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Journal of the American Pharmacists... 2023Despite national and state policies aimed at increasing naloxone access via pharmacies, opioid overdose death rates rose during the COVID-19 pandemic, particularly among...
BACKGROUND
Despite national and state policies aimed at increasing naloxone access via pharmacies, opioid overdose death rates rose during the COVID-19 pandemic, particularly among Blacks and American Indians (AIs) in rural areas. Caregivers, or third parties who can administer naloxone during an overdose event, are important individuals in the naloxone administration cascade, yet no studies have explored rural caregivers' opioid overdose terminology and naloxone analogy preferences or whether these preferences differ by race.
OBJECTIVES
To identify rural caregivers' overdose terminology and naloxone analogy preferences and determine whether preferences differ by race.
METHODS
A sample of 40 caregivers who lived with someone at high risk of overdose and used pharmacies in 4 largely rural states was recruited. Each caregiver completed a demographic survey and a 20- to 45-minute audio-recorded semi-structured interview that was transcribed, de-identified, and imported into a qualitative software package for thematic analysis by 2 independent coders using a codebook. Overdose terminology and naloxone analogy preferences were analyzed for differences by race.
RESULTS
The sample was 57.5% white, 35% Black, and 7.5% AIs. Many participants (43%) preferred that pharmacists use the term "bad reaction" to refer to overdose events over the terms "accidental overdose" (37%) and "overdose" (20%). The majority of white and Black participants preferred "bad reaction" while AI participants preferred "accidental overdose." For naloxone analogies, "EpiPen" was most preferred (64%), regardless of race. "Fire extinguisher" (17%), "lifesaver" (9.5%), and other analogies (9.5%) were preferred by some white and Black participants but not AI participants.
CONCLUSION
Our findings suggest that pharmacists should use the "bad reaction" term and "EpiPen" analogy when counseling rural caregivers about overdose and naloxone, respectively. Caregivers' preferences varied by race, suggesting that pharmacists may want to tailor the terminology and analogy they use when discussing naloxone with caregivers.
Topics: Humans; Naloxone; Caregivers; Narcotic Antagonists; Opioid-Related Disorders; Opiate Overdose; Pandemics; Drug Overdose; Analgesics, Opioid
PubMed: 37149142
DOI: 10.1016/j.japh.2023.05.001 -
Journal of Analytical Toxicology Mar 2021Analysis of postmortem samples with the presence of morphine can sometimes be challenging to interpret. Tolerance complicates interpretation of intoxications and causes...
Analysis of postmortem samples with the presence of morphine can sometimes be challenging to interpret. Tolerance complicates interpretation of intoxications and causes of death due to overlap in therapeutic and fatal concentrations. Determination of metabolites and metabolic ratios can potentially differentiate between abstinence, continuous administration, and perhaps time of administration. The purpose of this study was to (a) develop and validate a method for quantitation of morphine-3β-D-glucuronide, morphine-6β-D-glucuronide, normorphine, codeine-6β-D-glucuronide, norcodeine, codeine, 6-acetylmorphine, and ethylmorphine in urine using liquid chromatography-tandem mass spectrometry; (b) apply the method to opiate related deaths; (c) compare metabolic ratios in urine in different causes of death (CoD) and after different drug intakes and (d) compare heroin intoxications in rapid and delayed deaths. Validation parameters such as precision, bias, matrix effects, stability, process efficiency, and dilution integrity were assessed and deemed acceptable. Lower limits of quantitation ranged from 0.01-0.2 μg/mL for all analytes. Autopsy cases (n=135) with paired blood and urine samples were analyzed. Cases were divided into three groups based on CoD; opiate intoxication, intoxication with other drugs than opiates, and other CoD. The cases were classified by intake: codeine (n=42), heroin (n=36), morphine (n=49), and ethylmorphine (n=3). Five cases were classified as mixed intakes and excluded. Heroin intoxications (n=35) were divided into rapid (n=15) or delayed (n=20) deaths. Parent drug groups were compared using metabolic ratio morphine-3β-D-glucuronide/morphine and significant differences were observed between codeine vs morphine (p=0.005) and codeine vs heroin (p≤0.0001). Urine and blood concentrations, and metabolic ratios in rapid and delayed heroin intoxications were compared and determined a significant difference for morphine (p=0.001), codeine (p=0.009), 6-acetylmorphine (p=0.02) in urine, and morphine (p=0.02) in blood, but there was no significant difference (p=0.9) between metabolic ratios. Morphine-3β-D-glucuronide results suggested a period of abstinence prior to death in 25% of the heroin intoxications.
Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; Heroin; Morphine; Morphine Derivatives; Substance Abuse Detection; Tandem Mass Spectrometry
PubMed: 33031535
DOI: 10.1093/jat/bkaa157 -
Addiction (Abingdon, England) May 2022Tracking specific drugs contributing to drug overdose deaths is limited when relying on death certificate (DC) data alone. This study aimed to determine whether...
Using death scene and toxicology evidence to define involvement of heroin, pharmaceutical morphine, illicitly manufactured fentanyl and pharmaceutical fentanyl in opioid overdose deaths, 38 states and the District of Columbia, January 2018-December 2019.
BACKGROUND AND AIMS
Tracking specific drugs contributing to drug overdose deaths is limited when relying on death certificate (DC) data alone. This study aimed to determine whether integrating DC data with medical examiner/coroner reports, including postmortem toxicology and death investigation findings, would enhance identification of (1) heroin and pharmaceutical morphine involvement in overdose deaths and (2) fentanyl source (illicitly manufactured versus pharmaceutical).
DESIGN
Retrospective analysis of heroin, pharmaceutical morphine, illicitly manufactured fentanyl (IMF) and pharmaceutical fentanyl involvement in fatal overdoses. DC and toxicology data were compared with enhanced definitions integrating overdose scene, witness and toxicology evidence.
SETTING
United States: 38 states and the District of Columbia, participating in Centers for Disease Control and Prevention (CDC)-funded opioid overdose death surveillance.
CASES
Opioid overdose decedents from funded jurisdictions; deaths during 1 January 2018-31 December 2019.
MEASUREMENTS
Using medical examiner/coroner report data, deaths with 6-acetylmorphine and/or morphine detected by postmortem toxicology were defined as confirmed, probable or suspected heroin deaths, or probable pharmaceutical morphine deaths. Fentanyl was defined as probable or suspected IMF or probable pharmaceutical fentanyl.
FINDINGS
The enhanced definition defined 18 393 deaths as confirmed, probable, or suspected heroin deaths (including 2678 with morphine listed as cause of death on the DC) and 404 as probable pharmaceutical morphine deaths. Among deaths with fentanyl detected, 89.3% were defined as probable or suspected IMF and 1.0% as probable pharmaceutical fentanyl. Fentanyl source could not be determined for 9.7% of deaths.
CONCLUSIONS
Integrating drug overdose scene, witness and toxicology findings can improve identification of specific drugs contributing to overdose deaths and enhance overdose intervention targeting.
Topics: Analgesics, Opioid; District of Columbia; Drug Overdose; Fentanyl; Heroin; Humans; Illicit Drugs; Morphine; Opiate Overdose; Retrospective Studies; United States
PubMed: 34882865
DOI: 10.1111/add.15768 -
Substance Use & Misuse 2022Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Illicit opioid use in pregnancy is associated with adverse maternal, neonatal, and childhood outcomes. Opioid substitution is recommended, but whether methadone or buprenorphine is the optimal agent remains unclear.
METHODS
We searched EMBASE, PubMed, Web of Science, Scopus, Open Gray, CINAHL and the Cochrane Central Registry of Controlled Trials (CENTRAL) from inception to April 2020 for randomized controlled trials (RCTs) and cohort studies comparing methadone and buprenorphine treatment for opioid-using mothers. Included studies assessed maternal and or neonatal outcomes. We used random-effects meta-analyses to estimate summary measures for outcomes and report these separately for RCTs and cohort studies.
RESULTS
Of 408 abstracts screened, 20 papers were included (4 RCTs, 16 cohort, 223 and 7028 participants respectively). All RCTs (4/4) had a high risk of bias and median (IQR) Newcastle Ottawa Scale for cohort studies was 7.5 (6-9). In both RCTs and cohort studies, buprenorphine was associated with; greater offspring birth weight (weighted mean difference [WMD] 343 g (95% CI: 40-645 g) in RCT and 184 g (95% CI: 121-247 g) in cohort studies); body length at birth (WMD 2.28 cm (95% CI: 1.06-3.49 cm) in RCTs and 0.65 cm (95% CI: 0.31-0.98 cm) in cohort studies); and reduced risk of prematurity (risk ratio [RR] 0.41 (95% CI: 0.18-0.93) in RCTs and 0.63 [95% CI: 0.53-0.75] in cohort studies) when compared to methadone. All other clinical outcomes were comparable.
CONCLUSIONS
Compared to methadone, buprenorphine was consistently associated with improved birthweight and gestational age, however given potential biases, results should be interpreted with caution.
Topics: Analgesics, Opioid; Buprenorphine; Child; Female; Humans; Infant, Newborn; Methadone; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy
PubMed: 35758300
DOI: 10.1080/10826084.2022.2083174 -
Scientific Reports Sep 2020In the U.S., opioid prescription for treatment of pain nearly quadrupled from 1999 to 2014. The diversion and misuse of prescription opioids along with increased use of...
In the U.S., opioid prescription for treatment of pain nearly quadrupled from 1999 to 2014. The diversion and misuse of prescription opioids along with increased use of drugs like heroin and fentanyl, has led to an epidemic in addiction and overdose deaths. The most common cause of opioid overdose and death is opioid-induced respiratory depression (OIRD), a life-threatening depression in respiratory rate thought to be caused by stimulation of opioid receptors in the inspiratory-generating regions of the brain. Studies in mice have revealed that variation in opiate lethality is associated with strain differences, suggesting that sensitivity to OIRD is genetically determined. We first tested the hypothesis that genetic variation in inbred strains of mice influences the innate variability in opioid-induced responses in respiratory depression, recovery time and survival time. Using the founders of the advanced, high-diversity mouse population, the Diversity Outbred (DO), we found substantial sex and genetic effects on respiratory sensitivity and opiate lethality. We used DO mice treated with morphine to map quantitative trait loci for respiratory depression, recovery time and survival time. Trait mapping and integrative functional genomic analysis in GeneWeaver has allowed us to implicate Galnt11, an N-acetylgalactosaminyltransferase, as a gene that regulates OIRD.
Topics: Analgesics, Opioid; Animals; Female; Genetic Variation; Male; Mice; Morphine; N-Acetylgalactosaminyltransferases; Quantitative Trait Loci; Respiratory Insufficiency
PubMed: 32917924
DOI: 10.1038/s41598-020-71804-2 -
Journal of Nursing Scholarship : An... May 2023Drug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled...
INTRODUCTION
Drug overdoses have reached a historic milestone of over 100,000 deaths in a single year, 75,673 related to opioids. The acceleration in opioid-related deaths coupled with stark health inequities demands a close examination of opioid use disorder (OUD) treatment barriers and swift consideration of policy changes.
DESIGN
The aim of this buprenorphine policy analysis is to summarize existing buprenorphine barriers and present policy solutions to improve access and actualize the contributions of Advanced Practice Registered Nurses (APRNs).
METHODS
The policy analysis follows five sequential steps: (1) defining the problem, (2) identifying key stakeholders, (3) assessing the landscape of relevant policies, (4) describing viable policy options, and (5) making final recommendations.
RESULTS
Although there are laudable efforts to improve buprenorphine access, such as the new buprenorphine guidelines issued in April 2021, without larger-scale changes to federal, state, and scope of practice laws, overdose rates will continue to rise. We recommend a multipronged policy approach to improve buprenorphine treatment access, including eliminating the DEA X waiver, improving OUD education, and adopting full practice authority for APRNs in all states.
CONCLUSION
Incremental change is no longer sufficient to address opioid overdose deaths. Bolder and coordinated policy action is possible and necessary to empower the full clinical workforce to apply evidence-based life-saving treatments for OUD. The critical contributions of nurses in advancing equitable access to OUD care are emphasized in the National Academy of Medicine's Report, Future of Nursing: Charting a Path to Achieve Health Equity. Nurses are named as instrumental in improving buprenorphine access. Policy changes that acknowledge and build on evidence-based treatment expansion strategies are sorely needed.
CLINICAL RELEVANCE
One of the most robust tools to combat opioid overdose deaths is buprenorphine, a partial opioid agonist, and gold standard medication treatment for OUD, but only 5% of the prescribing workforce possess the required Drug Enforcement Agency (DEA) X waiver. A growing body of evidence demonstrates that Advanced Practice Registered Nurses are accelerating the growth in waiver update and buprenorphine use, despite the considerable barriers and limitations described in this policy analysis.
Topics: Humans; Buprenorphine; Opiate Substitution Treatment; Opiate Overdose; Opioid-Related Disorders; Analgesics, Opioid; Policy Making
PubMed: 36624606
DOI: 10.1111/jnu.12871 -
JAMA Network Open Jul 2022The opioid crisis has been exacerbated by the COVID-19 pandemic in the US, with concerns over major disruptions to medication treatment of opioid use disorder.
IMPORTANCE
The opioid crisis has been exacerbated by the COVID-19 pandemic in the US, with concerns over major disruptions to medication treatment of opioid use disorder.
OBJECTIVE
To investigate whether the COVID-19 pandemic was associated with disruption of buprenorphine and methadone supplies in the US.
DESIGN, SETTING, AND PARTICIPANTS
This repeated cross-sectional study used ARCOS (Automated Reports and Consolidated Ordering System) data, which monitor the flow of controlled substances in the US, from January 1, 2012, through June 30, 2021. Manufacturers and point of sale or distribution at the dispensing or retail level, including hospitals, retail pharmacies, clinicians, midlevel clinicians, and teaching institutions, were included in the analysis.
EXPOSURES
COVID-19 pandemic.
MAIN OUTCOMES AND MEASURES
Quarterly supplies of buprenorphine and methadone per capita in milligrams.
RESULTS
The per capita supply of methadone dropped from 13.2 mg in the first quarter of 2020 to 10.5 mg in the second quarter of 2020, whereas the per capita supply of buprenorphine increased from 3.6 mg to 3.7 mg in the same period. The per capita supply of methadone declined 20% (-2.7 mg) in the second quarter of 2020 compared with the first quarter of 2020, and the supply had not returned to 2019 levels as of June 2021, whereas the supply of buprenorphine per person increased consistently during the same period. There were considerable state disparities in the reduction of the methadone supply during the pandemic, with many states experiencing pronounced per capita supply decreases, including reductions as great as 50% in New Hampshire and Florida. These decreases in per capita methadone supply were not compensated by proportional increases in the per capita buprenorphine supply (linear fit, 0.17 [95% CI, -0.43 to 0.76]; P = .47).
CONCLUSIONS AND RELEVANCE
This cross-sectional study of buprenorphine and methadone supplies during the COVID-19 pandemic found a pronounced decline in the methadone supply but no disruption to the buprenorphine supply. Future research is needed to explain the pronounced state disparities in the methadone supply.
Topics: Buprenorphine; Cross-Sectional Studies; Humans; Methadone; Opiate Substitution Treatment; Pandemics; COVID-19 Drug Treatment
PubMed: 35881394
DOI: 10.1001/jamanetworkopen.2022.23708 -
Journal of Addiction MedicineThis analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).
BACKGROUND
This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).
METHODS
The RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months. Results were analyzed within the full cohort and by duration of BUP-XR treatment (0-2 months, 3-5 months, 6-11 months, 12 months, or 13-18 months) with and without inverse probability weights adjusting for differences in baseline characteristics.
RESULTS
Of 533 participants, 529 were assessed over the 18-month study period. Further posttrial pharmacotherapy was reported by 33% of participants. At RECOVER baseline, longer BUP-XR was associated with higher abstinence (0-2 months BUP-XR [n = 116]: 38.8%; 3-5 months BUP-XR [n = 61]: 41.0%; 6-11 months BUP-XR [n = 86]: 68.6%; 12 months BUP-XR [n = 135]: 71.9%; 18 months BUP-XR [n = 131]: 88.2%) and greater 12-Item Short Form Health Survey mental component scores. Over 60% of participants had stable or improved outcomes at 6, 12, and 18 months assessments. Overall 47% of participants self-reported sustained opioid abstinence for the full 18-month follow-up, with greater sustained abstinence associated with longer BUP-XR treatment duration. A sensitivity analysis, removing patients receiving medications for OUD, yielded similar results.
CONCLUSIONS
Participants from BUP-XR clinical trials who continued into RECOVER maintained or improved on numerous outcomes over 18 months, demonstrating the long-term positive impact of OUD pharmacotherapy.
Topics: Humans; Analgesics, Opioid; Narcotic Antagonists; Naltrexone; Quality of Life; Buprenorphine; Opioid-Related Disorders; Delayed-Action Preparations
PubMed: 36111991
DOI: 10.1097/ADM.0000000000001070 -
Annals of Emergency Medicine Mar 2022Nonfatal emergency department (ED) visits for opioid overdose are important opportunities to prescribe naloxone and buprenorphine, both of which can prevent future...
STUDY OBJECTIVE
Nonfatal emergency department (ED) visits for opioid overdose are important opportunities to prescribe naloxone and buprenorphine, both of which can prevent future overdose-related mortality. We assessed the rate of this prescribing using national data from August 2019 to April 2021, a period during which US opioid overdose deaths reached record levels.
METHODS
We conducted a retrospective cohort analysis using Symphony Health's Integrated Dataverse, which includes data from 5,800 hospitals and 70,000 pharmacies. Of ED visits for opioid overdose between August 4, 2019, and April 3, 2021, we calculated the proportion with at least 1 naloxone prescription within 30 days and repeated this analysis for buprenorphine. To contextualize the naloxone prescribing rate, we calculated the proportion of ED visits for anaphylaxis with at least 1 prescription for epinephrine-another life-saving rescue medication-within 30 days.
RESULTS
Analyses included 148,966 ED visits for opioid overdose. Mean weekly visits increased 23.6% during the period between April 26, 2020 and October 3, 2020 compared with the period between August 4, 2019 to April 25, 2020. Visits declined to prepandemic levels between October 4, 2020 and March 13, 2021, after which visits began to rise. Naloxone and buprenorphine were prescribed within 30 days at 7.4% and 8.5% of the 148,966 visits, respectively. The naloxone prescribing rate (7.4%) was substantially lower than the epinephrine prescribing rate (48.9%) after ED visits for anaphylaxis.
CONCLUSION
Between August 4, 2019, and April 3, 2021, naloxone and buprenorphine were only prescribed after 1 in 13 and 1 in 12 ED visits for opioid overdose, respectively. Findings suggest that clinicians are missing critical opportunities to prevent opioid overdose-related mortality.
Topics: Adolescent; Adult; Buprenorphine; Databases, Factual; Emergency Service, Hospital; Female; Humans; Male; Naloxone; Narcotic Antagonists; Opiate Overdose; Practice Patterns, Physicians'; Retrospective Studies; United States; Young Adult
PubMed: 34802772
DOI: 10.1016/j.annemergmed.2021.10.005 -
American Journal of Public Health Aug 2021Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been... (Review)
Review
Opioids contribute to more than 60 000 deaths annually in North America. While the expansion of overdose education and naloxone distribution (OEND) programs has been recommended in response to the opioid crisis, their effectiveness remains unclear. To conduct an umbrella review of systematic reviews to provide a broad-based conceptual scheme of the effect and feasibility of OEND and to identify areas for possible optimization. We conducted the umbrella review of systematic reviews by searching PubMed, Embase, PsycINFO, Epistemonikos, the Cochrane Database of Systematic Reviews, and the reference lists of relevant articles. Briefly, an academic librarian used a 2-concept search, which included opioid subject headings and relevant keywords with a modified PubMed systematic review filter. Eligible systematic reviews described comprehensive search strategies and inclusion and exclusion criteria, evaluated the quality or risk of bias of included studies, were published in English or French, and reported data relevant to either the safety or effectiveness of OEND programs, or optimal strategies for the management of opioid overdose with naloxone in out-of-hospital settings. Two reviewers independently extracted study characteristics and the quality of included reviews was assessed in duplicate with AMSTAR-2, a critical appraisal tool for systematic reviews. Review quality was rated critically low, low, moderate, or high based on 7 domains: protocol registration, literature search adequacy, exclusion criteria, risk of bias assessment, meta-analytical methods, result interpretation, and presence of publication bias. Summary tables were constructed, and confidence ratings were provided for each outcome by using a previously modified version of the Royal College of General Practitioners' clinical guidelines. Six systematic reviews containing 87 unique studies were included. We found that OEND programs produce long-term knowledge improvement regarding opioid overdose, improve participants' attitudes toward naloxone, provide sufficient training for participants to safely and effectively manage overdoses, and effectively reduce opioid-related mortality. High-concentration intranasal naloxone (> 2 mg/mL) was as effective as intramuscular naloxone at the same dose, whereas lower-concentration intranasal naloxone was less effective. Evidence was limited for other naloxone formulations, as well as the need for hospital transport after overdose reversal. The preponderance of evidence pertained persons who use heroin. Evidence suggests that OEND programs are effective for reducing opioid-related mortality; however, additional high-quality research is required to optimize program delivery. Community-based OEND programs should be implemented widely in high-risk populations.
Topics: Health Education; Humans; Naloxone; Narcotic Antagonists; Opiate Overdose; Public Health; Systematic Reviews as Topic
PubMed: 34214412
DOI: 10.2105/AJPH.2021.306306