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The Annals of Pharmacotherapy Oct 2023To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its... (Review)
Review
OBJECTIVE
To review the available literature regarding the treatment effects and efficacy of benzonatate needed to better inform patients, providers, and regulators evaluating its role in modern medical therapies.
DATA SOURCES
Comprehensive literature searches were conducted in PubMed, Embase (Elsevier), Cochrane Library, and Scopus for original research articles evaluating the effectiveness, tolerability, and safety profile of benzonatate from January 1956 through August 2022.
STUDY SELECTION AND DATA EXTRACTION
The identified studies were screened for relevance and then assessed for inclusion through a full-text review, data extraction, and quality assessment by multiple reviewers using the online software Covidence.
DATA SYNTHESIS
The selection process resulted in 37 articles consisting of 21 cohort studies, 5 experimental studies, and 11 case studies and series. Initial clinical studies exploring potential therapeutic benefits collected data from very small populations and limited clinical settings. Safety is primarily assessed in terms of toxicity due to overdose or inappropriate use. Quality assessment raised concerns for high degrees of biases primarily related to the limited sample size, data collection, generalizability, and study design.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review reveals substantial limitations within existing evidence pertaining to the safety and clinical effectiveness of benzonatate and thus, a need for large observational studies or randomized trials to better characterize its role and value in modern medical practice.
CONCLUSIONS
Rising safety concerns should bring closer scrutiny upon the prescription of benzonatate whose approval is founded upon evidence that would not stand up to current regulatory review.
Topics: Humans; Butylamines; Drug Overdose; Text Messaging
PubMed: 36688284
DOI: 10.1177/10600280221135750 -
Antibiotics (Basel, Switzerland) Dec 2022The effects of bismuth toxicity on the kidney-the main organ responsible for blood filtration-were systematically reviewed. This review was motivated by availability of... (Review)
Review
The effects of bismuth toxicity on the kidney-the main organ responsible for blood filtration-were systematically reviewed. This review was motivated by availability of several sources of bismuth in contact with humans including environmental, medications, dental materials, and cosmetics, potentially leading to kidney filtration of this chemical. No previous studies have systematically reviewed the literature considering this association. A total of 22 studies with a total of 46 individuals met the inclusion criteria, 19 being case reports with only one patient enrolled. The included studies publication dates ranged from 1961 to 2021 and the countries of publication were the United States of America, United Kingdom, Germany, Turkey, Switzerland, and Canada. Bismuth sources affecting the kidneys were uniquely reported as from medical purposes and mostly associated to overdoses with several symptoms, apparently with dose-dependent consequences. Patient history of renal impairment seemed to affect the outcome of the case. Several therapies were conducted following bismuth intoxication, and few studies performed renal biopsies describing its histological findings. It is crucial to reconsider the nephrotoxicity of bismuth compounds, mainly in patients with previous history of renal impairment.
PubMed: 36551397
DOI: 10.3390/antibiotics11121741 -
Social Science & Medicine (1982) Jan 2023The Opioid Overdose Crisis (OOC) continues to generate morbidity and mortality in the United States, outpacing other prominent accident-related reasons. Multiple... (Review)
Review
BACKGROUND
The Opioid Overdose Crisis (OOC) continues to generate morbidity and mortality in the United States, outpacing other prominent accident-related reasons. Multiple disciplines have applied geographic information science (GIScience) to understand geographical patterns in opioid-related health measures. However, there are limited reviews that assess how GIScience has been used.
OBJECTIVES
This scoping review investigates how GIScience has been used to conduct research on the OOC. Specific sub-objectives involve identifying bibliometric trends, the location and scale of studies, the frequency of use of various GIScience methodologies, and what direction future research can take to address existing gaps.
METHODS
The review was pre-registered with the Open Science Framework ((https://osf.io/h3mfx/) and followed the PRISMA-ScR guidelines. Scholarly research was gathered from the Web of Science Core Collection, PubMed, IEEE Xplore, ACM Digital Library. Inclusion criteria was defined as having a publication date between January 1999 and August 2021, using GIScience as a central part of the research, and investigating an opioid-related health measure.
RESULTS
231 studies met the inclusion criteria. Most studies were published from 2017 onward. While many (41.6%) of studies were conducted using nationwide data, the majority (58.4%) occurred at the sub-national level. California, New York, Ohio, and Appalachia were most frequently studied, while the Midwest, north Rocky Mountains, Alaska, and Hawaii lacked studies. The most common GIScience methodology used was descriptive mapping, and county-level data was the most common unit of analysis across methodologies.
CONCLUSIONS
Future research of GIScience on the OOC can address gaps by developing use cases for machine learning, conducting analyses at the sub-county level, and applying GIScience to questions involving illicit fentanyl. Research using GIScience is expected to continue to increase, and multidisciplinary research efforts amongst GIScientists, epidemiologists, and other medical professionals can improve the rigor of research.
Topics: United States; Humans; Analgesics, Opioid; Opiate Overdose; Drug Overdose; New York; Information Science
PubMed: 36493502
DOI: 10.1016/j.socscimed.2022.115525 -
Drug and Alcohol Dependence Jan 2023This systematic review summarized published literature on county-level predictors of drug overdose mortality in the United States (US). (Review)
Review
BACKGROUND
This systematic review summarized published literature on county-level predictors of drug overdose mortality in the United States (US).
METHODS
Peer-reviewed studies and doctoral dissertations published in English between 1990 and July 19, 2022 were identified from PubMed, Web of Science, ProQuest Dissertations & Theses, PsycINFO, CINAHL, and EconLit. Eligible studies examined at least one county-level predictor of drug overdose mortality in US counties. Two reviewers independently completed screening, quality assessment (with an adapted National Institutes of Health Quality Assessment Tool), and data extraction. Results were qualitatively summarized and grouped by predictor categories.
RESULTS
Of 56 studies included, 42.9% were subnational, and 53.6% were limited to opioid overdose. In multiple studies, measures related to opioid prescribing, illness/disability, economic distress, mining employment, incarceration, family distress, and single-parent families were positively associated with drug overdose mortality outcomes, while measures related to cannabis dispensaries, substance use treatment, social capital, and family households were negatively associated with drug overdose mortality outcomes. Both positive and negative associations were documented for smoking, uninsurance, healthcare professional shortage status, physicians per capita, unemployment, income, poverty, educational attainment, racial composition, and rurality. Findings within studies also differed by subpopulation (by race/ethnicity, gender, age, or rurality) and the type of drugs involved in overdose.
CONCLUSIONS
The findings of this review provide relatively mixed evidence regarding many county-level predictors of overdose mortality, several of which also vary between subpopulations, supporting the importance of additional research to elucidate pathways through which the county context may shape risk of fatal overdose.
Topics: Humans; United States; Analgesics, Opioid; Practice Patterns, Physicians'; Drug Overdose; Substance-Related Disorders; Ethnicity
PubMed: 36463764
DOI: 10.1016/j.drugalcdep.2022.109714 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2023Risk stratification in paracetamol (acetaminophen) poisoning is crucial because hepatotoxicity is common and can be mitigated with treatment. However, current risk... (Meta-Analysis)
Meta-Analysis
Performance of the paracetamol-aminotransferase multiplication product in risk stratification after paracetamol (acetaminophen) poisoning: a systematic review and meta-analysis.
BACKGROUND
Risk stratification in paracetamol (acetaminophen) poisoning is crucial because hepatotoxicity is common and can be mitigated with treatment. However, current risk stratification tools have limitations.
AIMS
We evaluated the diagnostic performance of the paracetamol concentration × aminotransferase multiplication product, for predicting hepatotoxicity after paracetamol overdose.
METHODS
Medline, Cochrane Library and Embase were searched for eligible papers. We used random effects models to obtain pooled estimates of the likelihood ratios and diagnostic odds ratios, from which sensitivity and specificity were computed. We assessed two commonly used cut-off values of paracetamol × aminotransferase, 1500 mg/L × IU/L and 10,000 mg/L × IU/L. Using the confusion matrices of these two cut-offs, area under the summary receiver operator characteristic curve and optimal cut-off values in different clinical scenarios were established.
RESULTS
Six studies comprising 5036 participants were included. In 4051 patients, using the cut-off of 1500 mg/L × IU/L, a diagnostic odds ratio of 31.90 (95%CI: 9.52-106.90), sensitivity of 0.98 (95%CI: 0.94-1.00) and specificity of 0.66 (95%CI: 0.49-0.89) were obtained. In 3983 patients, using the cut-off of 10,000 mg/L × IU/L, a diagnostic odds ratio of 99.34 (95%CI: 12.26-804.87), sensitivity of 0.65 (95%CI: 0.51-0.82) and specificity of 0.97 (95%CI: 0.95-1.00) were obtained. For staggered ingestions, the 1500 mg/L × IU/L cut-off yielded a diagnostic odds ratio of 69.53 (95%CI: 4.03-1199.75), sensitivity of 1.00 (95%CI: 0.87-1.00) and specificity of 0.74 (95%CI: 0.43-1.00). Next, using the 10,000 mg/L × IU/L cut-off in this scenario yielded a diagnostic odds ratio of 254.58 (95%CI: 11.12-5827.60), sensitivity of 0.79 (95%CI: 0.59-1.00) and specificity of 0.98 (95%CI: 0.94-1.00). The overall summary receiver operator characteristic curve was 0.91 (95%CI: 0.75-0.97), and the optimal cut-off value was 3840 mg/L × IU/L. The summary receiver operator characteristic curve in patients with staggered ingestions was 0.96 (95%CI: 0.85-0.99). The summary receiver operator characteristic curve in patients with staggered ingestions and whose paracetamol concentration was below the detectable limit of 10 mg/L at presentation was 0.97 (95%CI: 0.94-0.99).
CONCLUSION
In this first meta-analysis, paracetamol × aminotransferase demonstrates its use in prognosticating hepatotoxicity in patients with paracetamol poisoning. It complements the Rumack-Matthew nomogram as it has shown promise in addressing two key limitations of the nomogram: it is usable after more than 24 h between overdose and acetylcysteine treatment, and it is applicable in staggered ingestions.
Topics: Humans; Acetaminophen; Analgesics, Non-Narcotic; Chemical and Drug Induced Liver Injury; Alanine Transaminase; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Risk Assessment; Retrospective Studies
PubMed: 36444937
DOI: 10.1080/15563650.2022.2152350 -
Regional Anesthesia and Pain Medicine May 2024
Topics: Humans; Analgesics, Opioid; Canada; COVID-19; Drug Overdose; Opiate Overdose; Opioid-Related Disorders; Pandemics; United States
PubMed: 36427903
DOI: 10.1136/rapm-2022-104169 -
The American Journal of Drug and... Mar 2023Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental...
Although the misuse of ketamine constitutes a worldwide issue, ketamine is quickly taking its place as a therapeutic option in the management of several mental disorders. However, the use of ketamine and/or its analogues, as well as combinations with other drugs, can be fatal. To outline the cases of overdoses and deaths related to the use of ketamine and/or its analogues, as reported in the scientific literature. To investigate if ketamine is safe in a therapeutic context, particularly in its use as an antidepressant. Electronic searches were performed on three medical databases. Articles describing cases of overdose and/or death associated with ketamine and/or its analogues were included. After the removal of duplicates, title analysis and full-text analysis, 34 articles were included in this review. Eighteen articles described fatal cases and sixteen described overdoses. Poly-substance use was mentioned in 53% of the selected articles. Most cases were males and the ages varied from two to 65 years old. A total of 312 overdose cases and 138 deaths were reported. In both death reports and overdose cases, ketamine was preponderant: 89.1% and 79%, respectively. No cases of overdose or death related to the use of ketamine as an antidepressant in a therapeutic setting were found; most of the deaths occurred in the circumstances of polydrug use and overdoses left no sequelae. There is legitimate concern about the risks involving the use of ketamine and its analogues, especially in recreational settings. On the other hand, ketamine as medicine is considered safe and it is listed as an essential medicine by the World Health Organization. Although clinicians must remain vigilant, this should not deter appropriate prescription.
Topics: Male; Humans; Child, Preschool; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Female; Ketamine; Drug Overdose; Substance-Related Disorders; Analgesics, Opioid
PubMed: 36410032
DOI: 10.1080/00952990.2022.2132506 -
Drug and Alcohol Dependence Dec 2022Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.
BACKGROUND
Evidence maps are emerging data visualization of a systematic review. There are no published evidence maps summarizing opioid use disorder (OUD) interventions.
AIM
Our aim was to publish an interactive summary of all peer-reviewed interventional and observational trials assessing the treatment of OUD and common clinical outcomes.
METHODS
PubMed, Embase, PsycInfo, Cochrane Central Register of Clinical Trials, and Web of Science were queried using multiple OUD-related MESH terms, without date limitations, for English-language publications. Inclusions were human subjects, treatment of OUD, OUD patient or community-level outcomes, and systematic reviews of OUD interventions. Exclusions were laboratory studies, reviews, and case reports. Two reviewers independently scanned abstracts for inclusion before coding eligible full-text articles by pre-specified filters: research design, study population, study setting, intervention, outcomes, sample size, study duration, geographical region, and funding sources.
RESULTS
The OUD Evidence Map (https://med.nyu.edu/research/lee-lab/research/opioid-use-disorder-treatment-evidence-map) identified and assessed 12,933 relevant abstracts through 2020. We excluded 9455 abstracts and full text reviewed 2839 manuscripts; 888 were excluded, 1591 were included in the final evidence map. The most studied OUD interventions were methadone (n = 754 studies), buprenorphine (n = 499), and naltrexone (n = 134). The most common outcomes were heroin/opioid use (n = 708), treatment retention (n = 557), and non-opioid drug use (n = 368). Clear gaps included a wider array of opioid agonists for treatment, digital behavioral interventions, studies of OUD treatments in criminal justice settings, and overdose as a clinical outcome.
CONCLUSION
This OUD Evidence Map highlights the importance of pharmacologic interventions for OUD and reductions in opioid use. Future iterations will update results annually and scan policy-level interventions.
Topics: Humans; Opiate Substitution Treatment; Analgesics, Opioid; Opioid-Related Disorders; Buprenorphine; Methadone; Naltrexone
PubMed: 36332588
DOI: 10.1016/j.drugalcdep.2022.109657 -
Heart (British Cardiac Society) Jan 2023There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with... (Meta-Analysis)
Meta-Analysis
Outcomes and drivers of inappropriate dosing of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation: a systematic review and meta-analysis.
OBJECTIVE
There has been limited systematic evaluation of outcomes and drivers of inappropriate non-vitamin K antagonist oral anticoagulants (NOACs) dosing among patients with atrial fibrillation (AF). This review identified and systematically evaluated literature on clinical and economic outcomes of inappropriate NOAC dosing and associated patient characteristics.
METHODS
MEDLINE, Embase, Cochrane Library, International Pharmaceutical Abstracts, Econlit, PubMed and NHS EEDs databases were searched for English language observational studies from all geographies published between 2008 and 2020, examining outcomes of, or factors associated with, inappropriate NOAC dosing in adult patients with AF.
RESULTS
One hundred and six studies were included in the analysis. Meta-analysis showed that compared with recommended NOAC dosing, off-label underdosing was associated with a null effect on stroke outcomes (ischaemic stroke and stroke/transient ischaemic attack (TIA), stroke/systemic embolism (SE) and stroke/SE/TIA). Meta-analysis of 15 studies examining clinical outcomes of inappropriate NOAC dosing found a null effect of underdosing on bleeding outcomes (major bleeding HR=1.04, 95% CI 0.90 to 1.19; p=0.625) but an increased risk of all-cause mortality (HR=1.28, 95% CI 1.10 to 1.49; p=0.006). Overdosing was associated with an increased risk of major bleeding (HR=1.41, 95% CI 1.07 to 1.85; p=0.013). No studies were found examining economic outcomes of inappropriate NOAC dosing. Narrative synthesis of 12 studies examining drivers of inappropriate NOAC dosing found that increased age, history of minor bleeds, hypertension, congestive heart failure and low creatine clearance (CrCl) were associated with an increased risk of underdosing. There was insufficient evidence to assess drivers of overdosing.
CONCLUSIONS
Our analysis suggests that off-label underdosing of NOACs does not reduce bleeding outcomes. Patients prescribed off-label NOAC doses are at an increased risk of all-cause mortality. These data underscore the importance of prescriber adherence to NOAC dosing guidelines to achieve optimal clinical outcomes for patients with AF.
PROSPERO REGISTRATION NUMBER
CRD42020219844.
Topics: Adult; Humans; Anticoagulants; Atrial Fibrillation; Stroke; Administration, Oral; Brain Ischemia; Ischemic Attack, Transient; Hemorrhage; Embolism
PubMed: 36316100
DOI: 10.1136/heartjnl-2022-321114 -
Harm Reduction Journal Oct 2022Opioid overdose epidemic is hitting record highs worldwide, accounting for 76% of mortality related to substance use. Take-home naloxone (THN) strategies are being...
BACKGROUND
Opioid overdose epidemic is hitting record highs worldwide, accounting for 76% of mortality related to substance use. Take-home naloxone (THN) strategies are being implemented in many developed countries that suffer from high opioid overdose death rates. They aim to provide overdose identification and naloxone administration training, along with THN delivery to opioid users and others likely to witness an overdose incident such as family members and peers. However, little is known about such measures in low- and middle-income countries (LMIC), where opioid use and opioid-related deaths are reportedly high. This systematic literature review aims to examine the distribution of THN in LMIC, review studies identifying barriers to the implementation of THN programs worldwide, and assess their applicability to LMIC.
METHODS
The literature was searched and analyzed for eligible studies with quality assessment.
RESULTS
Two studies were found from LMIC on THN programs with promising results, and 13 studies were found on the barriers identified in implementing THN programs worldwide. The main barriers to THN strategies were the lack of training of healthcare providers, lack of privileges, time constraints, cost, legislative/policy restrictions, stigma, fear of litigation, and some misperceptions around THN.
CONCLUSIONS
The barriers outlined in this paper are probably applicable to LMIC, but more difficult to overcome considering the differences in their response to opioid overdose, their cultural attitudes and norms, the high cost, the waivers required, the legislative differences and the severe penalties for drug-related offenses in some of these countries. The solutions suggested to counter-act these obstacles can also be more difficult to achieve in LMIC. Further research is required in this area with larger sample sizes to provide a better understanding of the obstacles to the implementation, feasibility, accessibility, and utilization of THN programs in LMIC.
Topics: Humans; Naloxone; Developing Countries; Narcotic Antagonists; Analgesics, Opioid; Opiate Overdose; Drug Overdose; Opioid-Related Disorders
PubMed: 36266701
DOI: 10.1186/s12954-022-00700-x