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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 -
JAMA Network Open Aug 2023Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training...
IMPORTANCE
Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors.
OBJECTIVE
To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training.
EXPOSURE
In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis.
MAIN OUTCOMES AND MEASURES
Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs.
RESULTS
There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training.
CONCLUSIONS AND RELEVANCE
This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.
Topics: Male; Adult; Humans; Naloxone; Narcotic Antagonists; Analgesics, Opioid; Cohort Studies; Drug Overdose; Victoria
PubMed: 37540514
DOI: 10.1001/jamanetworkopen.2023.27319 -
Journal of Substance Abuse Treatment Jun 2017There are high levels of prescription and consumption of prescription opioids in the US. Misuse of prescription opioids has been shown to be highly correlated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There are high levels of prescription and consumption of prescription opioids in the US. Misuse of prescription opioids has been shown to be highly correlated with prescription opioid-related morbidity and mortality including fatal and non-fatal overdose. We characterized the past-year prevalence of prescription opioid misuse among those 11-30years of age in the US.
METHODS
A systematic review and meta-analysis were carried out following a published protocol and PRISMA guidelines. We searched electronic databases; reports were eligible if they were published between 1/1/1990-5/30/2014, and included data on individuals 11-30years of age from the US. Study quality was assessed using the Newcastle-Ottawa Scale.
RESULTS
A total of 3211 abstracts were reviewed for inclusion; after discarding duplicates and identifying non-eligible reports, a total of 19 unique reports, providing 34 estimates, were included in the final systematic review and meta-analysis. The range of past-year prescription opioid misuse prevalence the reports was 0.7%-16.3%. An increase in prevalence of 0.4% was observed over the years of data collection.
CONCLUSIONS
This systematic review and meta-analysis found a high prevalence of past-year prescription opioid misuse among individuals 11-30years of age. Importantly, we identified an increase in past-year prevalence 1990-2014. Misuse of prescription opioids has played an important role in national increases of fatal and non-fatal drug overdose, heroin use and injection, and HIV and HCV infection among young people. The observed high and increasing prevalence of prescription opioid misuse is an urgent public health issue.
Topics: Adolescent; Adult; Analgesics, Opioid; Child; Drug Overdose; Humans; Opioid-Related Disorders; Prescription Drug Misuse; Prevalence; Public Health; United States; Young Adult
PubMed: 28476268
DOI: 10.1016/j.jsat.2017.03.007 -
Journal of Pain Research 2021Mortalities due to fentanyl derivatives are on the rise with novel fentanyl analogues and still emerging on the global illicit drug market. They are highly potent and... (Review)
Review
OBJECTIVE
Mortalities due to fentanyl derivatives are on the rise with novel fentanyl analogues and still emerging on the global illicit drug market. They are highly potent and very fatal in low doses, yet there has been a lack of systematic research surrounding this subject. This review aims to assess the causes, nature, and toxicology of fatalities associated with fentanyl analogues.
METHODS
Five databases: Scopus, Embase, Medline, PubMed and Google Scholar were searched from inception to October 2020 to identify case studies and case series reporting fentanyl analogue-related fatalities. Two independent reviewers screened and selected the articles followed by the data extraction from each article, which included demography, route of administration, causes and nature of death, and the fentanyl analogue implicated. All articles were then subject to quality assessment tools developed by the Joanna Briggs Institute (JBI). A narrative synthesis was undertaken.
RESULTS
The initial data search yielded 834 articles, only 14 of which met the inclusion criteria - this included nine case reports and five case series. Of the 1079 fentanyl-analogue related deaths reported, the majority of them occurred in the US (n=1044, 96.8%). The majority of fatalities were male (n=766, 71%), white (n=884, 87%) and in the age ranges 25-34 and 35-44 years (30.5% and 29.6%, respectively). The most common route of administration was intravenous (n=319, 66%) and the manner of death was almost exclusively accidental (99.7%). The predominant cause of death was fentanyl-analogue toxicity (n=292, 85.4%) and involved mixed drug toxicity (n=47, 13.7%). The mean post-mortem fentanyl analogue concentration was 31.6 ng/mL.
CONCLUSION
Most fatalities were reported in the US involving young white males. Overdose through intravenous administration and by mixed drug toxicities with other opioids were the major causes of death. Deaths reported in peer-reviewed literature were relatively less than those reported by real-world data.
PubMed: 34466028
DOI: 10.2147/JPR.S312227 -
Behavioural Brain Research Nov 2013The serotonin syndrome (SS) is a potentially life-threatening disorder in humans which is induced by ingestion of an overdose or by combination of two or more serotonin... (Review)
Review
The serotonin syndrome (SS) is a potentially life-threatening disorder in humans which is induced by ingestion of an overdose or by combination of two or more serotonin (5-HT)-enhancing drugs. In animals, acute administration of direct and indirect 5-HT agonists also leads to a set of behavioral and autonomic responses. In the current review, we provide an overview of the existing versions of the animal model of the SS. With a focus on studies in rats and mice, we analyze the frequency of behavioral and autonomic responses following administration of 5-HT-enhancing drugs and direct 5-HT agonists administered alone or in combination, and we briefly discuss the receptor mediation of these responses. Considering species differences, we identify a distinct set of behavioral and autonomic responses that are consistently observed following administration of direct and indirect 5-HT agonists. Finally, we discuss the importance of a standardized assessment of SS responses in rodents and the utility of animal models of the SS in translational studies, and provide suggestions for future research.
Topics: Animals; Disease Models, Animal; Humans; Mice; Rats; Serotonin Agents; Serotonin Syndrome
PubMed: 24004848
DOI: 10.1016/j.bbr.2013.08.045 -
Palliative Medicine Sep 2021Providing unawareness and pain relief are core elements of palliative sedation. In addition to clinical scales, nociception and electroencephalogram-based depth of...
BACKGROUND
Providing unawareness and pain relief are core elements of palliative sedation. In addition to clinical scales, nociception and electroencephalogram-based depth of sedation monitoring are used to assess the level of consciousness and analgesia during sedation in intensive care units and during procedures.
AIM
To determine whether reported devices impact the outcomes of palliative sedation.
DESIGN
Systematic review and narrative synthesis of research published between January 2000 and December 2020.
DATA SOURCES
Embase, Google Scholar, PubMed, CENTRAL, and the Cochrane Library. All reports describing the use of any monitoring device to assess the level of consciousness or analgesia during palliative sedation were screened for inclusion. Data concerning safety and efficacy were extracted. Patient comfort was the primary outcome of interest. Articles reporting sedation but that did not meet guidelines of the European Association for Palliative Care were excluded.
RESULTS
Six reports of five studies were identified. Four of these were case series and two were case reports. Together, these six reports involved a total of 67 sedated adults. Methodological quality was assessed fair to good. Medication regimens were adjusted to bispectral index monitoring values in two studies, which found poor correlation between monitoring values and observational scores. In another study, high nociception index values, representing absence of pain, were used to detect opioid overdosing. Relatives and caregivers found the procedures feasible and acceptable.
Topics: Adult; Analgesia; Anesthesia; Conscious Sedation; Humans; Hypnotics and Sedatives; Nociception; Palliative Care
PubMed: 34109873
DOI: 10.1177/02692163211022943 -
Harm Reduction Journal Feb 2022Naloxone-based interventions as part of health systems can reverse an opioid overdose. Previous systematic reviews have identified the effectiveness of naloxone;...
BACKGROUND
Naloxone-based interventions as part of health systems can reverse an opioid overdose. Previous systematic reviews have identified the effectiveness of naloxone; however, the role of context and mechanisms for its use has not been explored. This realist systematic review aims to identify a theory of how naloxone works based on the contexts and mechanisms that contribute to the success of the intervention for improved outcomes.
METHODS
Pre-registered at PROSPERO, this realist review followed RAMESES standards of reporting. Keywords included 'naloxone' and ' opioid overdose'. All study designs were included. Data extraction using 55 relevant outputs based on realist logic produced evidence of two middle-range theories: Naloxone Bystander Intervention Theory and Skills Transfer Theory.
RESULTS
Harm reduction and/or low threshold contexts provide a non-judgemental approach which support in-group norms of helping and empower the social identity of the trained and untrained bystander. This context also creates the conditions necessary for skills transfer and diffusion of the intervention into social networks. Stigma and negative attitudes held by first responders and stakeholders involved in the implementation process, such as police or GPs, can prohibit the bystander response by inducing fear in responding. This interferes with skills transfer, naloxone use and carriage of naloxone kits.
CONCLUSIONS
The findings provide theoretically informed guidance regarding the harm reduction contexts that are essential for the successful implementation of naloxone-based interventions. Peer-to-peer models of training are helpful as it reinforces social identity and successful skills transfer between bystanders. Health systems may want to assess the prevalence of, and take steps to reduce opioid-related stigma with key stakeholders in contexts using a low threshold training approach to build an environment to support positive naloxone outcomes.
TRIAL REGISTRATION
PROSPERO 2019 CRD42019141003.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opiate Overdose; Opioid-Related Disorders
PubMed: 35197057
DOI: 10.1186/s12954-022-00599-4 -
Bulletin of the World Health... Feb 2013To systematically review cohort studies of mortality among people who inject drugs, examine mortality rates and causes of death in this group, and identify participant-... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review cohort studies of mortality among people who inject drugs, examine mortality rates and causes of death in this group, and identify participant- and study-level variables associated with a higher risk of death.
METHODS
Tailored search strings were used to search EMBASE, Medline and PsycINFO. The grey literature was identified through online grey literature databases. Experts were consulted to obtain additional studies and data. Random effects meta-analyses were performed to estimate pooled crude mortality rates (CMRs) and standardized mortality ratios (SMRs).
FINDINGS
Sixty-seven cohorts of people who inject drugs were identified, 14 of them from low- and middle-income countries. The pooled CMR was 2.35 deaths per 100 person-years (95% confidence interval, CI: 2.12-2.58). SMRs were reported for 32 cohorts; the pooled SMR was 14.68 (95% CI: 13.01-16.35). Comparison of CMRs and the calculation of CMR ratios revealed mortality to be higher in low- and middle-income country cohorts, males and people who injected drugs that were positive for human immunodeficiency virus (HIV). It was also higher during off-treatment periods. Drug overdose and acquired immunodeficiency syndrome (AIDS) were the primary causes of death across cohorts.
CONCLUSION
Compared with the general population, people who inject drugs have an elevated risk of death, although mortality rates vary across different settings. Any comprehensive approach to improving health outcomes in this group must include efforts to reduce HIV infection as well as other causes of death, particularly drug overdose.
Topics: Cause of Death; Databases, Bibliographic; Drug Overdose; Female; HIV Seropositivity; Humans; Male; Sex Distribution; Substance Abuse, Intravenous
PubMed: 23554523
DOI: 10.2471/BLT.12.108282 -
Drug and Alcohol Dependence Jul 2021The opioid-related overdose epidemic remains a persistent public health problem in the United States and has been accelerated by the 2019 coronavirus disease pandemic....
BACKGROUND
The opioid-related overdose epidemic remains a persistent public health problem in the United States and has been accelerated by the 2019 coronavirus disease pandemic. Existing, evidence-based treatment options for opioid use disorder (OUD) are broadly underutilized, particularly by people experiencing homelessness (PEH). PEH are also more likely to misuse and overdose on opioids. To better understand current gaps and disparities in OUD treatment experienced by PEH and efforts to address them, we synthesized the literature reporting on the intersection of housing status and OUD treatment.
METHODS
We conducted a scoping review of the literature from the electronic databases MEDLINE, Embase, PsycINFO, and Web of Science Core Collection. We included studies describing treatment-related outcomes specific to PEH and articles assessing OUD treatment interventions tailored to this population. Relevant findings were compiled via thematic analysis and narratively synthesized.
RESULTS
60 articles met our inclusion criteria, including 43 descriptive and 17 intervention-focused studies. These studies demonstrated that PEH experience more barriers to OUD treatment than their housed counterparts and access inpatient and detoxification treatment more commonly than pharmacotherapy. However, the reviewed literature indicated that PEH have similar outcomes once engaged in pharmacotherapy. Efficacious interventions for PEH were low-barrier and targeted, with housing interventions also demonstrating benefit.
CONCLUSIONS
PEH have diminished access to evidence-based OUD treatment, particularly medications, and require targeted approaches to improve engagement and retention. To mitigate the disproportionate opioid-related morbidity and mortality PEH experience, innovative, flexible, and interdisciplinary OUD treatment models are necessary, with housing support playing an important role.
Topics: Buprenorphine; Health Services Accessibility; Health Services Misuse; Ill-Housed Persons; Humans; Methadone; Naltrexone; Opiate Substitution Treatment; Opioid-Related Disorders; United States
PubMed: 33985863
DOI: 10.1016/j.drugalcdep.2021.108717 -
Frontiers in Pharmacology 2021In routine clinical practice, non-standard doses of direct oral anticoagulants (DOACs) are commonly used in patients with atrial fibrillation (AF). However, data on the... (Review)
Review
Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies.
In routine clinical practice, non-standard doses of direct oral anticoagulants (DOACs) are commonly used in patients with atrial fibrillation (AF). However, data on the clinical outcomes of non-standard doses of DOACs are limited. The MEDLINE, Embase, and Cochrane Library databases were systematically searched from their inception until 30 June 2020 for studies that reported the effectiveness or safety outcomes of non-standard doses of DOACs compared with on-label doses of DOACs in patients with atrial fibrillation. Non-standard doses of DOACs were defined as under or over-dose of DOACs based on the recommended standard doses in drug labels. A random-effects meta-analysis was performed to calculate the pooled hazard ratio and associated 95% confidence interval (95% confidence interval). Subgroup analyses were conducted according to individual DOACs and different geographic regions. Ten articles involving 148,909 patients with AF were included. There were no significant differences between under-dosing and on-label dosing with respect to stroke/systematic embolism (HR: 1.01, 95% CI: 0.93-1.09), major bleeding (HR: 0.98, 95% CI: 0.77-1.19), intracranial haemorrhage (HR: 1.07, 95% CI: 0.74-1.40), gastrointestinal bleeding (HR: 1.10, 95% CI: 0.82-1.39), and myocardial infarction (HR: 1.07, 95% CI: 0.89-1.25), except for an increased risk of death (HR: 1.37, 95% CI: 1.01-1.73). We observed a significant association between over-dosing of DOACs and increased risk of stroke/systematic embolism (HR: 1.18, 95% CI: 1.04-1.32), major bleeding (HR: 1.16, 95% CI: 1.03-1.29), and death (HR: 1.21, 95% CI: 1.03-1.38) compared with on-label dosing. Furthermore, over-dosing of DOACs increased the risk of stroke/systematic embolism (HR: 1.16; 95% CI: 1.00-1.33) and major bleeding events (HR: 1.18; 95% CI: 1.00-1.37) in Asian patients. A reduced dose of DOACs might be safely and effectively used in clinical practice, especially in Asian patients, whereas high-dose DOACs might not be well tolerated by Asian patients.
PubMed: 33815125
DOI: 10.3389/fphar.2021.645479