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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 -
Cureus Aug 2023Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified... (Review)
Review
Calcium channel blocker poisoning is one of the most common poisonings encountered which presents with life-threatening complications. However, there is no unified approach for treating these patients in the existing literature. This study aimed to assess the effects of different treatment modalities used in calcium channel blocker poisoning, as reported by previous studies. The primary outcomes studied were mortality and hemodynamic parameters after treatment. The secondary outcomes were the length of hospital stay, length of intensive care unit stay, duration of vasopressor use, functional outcomes, and serum calcium channel blocker concentrations. A thorough literature search was performed through Ovid, PubMed, Cochrane Library, and Google Scholar from January 2014 to December 31, 2022, to identify all studies analyzing the effects of the treatment of calcium channel blocker poisoning on the desired outcomes. Two reviewers reviewed 607 published articles from January 2014 to December 2022 to identify studies analyzing the effects of the treatment of calcium channel blocker poisoning on desired outcomes. In this review, 18 case reports, one case series, and one cohort study were included. Most patients were treated with an injection of calcium gluconate or calcium chloride. The use of calcium along with dopamine and norepinephrine was found to have lower mortality rates. A few patients were also treated with injection atropine for bradycardia. High-dose insulin therapy was used in 14 patients, of whom two did not survive. In the cohort study, 66 calcium channel blocker toxicity patients were included. These patients were treated with high-dose insulin therapy. A total of 11 patients with calcium channel blocker toxicity succumbed. Although it was found to be associated with improved hemodynamic parameters and lower mortality, side effects such as hypokalemia and hypoglycemia were noted. Intravenous lipid emulsion therapy (administered to eight patients), extracorporeal life support (used in three patients with refractory shock or cardiac arrest), injection glucagon, methylene blue, albumin infusion, and terlipressin were associated with a lower mortality rate as well as improvement in hemodynamic parameters. None of the case reports provided any information on end-organ damage on long-term follow-up.
PubMed: 37664357
DOI: 10.7759/cureus.42854 -
Addiction & Health Apr 2023Suicide is considered a fundamental problem in discussions on public and global health. Thus, the current study aimed to review the prevalence of and reasons for... (Review)
Review
BACKGROUND
Suicide is considered a fundamental problem in discussions on public and global health. Thus, the current study aimed to review the prevalence of and reasons for successful suicide attempts in heroin users.
METHODS
This study was conducted by systematically searching the electronic databases of PubMed, Scopus, Web of Science, and PsycINFO from 1960/1/1 to 2021/11/1 based on the PRISMA checklist and using MeSH keywords with no temporal or linguistic limitations. The primary and secondary impacts of suicide were identified, and all studies following an observational design (cohort, case-control, and cross-sectional studies) were included in the research. Data analysis was performed using Stata version 13. Finally, 17 studies were included in the work process for systematic review and meta-analysis.
FINDINGS
The results showed the most frequent reasons for suicide among the studied individuals were gender (being female), youngness, heroin overdose, multi-drug abuse, history of repeated suicide attempts, history of psychiatric disorder (especially depression), joblessness, homelessness, distorted family relationships, etc. Moreover, the results of synthesizing the studies revealed the prevalence of suicide attempts equaled the effect size (95% CI=0.3 [0.23-0.37]) among these individuals, and the prevalence of successful suicides approached the effect size (95% CI=0.03 [0.01-0.05]).
CONCLUSION
The results of the present study showed the high prevalence of suicidal thoughts and suicide attempts among the heroin-abusing population. Furthermore, according to the findings, the prevalence of unsuccessful suicide attempts was ten times more than that of successful ones in the target population.
PubMed: 37560393
DOI: 10.34172/ahj.2023.1363 -
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 -
Health & Place Sep 2023The objective of this prospectively registered systematic review was to identify the factors that contribute to sense of safety, victimization, and overdose risk in... (Review)
Review
The objective of this prospectively registered systematic review was to identify the factors that contribute to sense of safety, victimization, and overdose risk in homeless shelters, as well as groups that are at greater risk of shelter-based victimization. Fifty-five articles were included in the review. Findings demonstrated that fears of violence and other forms of harm were prominent concerns for people experiencing homelessness when accessing shelters. Service users' perceptions of shelter dangerousness were shaped by the service model and environment, interpersonal relationships and interactions in shelter, availability of drugs, and previous living arrangements. 2SLGBTQ+ individuals were identified as being at heightened risk of victimization in shelters. No studies examined rates of shelter-based victimization or tested interventions to improve safety, with the exception of overdose risk. These knowledge gaps hinder the establishment of evidence-based practices for promoting safety and preventing violence in shelter settings.
Topics: Humans; Ill-Housed Persons; Drug Overdose; Housing; Interpersonal Relations; Crime Victims
PubMed: 37515964
DOI: 10.1016/j.healthplace.2023.103092 -
Drug and Alcohol Dependence Sep 2023Novel strategies are required to address rising overdose deaths across the globe. We sought to identify the breadth and depth of the existing evidence around electronic... (Review)
Review
BACKGROUND
Novel strategies are required to address rising overdose deaths across the globe. We sought to identify the breadth and depth of the existing evidence around electronic harm reduction (e-harm reduction) interventions that aimed to reduce the harms associated with substance use.
METHODS
We conducted a scoping review according to the PRISMA-ScR and PRISMA for Searching guidelines. A health sciences librarian systematically searched seven health databases from inception until January 20, 2023. Citation chaining and reference lists of included studies were searched to identify additional articles. Two reviewers independently screened, extracted and charted the data. Additionally, we conducted a gray literature search and environmental scan to supplement the findings.
RESULTS
A total of 51 studies met the criteria for inclusion (30 peer-reviewed articles and 21 non-peer reviewed). Most peer-reviewed studies were conducted in Western countries (USA = 23, Canada = 3, Europe = 3, China = 1) and among adult samples (adult = 27, youth/adults =1, unspecified = 2). Study designs were predominantly quantitative (n = 24), with a minority using qualitative (n = 4) or mixed methods (n = 2). Most e-harm reduction interventions were harm reduction (n = 15), followed by education (n = 6), treatment (n = 2), and combined/other approaches (n = 7). Interventions utilized web-based/mobile applications (n = 15), telephone/telehealth (n = 10), and other technology (n = 5).
CONCLUSIONS
While e-harm reduction technology is promising, further research is required to establish the efficacy and effectiveness of these novel interventions.
Topics: Adult; Adolescent; Humans; Harm Reduction; Drug Overdose; Substance-Related Disorders; Europe; Telemedicine
PubMed: 37441959
DOI: 10.1016/j.drugalcdep.2023.110878 -
The Journal of Mental Health Training,... Jan 2023The purpose of the current study is to conduct a systematic review of peer-reviewed work on culturally tailored interventions for alcohol and drug use in Indigenous...
PURPOSE–
The purpose of the current study is to conduct a systematic review of peer-reviewed work on culturally tailored interventions for alcohol and drug use in Indigenous adults in North America. Substance use has been reported as a health concern for many Indigenous communities. Indigenous groups experienced the highest drug overdose death rates in 2015, the largest percentage increase in the number of deaths over time from 1999 to 2015 compared to any other racial group. However, few Indigenous individuals report participating in treatment for alcohol or drug use, which may reflect the limited engagement that Indigenous groups have with treatment options that are accessible, effective and culturally integrative.
DESIGN/METHODOLOGY/APPROACH–
Electronic searches were conducted from 2000 to April 21, 2021, using PsycINFO, Cumulative Index to Nursing and Allied Health Literature, MEDLINE and PubMed. Two reviewers classified abstracts for study inclusion, resulting in 18 studies.
FINDINGS–
Most studies were conducted in the USA (89%). Interventions were largely implemented in Tribal/rural settings (61%), with a minority implemented in both Tribal and urban contexts (11%). Study samples ranged from 4 to 742 clients. Interventions were most often conducted in residential treatment settings (39%). Only one (6%) intervention focused on opioid use among Indigenous people. Most interventions addressed the use of both drugs and alcohol (72%), with only three (17%) interventions specifically intended to reduce alcohol use.
ORIGINALITY/VALUE–
The results of this research lend insight into the characteristics of culturally integrative treatment options for Indigenous groups and highlight the need for increased investment in research related to culturally tailored treatment across the diverse landscape of Indigenous populations.
PubMed: 37292247
DOI: 10.1108/jmhtep-07-2021-0088 -
Clinical and Applied... 2023Off-label, under-, and overdosed direct oral anticoagulants (DOACs) are commonly prescribed to patients with atrial fibrillation (AF), but real-world evidence on their... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Off-label, under-, and overdosed direct oral anticoagulants (DOACs) are commonly prescribed to patients with atrial fibrillation (AF), but real-world evidence on their effectiveness and safety is limited.
METHODS
MEDLINE, Embase, and Cochrane Library databases were systematically searched from 01 July 2020 to 28 February 2022 to update a previous systematic review with the same search strategy from the inception to 30 June 2020. Eligible studies were those that reported effectiveness (stroke/systemic embolism and myocardial infarction) or safety (gastrointestinal or major bleeding and death) outcomes of off-label doses of DOACs compared to on-label doses in AF patients. A random-effects meta-analysis was performed to estimate the pooled hazard ratio (HR) and 95% confidence interval (CI). Subgroup analyses were performed by specific DOACs and geographic regions.
RESULTS
Twenty-two studies were included. Off-label, underdosed DOACs, compared to on-label doses, were not associated with an increased risk of stroke (HR 1.03, 95%CI: 0.88-1.17) but were associated with an increased risk of death (HR 1.26, 95%CI: 1.09-1.43). However, risk varied depending on the active ingredient. No other safety outcomes were associated with underdosed DOACs. No significant differences were observed by geographic regions. Compared to on-label DOACs, overdosing increased the risk of stroke (HR 1.17, 95%CI: 1.04-1.31), major bleeding (HR 1.18, 95%CI: 1.05-1.31), and death (HR 1.19, 95%CI: 1.03-1.35). Risk varied between geographical regions.
CONCLUSIONS
Off-label underdoses, compared to on-label dosing of DOACs, did not increase the risk of stroke but did increase overall mortality. Overdosed DOACs, compared to on-label doses, were associated with an increased risk of stroke, major bleeding, and death. Future studies must examine these associations, focusing on specific active ingredients and geographic settings.
Topics: Humans; Atrial Fibrillation; Anticoagulants; Off-Label Use; Stroke; Hemorrhage; Administration, Oral
PubMed: 37264798
DOI: 10.1177/10760296231179439 -
The Cochrane Database of Systematic... May 2023The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine... (Review)
Review
BACKGROUND
The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES
To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms.
DATA COLLECTION AND ANALYSIS
We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropouts due to treatment. We carried out meta-analyses where appropriate.
MAIN RESULTS
We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression.
AUTHORS' CONCLUSIONS
There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.
Topics: Adolescent; Adult; Child; Humans; Young Adult; Antidepressive Agents; Bupropion; Nicotinic Agonists; Nortriptyline; Smoking Cessation; Varenicline
PubMed: 37230961
DOI: 10.1002/14651858.CD000031.pub6 -
Drug and Alcohol Dependence Jun 2023Prescription drug monitoring programs (PDMPs) are used to mitigate harms from high-risk medicines including misuse, prescription shopping, overdoses, and death. Previous... (Review)
Review
BACKGROUND
Prescription drug monitoring programs (PDMPs) are used to mitigate harms from high-risk medicines including misuse, prescription shopping, overdoses, and death. Previous systematic reviews report inconsistent findings. We undertook a systematic review of reviews to 1) describe and identify the methods and outcome measures used to evaluate PDMPs, 2) summarise existing evidence on outcomes and factors that influence PDMP success or benefit realisation.
METHODS
MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews, and PROSPERO were used to identify systematic reviews on PDMPs. Twelve papers met the inclusion criteria. Data extracted included review aim, study designs, settings, outcome measures, and key findings. Quality was assessed using AMSTAR 2 quality assessment tool.
RESULTS
Review papers were categorised as outcome or process evaluation reviews. Process evaluation reviews described implementation processes, barriers and facilitators to PDMP use and/or implementation. Most (57%) papers described barriers which frequently included usability and data integration. Outcome evaluation papers reported impact of PDMPs on outcomes, which were opioid-focused, and findings were highly variable. Most reviews (67%) were rated as low quality, limiting the conclusions that can be drawn.
CONCLUSIONS
Inconsistent methods and outcome measures were used to evaluate PDMPs. No economic evaluations of PDMPs were found. Standardising assessment and reporting of results may improve the quality and confidence in an evidence-base to inform future roll-out and evaluation of PDMPs. Targeting barriers such as system-related challenges and negative end-user perceptions could improve sustained uptake of PDMPs, and potentially facilitate benefits realisation, including mitigating harms of high-risk prescription medicines.
Topics: Humans; Analgesics, Opioid; Drug Overdose; Opioid-Related Disorders; Prescription Drug Misuse; Prescription Drug Monitoring Programs; Systematic Reviews as Topic
PubMed: 37126936
DOI: 10.1016/j.drugalcdep.2023.109887