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Frontiers in Pharmacology 2022N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to...
N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment. Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs). In total, 34 studies of NAC usage in APAP-related DILI cases with 19,580 patients were identified, of which 2,376 patients developed hepatotoxicities. The mortality rate across different studies ranged from 0 to 52%. Large variability of NAC regimens was found, i.e., intravenous (I.V.) (100-150 mg/kg) and oral (70-140 mg/kg), and length of treatment varied-12, 24, or 48 h for I.V. regimen and 72 h for oral administration. The timing of initiation of NAC treatment showed different results in terms of occurrence of hepatotoxicity and mortality; if started within 8 h and no more than 24 h from APAP overdose, either intravenously or orally, NAC administration was efficacious in terms of mortality. The most frequent AEs reported were anaphylactic reactions, followed by cutaneous AEs for the IV route and intestinal AEs for the oral one. NAC improves hepatotoxicity and reduces mortality. Timing of treatment, ranging from 8 to 24 h from APAP overdose, regardless of the regimen or route of administration, is important to prevent or minimize liver damage, particularly in children and in elderly and obese patients.
PubMed: 36034775
DOI: 10.3389/fphar.2022.828565 -
Journal of Hospital Medicine Sep 2022Hospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD...
BACKGROUND
Hospitalizations related to the consequences of opioid use are rising. National guidelines directing in-hospital opioid use disorder (OUD) management do not exist. OUD treatment guidelines intended for other treatment settings could inform in-hospital OUD management.
OBJECTIVE
Evaluate the quality and content of existing guidelines for OUD treatment and management.
DATA SOURCES
OVID MEDLINE, PubMed, Ovid PsychINFO, EBSCOhost CINHAL, ERCI Guidelines Trust, websites of relevant societies and advocacy organizations, and selected international search engines.
STUDY SELECTION
Guidelines published between January 2010 to June 2020 addressing OUD treatment, opioid withdrawal management, opioid overdose prevention, and care transitions among adults.
DATA EXTRACTION
We assessed quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument.
DATA SYNTHESIS
Nineteen guidelines met the selection criteria. Most recommendations were based on observational studies or expert consensus. Guidelines recommended the use of nonstigmatizing language among patients with OUD; to assess patients with unhealthy opioid use for OUD using the Diagnostic Statistical Manual of Diseases-5th Edition criteria; use of methadone or buprenorphine to treat OUD and opioid withdrawal; use of multimodal, nonopioid therapy, and when needed, short-acting opioid analgesics in addition to buprenorphine or methadone, for acute pain management; ensuring linkage to ongoing methadone or buprenorphine treatment; referring patients to psychosocial treatment; and ensuring access to naloxone for opioid overdose reversal.
CONCLUSIONS
Included guidelines were informed by studies with various levels of rigor and quality. Future research should systematically study buprenorphine and methadone initiation and titration among people using fentanyl and people with pain, especially during hospitalization.
Topics: Adult; Analgesics, Opioid; Buprenorphine; Hospitalization; Humans; Methadone; Opiate Overdose; Opioid-Related Disorders
PubMed: 35880821
DOI: 10.1002/jhm.12908 -
Harm Reduction Journal Mar 2023Community-based harm reduction vending machines (HRVM) are not new to the field of public health; numerous countries have implemented them in response to the needs of... (Review)
Review
BACKGROUND
Community-based harm reduction vending machines (HRVM) are not new to the field of public health; numerous countries have implemented them in response to the needs of people who use drugs over the last three decades. However, until recently, few existed in the United States. Given the rapidity with which communities are standing up harm reduction vending machines, there is a pressing need for a consolidated examination of implementation evidence. This scoping review summarizes existing literature using multiple implementation science frameworks.
METHODS
The scoping review was conducted in five stages including (1) Identify the research question; (2) Identify relevant studies; (3) Select the publications based on inclusion/exclusion criteria; (4) Review and extract data; and, (5) Summarize results. PubMed, Embase, and Web of Science were searched and authors screened publications in English from any year. Data were extracted by applying implementation constructs from RE-AIM and the Consolidated Framework for Implementation Research (CFIR). Both frameworks provided a useful lens through which to develop knowledge about the facilitators and barriers to HRVM implementation. The review is reported according to PRISMA guidelines.
RESULTS
After applying the full inclusion and exclusion criteria, including the intervention of interest ("vending machines") and population of interest ("people who use drugs"), a total of 22 studies were included in the scoping review. None of the studies reported on race, making it difficult to retroactively apply a racial equity lens. Among those articles that examined effectiveness, the outcomes were mixed between clear effectiveness and inconclusive results. Evidence emerged, however, to address all CFIR constructs, and positive outcomes were observed from HRVM's after-hour availability and increased program reach.
RECOMMENDATIONS
HRVM implementation best practices include maximizing accessibility up to 24 h, 7 days a week, offering syringe disposal options, ensuring capability of data collection, and allowing for anonymity of use. Organizations that implement HRVM should establish strong feedback loops between them, their program participants, and the broader community upfront. Considerations for future research include rigorous study designs to evaluate effectiveness outcomes (e.g. reduced drug overdose deaths) and examination of HRVM reach among ethnic and racial communities.
Topics: Humans; Harm Reduction; United States; Drug Users; Substance-Related Disorders
PubMed: 36927354
DOI: 10.1186/s12954-023-00765-2 -
Drug and Alcohol Dependence Sep 2021Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive... (Review)
Review
BACKGROUND
Non-fatal opioid-related overdoses have increased significantly over the past two decades and there have been increasing reports of brain injuries and/or neurocognitive impairments following overdose events. Limited preclinical research suggests that opioid overdoses may cause brain injury; however, little is known about such injuries in humans. The purpose this systematic review is to summarize existing studies on neurocognitive impairments and/or brain abnormalities associated with an opioid-related overdose in humans.
METHODS
PubMed, Web of Science, Ovid MEDLINE and PsyINFO were searched, without year restrictions, and identified 3099 articles. An additional 24 articles were identified by reviewing references. Articles were included if they were published in English, reported study findings in humans, included individuals 18 years of age or older, and reported an objective measure of neurocognitive impairments and/or brain abnormalities resulting from an opioid-related overdose. Six domains of bias (selection, performance, attrition, detection (two dimensions) and reporting were evaluated and themes were summarized.
RESULTS
Seventy-nine journal articles, published between 1973-2020, were included in the review. More than half of the articles were case reports (n = 44) and there were 11 cohort studies, 18 case series, and 6 case-control studies. All of the studies were categorized as at-risk of bias, few controlled for confounding factors, and methodological differences made direct comparisons difficult. Less than half of the studies reported toxicology results confirming an opioid-related overdose; 64.6 % reported brain MRI results and 27.8 % reported results of neuropsychological testing. Only two studies had within subject comparative data to document changes in the brain possibly associated with an overdose. Despite these limitations, existing publications suggest that brain injuries and neurocognitive impairments are associated with opioid overdose. Additional research is needed to establish the incidence of overdose-related brain injuries and the potential impact on functioning, as well as engagement in treatment of substance use disorders.
CONCLUSIONS
Respiratory depression is a defining characteristic of opioid overdose and prolonged cerebral hypoxia may cause brain injuries and/or neurocognitive impairments. The onset, characteristics, and duration of such injuries is variable and additional research is needed to understand their clinical implications.
Topics: Adolescent; Adult; Analgesics, Opioid; Brain; Drug Overdose; Humans; Opiate Overdose; Substance-Related Disorders
PubMed: 34271512
DOI: 10.1016/j.drugalcdep.2021.108838 -
The Journal of Nutrition, Health & Aging 2016The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We... (Review)
Review
BACKGROUND
The estimation of the risk of poor tolerance and overdose of antineoplastic agents protocols represents a major challenge in oncology, particularly in older patients. We hypothesize that age-related modifications of body composition (i.e. increased fat mass and decreased lean mass) may significantly affect tolerance to chemotherapy.
METHOD
We conducted a systematic review for the last 25 years (between 1990 and 2015), using US National library of Medicine Medline electronic bibliographic database and Embase database of cohorts or clinical trials exploring (i) the interactions of body composition (assessed by Dual X-ray Absorptiometry, Bioelectrical Impedance Analyses, or Computerized Tomography) with pharmacokinetics parameters, (ii) the tolerance to chemotherapy, and (iii) the consequences of chemotherapies or targeted therapies on body composition.
RESULTS
Our search identified 1504 articles. After a selection (using pre-established criteria) on titles and abstract, 24 original articles were selected with 3 domains of interest: impact of body composition on pharmacokinetics (7 articles), relationship between body composition and chemotoxicity (14 articles), and effect of anti-cancer chemotherapy on body composition (11 articles). The selected studies suggested that pharmacokinetic was influenced by lean mass, that lower lean mass could be correlated with toxicity, and that sarcopenic patients experienced more toxicities that non-sarcopenic patients. Regarding fat mass, results were less conclusive. No studies specifically explored the topic of body composition in older cancer patients.
CONCLUSIONS
Plausible pathophysiological pathways linking body composition, toxicity, and pharmacokinetics are sustained by the actual review. However, despite the growing number of older cancer patients, our review highlighted the lack of specific studies in the field of anti-neoplastic agents toxicity regarding body composition conducted in elderly.
Topics: Aged; Antineoplastic Agents; Body Composition; Female; Humans; Male; Middle Aged; Neoplasms
PubMed: 27709238
DOI: 10.1007/s12603-015-0653-2 -
Addiction (Abingdon, England) Jul 2016Fatal outcome of opioid overdose, once detected, is preventable through timely administration of the antidote naloxone. Take-home naloxone provision directly to opioid... (Review)
Review
BACKGROUND AND AIMS
Fatal outcome of opioid overdose, once detected, is preventable through timely administration of the antidote naloxone. Take-home naloxone provision directly to opioid users for emergency use has been implemented recently in more than 15 countries worldwide, albeit mainly as pilot schemes and without formal evaluation. This systematic review assesses the effectiveness of take-home naloxone, with two specific aims: (1) to study the impact of take-home naloxone distribution on overdose-related mortality; and (2) to assess the safety of take-home naloxone in terms of adverse events.
METHODS
PubMed, MEDLINE and PsychINFO were searched for English-language peer-reviewed publications (randomized or observational trials) using the Boolean search query: (opioid OR opiate) AND overdose AND prevention. Evidence was evaluated using the nine Bradford Hill criteria for causation, devised to assess a potential causal relationship between public health interventions and clinical outcomes when only observational data are available.
RESULTS
A total of 1397 records (1164 after removal of duplicates) were retrieved, with 22 observational studies meeting eligibility criteria. Due to variability in size and quality of the included studies, meta-analysis was dismissed in favour of narrative synthesis. From eligible studies, we found take-home naloxone met all nine Bradford Hill criteria. The additional five World Health Organization criteria were all either met partially (two) or fully (three). Even with take-home naloxone administration, fatal outcome was reported in one in 123 overdose cases (0.8%; 95% confidence interval = 0.4, 1.2).
CONCLUSIONS
Take-home naloxone programmes are found to reduce overdose mortality among programme participants and in the community and have a low rate of adverse events.
Topics: Analgesics, Opioid; Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders
PubMed: 27028542
DOI: 10.1111/add.13326 -
The Journal of Pain Apr 2014The number of deaths associated with methadone use increased dramatically in parallel with marked increases in its use, particularly for treatment of chronic pain. To... (Review)
Review
Methadone overdose and cardiac arrhythmia potential: findings from a review of the evidence for an American Pain Society and College on Problems of Drug Dependence clinical practice guideline.
UNLABELLED
The number of deaths associated with methadone use increased dramatically in parallel with marked increases in its use, particularly for treatment of chronic pain. To develop a clinical guideline on methadone prescribing to reduce potential harms, the American Pain Society commissioned a review of various aspects related to methadone safety. This article summarizes evidence related to unintentional overdose due to methadone and harms related to cardiac arrhythmia potential. We searched Ovid MEDLINE, the Cochrane Library, and PsycINFO databases through January 2014 for studies assessing harms associated with methadone use; we judged 70 studies to be relevant and to meet inclusion criteria. The majority of studies on overdose and cardiac arrhythmia risk are observational and provide weak evidence on which to base clinical guidelines. In patients prescribed methadone for treatment of opioid dependence, data suggest that mortality benefits related to reduction in illicit drug use outweigh harms. Despite epidemiologic data showing marked increases in the numbers of methadone-related deaths that have been primarily attributed to increased use of methadone for chronic pain, evidence on methadone and mortality risk in this population has been somewhat contradictory. There is some evidence that recent initiation of methadone, psychiatric admissions, and concomitant use of benzodiazepines are associated with a higher risk for overdose. Evidence on cardiac risks is primarily limited to case reports of torsades de pointes, primarily in patients on high doses of methadone, and to studies showing an association between methadone use and prolongation of QTc intervals. Research is needed to understand the effectiveness of dosing methods, electrocardiogram monitoring, and other risk mitigation strategies in patients prescribed methadone.
PERSPECTIVE
This systematic review synthesizes the evidence related to methadone use and risk for overdose and cardiac arrhythmia. Findings regarding the association between methadone use and QTc interval prolongation and risk factors for methadone-associated overdose suggest potential targets for risk mitigation strategies, though research is needed to determine the effectiveness of such strategies at reducing adverse outcomes.
Topics: Arrhythmias, Cardiac; Chronic Pain; Drug Overdose; Humans; Methadone; Opioid-Related Disorders; Practice Guidelines as Topic
PubMed: 24685459
DOI: 10.1016/j.jpain.2014.01.495 -
The Lancet. Global Health May 2023People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to...
Epidemiology of injecting drug use, prevalence of injecting-related harm, and exposure to behavioural and environmental risks among people who inject drugs: a systematic review.
BACKGROUND
People who inject drugs are exposed to various and changing risk environments and are at risk of multiple harms related to injecting drug use (IDU). We aimed to undertake a global systematic review of the prevalence of IDU, key IDU-related harms (including HIV, hepatitis C virus [HCV], and hepatitis B virus [HBV] infection and overdose), and key sociodemographic characteristics and risk exposures for people who inject drugs.
METHODS
We systematically searched for data published between Jan 1, 2017, and March 31, 2022, in databases of peer-reviewed literature (MEDLINE, Embase, and PsycINFO) and grey literature as well as various agency or organisational websites, and disseminated data requests to international experts and agencies. We searched for data on the prevalence, characteristics, and risks of people who inject drugs, including gender, age, sexuality, drug-use patterns, HIV, HCV, and HBV infections, non-fatal overdose, depression, anxiety, and injecting-related disease. Additional data were extracted from studies identified in our previous review. Meta-analyses were used to pool the data where multiple estimates were available for a country. We present country, regional, and global estimates for each variable examined.
FINDINGS
We screened 40 427 reports published between 2017 and 2022, and the 871 eligible reports identified were added to the 1147 documents from the previous review. Evidence of IDU was documented in 190 of 207 countries and territories, and 14·8 million people (95% uncertainty interval [UI] 10·0-21·7) aged 15-64 years globally were estimated to inject drugs. Existing evidence suggests that there might be 2·8 million (95% UI 2·4-3·2) women and 12·1 million (95% UI 11·0-13·3) men who inject drugs globally, and that 0·4% (95% CI 0·3-1·3) of people who inject drugs identify as transgender. The amount of available data on key health and social risks among people who inject drugs varied widely across countries and regions. We estimated that 24·8% (95% CI 19·5-31·6) of people who inject drugs globally had experienced recent homelessness or unstable housing, 58·4% (95% CI 52·0-64·8) had a lifetime history of incarceration, and 14·9% (95% CI 8·1-24·3) had recently engaged in sex work, with substantial geographical variation. Injecting and sexual risk behaviour varied considerably geographically, as did risks of harms. Globally, we estimated that 15·2% (95% CI 10·3-20·9) of people who inject drugs are living with HIV, 38·8% (95% CI 31·4-46·9) have current HCV infection, 18·5% (95% CI 13·9-24·1) have recently overdosed, and 31·7% (95% CI 23·6-40·5) have had a recent skin or soft tissue infection.
INTERPRETATION
IDU is being identified in a growing number of countries and territories that comprise more than 99% of the global population. IDU-related health harms are common, and people who inject drugs continue to be exposed to multiple adverse risk environments. However, quantification of many of these exposure and harms is inadequate and must be improved to allow for better targeting of harm-reduction interventions for these risks.
FUNDING
Australian National Health and Medical Research Council.
Topics: Male; Humans; Female; Substance Abuse, Intravenous; Prevalence; Drug Users; Australia; Hepatitis C; Hepatitis B; Substance-Related Disorders; Hepacivirus; Hepatitis B virus; HIV Infections
PubMed: 36996857
DOI: 10.1016/S2214-109X(23)00057-8 -
Skin Appendage Disorders Oct 2018There are a number of toxic agents that can cause alopecia. In this review we summarize the known substances that cause alopecia as one of the clinical signs of overdose... (Review)
Review
IMPORTANCE/OBJECTIVE
There are a number of toxic agents that can cause alopecia. In this review we summarize the known substances that cause alopecia as one of the clinical signs of overdose or toxicity.
EVIDENCE REVIEW
A search was conducted using PubMed, EMBASE, and Cochrane for studies describing hair loss of any type as a result of exposure to or ingestion of a toxic agent. The search yielded 856 articles, with 47 studies included in this review.
FINDINGS
Agents with the strongest evidence of association to alopecia include thallium, mercury, selenium, and colchicine. Agents with described incidents include boric acid, arsenic, vitamin A, botulinum toxin, , and the synthetic opioid MT-45.
CONCLUSIONS AND RELEVANCE
Numerous toxic agents have been implicated in alopecia, and the strength of evidence behind each agent varies. Toxic levels of thallium and colchicine have long been established to cause alopecia, as compared to agents such as botulinum toxin A and synthetic recreational drugs which have less literature describing their links to alopecia and will need further investigation to characterize their relationships to hair loss. Knowledge of typical presentations of hair loss will aid in the development of a differential diagnosis for patients presenting with alopecia.
PubMed: 30410891
DOI: 10.1159/000485749 -
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