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Harm Reduction Journal Oct 2022Opioid overdose epidemic is hitting record highs worldwide, accounting for 76% of mortality related to substance use. Take-home naloxone (THN) strategies are being...
BACKGROUND
Opioid overdose epidemic is hitting record highs worldwide, accounting for 76% of mortality related to substance use. Take-home naloxone (THN) strategies are being implemented in many developed countries that suffer from high opioid overdose death rates. They aim to provide overdose identification and naloxone administration training, along with THN delivery to opioid users and others likely to witness an overdose incident such as family members and peers. However, little is known about such measures in low- and middle-income countries (LMIC), where opioid use and opioid-related deaths are reportedly high. This systematic literature review aims to examine the distribution of THN in LMIC, review studies identifying barriers to the implementation of THN programs worldwide, and assess their applicability to LMIC.
METHODS
The literature was searched and analyzed for eligible studies with quality assessment.
RESULTS
Two studies were found from LMIC on THN programs with promising results, and 13 studies were found on the barriers identified in implementing THN programs worldwide. The main barriers to THN strategies were the lack of training of healthcare providers, lack of privileges, time constraints, cost, legislative/policy restrictions, stigma, fear of litigation, and some misperceptions around THN.
CONCLUSIONS
The barriers outlined in this paper are probably applicable to LMIC, but more difficult to overcome considering the differences in their response to opioid overdose, their cultural attitudes and norms, the high cost, the waivers required, the legislative differences and the severe penalties for drug-related offenses in some of these countries. The solutions suggested to counter-act these obstacles can also be more difficult to achieve in LMIC. Further research is required in this area with larger sample sizes to provide a better understanding of the obstacles to the implementation, feasibility, accessibility, and utilization of THN programs in LMIC.
Topics: Humans; Naloxone; Developing Countries; Narcotic Antagonists; Analgesics, Opioid; Opiate Overdose; Drug Overdose; Opioid-Related Disorders
PubMed: 36266701
DOI: 10.1186/s12954-022-00700-x -
International Journal of Environmental... Oct 2022This systematic review synthesized literature on potential impacts of protracted isolation and other disruptions during the COVID-19 pandemic on deaths of despair... (Review)
Review
This systematic review synthesized literature on potential impacts of protracted isolation and other disruptions during the COVID-19 pandemic on deaths of despair (suicide, overdoses, and drug-related liver diseases). Five electronic databases were searched yielding 70 eligible articles. Extant evidence mostly from high-income countries indicates COVID-19-related disruption may not have influenced suicide rates so far, but there have been reports of increased drug-related and liver disease mortality. Minority groups and women were more vulnerable, indicating the need for stronger equity focus on pandemic recovery and resilience strategies. Further high-quality studies with longer-term follow-up, especially from low-income countries, will inform these strategies.
Topics: COVID-19; Drug Overdose; Female; Humans; Income; Pandemics; Suicide
PubMed: 36232135
DOI: 10.3390/ijerph191912835 -
Harm Reduction Journal Oct 2022Given the ongoing opioid crisis, novel interventions to treat severe opioid use disorder (OUD) are urgently needed. Injectable opioid agonist therapy (iOAT) with... (Review)
Review
BACKGROUND AND AIMS
Given the ongoing opioid crisis, novel interventions to treat severe opioid use disorder (OUD) are urgently needed. Injectable opioid agonist therapy (iOAT) with diacetylmorphine or hydromorphone is effective for the treatment of severe, treatment-refractory OUD, however barriers to implementation persist. Intravenous buprenorphine for the treatment of OUD (BUP iOAT) has several possible advantages over traditional iOAT, including a safety profile that might enable take-home dosing. We aimed to characterize injecting practices among real-world populations of persons who regularly inject buprenorphine, as well as associated adverse events reported in order to inform a possible future BUP iOAT intervention.
METHODS
We conducted a systematic review. We searched MEDLINE, EMBASE, and PsycINFO from inception through July 2020 and used backwards citation screening to search for publications reporting on dose, frequency among persons who regularly inject the drug, or adverse events associated with intravenous use of buprenorphine. The review was limited to English language publications and there was no limitation on study type. Study quality and risk of bias was assessed using the Mixed Methods Appraisal Tool. Narrative synthesis was used in reporting the results.
RESULTS
Eighty-eight studies were included in our review. Regular injection of buprenorphine was identified across diverse settings world-wide. Daily dose of oral buprenorphine injected was < 1-12 mg. Frequency of injection was 0-10 times daily. Adverse events could be characterized as known side effects of opioids/buprenorphine or injection-related complications. Most studies were deemed to be of low quality.
CONCLUSIONS
Extramedical, intravenous use of buprenorphine, continues to be documented. BUP iOAT may be feasible and results may inform the development of a study to test the efficacy and safety of such an intervention. Future work should also examine acceptability among people with severe OUD in North America. Our review was limited by the quality of included studies.
Topics: Analgesics, Opioid; Buprenorphine; Heroin; Humans; Hydromorphone; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 36229831
DOI: 10.1186/s12954-022-00695-5 -
The Cochrane Database of Systematic... Sep 2022There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People... (Review)
Review
BACKGROUND
There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.
SEARCH METHODS
We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods.
MAIN RESULTS
We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms.
AUTHORS' CONCLUSIONS
There is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.
Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Opioid-Related Disorders; Pharmaceutical Preparations
PubMed: 36063082
DOI: 10.1002/14651858.CD011117.pub3 -
Frontiers in Pharmacology 2022N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to...
N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.
PubMed: 36034775
DOI: 10.3389/fphar.2022.828565 -
Drug Safety Nov 2022Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is...
INTRODUCTION
Drug-induced liver injury (DILI) is a rare but serious adverse event that can progress to acute liver failure (ALF). The evidence for treatment of DILI in children is scarce.
OBJECTIVE
We aimed to comprehensively review the available literature on the therapies for both acetaminophen overdose (APAP) and idiosyncratic DILI in the paediatric population.
METHODS
We included original articles conducted in a paediatric population (< 18 years) in which a therapeutic intervention was described to manage APAP or idiosyncratic DILI. Findings were summarized based on age groups (preterm newborn neonates, term and post-term neonates, infants, children and adolescents).
RESULTS
Overall, 25 publications (fifteen case reports, six case series and four retrospective cohort studies) were included, including a total of 140 paediatric DILI cases, from preterm newborn neonates to adolescents. N-acetylcysteine was used to treat 19 APAP cases. N-acetylcysteine (n = 14), ursodeoxycholic acid (n = 3), corticosteroids (n = 31), carnitine (n = 16) and the combination of glycyrrhizin, reduced glutathione, polyene phosphatidylcholine and S-adenosylmethionine (n = 31) were the therapeutic options for treating idiosyncratic DILI. The molecular adsorbent recirculating system was used in the management of either APAP (n = 4) or idiosyncratic DILI (n = 2), while 20 paediatric ALF cases received continuous renal replacement therapy.
CONCLUSIONS
This systematic review identified DILI in the paediatric population who have received specific treatment. These interventions appear to be mainly extrapolated from low-quality evidence from the adult population. Thus, there is a need for high-quality studies to test the efficacy of known and novel therapies to treat DILI specifically addressed to the paediatric population. PROSPERO registration number CRD42021214702.
Topics: Acetaminophen; Acetylcysteine; Adolescent; Adrenal Cortex Hormones; Adult; Carnitine; Chemical and Drug Induced Liver Injury; Child; Drug-Related Side Effects and Adverse Reactions; Glutathione; Glycyrrhizic Acid; Humans; Infant, Newborn; Liver; Liver Failure, Acute; Retrospective Studies; S-Adenosylmethionine; Ursodeoxycholic Acid
PubMed: 36006605
DOI: 10.1007/s40264-022-01224-w -
Medical Research Archives Aug 2022Opioid use disorder (OUD) is an epidemic in the United States. In the past 12 months alone, there have been 75,000+ deaths attributed to opioid overdose: more than any...
Opioid use disorder (OUD) is an epidemic in the United States. In the past 12 months alone, there have been 75,000+ deaths attributed to opioid overdose: more than any other year in American history. Current pharmacotherapies for the treatment of OUD effectively suppress opioid withdrawal symptoms, but long-term relapse rates remain unacceptably high. Novel treatments for OUD are desperately needed to curb this epidemic. One target that has received considerable recent interest is the neuroimmune system. The neuroimmune system is anchored by glial cells, i.e., microglia and astrocytes, but neuroimmune signaling is known to influence neurons, including altering neurotransmission, synapse formation, and ultimately, brain function. Preclinical studies have shown that experimental attenuation of pro-inflammatory neuroimmune signaling modulates opioid addiction processes, including opioid reward, tolerance, and withdrawal symptoms, which suggests potential therapeutic benefit in patients. Whereas the peripheral immune system in OUD patients has been studied for decades and is well-understood, little is known about the immune system in OUD patients or its viability as a treatment target. Herein, we review the literature describing relationships between opioid administration and the neuroimmune system, the influence of neuroimmune signaling on opioid addiction processes, and the therapeutic potential for targeting the neuroimmune system in OUD subjects using glial modulator medications.
PubMed: 37744743
DOI: 10.18103/mra.v10i8.2955 -
Frontiers in Public Health 2022The potential for digital initiatives for opioid harm reduction is boundless. Synthesized evidence on current interventions and their efficacy are emerging. This scoping...
BACKGROUND
The potential for digital initiatives for opioid harm reduction is boundless. Synthesized evidence on current interventions and their efficacy are emerging. This scoping review is an effort to aggregate Canadian and Australian digital health initiatives used to prevent opioid-related deaths and minimize harm, prior to and particularly during the pandemic of SARs-COVID-19, when the crisis escalated.
METHODS
The Joanna Briggs Institute's methodological framework for conducting scoping reviews was used. Peer reviewed and gray literature published between January 2016 to October 2021 were included. Search translation was performed across CINAHL, Cochrane, SCOPUS, MEDLINE Complete, and ProQuest Public Health with consistent use of key search terms. Citation checks were also conducted. Studies included were written in English and reported on digital technologies to prevent opioid-related harm and/or mortality in participants aged 18 years or older in Australia and Canada.
RESULTS
A total of 16 publications were included in the final analysis (Australia = 5; Canada = 11). The most frequently reported digital technologies were telehealth to support access to treatment ( = 3) and mobile applications for overdose monitoring and prevention ( = 3). Telehealth-delivered opioid replacement therapy demonstrated equal outcomes and treatment retention rates compared to in-person and mobile applications for overdose monitoring demonstrated lifesaving capability through direct linkages with emergency response services.
CONCLUSIONS
Digital interventions to minimize opioid crisis related harm and overdose prevention are fast emerging in Australia and Canada. During the pandemic, the crisis escalated in both countries as a public health emergency, and different initiatives were trialed. Digital harm reduction solutions via mobile apps (or SaaS solutions) were found to have the potential to prevent accidental overdose deaths and save lives, if rendered through privacy preserved, secure and trust enabled methods that empower users. Knowledge sharing between the two countries, relating to suitable interventions, may add significant value in combatting the escalating opioid crisis in the post pandemic era.
Topics: Analgesics, Opioid; Australia; COVID-19; Canada; Drug Overdose; Humans; Opioid Epidemic; Pandemics
PubMed: 35903371
DOI: 10.3389/fpubh.2022.900733 -
Journal of Hospital Medicine Sep 2022Hospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD...
BACKGROUND
Hospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD treatment guidelines intended for other treatment settings could inform in-hospital OUD management.
OBJECTIVE
Evaluate the quality and content of existing guidelines for OUD treatment and management.
DATA SOURCES
OVID MEDLINE, PubMed, Ovid PsychINFO, EBSCOhost CINHAL, ERCI Guidelines Trust, websites of relevant societies and advocacy organizations, and selected international search engines.
STUDY SELECTION
Guidelines published between January 2010 to June 2020 addressing OUD treatment, opioid withdrawal management, opioid overdose prevention, and care transitions among adults.
DATA EXTRACTION
We assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.
DATA SYNTHESIS
Nineteen guidelines met the selection criteria. Most recommendations were based on observational studies or expert consensus. Guidelines recommended the use of nonstigmatizing language among patients with OUD; to assess patients with unhealthy opioid use for OUD using the Diagnostic Statistical Manual of Diseases-5th Edition criteria; use of methadone or buprenorphine to treat OUD and opioid withdrawal; use of multimodal, nonopioid therapy, and when needed, short-acting opioid analgesics in addition to buprenorphine or methadone, for acute pain management; ensuring linkage to ongoing methadone or buprenorphine treatment; referring patients to psychosocial treatment; and ensuring access to naloxone for opioid overdose reversal.
CONCLUSIONS
Included guidelines were informed by studies with various levels of rigor and quality. Future research should systematically study buprenorphine and methadone initiation and titration among people using fentanyl and people with pain, especially during hospitalization.
Topics: Adult; Analgesics, Opioid; Buprenorphine; Hospitalization; Humans; Methadone; Opiate Overdose; Opioid-Related Disorders
PubMed: 35880821
DOI: 10.1002/jhm.12908 -
Journal of Hospital Medicine Sep 2022Hospital-based clinicians frequently care for patients with opioid withdrawal or opioid use disorder (OUD) and are well-positioned to identify and initiate treatment for...
Hospital-based clinicians frequently care for patients with opioid withdrawal or opioid use disorder (OUD) and are well-positioned to identify and initiate treatment for these patients. With rising numbers of hospitalizations related to opioid use and opioid-related overdose, the Society of Hospital Medicine convened a working group to develop a Consensus Statement on the management of OUD and associated conditions among hospitalized adults. The guidance statement is intended for clinicians practicing medicine in the inpatient setting (e.g., hospitalists, primary care physicians, family physicians, advanced practice nurses, and physician assistants) and is intended to apply to hospitalized adults at risk for, or diagnosed with, OUD. To develop the Consensus Statement, the working group conducted a systematic review of relevant guidelines and composed a draft statement based on extracted recommendations. Next, the working group obtained feedback on the draft statement from external experts in addiction medicine, SHM members, professional societies, harm reduction organizations and advocacy groups, and peer reviewers. The iterative development process resulted in a final Consensus Statement consisting of 18 recommendations covering the following topics: (1) identification and treatment of OUD and opioid withdrawal, (2) perioperative and acute pain management in patients with OUD, and (3) methods to optimize care transitions at hospital discharge for patients with OUD. Most recommendations in the Consensus Statement were derived from guidelines based on observational studies and expert consensus. Due to the lack of rigorous evidence supporting key aspects of OUD-related care, the working group identified important issues necessitating future research and exploration.
Topics: Adult; Analgesics, Opioid; Consensus; Hospital Medicine; Hospitalization; Humans; Opioid-Related Disorders
PubMed: 35880813
DOI: 10.1002/jhm.12893