-
Substance Abuse Treatment, Prevention,... Nov 2021There are preliminary indications that the trajectory of drug overdose-related deaths in North America has been exacerbated due to the novel coronavirus disease pandemic... (Review)
Review
The impact of the novel coronavirus disease (COVID-19) pandemic on drug overdose-related deaths in the United States and Canada: a systematic review of observational studies and analysis of public health surveillance data.
BACKGROUND
There are preliminary indications that the trajectory of drug overdose-related deaths in North America has been exacerbated due to the novel coronavirus disease pandemic (COVID-19). As such, the impact of COVID-19 on drug overdose-related deaths was examined through a systematic review of the literature and percentage change analyses of surveillance data.
METHODS
Systematic searches in electronic databases were conducted, a topical issue brief and bibliography were reviewed, reference lists of included studies were searched and expert consultations were held to identify studies (Registration # CRD42021230223). Observational studies from the United States and Canada were eligible for inclusion if drug overdose-related deaths were assessed in quantitative or qualitative analyses onwards from at least March 2020. In addition, percentage changes comparing drug overdose-related deaths in the second annual quarter (Q2 2020 [April to June]) with the first annual quarter (Q1 2020 [January to March]) were generated using national and subnational data from public health surveillance systems and reports from jurisdictions in the United States and Canada.
RESULTS
Nine studies were included in the systematic review, eight from the United States and one from Canada. The maximum outcome assessment period in the included studies extended until September 2020. Drug overdose-related deaths after the onset of COVID-19 were higher compared with the months leading up to the pandemic in 2020 and the comparative months in 2019. In additional percentage change analyses, drug overdose-related deaths increased by 2 to 60% in jurisdictions in the United States and by 58% in Canada when comparing Q2 2020 with Q1 2020.
CONCLUSIONS
Drug overdose-related deaths increased after the onset of COVID-19. The current situation necessitates a multi-pronged approach, encompassing expanded access to substance use disorder treatment, undisrupted access to harm reduction services, emphasis on risk reduction strategies, provision of a safe drug supply and decriminalization of drug use.
Topics: COVID-19; Canada; Drug Overdose; Humans; Pandemics; Public Health Surveillance; SARS-CoV-2; United States
PubMed: 34844624
DOI: 10.1186/s13011-021-00423-5 -
Social Psychiatry and Psychiatric... Apr 2022This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids. (Review)
Review
PURPOSE
This systematic review summarizes and presents the current state of research quantifying the relationship between mental disorder and overdose for people who use opioids.
METHODS
The protocol was published in Open Science Framework. We used the PECOS framework to frame the review question. Studies published between January 1, 2000, and January 4, 2021, from North America, Europe, the United Kingdom, Australia, and New Zealand were systematically identified and screened through searching electronic databases, citations, and by contacting experts. Risk of bias assessments were performed. Data were synthesized using the lumping technique.
RESULTS
Overall, 6512 records were screened and 38 were selected for inclusion. 37 of the 38 studies included in this review show a connection between at least one aspect of mental disorder and opioid overdose. The largest body of evidence exists for internalizing disorders generally and mood disorders specifically, followed by anxiety disorders, although there is also moderate evidence to support the relationship between thought disorders (e.g., schizophrenia, bipolar disorder) and opioid overdose. Moderate evidence also was found for the association between any disorder and overdose.
CONCLUSION
Nearly all reviewed studies found a connection between mental disorder and overdose, and the evidence suggests that having mental disorder is associated with experiencing fatal and non-fatal opioid overdose, but causal direction remains unclear.
Topics: Analgesics, Opioid; Drug Overdose; Europe; Humans; Opiate Overdose; Psychotic Disorders
PubMed: 34796369
DOI: 10.1007/s00127-021-02199-2 -
Epidemiologic Reviews Jan 2022The opioid overdose crisis is driven by an intersecting set of social, structural, and economic forces. Simulation models are a tool to help us understand and address...
The opioid overdose crisis is driven by an intersecting set of social, structural, and economic forces. Simulation models are a tool to help us understand and address thiscomplex, dynamic, and nonlinear social phenomenon. We conducted a systematic review of the literature on simulation models of opioid use and overdose up to September 2019. We extracted modeling types, target populations, interventions, and findings; created a database of model parameters used for model calibration; and evaluated study transparency and reproducibility. Of the 1,398 articles screened, we identified 88 eligible articles. The most frequent types of models were compartmental (36%), Markov (20%), system dynamics (16%), and agent-based models (16%). Intervention cost-effectiveness was evaluated in 40% of the studies, and 39% focused on services for people with opioid use disorder (OUD). In 61% of the eligible articles, authors discussed calibrating their models to empirical data, and in 31%, validation approaches used in the modeling process were discussed. From the 63 studies that provided model parameters, we extracted the data sources on opioid use, OUD, OUD treatment, cessation or relapse, emergency medical services, and death parameters. From this database, potential model inputs can be identified and models can be compared with prior work. Simulation models should be used to tackle key methodological challenges, including the potential for bias in the choice of parameter inputs, investment in model calibration and validation, and transparency in the assumptions and mechanics of simulation models to facilitate reproducibility.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Opiate Overdose; Opioid Epidemic; Opioid-Related Disorders; Reproducibility of Results
PubMed: 34791110
DOI: 10.1093/epirev/mxab013 -
PharmacoEconomics - Open May 2022As a core component of harm-reduction strategies to address the opioid crisis, several countries have instituted publicly funded programs to distribute naloxone for lay...
BACKGROUND
As a core component of harm-reduction strategies to address the opioid crisis, several countries have instituted publicly funded programs to distribute naloxone for lay administration in the community. The effectiveness in reducing mortality from opioid overdose has been demonstrated in multiple systematic reviews. However, the economic impact of community naloxone distribution programs is not fully understood.
OBJECTIVES
Our objective was to conduct a review of economic evaluations of community distribution of naloxone, assessing for quality and applicability to diverse contexts and settings.
DATA SOURCES
The search strategy was performed on MEDLINE, Embase, and EconLit databases.
STUDY ELIGIBILITY CRITERIA AND INTERVENTIONS
Search criteria were developed based on two themes: (1) papers involving naloxone or narcan and (2) any form of economic evaluation. A focused search of the grey literature was also conducted. Studies exploring the intervention of community distribution of naloxone were selected.
STUDY APPRAISAL AND SYNTHESIS METHODS
Data extraction was done using the British Medical Journal guidelines for economic submissions, assigning quality levels based on the impact of the missing or unclear components on the strength of the conclusions.
RESULTS
A total of nine articles matched our inclusion criteria: one cost-effectiveness analysis, eight cost-utility analyses, and one cost-benefit analysis. Overall, the quality of the studies was good (six of high quality, two of moderate quality, and one of low quality). All studies concluded that community distribution of naloxone was cost effective, with an incremental cost-utility ratio range of $US111-58,738 (year 2020 values) per quality-adjusted life-year gained.
LIMITATIONS
Our search strategy was developed iteratively, rather than following an a priori design. Additionally, our search was limited to English terms.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Based on this review, community distribution of naloxone is a worthwhile investment and should be considered by other countries dealing with the opioid epidemic.
PubMed: 34762276
DOI: 10.1007/s41669-021-00309-z -
Expert Opinion on Drug Metabolism &... Nov 2021Idiosyncratic drug-induced liver injury (DILI) is an unpredictable event, and there are no specific biomarkers that can distinguish DILI from alternative explanations or...
INTRODUCTION
Idiosyncratic drug-induced liver injury (DILI) is an unpredictable event, and there are no specific biomarkers that can distinguish DILI from alternative explanations or predict its clinical outcomes.
AREAS COVERED
This systematic review summarizes the available evidence for all biomarkers proposed to have a role in the diagnosis or prognosis of DILI. Following a comprehensive search, we included all types of studies in humans. We included DILI cases based on any threshold criteria but excluded intrinsic DILI, commonly caused by paracetamol overdose. We classified studies into diagnostic and prognostic categories and assessed their methodological quality. After reviewing the literature, 14 studies were eligible.
EXPERT OPINION
Diagnostic studies were heterogeneous with regard to the study population and outcomes measured. Prognostic models were developed by integrating novel biomarkers, risk scores, and traditional biomarkers, which increased their prognostic ability to predict death or transplantation by 6 months. This systematic review highlights the case of need for non-genetic biomarkers that distinguish DILI from acute liver injury related to alternative etiology. Biomarkers with the potential to identify serious adverse outcomes from acute DILI should be validated in independent prospective cohorts with a substantial number of cases.
Topics: Biomarkers; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Humans; Liver; Prospective Studies; Risk Factors
PubMed: 34727797
DOI: 10.1080/17425255.2021.1999410 -
Scientometrics 2021Bibliometric analyses of systematic reviews offer unique opportunities to explore the character of specific scientific fields. In this time series-based analysis,...
Time series-based bibliometric analysis of a systematic review of multidisciplinary care for opioid dose reduction: exploring the origins of the North American opioid crisis.
Bibliometric analyses of systematic reviews offer unique opportunities to explore the character of specific scientific fields. In this time series-based analysis, dynamics of multidisciplinary care for chronic pain and opioid prescribing are analyzed over a forty-four year time span. Three distinct periods are identified, each defined by distinct research areas, as well as priorities regarding the use of opioids and the appropriate management of chronic pain. These scientometrically defined periods align with timelines identified previously by narrative historical accounts. Through cross-correlation with a mortality time series, a significant two-year lag between opioid overdose mortality and citation dynamics is identified between 2004 and 2019. This analysis demonstrates a bidirectional relationship between the scientific literature and the North American opioid overdose crisis, suggesting that the scientific literature is both reflective and generative of an important health and social phenomenon. A scientometric phenomenon of memory lapse, namely an overt and prolonged failure to cite older relevant literature, is identified using a metric of mean time to citation. It is proposed that this metric can be used to analyze changes in emerging literature and thus predict the nature of clinical and policy responses to the opioid crisis, and thus potentially to other health and social phenomena.
PubMed: 34658459
DOI: 10.1007/s11192-021-04154-z -
Addiction Science & Clinical Practice Oct 2021Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these... (Review)
Review
BACKGROUND
Methamphetamine/amphetamine use has sharply increased among people with opioid use disorder (OUD). It is therefore important to understand whether and how use of these substances may impact receipt of, and outcomes associated with, medications for OUD (MOUD). This systematic review identified studies that examined associations between methamphetamine/amphetamine use or use disorder and 3 classes of outcomes: (1) receipt of MOUD, (2) retention in MOUD, and (3) opioid abstinence during MOUD.
METHODS
We searched 3 databases (PubMed/MEDLINE, PsycINFO, CINAHL Complete) from 1/1/2000 to 7/28/2020 using key words and subject headings, and hand-searched reference lists of included articles. English-language studies of people with documented OUD/opioid use that reported a quantitative association between methamphetamine/amphetamine use or use disorder and an outcome of interest were included. Study data were extracted using a standardized template, and risk of bias was assessed for each study. Screening, inclusion, data extraction and bias assessment were conducted independently by 2 authors. Study characteristics and findings were summarized for each class of outcomes.
RESULTS
Thirty-nine studies met inclusion criteria. Studies generally found that methamphetamine/amphetamine use or use disorder was negatively associated with receiving methadone and buprenorphine; 2 studies suggested positive associations with receiving naltrexone. Studies generally found negative associations with retention; most studies finding no association had small samples, and these studies tended to examine shorter retention timeframes and describe provision of adjunctive services to address substance use. Studies generally found negative associations with opioid abstinence during treatment among patients receiving methadone or sustained-release naltrexone implants, though observed associations may have been confounded by other polysubstance use. Most studies examining opioid abstinence during other types of MOUD treatment had small samples.
CONCLUSIONS
Overall, existing research suggests people who use methamphetamine/amphetamines may have lower receipt of MOUD, retention in MOUD, and opioid abstinence during MOUD. Future research should examine how specific policies and treatment models impact MOUD outcomes for these patients, and seek to understand the perspectives of MOUD providers and people who use both opioids and methamphetamine/amphetamines. Efforts to improve MOUD care and overdose prevention strategies are needed for this population.
Topics: Buprenorphine; Humans; Methadone; Methamphetamine; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 34635170
DOI: 10.1186/s13722-021-00266-2 -
Frontiers in Cardiovascular Medicine 2021Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to...
Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to compare the effectiveness and safety outcomes between off-label underdose or overdose vs. on-label dose of NOACs in AF patients. The PubMed database was systematically searched until August 2021. Observational cohorts were included if they compared the outcomes of off-label underdose or overdose with on-label dose of NOACs in AF patients. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a fixed-effects model ( ≤ 50%) or a random-effects model ( > 50%). A total of 15 observational studies were included. Compared with on-label dose of NOACs, off-label underdose of NOACs was associated with increased risks of stroke or systemic embolism (RR = 1.09, 95% CI 1.02-1.16), and all-cause death (RR = 1.29, 95% CI 1.10-1.52) but not ischemic stroke (RR = 1.34, 95% CI 0.76-2.36), myocardial infarction (RR = 1.08, 95% CI 0.92-1.28), major bleeding (RR = 0.97, 95% CI 0.89-1.05), intracranial hemorrhage (RR = 1.12, 95% CI 0.90-1.40), and gastrointestinal bleeding (RR = 0.96, 95% CI 0.85-1.07), whereas off-label overdose of NOACs was associated with increased risks of SSE (RR = 1.20, 95% CI 1.05-1.36), all-cause death (RR = 1.22, 95% CI 1.06-1.39), and major bleeding (RR = 1.33, 95% CI 1.16-1.52) but not gastrointestinal bleeding (RR = 1.18, 95% CI 0.99-1.42) and myocardial infarction (RR = 0.98, 95% CI 0.75-1.30). Compared with on-label dose of NOACs, off-label underdose was associated with increased risks of stroke or systemic embolism and all-cause death, whereas off-label overdose of NOACs was associated with increased risks of stroke or systemic embolism, all-cause death, and major bleeding.
PubMed: 34568462
DOI: 10.3389/fcvm.2021.724301 -
Biomedicine & Pharmacotherapy =... Oct 2021Adequate opioid prescribing is critical for therapeutic success of pain management. Despite the widespread use of opioids, optimized opioid therapy remains unresolved...
BACKGROUND
Adequate opioid prescribing is critical for therapeutic success of pain management. Despite the widespread use of opioids, optimized opioid therapy remains unresolved with risk of accidental lethal overdosing. With the emergence of accumulating evidence linking genetic variation to opioid response, pharmacogenetic based treatment recommendations have been proposed.
OBJECTIVE
The aim of this review is to evaluate pharmacogenetic evidence and provide an overview on genes involved in the pharmacokinetics and pharmacodynamics of opioids.
METHODS
For this review, a systematic literature search of published articles was used in PubMed®, with no language restriction and between the time period of January 2000 to December 2020. We reviewed randomized clinical studies, study cohorts and case reports that investigated the influence of genetic variants on selected opioid pharmacokinetics and pharmacodynamics. In addition, we reviewed current CPIC clinical recommendations for pharmacogenetic testing.
RESULTS
Results of this review indicate consistent evidence supporting the association between selected genetic variants of CYP2D6 for opioid metabolism. CPIC guidelines include recommendations that indicate the avoidance of tramadol use, in addition to codeine, in CYP2D6 poor metabolizers and ultrarapid metabolizers, and to monitor intermediate metabolizers for less-than-optimal response. While there is consistent evidence for OPRM1 suggesting increased postoperative morphine dosing requirements in A118G G-allele carriers, the clinical relevance remains limited.
CONCLUSION
There is emerging evidence of clinical relevance of CYP2D6 and, to a lesser extent, OPRM1 polymorphism in personalized opioid drug dosing. As a result, first clinics have started to implement pharmacogenetic guidelines for CYP2D6 and codeine.
Topics: Analgesics, Opioid; Animals; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Humans; Pain; Pharmacogenetics; Precision Medicine; Randomized Controlled Trials as Topic; Receptors, Opioid, mu
PubMed: 34523422
DOI: 10.1016/j.biopha.2021.112060 -
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