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Frontiers in Psychiatry 2024Fentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However,...
OBJECTIVES
Fentanyl is a highly potent opioid and has, until recently, been considered an unwanted contaminant in the street drug supply among people who use drugs (PWUD). However, it has become a drug of choice for an increasing number of individuals. This systematic review evaluated intentional non-medical fentanyl use among PWUD, specifically by summarizing demographic variance, reasons for use, and resulting patterns of use.
METHODS
The search strategy was developed with a combination of free text keywords and MeSH and non-MeSH keywords, and adapted with database-specific filters to Ovid MEDLINE, Embase, Web of Science, and PsychINFO. Studies included were human studies with intentional use of non-medical fentanyl or analogues in individuals older than 13. Only peer-reviewed original articles available in English were included.
RESULTS
The search resulted in 4437 studies after de-duplication, of which 132 were selected for full-text review. Out of 41 papers included, it was found that individuals who use fentanyl intentionally were more likely to be young, male, and White. They were also more likely to have experienced overdoses, and report injection drug use. There is evidence that fentanyl seeking behaviours are motivated by greater potency, delay of withdrawal, lower cost, and greater availability.
CONCLUSIONS
Among PWUD, individuals who intentionally use fentanyl have severe substance use patterns, precarious living situations, and extensive overdose history. In response to the increasing number of individuals who use fentanyl, alternative treatment approaches need to be developed for more effective management of withdrawal and opioid use disorder.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42021272111.
PubMed: 38414500
DOI: 10.3389/fpsyt.2024.1347678 -
Value in Health : the Journal of the... May 2024Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be... (Review)
Review
OBJECTIVES
Overdose prevention centers (OPCs) provide a safe place where people can consume preobtained drugs under supervision so that a life-saving medical response can be provided quickly in the event of an overdose. OPCs are programs that are established in Canada and have recently become legally sanctioned in only a few United States jurisdictions.
METHODS
We conducted a systematic review that summarizes and identifies gaps of economic evidence on establishing OPCs in North America to guide future expansion of OPCs.
RESULTS
We included 16 final studies that were evaluated with the Consolidated Health Economic Evaluation Reporting Standards and Drummond checklists. Eight studies reported cost-effectiveness results (eg, cost per overdose avoided or cost per quality-adjusted life-year), with 6 also including cost-benefit; 5 reported only cost-benefit results, and 3 cost offsets. Health outcomes primarily included overdose mortality outcomes or HIV/hepatitis C virus infections averted. Most studies used mathematical modeling and projected OPC outcomes using the experience of a single facility in Vancouver, BC.
CONCLUSIONS
OPCs were found to be cost-saving or to have favorable cost-effectiveness or cost-benefit ratios across all studies. Future studies should incorporate the experience of OPCs established in various settings and use a greater diversity of modeling designs.
Topics: Humans; Cost-Benefit Analysis; Opiate Overdose; North America; Quality-Adjusted Life Years; Canada
PubMed: 38401795
DOI: 10.1016/j.jval.2024.02.004 -
Schizophrenia Research Jun 2024The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
BACKGROUND
The literature has paid very little attention to pericarditis, pericardial effusion and pancreatitis during clozapine treatment in children and adolescents.
METHODS
Cases of clozapine-associated pericarditis and pancreatitis in children were studied using searches in: 1) PubMed (June 16, 2023), and 2) the World Health Organization's pharmacovigilance database (June 1, 2022), VigiBase. VigiBase uses a logarithmic measure of disproportionality called the information component (IC).
RESULTS
The PubMed search yielded 3 clozapine-associated pericarditis cases, 1 pancreatitis case and 1 with both. VigiBase provided a significant clozapine-associated pericarditis IC = 3.6 with an IC = 2.9 (only 3 cases were expected while 22 were observed). VigiBase provided a significant clozapine-associated pancreatitis IC = 2.2 with an IC = 1.4 (only 3 cases were expected while 16 were observed). In VigiBase clozapine-associated pericarditis and pericardial effusion in youth looked similar and on a continuum with myocarditis, as myocarditis, pericarditis and pancreatitis appeared to occur mainly during clozapine titration. Combining PubMed and VigiBase we identified: 1) 29 cases of at least possible clozapine-associated pericarditis/pericardial effusion (6 probable and 23 possible) including 7 cases with and 22 without myocarditis, and 2) 17 cases of clozapine-associated pancreatitis (1 definite and 16 possible). Two of the pancreatitis cases occurred during overdoses. No fatal outcomes were found in any clozapine-associated pericarditis and pancreatitis cases.
CONCLUSIONS
Despite the lack of attention in the literature to clozapine-associated pericarditis and pancreatitis, results demonstrate that they can happen in youth, particularly during titration. Pericarditis and pancreatitis appear to be forms of clozapine-associated inflammation during dose titration.
Topics: Humans; Pancreatitis; Clozapine; Pericarditis; Pharmacovigilance; Adolescent; Child; Antipsychotic Agents; Databases, Factual; Male; Female; Pericardial Effusion
PubMed: 37981478
DOI: 10.1016/j.schres.2023.10.027 -
Molecular Psychiatry Nov 2023In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a...
In the past two decades, over-prescription of opioids for pain management has driven a steep increase in opioid use disorder (OUD) and death by overdose, exerting a dramatic toll on western countries. OUD is a chronic relapsing disease associated with a lifetime struggle to control drug consumption, suggesting that opioids trigger long-lasting brain adaptations, notably through functional genomic and epigenomic mechanisms. Current understanding of these processes, however, remain scarce, and have not been previously reviewed systematically. To do so, the goal of the present work was to synthesize current knowledge on genome-wide transcriptomic and epigenetic mechanisms of opioid action, in primate and rodent species. Using a prospectively registered methodology, comprehensive literature searches were completed in PubMed, Embase, and Web of Science. Of the 2709 articles identified, 73 met our inclusion criteria and were considered for qualitative analysis. Focusing on the 5 most studied nervous system structures (nucleus accumbens, frontal cortex, whole striatum, dorsal striatum, spinal cord; 44 articles), we also conducted a quantitative analysis of differentially expressed genes, in an effort to identify a putative core transcriptional signature of opioids. Only one gene, Cdkn1a, was consistently identified in eleven studies, and globally, our results unveil surprisingly low consistency across published work, even when considering most recent single-cell approaches. Analysis of sources of variability detected significant contributions from species, brain structure, duration of opioid exposure, strain, time-point of analysis, and batch effects, but not type of opioid. To go beyond those limitations, we leveraged threshold-free methods to illustrate how genome-wide comparisons may generate new findings and hypotheses. Finally, we discuss current methodological development in the field, and their implication for future research and, ultimately, better care.
Topics: Animals; Humans; Analgesics, Opioid; Opioid-Related Disorders; Drug Overdose; Chronic Disease; Genomics; Models, Animal
PubMed: 37723284
DOI: 10.1038/s41380-023-02238-1 -
Substance Abuse Treatment, Prevention,... Sep 2023The COVID-19 pandemic led to an unprecedented relaxation of restrictions on take-home doses in opioid agonist treatment (OAT). We conducted a mixed methods systematic... (Review)
Review
The impact of relaxing restrictions on take-home doses during the COVID-19 pandemic on program effectiveness and client experiences in opioid agonist treatment: a mixed methods systematic review.
BACKGROUND
The COVID-19 pandemic led to an unprecedented relaxation of restrictions on take-home doses in opioid agonist treatment (OAT). We conducted a mixed methods systematic review to explore the impact of these changes on program effectiveness and client experiences in OAT.
METHODS
The protocol for this review was registered in PROSPERO (CRD42022352310). From Aug.-Nov. 2022, we searched Medline, Embase, CINAHL, PsycInfo, Web of Science, Cochrane Register of Controlled Trials, and the grey literature. We included studies reporting quantitative measures of retention in treatment, illicit substance use, overdose, client health, quality of life, or treatment satisfaction or using qualitative methods to examine client experiences with take-home doses during the pandemic. We critically appraised studies using the Mixed Methods Appraisal Tool. We synthesized quantitative data using vote-counting by direction of effect and presented the results in harvest plots. Qualitative data were analyzed using thematic synthesis. We used a convergent segregated approach to integrate quantitative and qualitative findings.
RESULTS
Forty studies were included. Most were from North America (23/40) or the United Kingdom (9/40). The quantitative synthesis was limited by potential for confounding, but suggested an association between take-home doses and increased retention in treatment. There was no evidence of an association between take-home doses and illicit substance use or overdose. Qualitative findings indicated that take-home doses reduced clients' exposure to unregulated substances and stigma and minimized work/treatment conflicts. Though some clients reported challenges with managing their medication, the dominant narrative was one of appreciation, reduced anxiety, and a renewed sense of agency and identity. The integrated analysis suggested reduced treatment burden as an explanation for improved retention and revealed variation in individual relationships between take-home doses and illicit substance use. We identified a critical gap in quantitative measures of patient-important outcomes.
CONCLUSION
The relaxation of restrictions on take-home doses was associated with improved client experience and retention in OAT. We found no evidence of an association with illicit substance use or overdose, despite the expansion of take-home doses to previously ineligible groups. Including patient-important outcome measures in policy, program development, and treatment planning is essential to ensuring that decisions around take-home doses accurately reflect their value to clients.
Topics: Humans; COVID-19; Analgesics, Opioid; Pandemics; Quality of Life; Program Evaluation
PubMed: 37777766
DOI: 10.1186/s13011-023-00564-9 -
International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Archives of Sexual Behavior Aug 2023Drug use before or during sex is a high-risk sexual behavior associated with adverse health risks and outcomes, such as increasing the likelihood of overdoses and of... (Meta-Analysis)
Meta-Analysis
Drug use before or during sex is a high-risk sexual behavior associated with adverse health risks and outcomes, such as increasing the likelihood of overdoses and of acquiring sexually-transmitted diseases. This systematic review and meta-analysis of three scientific databases examined the prevalence of the use of intoxicating substances, those tending to excite or stupefy the user on a psychoactive level, before or during sex, among young adults (18-29 years old). A total of 55 unique empirical studies met the inclusion criteria (48,145 individuals; 39% males), were assessed for risk of bias using the tools of Hoy et al. (2012), and were analyzed via a generalized linear mixed-effects model. The results produced a global mean prevalence of this sexual risk behavior of 36.98% (95% CI: 28.28%, 46.63%). Nonetheless, significant differences were identified between different intoxicating substances, with the use of alcohol (35.10%; 95% CI: 27.68%, 43.31%), marijuana (27.80%; 95% CI: 18.24%, 39.92%), and ecstasy (20.90%; 95% CI: 14.34%, 29.45%) significantly more prevalent than that of cocaine (4.32%; 95% CI: 3.64%, 5.11%), heroin (.67%; 95% CI: .09%, 4.65%), methamphetamine (7.10%; 95% CI: 4.57%, 10.88%), and GHB (6.55%; 95% CI: 4.21%, 10.05%). Moderator analyses showed that the prevalence of alcohol use before or during sex differed according to geographical sample origin, and increased as the proportion of ethnic whites in samples increased. The remaining demographic (e.g., gender, age, reference population), sexual (e.g., sexual orientation, sexual activity), health (e.g., drug consumption, STI/STD status), methodological (e.g., sampling technique), and measurement (e.g., timeframe) variables that were examined did not moderate prevalence estimates. Implications for sexual development interventions were discussed.
Topics: Humans; Male; Female; Young Adult; Adolescent; Adult; Prevalence; Sexual Behavior; Substance-Related Disorders; Sexually Transmitted Diseases; Alcohol Drinking
PubMed: 36897426
DOI: 10.1007/s10508-023-02572-z -
Frontiers in Psychiatry 2023The global or multinational scientific evidence on the distribution of opioid fatality is unknown. Hence, the current study collects epidemiological characteristics to...
BACKGROUND
The global or multinational scientific evidence on the distribution of opioid fatality is unknown. Hence, the current study collects epidemiological characteristics to shed light on the ongoing global or multinational opioid crisis and to promote the development of public health prevention/management strategies.
METHOD
All documents on PRISMA standards were retrieved via electronic databases.
RESULTS
Among the 47 articles relevant to our studies, which depict a total population size of 10,191 individuals, the prevalence of opioid fatal overdose was 15,022 (14.74%). Among the 47 articles, 14 of them reported the gender of the participants, with 22,125 (15.79%) male individuals and 7,235 (5.17%) female individuals, and the age distribution of the participants that was most affected by the overdose was as follows: 29,272 (31.13%) belonged to the 18-34-year-old age group and 25,316 (26.92%) belonged to the less than 18-year-old age group. Eighteen studies qualified for the meta-analysis of the multinational prevalence of fatal opioid overdose, depicting an overall pooled prevalence estimate of 19.66%, with 95% CIs (0.13-0.29), = 99.76% determined using the random-effects model, and Q statistic of 7198.77 ( < 0.0001). The Egger test models of publication bias revealed an insubstantial level of bias ( = 0.015). The subgroup analysis of the study design (cohort or other) revealed that others have the highest prevalence estimate of 34.37, 95% CIs (0.1600-0.5901), = 97.04%, and a sample size of less than 1,000 shows the highest prevalence of 34.66, 95% CIs (0.2039-0.5234), = 97.82%, compared to that of more than 1,000 with a prevalence of 12.28, 95% CIs (0.0675-0.2131), = 99.85%. The meta-regression analysis revealed that sample size (less-than or greater-than 1,000), ( = 0.0098; R = 3.83%) is significantly associated with the observed heterogeneity.
CONCLUSION
Research-based findings of fatal opioid overdose are grossly lacking in middle- and low-income nations. We established that there is a need for opioid fatality surveillance systems in developing nations.
PubMed: 38250280
DOI: 10.3389/fpsyt.2023.1290461 -
The International Journal on Drug Policy Apr 2024Comorbid substance use disorders (SUDs) among people with opioid use disorder (OUD) contribute to poor clinical outcomes, including overdose and mortality. We present... (Review)
Review
BACKGROUND
Comorbid substance use disorders (SUDs) among people with opioid use disorder (OUD) contribute to poor clinical outcomes, including overdose and mortality. We present the first systematic review and meta-analysis to estimate the prevalence of specific non-opioid SUDs among people with OUD.
METHODS
We searched Embase, PsycINFO, and MEDLINE from 1990 to 2022 for studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria to assess the prevalence of non-opioid SUDs among individuals with OUD. We used random-effects meta-analyses with 95% Confidence Intervals (CIs) to pool current and lifetime prevalence estimates separately. Meta-regressions and stratified meta-analyses were used to examine differences in prevalence estimates by sample characteristics and methodological factors.
RESULTS
Of the 36,971 publications identified, we included data from 194 studies and 77,212 participants with OUD. The prevalence of any comorbid SUD among people with OUD was 59.5% (95%CI 49.1-69.5%) for current non-opioid SUDs, with 72.0% (95%CI 52.5-87.9%) experiencing a comorbid SUD in their lifetime. Of the studies that examined current comorbid SUDs, cocaine use disorder (30.5%, 95%CI 23.0-38.7%) was most common, followed by alcohol (27.1%, 95%CI 24.4- 30.0%), cannabis (22.7%, 95%CI 19.0-26.6%), sedative (16.1%, 95%CI 13.1-19.3%), and methamphetamine (11.4%, 95%CI 6.8-17.1%) use disorders. Substantial heterogeneity (I>90%) across estimates was observed. Substantial heterogeneity (I2>90%) was observed across estimates, with significant variations in prevalence identified across geographic locations, recruitment settings, and other study-level factors.
CONCLUSION
Findings from this study emphasize the importance of comorbid SUD treatment access for people with OUD. Our estimates can inform the provision of treatment and harm reduction strategies for people with OUD and specific subpopulations.
PubMed: 38677160
DOI: 10.1016/j.drugpo.2024.104434 -
CMAJ : Canadian Medical Association... Nov 2023
PubMed: 37963627
DOI: 10.1503/cmaj.231529