenue chez les consommateurs d'opium par voie orale.

Nous décrivons les directives du gouvernement en matière de traitement et

d'orientation vers des services spécialisés suite à cette flambée. À partir du

nombre de personnes traitées et de précédentes études sur la prévalence de la

consommation d'opium par voie orale, nous avons estimé le nombre total de

personnes susceptibles de consommer de l'opium contaminé au plomb dans le pays.En

février 2016, nous avons constaté une forte augmentation du nombre de

consommateurs d'opium par voie orale orientés vers notre centre antipoison avec

des douleurs abdominales, une anémie et une constipation. Cette hausse a culminé

au mois de juin 2016 mais la vague se poursuivait en août 2017. La plombémie

moyenne, sur un échantillon de 80 patients, était de 140,3 µg/dL (écart type:

122,6). L'analyse d'un échantillon d'opium illicite a révélé la présence de

3,55 mg de plomb dans 1 g d'opium. Le traitement a consisté à réduire

l'exposition et à prendre des substituts aux opiacés et des laxatifs, ou des

agents chélateurs lorsque cela était indiqué. Sur 7 mois, 4294 personnes

intoxiquées ont été reçues dans les principaux hôpitaux centraux de Téhéran, sur

un total estimé de 31 914 consommateurs d'opium par voie orale dans la ville.

Nous estimons que plus de 260 000 consommateurs sur 773 800 dans le pays n'ont, à

ce jour, pas reçu de traitement et courent un risque d'intoxication.L'opium

contaminé au plomb et l'héroïne qui ont transité sur les marchés iraniens

représentent un risque mondial et mettent en avant la nécessité de mieux

contrôler l'offre de drogues illicites.Publisher: Describir un brote de

intoxicación con plomo entre consumidores de opio en la República Islámica del

Irán y estimar la cantidad de personas afectadas en el país.Utilizamos datos del

centro de tratamiento de intoxicaciones más grande del país para ilustrar la

epidemiología de un brote de intoxicación con plomo en consumidores de opio por

vía oral. Describimos la referencia y orientaciones de tratamiento del gobierno

en respuesta al brote. Basado en el número de individuos tratados y estudios

anteriores sobre la prevalencia del uso de opio por vía oral, estimamos el número

total de personas en riesgo por el opio contaminado con plomo a nivel nacional.En

febrero de 2016, advertimos un aumento pronunciado en los números de consumidores

de opio por vía oral remitidos a nuestro centro de tratamiento de intoxicación

con dolor abdominal, anemia y constipación. Los números tuvieron un pico en junio

de 2016 pero el brote fue continuo en agosto de 2017. La media del nivel de plomo

en sangre en una muestra de 80 pacientes fue 140.3 µg/dL (desviación estándar:

122.6). El análisis de una muestra ilegal de opio mostró 3.55 mg de plomo en 1 g

de opio. El tratamiento fue la reducción de la exposición con sustitutos de opio

y laxantes, o terapia de quelación si se indicó. Durante 7 meses, 4294 casos de

intoxicación se atendieron en hospitales principales de referencia en Teherán de

un estimado de 31 914 consumidores de opio por vía oral en la ciudad. Estimamos

que más de 260 000 de 773 800 consumidores en toda la nación continúan sin

tratamiento y en riesgo de intoxicación.El opio y la heroína contaminados con

plomo, que transitó a través de los mercados iraníes, es un riesgo global y

destaca la necesidad de un mejor control de los suministros de droga

ilegal.Publisher: وصف تفشي الإصابة بالتسمم بالرصاص بين متعاطي الأفيون في جمهورية

إيران الإسلامية وتقدير عدد المصابين في البلاد.لقد استخدمنا بيانات من أكبر مركز

لعلاج التسمم في البلاد لتوضيح الانتشار الوبائي لتفشي الإصابة بتسمم الرصاص بين

متعاطي الأفيون عن طريق الفم. ونحن نصف المبادئ التوجيهية التي تتبعها الحكومة

لتقديم العلاج وتحويل المرضى في إطار التصدي لتفشي الإصابة. وبناءً على عدد الأفراد

الذين تم علاجهم والدراسات السابقة حول انتشار تعاطي الأفيون عن طريق الفم، فقد قمنا

بتقدير العدد الإجمالي للأشخاص المعرضين لخطر الإصابة بالتسمم بفعل الأفيون الملوث

بالرصاص على مستوى البلاد.في شهر فبراير/شباط عام 2016، لاحظنا ارتفاعًا حادًا في

أعداد من يتعاطون الأفيون عن طريق الفم الذين تمت إحالتهم إلى مركز علاج التسمم

الخاص بنا وكانوا يعانون من آلام في البطن وفقر الدم والإمساك. في شهر يونيو/حزيران

عام 2016 بلغت الأعداد ذروتها ولكن استمر التفشي في شهر أغسطس/آب عام 2017. وكان

متوسط مستوي الرصاص في الدم المقاس في عينة مكونة من 80 مريضًا 140.3

ميكروجرام/ديسيلتر (الانحراف المعياري: 122.6). وقد أظهر التحليل لعينة من الأفيون

غير الشرعي وجود 3.55 ميكروجرام من الرصاص في كل 1 جرام من الأفيون. كان العلاج يتم

من خلال تخفيض وجود الأفيون باستخدام البدائل الأفيونية والملينات، أو عملية استخلاب

(إزالة المعادن) عند الاقتضاء. على مدى 7 أشهر، شوهدت 4294 حالة تسمم في مستشفيات

الإحالة الرئيسية في طهران من بين ما يقدر بنحو 31914 من متعاطي الأفيون عن طريق

الفم في المدينة. وتشير تقديراتنا إلى وجود ما يزيد عن 260000 من بين 773800 متعاط

على مستوى البلد بأكملها لا يزالون بلا علاج ومعرضين لخطر الإصابة بالتسمم.يمثل

الهيروين والأفيون المسممان بالرصاص الذي انتقل عبر الأسواق الإيرانية خطرًا

عالميًا، ويلقي الضوء على الحاجة إلى رقابة أفضل لإمدادات العقاقير غير

الشرعية.Publisher:

描述伊朗伊斯兰共和国鸦片使用者的铅中毒疫情,并估算该国的受影响人数。.使用该国最大的中毒治疗中心的数据来说明口服鸦片使用者铅中毒暴发的流行病学特征。我们描述了政府

应对疫情的转诊和治疗指南。根据接受治疗的个体数量和之前关于口服鸦片使用率的研究,我们估计了全国范围内受到含铅鸦片影响的总人数。.2016 年 2 月,我们注意到转

诊至中毒治疗中心的口服鸦片患者人数剧增,并伴有腹痛、贫血和便秘的症状。该数值在 2016 年 6 月达到峰值,但 2017 年 8 月时,疫情仍旧持续。80 例患

者中,其中一个样本的血铅平均值为 140.3 µg/dL(标准偏差:122.6)。对某非法鸦片样本的分析显示,1 克鸦片的含铅量为 3.55 毫克。治疗方案为使用

阿片类药物替代品和缓泻剂以降低接触影响,或者如有说明,则使用螯合疗法。7 个多月以来,德黑兰的主要转诊医院看诊了 4294 例中毒病例,据估计,该市约有 31 9

14 位口服鸦片使用者。我们预估全国范围内有 773800 位鸦片使用者中,其中超过 260000 位未接受治疗,有中毒风险。.通过伊朗市场流转的含铅鸦片和海洛因

是一项全球性风险,突出了对更好地监管非法药物供应的需求。.Publisher: Описать вспышку отравления свинцом среди

потребителей опиума в Исламской Республике Иран и оценить количество пострадавших

людей в стране.Мы использовали данные, полученные от крупнейшего в стране

токсикологического центра, чтобы проиллюстрировать эпидемиологию вспышки

отравления свинцом у потребителей опиума пероральным путем. Мы приводим описание

рекомендаций правительства в отношении направления и лечения в условиях вспышки.

Основываясь на количестве лиц, получивших медицинскую помощь, и предыдущих

исследованиях распространенности перорального потребления опиума, мы подсчитали

общее число людей по всей стране, которые входят в группу риска отравления

опиумом, загрязненным свинцом.В феврале 2016 года мы заметили резкое увеличение

числа потребителей опиума пероральным путем, поступивших в наш токсикологический

центр с болью в животе, анемией и запорами. Пик их количества пришелся на июнь

2016 года, но в августе 2017 года вспышка еще продолжалась. Средний уровень

свинца в крови у 80 пациентов составил 140,3 мкг/дл (стандартное отклонение:

122,6). Анализ образца незаконного опиума выявил содержание свинца, равное

3,55 мг в 1 г опиума. В качестве лечения для снижения воздействия использовались

опиоиды-заместители и слабительные или при необходимости терапия хелатами. За

7 месяцев в основных больницах Тегерана было зарегистрировано 4294 случая

отравления из приблизительно 31 914 потребителей опиума пероральным путем. По

нашим оценкам, более 260 000 из 773 800 потребителей по всей стране остаются без

медицинской помощи и подвергаются риску отравления.Загрязненные свинцом опиум и

героин, которые проходят через иранские рынки, представляют собой глобальный риск

и указывают на необходимость лучшего мониторинга незаконных поставок наркотиков.

DOI: 10.2471/BLT.17.196287

PMCID: PMC5840624

PMID: 29531415 [Indexed for MEDLINE]

158. MMWR Morb Mortal Wkly Rep. 2018 Mar 9;67(9):279-285. doi: 10.15585/mmwr.mm6709e1.

Vital Signs: Trends in Emergency Department Visits for Suspected Opioid Overdoses

- United States, July 2016-September 2017.

Vivolo-Kantor AM, Seth P, Gladden RM, Mattson CL, Baldwin GT, Kite-Powell A,

Coletta MA.

INTRODUCTION: From 2015 to 2016, opioid overdose deaths increased 27.7%,

indicating a worsening of the opioid overdose epidemic and highlighting the

importance of rapid data collection, analysis, and dissemination.

METHODS: Emergency department (ED) syndromic and hospital billing data on

opioid-involved overdoses during July 2016-September 2017 were examined. Temporal

trends in opioid overdoses from 52 jurisdictions in 45 states were analyzed at

the regional level and by demographic characteristics. To assess trends based on

urban development, data from 16 states were analyzed by state and urbanization

level.

RESULTS: From July 2016 through September 2017, a total of 142,557 ED visits

(15.7 per 10,000 visits) from 52 jurisdictions in 45 states were suspected

opioid-involved overdoses. This rate increased on average by 5.6% per quarter.

Rates increased across demographic groups and all five U.S. regions, with largest

increases in the Southwest, Midwest, and West (approximately 7%-11% per quarter).

In 16 states, 119,198 ED visits (26.7 per 10,000 visits) were suspected

opioid-involved overdoses. Ten states (Delaware, Illinois, Indiana, Maine,

Missouri, Nevada, North Carolina, Ohio, Pennsylvania, and Wisconsin) experienced

significant quarterly rate increases from third quarter 2016 to third quarter

2017, and in one state (Kentucky), rates decreased significantly. The highest

rate increases occurred in large central metropolitan areas.

CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: With continued increases

in opioid overdoses, availability of timely data are important to inform actions

taken by EDs and public health practitioners. Increases in opioid overdoses

varied by region and urbanization level, indicating a need for localized

responses. Educating ED physicians and staff members about appropriate services

for immediate care and treatment and implementing a post-overdose protocol that

includes naloxone provision and linking persons into treatment could assist EDs

with preventing overdose.

DOI: 10.15585/mmwr.mm6709e1

PMCID: PMC5844282

PMID: 29518069 [Indexed for MEDLINE]

Conflict of interest statement: No conflicts of interest were reported.

159. CNS Drugs. 2018 Feb;32(2):101-116. doi: 10.1007/s40263-018-0499-3.

Prescribed Dose of Opioids and Overdose: A Systematic Review and Meta-Analysis of

Unintentional Prescription Opioid Overdose.

Adewumi AD(1)(2)(3), Hollingworth SA(4), Maravilla JC(5), Connor JP(6)(7), Alati

R(5).

Author information:

(1)Institute for Social Science Research, The University of Queensland,

Indooroopilly, 4068, QLD, Australia. a.adewumi@uqconnect.edu.au.

(2)Maryborough Hospital Pharmacy, Wide Bay Hospital and Health Service, 185

Walker Street, Maryborough, QLD, 4650, Australia. a.adewumi@uqconnect.edu.au.

(3)School of Clinical Medicine, Rural Clinical School, The University of

Queensland, Hervey Bay, 4655, QLD, Australia. a.adewumi@uqconnect.edu.au.

(4)School of Pharmacy, The University of Queensland, 20 Cornwall St,

Woolloongabba, QLD, 4102, Australia.

(5)Institute for Social Science Research, The University of Queensland,

Indooroopilly, 4068, QLD, Australia.

(6)Centre for Youth Substance Abuse Research, The University of Queensland, St

Lucia, 4067, QLD, Australia.

(7)Discipline of Psychiatry, The University of Queensland, Herston, QLD, 4029,

Australia.

BACKGROUND: The rate of an unintentional drug overdose involving prescription

opioids continues to rise. An understanding of the threshold dose and dose(s)

associated with unintentional prescription opioid overdose will help to mitigate

this epidemic.

OBJECTIVE: The objective of this systematic review is to systematically

synthesise and meta-analyse studies on doses of prescription opioids and

ascertain the doses of opioids that are associated with increased risk of severe

opioid poisoning or mortality.

DATA SOURCES: A search of PubMed, EMBASE, CINAHL and Web of Science from

inception to 16 January 2017 was conducted using search strategies and the MeSH

(Medical Subject Headings) terms for studies of adult patients using prescription

opioids who experienced an accidental overdose.

STUDY SELECTION: Of the 1332 studies identified, 117 were selected for full

article review. Ten met the inclusion criteria for qualitative analysis, but only

seven studies were meta-analysed. The included studies were in English, and

participants met predetermined International Classification of Diseases (ICD)

codes. Studies were excluded if they included only paediatric participants or the

participants met the ICD code for intentional self-harm.

DATA EXTRACTION AND SYNTHESIS: Two researchers elaborated and validated a data

extraction form. Data were then independently extracted by both reviewers as per

this form. We assessed study quality using the Newcastle-Ottawa Scale (NOS) for

non-randomised studies in meta-analyses. We performed a meta-regression using a

random-effect model and summarised the results using relative risk (RR) and 95%

confidence intervals (CIs). The threshold dose for an unintentional overdose is

20 morphine milligram equivalents (MME)/day. There were higher risks with larger

doses: (1) ≤ 20 versus ≥ 21 MME/day: RR 2.81, 95% CI 1.09-7.22, p < 0.001;

(2) ≤ 50 versus > 50 MME/day: RR 3.87, 95% CI 2.36-6.33, p < 0.001; (3) ≤ 100

versus > 100 MME/day: RR 4.28, 95% CI 2.61-7.1, p < 0.001; and (4) ≤ 50

versus > 50-100 MME/day: RR 3.09, 95% CI 1.84-5.18, p < 0.001). Heterogeneity was

explained by the type of overdose event, inpatient or outpatient status, and

length of observation. Type of pain (cancer or non-cancer pain) had no impact on

heterogeneity.

LIMITATIONS: The definition of exposure in studies included in the meta-analysis

was heterogeneous. Some studies defined exposure as the filling of a prescription

while others defined exposure as the prescription of an opioid to the patient,

and all studies assumed that patients took the prescribed opioid. Medications

that may contribute to overdose, such as benzodiazepines and other drugs, were

not considered.

CONCLUSIONS: A significantly increased risk of inadvertent prescription opioid

overdose was found with 20-50 MME/day, with fatality more likely with opioid

doses above 50 MME/day, although extensive heterogeneity was found with the dose

comparisons. Clinicians should inform patients of this risk and monitor them

closely.

PROTOCOL REGISTRATION: This protocol was registered with PROSPERO 2017:

CRD42017058426.

DOI: 10.1007/s40263-018-0499-3

PMID: 29498021 [Indexed for MEDLINE]

160. R I Med J (2013). 2018 Mar 1;101(2):41-44.

Suboptimal Opioid Prescribing: A Practice Change Project.

Young LS(1), Crausman RS(2), Fulton JP(3).

Author information:

(1)Advanced Practice Clinician, Ocean State Urgent Care and Greenville Primary

Care.

(2)Clinical Professor of Medicine Alpert Medical School; Partner Ocean State

Urgent Care.

(3)Clinical Assistant Professor of Behavioral and Social Sciences, Brown

University School of Public Health.

In the U.S. in 2015, the proportion of people dependent on opioids approached one

percent, and opioid overdose rivaled auto accidents as the leading cause of

accidental death. The literature suggests a credible link between increased

opioid prescribing and increased opioid addiction. Accordingly, some have

suggested that limiting the number of opioid prescriptions (and the number of

doses per prescription) might be effective in reducing the number of

opioid-related deaths. Toward this end, we designed and piloted an evidence-based

quality-improvement project in four urgent care clinics. Results of the

intervention were monitored with data from a state-sponsored prescription

drug-monitoring program (PDMP) by comparing opioid prescribing before and after

adoption of the guideline, and in this manner, a statistically significant (P <

0.05) decline in the rate of opioid prescribing was revealed. On average, 2.43

fewer opioid prescriptions were written, per provider, per week, in weeks five

through eight after promulgation (5.21, SD =4.37) than in the eight weeks before

promulgation (7.64, SD =7.73). Our results suggest that implementing a simple

opioid-prescribing guideline, with monitoring, can reduce sub-optimal opioid

prescribing, and therefore the volume of opioids available in the community for

diversion, abuse, and addiction.

PMID: 29490325 [Indexed for MEDLINE]

161. Drug Alcohol Depend. 2018 Apr 1;185:322-327. doi:

10.1016/j.drugalcdep.2017.12.032. Epub 2018 Feb 20.

Fentanyl and heroin contained in seized illicit drugs and overdose-related deaths

in British Columbia, Canada: An observational analysis.

Baldwin N(1), Gray R(2), Goel A(3), Wood E(4), Buxton JA(5), Rieb LM(6).

Author information:

(1)Department of Family Practice, University of British Columbia, St. Paul's

Hospital, 1081 Burrard St., Vancouver, B.C., Canada. Electronic address:

nicholas.jc.baldwin@gmail.com.

(2)Department of Family Practice, University of British Columbia, St. Paul's

Hospital, 1081 Burrard St., Vancouver, B.C., Canada. Electronic address:

roger.gray@mail.mcgill.ca.

(3)Department of Family Practice, University of British Columbia, St. Paul's

Hospital, 1081 Burrard St., Vancouver, B.C., Canada. Electronic address:

anirudh.goel@medportal.ca.

(4)Department of Medicine, University of British Columbia, and B.C. Centre on

Substance Use, 2312 Pandosy St., Kelowna, B.C., Canada. Electronic address:

bccsu-ew@cfenet.ubc.ca.

(5)Department of Family Practice, University of British Columbia, St. Paul's

Hospital, 1081 Burrard St., Vancouver, B.C., Canada; School of Population and

Public Health, University of British Columbia, and B.C. Centre for Disease

Control, 655 W 12th Ave, Vancouver, B.C., Canada. Electronic address:

jane.buxton@ubc.ca.

(6)Department of Family Practice, University of British Columbia, St. Paul's

Hospital, 1081 Burrard St., Vancouver, B.C., Canada. Electronic address:

launette.rieb@ubc.ca.

Erratum in

Drug Alcohol Depend. 2019 Apr 1;197:48.

BACKGROUND: Due to the alarming rise in opioid-related overdose deaths, a public

health emergency was declared in British Columbia (BC). In this study, we

examined the relationship between illicit fentanyl and heroin found in seized

drugs and illicit overdose deaths in BC.

METHODS: An observational cross-sectional survey was conducted using BC data from

Health Canada's Drug Analysis Service, which analyzes drug samples seized by law

enforcement agencies, and non-intentional illicit overdoses from the BC Coroner's

Service, from 2000 to 2016. Initial scatter plots and subsequent multivariate

regression analysis were performed to describe the potential relationship between

seized illicit fentanyl samples and overdose deaths and to determine if this

differed from seized heroin and overdose deaths. Fentanyl samples were analyzed

for other drug content.

RESULTS: Fentanyl is increasingly being found combined with other opioid and

non-opioid illicit drugs. Strong positive relationships were found between the

number of seized fentanyl samples and total overdose deaths (R2 = 0.97) as well

as between seized fentanyl and fentanyl-detected overdose deaths (R2 = 0.99). A

positive association was found between the number of seized heroin samples and

total overdose deaths (R2 = 0.78).

CONCLUSION: This research contributes to the expanding body of evidence

implicating illicit fentanyl use (often combined with heroin or other substances)

in overdose deaths in BC. Policy makers and healthcare providers are urged to

implement drug treatment and harm reduction strategies for people at risk of

overdose associated with current trends in illicit opioid use.

Copyright © 2018 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.drugalcdep.2017.12.032

PMCID: PMC5889734

PMID: 29486421 [Indexed for MEDLINE]

162. Turk J Med Sci. 2018 Feb 23;48(1):136-141. doi: 10.3906/sag-1707-141.

Observational study of dermatological manifestations in patients admitted to a

tertiary poison center in Iran

Talaie H, Nasiri S, Gheisari M, Dadkhahfar S, Ahmadi S.

Background/aim: Acute unintentional and deliberate poisoning by medications and

chemicals is a frequent emergency, especially in Iran. This study aimed to

evaluate the frequency and character of skin findings occurring in patients with

acute intentional and aunintentional poisoning. Materials and methods: This

prospective observational study was performed at the Loghman Hakim Hospital

Poison Center over a period of 6 months from April 2016 to September 2016. Data

including patient demographics, cause of poisoning, and level of consciousness

were collected. Pediatric patients (under the age of 13) and patients who died in

the first hours of admission were excluded from the study. Results: The most

common cause of toxicity-related admission in our patients was methadone

overdose. The most common skin finding in these patients was xerosis. According

to our results, there was an association between tramadol poisoning and

self-induced lesions. Shin hyperpigmentation was found to be significantly more

frequent in patients with lead poisoning. Conclusion: Further study is

recommended to shed light on the possible association of drug poisoning and skin

lesions.

DOI: 10.3906/sag-1707-141

PMID: 29479972 [Indexed for MEDLINE]

163. Drug Alcohol Depend. 2018 Apr 1;185:189-191. doi:

10.1016/j.drugalcdep.2017.12.014. Epub 2018 Feb 9.

Risk of fentanyl-involved overdose among those with past year incarceration:

Findings from a recent outbreak in 2014 and 2015.

Brinkley-Rubinstein L(1), Macmadu A(2), Marshall BDL(3), Heise A(4), Ranapurwala

SI(5), Rich JD(6), Green TC(7).

Author information:

(1)Department of Social Medicine, University of North Carolina, 333 S. Columbia

St., Chapel Hill, NC 27516, USA; Center for Health Equity Research, University of

North Carolina at Chapel Hill, 335 S. Columbia St., Chapel Hill, NC 27516, USA.

Electronic address: Lauren_Brinkley@med.unc.edu.

(2)Center for Prisoner Health and Human Rights, The Miriam Hospital, 8 Third St.,

2nd floor, Providence, RI 02906, USA; Department of Health Services, Policy and

Practice, Brown University School of Public Health, 121 South Main St.,

Providence, RI 02903, USA.

(3)Department of Epidemiology, Brown University School of Public Health, 121

South Main St., Providence, RI 02903, USA.

(4)Center for Health Equity Research, University of North Carolina at Chapel

Hill, 335 S. Columbia St., Chapel Hill, NC 27516, USA.

(5)Department of Epidemiology, University of North Carolina, 135 Dauer Dr.,

Chapel Hill, NC 27599, USA.

(6)Center for Prisoner Health and Human Rights, The Miriam Hospital, 8 Third St.,

2nd floor, Providence, RI 02906, USA; Department of Epidemiology, Brown

University School of Public Health, 121 South Main St., Providence, RI 02903,

USA.

(7)Department of Emergency Medicine, Boston University, 1 Boston Medical Center

Pl., Boston, MA 02118, USA; Injury Prevention Research Center, Boston University,

1 Boston Medical Center Pl., Boston, MA 02118, USA.

Overdose is the leading cause of unintentional injury-related death. Rhode Island

(RI) has the highest rate of illicit drug use nationally and the 5th highest

overdose mortality rate. RI has experienced an outbreak of fentanyl-related

overdoses. In incarcerated populations, risk of overdose is greatly elevated.

However, little is known about fentanyl-related overdose post-release. In the

current analyses, we identify changes in fentanyl-related fatal overdose among

those who died in 2014 and 2015 who were incarcerated in the year before death.

We linked data from the RI Office of the Medical Examiner with records from the

RI Department of Corrections. We calculated risk ratios and 95% confidence

intervals using log-binomial regression to compare risk of fentanyl-involved

overdose death. We also compared median time to death since release, median

sentence length, and median number of incarcerations in 2014 and 2015. Results

indicate that the risk of dying of a fentanyl-related overdose increased (RR:

1.99 (95% CI: 1.11-3.57, p = 0.014)) from 2014 to 2015 among those with past year

incarceration. This study is one of the first to describe fentanyl-related fatal

overdose among those with past year incarceration. In 2015 the median sentence

was longer among those with a fentanyl-related overdose death and the median time

from release to death among all who had past year incarceration extended past

90 days. Access to medications for addiction treatment, overdose education, and

naloxone should be available during community re-entry and extended beyond the

early post-release period.

Copyright © 2018. Published by Elsevier B.V.

DOI: 10.1016/j.drugalcdep.2017.12.014

PMID: 29459328 [Indexed for MEDLINE]

164. Suicide Life Threat Behav. 2019 Feb;49(1):328-337. doi: 10.1111/sltb.12442. Epub

2018 Feb 14.

Completed Suicide Among Methamphetamine Users: A National Study.

Darke S(1), Kaye S(1)(2), Duflou J(1)(3), Lappin J(1)(4).

Author information:

(1)National Drug & Alcohol Research Centre, University of New South Wales,

Sydney, NSW, Australia.

(2)Justice Health and Forensic Mental Health Network, NSW Health, Sydney, NSW,

Australia.

(3)Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

(4)School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.

All Australian cases of methamphetamine-related suicide (2009-2015) retrieved

from the National Coronial Information System were examined to determine crude

mortality rates, characteristics and circumstances of death, and blood

toxicology. There were 300 cases, 18.2% of all methamphetamine-related deaths,

and 1.6% of all completed suicides. The mean age was 33.1 years, and 77.0% were

male. The crude mortality rate was 1.9 per 106 , with males having a

significantly higher rate than females (2.9 vs. 0.9 per 106 ). A quarter were

known to have previous suicide attempts, and a history of psychosis was noted in

12.3%. In 40.7% of cases, witnesses described the decedent as having been

agitated and/or aggressive immediately prior to the incident. The vast majority

(85.3%), and of both sexes (males 87.0%, females 79.7%), used violent methods.

Hanging (70.3%) was overwhelmingly the most frequent method among both males

(70.1%) and females (71.0%). Prescription medications were frequently present:

hypnosedatives (23.6%), antidepressants (19.5%), and antipsychotics (8.4%).

Self-poisoning cases were significantly more likely to have antidepressants (odds

ratio: 4.2) and opioids (4.9) present, but less likely to have cannabis (0.3).

Methamphetamine-related suicide makes a large contribution to

methamphetamine-related death and represents a substantial clinical and public

health problem.

© 2018 The American Association of Suicidology.

DOI: 10.1111/sltb.12442

PMID: 29444345 [Indexed for MEDLINE]

165. BMC Cancer. 2018 Feb 13;18(1):177. doi: 10.1186/s12885-018-4090-6.

High-dose thiotepa-related neurotoxicity and the role of tramadol in children.

Maritaz C(1), Lemare F(2)(3)(4), Laplanche A(5), Demirdjian S(2), Valteau-Couanet

D(6), Dufour C(6).

Author information:

(1)Department of Clinical Pharmacy, Gustave-Roussy cancer campus, 114 Rue Edouard

Vaillant, 94805, Villejuif, France. c.maritaz@gmail.com.

(2)Department of Clinical Pharmacy, Gustave-Roussy cancer campus, 114 Rue Edouard

Vaillant, 94805, Villejuif, France.

(3)Faculty of Pharmacy of Paris, Sorbonne-Paris University, 75 006, Paris,

France.

(4)EA 7348 MOS, Ecole des Hautes Etudes en Santé Publique, 35000, Rennes, France.

(5)Department of Biostatistics and Epidemiology, Gustave-Roussy, Villejuif,

France.

(6)Department of Pediatric and Adolescent Oncology, Gustave-Roussy, Villejuif,

France.

BACKGROUND: Serious neurological adverse events (NAE) have occurred during

treatment with high-dose thiotepa regimens of children with high-risk solid

tumours. The objective was to assess the incidence of NAE related to high-dose

thiotepa and to identify potential contributing factors that could exacerbate the

occurrence of this neurotoxicity.

METHODS: From May 1987 to March 2011, children with solid tumours treated with

high-dose thiotepa were retrospectively identified. Each NAE detected led to an

independent case analysis. Potential contributing factors were pre-specified and

univariate/multivariable analyses were performed.

RESULTS: Three hundred seven courses of thiotepa (251 patients) were identified.

The total dose per treatment ranged from 600 to 900 mg/m2. 81 NAE (26%) were

identified. 46 NAE were related to high-dose thiotepa during the first course

(18.3%) and 11 during the second course (19.6%). The symptoms appeared in a

median time of 2 days after the introduction of thiotepa. Central and peripheral

symptoms were headaches, tremors, confusion, seizures, cerebellar syndrome, and

coma. High-dose thiotepa was reintroduced in 18 cases and symptoms reappeared in

5 children. For 3 patients who had seizures during the first course,

premedication with clonazepam for the second course has prevented recurrence of

NAE. As contributing factors, brain tumour and tramadol treatment increased the

risk of thiotepa-related neurotoxicity by 2 to 6 times respectively.

CONCLUSIONS: The incidence of neurotoxicity was 18.3%. Brain tumours and tramadol

treatment are risk factors to consider when using high-dose thiotepa. The outcome

of patients was favourable without sequelae in all cases and rechallenge with

thiotepa was possible.

DOI: 10.1186/s12885-018-4090-6

PMCID: PMC5809829

PMID: 29433564 [Indexed for MEDLINE]

166. Clin Toxicol (Phila). 2018 Sep;56(9):846-851. doi: 10.1080/15563650.2018.1435887.

Epub 2018 Feb 12.

A 29-year analysis of acute peak salicylate concentrations in fatalities reported

to United States poison centers.

Warrick BJ(1), King A(2), Smolinske S(1), Thomas R(2), Aaron C(2).

Author information:

(1)a New Mexico Poison and Drug Information Center , Albuquerque , NM , USA.

(2)b Children's Hospital of Michigan Regional Poison Center , Detroit , MI , USA.

BACKGROUND/OBJECTIVES: The threshold salicylate concentration commonly

recommended to initiate extracorporeal elimination, in the absence of significant

end-organ toxicity, is 100 mg/dL. Unfortunately, the grade of evidence to support

this decision is low. Our primary aim is to describe highest reported salicylate

concentrations in patients who died from acute salicylate ingestions. Our

secondary aim is to determine if age or coingestants varied with highest reported

salicylate concentration.

METHODS: We analyzed acute salicylate fatalities reported to the National Poison

Data System (NPDS) between 1 January 1986 and 31 December 2014. Included were

patients who died during the index hospitalization and for which acute salicylate

toxicity was the primary cause of death. We used descriptive statistics with

standard deviations (SD) or 95% confidence intervals (CI) where appropriate. We

created a general linear model that evaluated the association of age and

coingestions with salicylate concentrations. We divided the patients into age

quartiles to assess a possible interaction between age and salicylate

concentration.

RESULTS: We identified 602 acute salicylate fatalities that fit inclusion

criteria. The mean peak reported fatal salicylate concentration across all age

groups was 99.19 mg/dL (± 50.2 mg/dL). The median peak fatal salicylate

concentration was 97.0 mg/dL. The oldest quartile had a lower mean concentration

(age >57 years; 90.4 mg/dL) than the youngest quartile (age <30 years;

111.6 mg/dL, mean difference 21.2 mg/dL, 95%CI 6.1-36.3). Fatalities with a

coingestant had a lower mean concentration of 91.5 mg/dL compared to 104.8 mg/dL

among those ingesting salicylates alone (mean difference 13.4 mg/dL, 95%CI

21.4-5.3). Increasing age and the presence of any coingestions were negatively

associated with fatal concentrations (estimates; 95%CI 0.41; 0.61-0.021 and

-14.43; 22.45-6.42, respectively). When opioids were a coingestant, mean

concentration was 72.8 (mean difference 32.1 95%CI 23.1-41.1).

CONCLUSIONS: Using the current recommended hemodialysis threshold of 100 mg/dL,

more than half of the patients would be deprived of this critical life-saving

therapy. Additionally, increasing age and ingestion of other substances,

especially opioids, are associated with lower peak fatal salicylate

concentrations. A prospective, randomized controlled trial considering salicylate

concentrations and other clinical factors may provide further guidance for

hemodialysis.

DOI: 10.1080/15563650.2018.1435887

PMID: 29431532

167. Addiction. 2018 Jul;113(7):1339-1344. doi: 10.1111/add.14144. Epub 2018 Feb 12.

Corrected US opioid-involved drug poisoning deaths and mortality rates,

1999-2015.

Ruhm CJ(1).

Author information:

(1)Frank Batten School of Leadership and Public Policy, University of Virginia,

Charlottesville, VA, USA.

BACKGROUND AND AIMS: Most prior estimates of opioid-involved drug poisoning

mortality counts or rates are understated because the specific drugs leading to

death are frequently not identified on death certificates. This analysis provides

corrected national estimates of opioid and heroin/synthetic opioid-involved

counts and mortality rates, as well as changes over time in them from 1999 to

2015.

METHODS: Data on drug poisoning deaths to US residents from 1999 to 2015,

obtained from the Centers for Disease Control and Prevention (CDC) Multiple Cause

of Death (MCOD) files, were used with the drugs involved in fatal overdoses

imputed when not identified on the death certificates.

RESULTS: The official CDC figure that 33 091 drug deaths involved opioids in 2015

is an undercount, with the actual number being approximately 39 999. Corrected

counts and rates of any opioid and heroin/synthetic opioid-involved drug deaths

are 20-35% higher in every year than reported figures. The corrections almost

always raise the changes estimated to have occurred since 1999, with the largest

differences observed in 2011 for any opioids (5677 deaths and 1.7 per 100 000)

and in 2015 for heroin/synthetic opioids (3228 deaths and 1.0 per 100 000).

However, percentage growth since 1999 is sometimes slower when based on corrected

rather than reported fatality data, and with sensitivity to the choice of base

years.

CONCLUSIONS: Death certificate reports understate the prevalence of and changes

over time in opioid and heroin/synthetic opioid-involved drug mortality in the

United States. Adjustments imputing the drugs involved for cases where none are

identified on the death certificates are likely to provide more accurate

estimates.

© 2018 Society for the Study of Addiction.

DOI: 10.1111/add.14144

PMID: 29430760