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The International Journal on Drug Policy Oct 2021Drug-related deaths globally are increasing year on year, with the largest proportion of these being opioid-related. The opioid antagonist naloxone distributed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Drug-related deaths globally are increasing year on year, with the largest proportion of these being opioid-related. The opioid antagonist naloxone distributed for take-home use ('Take-Home Naloxone (THN)') has been championed as one method of tackling this public health crisis, however to be effective it must be available at an opioid overdose. Ownership and carriage are therefore fundamental to THN success. This study aimed to assess the prevalence of ownership and carriage of THN internationally among people who use drugs (PWUD).
METHODS
NHS Scotland Journals, AMED, EMBASE, HMIC, MEDLINE, PsycINFO, CINAHL Complete, PubMed, Cochrane Library, PROSPERO and grey literature were searched for articles which measured prevalence of THN ownership or carriage between 1996 and 2020. Ownership was defined as report of a personal supply of THN. Carriage was defined as the participant carrying THN on their person at time of data collection or reporting a frequency of how often they carry THN. Risk of bias was evaluated using the Joanna Briggs Checklist for Prevalence Studies.
RESULTS
Systematic search yielded 6363 papers, with ten eligible papers identified. Eight articles were included in ownership prevalence and five articles included for carriage prevalence, with an overlap of three studies between both measures. Pooled prevalence indicated moderate ownership levels (57%, CI 47-67%) but lower carriage levels (20%, CI 12-31%). Analysis was complicated by the limited number of available studies and lack of standardised terminology and measurement.
CONCLUSION
Understanding naloxone ownership and carriage globally is hampered by limited evidence and heterogeneity across studies. From the available data, prevalence of THN carriage overall appears low, despite moderate ownership. Given the variation across studies, future research should seek to utilise more standardised terminology and methods of measurement. Furthermore, services distributing THN must ensure the importance of regular carriage of naloxone is consistently emphasised.
Topics: Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Ownership; Prevalence
PubMed: 34078563
DOI: 10.1016/j.drugpo.2021.103298 -
Drug and Alcohol Dependence Aug 2021The biomedical research enterprise invests greatly in discovery-oriented science, but significantly less in how to implement the most effective of these innovations. The... (Review)
Review
BACKGROUND
The biomedical research enterprise invests greatly in discovery-oriented science, but significantly less in how to implement the most effective of these innovations. The return on investment in public health benefit is therefore low. In the context of substance-related overdose epidemics, presently with opioids and/or stimulants, the gap in proven treatments and routine access is amplified. Implementation research is designed to deepen understanding of how best to scale-up proven treatments. This study assessed how implementation research has been deployed in the National Institute on Drug Abuse (NIDA) efforts to address the opioid and stimulant epidemics.
METHODS
Adapting a procedure developed to categorize HIV-focused research, a four-stage systematic mapping review of NIDA-funded R01, R34, R61, and U studies pertaining to opioids and/or stimulants funded between 2015 and 2019 was performed. Abstracts were retrieved using NIH Research Portfolio Online Reporting Tools. Key study characteristics were abstracted and coded by two independent reviewers.
RESULTS
An initial search across NIH institutes yielded 5963 relevant records. Of these, 666 (11.2 %) were NIDA funded. One-hundred-and-thirty-four (20.1 %) of the 666 studies were opioid and/or stimulant treatment related. Of these, 28 (4.2 %) were categorized as Implementation Preparation (IP), and 16 (2.4 %) were categorized as Implementation Research (IR). Over the five-year period, there was a gradual increase in both IP and IR studies.
CONCLUSIONS
Implementation research is a small but slowly growing component of the federal portfolio to address substance-related public health issues. To more effectively respond to contemporary overdose epidemics, implementation research must take on an even more significant role.
Topics: Analgesics, Opioid; Biomedical Research; Central Nervous System Stimulants; Drug Overdose; Humans; National Institute on Drug Abuse (U.S.); United States
PubMed: 34052689
DOI: 10.1016/j.drugalcdep.2021.108767 -
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 -
European Addiction Research 2021Between 2009 and 2018, the number of opioid-related deaths (ORDs) in Scotland showed a dramatic increase, whereas in England and Wales, a much lower increase in ORD was...
BACKGROUNDS
Between 2009 and 2018, the number of opioid-related deaths (ORDs) in Scotland showed a dramatic increase, whereas in England and Wales, a much lower increase in ORD was seen. This regional difference is remarkable, and the situation in Scotland is worrisome. Therefore, it is important to identify the drivers of ORD in Scotland.
METHODS
A systematic literature review according to PRISMA guidelines was conducted to identify peer-reviewed studies about key drivers for the observed differences in ORDs between Scotland and England/Wales. In addition, non-peer-reviewed reports on nationwide statistical data were retrieved via Google and Google Scholar and analysed to quantify differences in ORD drivers between Scotland and England/Wales.
RESULTS
The systematic review identified some important drivers of ORD, but none of these studies provided direct or indirect comparisons of ORD drivers in Scotland and England/Wales. However, the reports with nationwide statistical data showed important differences in ORD drivers between Scotland and England/Wales, including a higher prevalence of people using opioids in a problematic way (PUOP), more polydrug use in people using drugs in a problematic way (PUDP), a higher age of PUDP, and lower treatment coverage and efficacy of PUDP in Scotland compared to England/Wales, but no regional differences in injecting drug use, incarceration/prison release without treatment, and social deprivation in PUDP.
CONCLUSION
It is concluded that the opioid crisis in Scotland is best explained by a combination of drivers, consisting of a higher population involvement in (problematic) opioid use (notably methadone), relatively more polydrug use (notably benzodiazepines and gabapentinoids), a steeper ageing of the PUOP population in the past 2 decades, and lower treatment coverage and efficacy in Scotland compared to England/Wales. The findings have important consequences for strategies to handle the opioid crisis in Scotland.
Topics: Analgesics, Opioid; England; Humans; Opiate Overdose; Policy; Scotland; Wales
PubMed: 33965949
DOI: 10.1159/000516165 -
JAMA Network Open May 2021In the US and the United Kingdom, cocaine use is the second leading cause of illicit drug overdose death. Psychosocial treatments for cocaine use disorder are limited,... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
In the US and the United Kingdom, cocaine use is the second leading cause of illicit drug overdose death. Psychosocial treatments for cocaine use disorder are limited, and no pharmacotherapy is approved for use in the US or Europe.
OBJECTIVE
To compare treatments for active cocaine use among adults.
DATA SOURCES
PubMed and the Cochrane Database of Systematic Reviews were searched for clinical trials published between December 31, 1995, and December 31, 2017.
STUDY SELECTION
This meta-analysis was registered on Covidence.org (study 8731) on December 31, 2015. Clinical trials were included if they (1) had the term cocaine in the article title; (2) were published between December 31, 1995, and December 31, 2017; (3) were written in English; (4) enrolled outpatients 18 years or older with active cocaine use at baseline; and (5) reported treatment group size, treatment duration, retention rates, and urinalysis results for the presence of cocaine metabolites. A study was excluded if (1) more than 25% of participants were not active cocaine users or more than 80% of participants had negative test results for the presence of cocaine metabolites at baseline and (2) it reported only pooled urinalysis results indicating the presence of multiple substances and did not report the specific proportion of positive test results for cocaine metabolites. Multiple reviewers reached criteria consensus. Of 831 records screened, 157 studies (18.9%) met selection criteria and were included in the analysis.
DATA EXTRACTION AND SYNTHESIS
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Search results were imported from PubMed XML into Covidence.org then Microsoft Excel. Data extraction was completed in 2 iterations to ensure fidelity. Analyses included a multilevel random-effects model, a multilevel mixed-effects meta-regression model, and sensitivity analyses. Treatments were clustered into 11 categories (psychotherapy, contingency management programs, placebo, opioids, psychostimulants, anticonvulsants, dopamine agonists, antidepressants, antipsychotics, miscellaneous medications, and other therapies). Missing data were imputed using multiple imputation by chained equations. The significance threshold for all analyses was P = .05. Data were analyzed using the metafor and mice packages in R software, version 3.3.2 (R Foundation for Statistical Computing). Data were analyzed from January 1, 2018, to February 28, 2021.
MAIN OUTCOMES AND MEASURES
The primary outcome was the intention-to-treat logarithm of the odds ratio (OR) of having a negative urinalysis result for the presence of cocaine metabolites at the end of each treatment period compared with baseline. The hypothesis, which was formulated after data collection, was that no treatment category would have a significant association with objective reductions in cocaine use.
RESULTS
A total of 157 studies comprising 402 treatment groups and 15 842 participants were included. Excluding other therapies, the largest treatment groups across all studies were psychotherapy (mean [SD] number of participants, 40.04 [36.88]) and contingency management programs (mean [SD] number of participants, 37.51 [25.51]). Only contingency management programs were significantly associated with an increased likelihood of having a negative test result for the presence of cocaine (OR, 2.13; 95% CI, 1.62-2.80), and this association remained significant in all sensitivity analyses.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, contingency management programs were associated with reductions in cocaine use among adults. Research efforts and policies that align with this treatment modality may benefit those who actively use cocaine and attenuate societal burdens.
Topics: Clinical Trials as Topic; Cocaine-Related Disorders; Humans; Psychotherapy
PubMed: 33961037
DOI: 10.1001/jamanetworkopen.2021.8049 -
Cancer Science Jul 2021Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys,...
Chemotherapy for non-Hodgkin lymphoma (NHL) in the hemodialysis (HD) patient is a challenging situation. Because many drugs are predominantly eliminated by the kidneys, chemotherapy in the HD patient requires special considerations concerning dose adjustments to avoid overdose and toxicities. Conversely, some drugs are removed by HD and may expose the patient to undertreatment, therefore the timing of drug administration in relation to HD sessions must be carefully planned. Also, the metabolites of some drugs show different toxicities and dialysability as compared with the parent drug, therefore this must also be catered for. However, the pharmacokinetics of many chemotherapeutics and their metabolites in HD patients are unknown, and the fact that NHL patients are often treated with distinct multiagent chemotherapy regimens makes the situation more complicated. In a realm where uncertainty prevails, case reports and case series reporting on actual treatment and outcomes are extremely valuable and can aid physicians in decision making from drug selection to dosing. We carried out an exhaustive review of the literature and adopted 48 manuscripts consisting of 66 HD patients undergoing 71 chemotherapy regimens for NHL, summarized the data, and provide recommendations concerning dose adjustments and timing of administration for individual chemotherapeutics where possible. The chemotherapy regimens studied in this review include, but are not limited to, rituximab, cyclophosphamide + vincristine + prednisolone (CVP) and cyclophosphamide + doxorubicin + vincristine + prednisolone (CHOP)-like regimens, chlorambucil, ibrutinib, bendamustine, methotrexate, platinum compounds, cytarabine, gemcitabine, etoposide, ifosfamide, melphalan, busulfan, fludarabine, mogamulizumab, brentuximab vedotin, and Y-ibritumomab tiuxetan.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Female; Hematopoietic Stem Cell Transplantation; Humans; Kidney; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednisone; Renal Dialysis; Rituximab; Vincristine; Young Adult
PubMed: 33938097
DOI: 10.1111/cas.14933 -
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 -
Substance Abuse Treatment, Prevention,... Feb 2021There is a high risk of death from opioid overdose following release from prison. Efforts to develop and implement overdose prevention programs for justice-involved...
BACKGROUND
There is a high risk of death from opioid overdose following release from prison. Efforts to develop and implement overdose prevention programs for justice-involved populations have increased in recent years. An understanding of the gaps in knowledge on prevention interventions is needed to accelerate development, implementation, and dissemination of effective strategies.
METHODS
A systematic search process identified 43 published papers addressing opioid overdose prevention in criminal justice settings or among justice-involved populations from 2010 to February 2020. Cross-cutting themes were identified, coded and qualitatively analyzed.
RESULTS
Papers were coded into five categories: acceptability (n = 8), accessibility (n = 4), effectiveness (n = 5), feasibility (n = 7), and participant overdose risk (n = 19). Common themes were: (1) Acceptability of naloxone is associated with injection drug use, overdose history, and perceived risk within the situational context; (2) Accessibility of naloxone is a function of the interface between corrections and community; (3) Evaluations of overdose prevention interventions are few, but generally show increases in knowledge or reductions in opioid overdose; (4) Coordinated efforts are needed to implement prevention interventions, address logistical challenges, and develop linkages between corrections and community providers; (5) Overdose is highest immediately following release from prison or jail, often preceded by service-system interactions, and associated with drug-use severity, injection use, and mental health disorders, as well as risks in the post-release environment.
CONCLUSION
Study findings can inform the development of overdose prevention interventions that target justice-involved individuals and policies to support their implementation across criminal justice and community-based service systems.
Topics: Analgesics, Opioid; Criminal Law; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opiate Overdose; Opioid-Related Disorders
PubMed: 33618744
DOI: 10.1186/s13011-021-00346-1 -
Kidney International Reports Feb 2021N-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing...
INTRODUCTION
N-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C.
METHODS
A literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral).
RESULTS
Six studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], -2.80 μmol/L [95% confidence interval {CI} -5.6 to 0.0]; = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 μmol/L [95% CI -6.29 to -0.28]; = 0.04) than Jaffe (WMD, -0.51 μmol/L [95% CI -7.56 to 6.53]; = 0.89) and in particular with intravenous (WMD, -31.10 μmol/L [95% CI -58.37 to -3.83]; = 0.03) compared with oral NAC (WMD, -2.5 μmol/L [95% CI -5.32 to 0.32]; = 0.08). There was no change in cystatin C after NAC administration.
DISCUSSION
NAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.
PubMed: 33615065
DOI: 10.1016/j.ekir.2020.11.018 -
Value in Health : the Journal of the... Feb 2021The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare...
OBJECTIVES
The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature.
METHODS
A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study.
RESULTS
The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies' accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs.
CONCLUSION
The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.
Topics: Analgesics, Opioid; Costs and Cost Analysis; Humans; Methadone; Models, Economic; Naloxone; Narcotic Antagonists; Opiate Overdose; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders
PubMed: 33518022
DOI: 10.1016/j.jval.2020.07.013