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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 -
CMAJ : Canadian Medical Association... Oct 2023Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids.
METHODS
We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs).
RESULTS
Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose.
INTERPRETATION
We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/).
Topics: Humans; Analgesics, Opioid; Chronic Pain; Drug Overdose; Opiate Overdose; Prescriptions; Observational Studies as Topic
PubMed: 37871953
DOI: 10.1503/cmaj.230459 -
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 -
Social Psychiatry and Psychiatric... Jul 2024To synthesize the available evidence on the extent to which area-level socioeconomic conditions are associated with drug overdose deaths in the United States. (Review)
Review
PURPOSE
To synthesize the available evidence on the extent to which area-level socioeconomic conditions are associated with drug overdose deaths in the United States.
METHODS
We performed a systematic review (in MEDLINE, EMBASE, PsychINFO, Web of Science, EconLit) for papers published prior to July 2022. Eligible studies quantitatively estimated the association between an area-level measure of socioeconomic conditions and drug overdose deaths in the US, and were published in English. We assessed study quality using the Effective Public Health Practice Project Quality Assessment Tool. The protocol was preregistered at Prospero (CRD42019121317).
RESULTS
We identified 28 studies that estimated area-level effects of socioeconomic conditions on drug overdose deaths in the US. Studies were scored as having moderate to serious risk of bias attributed to both confounding and in analysis. Socioeconomic conditions and drug overdose death rates were moderately associated, and this was a consistent finding across a large number of measures and differences in study designs (e.g., cross-sectional versus longitudinal), years of data analyzed, and primary unit of analysis (e.g., ZIP code, county, state).
CONCLUSIONS
This review highlights the evidence for area-level socioeconomic conditions are an important factor underlying the geospatial distribution of drug overdose deaths in the US and the need to understand the mechanisms underlying these associations to inform future policy recommendations. The current evidence base suggests that, at least in the United States, employment, income, and poverty interventions may be effective targets for preventing drug overdose mortality rates.
Topics: Humans; Drug Overdose; United States; Socioeconomic Factors; Social Determinants of Health; Spatial Analysis
PubMed: 38356082
DOI: 10.1007/s00127-024-02622-4 -
The Cochrane Database of Systematic... Feb 2024Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used... (Review)
Review
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used disease-modifying antirheumatic drug (DMARD). This is an update of a 2001 Cochrane review. It supports a living guideline for children and young people with JIA.
OBJECTIVES
To assess the benefits and harms of methotrexate for children and young people with juvenile idiopathic arthritis.
SEARCH METHODS
The Australian JIA Living Guideline Working Group created a registry of all randomised controlled trials (RCTs) of JIA by searching CENTRAL, MEDLINE, Embase, and trials registries. The date of the most recent search of online databases was 1 February 2023.
SELECTION CRITERIA
We searched for RCTs that compared methotrexate with placebo, no treatment, or another DMARD (with or without concomitant therapies) in children and young people (aged up to 18 years) with JIA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. The main comparison was methotrexate versus placebo. Our outcomes were treatment response, sustained clinically inactive disease, function, pain, participant global assessment of well-being, serious adverse events, and withdrawals due to adverse events. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified three new trials in this update, bringing the total number of included RCTs to five (575 participants). Three trials evaluated oral methotrexate versus placebo, one evaluated methotrexate plus intra-articular glucocorticoid (IAGC) therapy versus IAGC therapy alone, and one evaluated methotrexate versus leflunomide. Doses of methotrexate ranged from 5 mg/m/week to 15 mg/m/week in four trials, and participants in the methotrexate group of the remaining trial received 0.5 mg/kg/week. Trial size varied from 31 to 226 participants. The average age of participants ranged from four to 10 years. Most participants were females and most had nonsystemic JIA. The study that evaluated methotrexate plus IAGC therapy versus IAGC therapy alone recruited children and young people with the oligoarticular disease subtype of JIA. Two placebo-controlled trials and the trial of methotrexate versus leflunomide were adequately randomised and blinded, and likely not susceptible to important biases. One placebo-controlled trial may have been susceptible to selection bias due to lack of adequate reporting of randomisation methods. The trial investigating the addition of methotrexate to IAGC therapy was susceptible to performance and detection biases. Methotrexate versus placebo Methotrexate compared with placebo may increase the number of children and young people who achieve treatment response up to six months (absolute difference of 163 more per 1000 people; risk ratio (RR) 1.67, 95% confidence interval (CI) 1.21 to 2.31; I = 0%; 3 trials, 328 participants; low-certainty evidence). However, methotrexate compared with placebo may have little or no effect on pain as measured on an increasing scale of 0 to 100 (mean difference (MD) -1.10 points, 95% CI -9.09 to 6.88; 1 trial, 114 participants), improvement in participant global assessment of well-being (absolute difference of 92 more per 1000 people; RR 1.23, 95% CI 0.88 to 1.72; 1 trial, 176 participants), occurrence of serious adverse events (absolute difference of 5 fewer per 1000 people; RR 0.63, 95% CI 0.04 to 8.97; 3 trials, 328 participants), and withdrawals due to adverse events (RR 3.46, 95% CI 0.60 to 19.79; 3 trials, 328 participants) up to six months. We could not estimate the absolute difference for withdrawals due to adverse events because there were no withdrawals in the placebo group. All outcomes were reported within six months of randomisation. We downgraded the certainty of the evidence to low for all outcomes due to indirectness (suboptimal dosing of methotrexate and diverse outcome measures) and imprecision (few participants and low event rates). No trials reported function or the number of participants with sustained clinically inactive disease. Serious adverse events included liver derangement, abdominal pain, and inadvertent overdose. Methotrexate plus intra-articular corticosteroid therapy versus intra-articular corticosteroid therapy alone Methotrexate plus IAGC therapy compared with IAGC therapy alone may have little or no effect on the probability of sustained clinically inactive disease or the rate of withdrawals due to adverse events up to 12 months in children and young people with the oligoarticular subtype of JIA (low-certainty evidence). We could not calculate the absolute difference in withdrawals due to adverse events because there were no withdrawals in the control group. We are uncertain if there is any difference between the interventions in the risk of severe adverse events, because none were reported. The study did not report treatment response, function, pain, or participant global assessment of well-being. Methotrexate versus an alternative disease-modifying antirheumatic drug Methotrexate compared with leflunomide may have little or no effect on the probability of treatment response or on function, participant global assessment of well-being, risk of serious adverse events, and rate of withdrawals due to adverse events up to four months. We downgraded the certainty of the evidence for all outcomes to low due to imprecision. The study did not report pain or sustained clinically inactive disease.
AUTHORS' CONCLUSIONS
Oral methotrexate (5 mg/m/week to 15 mg/m/week) compared with placebo may increase the number of children and young people achieving treatment response but may have little or no effect on pain or participant global assessment of well-being. Oral methotrexate plus IAGC injections compared to IAGC injections alone may have little or no effect on the likelihood of sustained clinically inactive disease among children and young people with oligoarticular JIA. Similarly, methotrexate compared with leflunomide may have little or no effect on treatment response, function, and participant global assessment of well-being. Serious adverse events due to methotrexate appear to be rare. We will update this review as new evidence becomes available to inform the living guideline.
Topics: Child; Female; Humans; Adolescent; Aged; Child, Preschool; Male; Methotrexate; Arthritis, Juvenile; Leflunomide; Australia; Antirheumatic Agents; Glucocorticoids; Pain
PubMed: 38334147
DOI: 10.1002/14651858.CD003129.pub2 -
Blood Reviews Nov 2023Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined. (Review)
Review
BACKGROUND
Optimal peri-operative management for women with Von Willebrand disease (VWD) and heavy menstrual bleeding (HMB) remains undetermined.
AIM AND METHODS
To evaluate (pre)operative management in relation to (post)operative bleeding after endometrial ablation (EA) and hysterectomy in VWD women with HMB by performing a database search between 1994 and 2023.
RESULTS
Eleven cohort studies and 1 case-report were included, of overall 'low' quality, describing 691 operative procedures. Prophylaxis (Desmopressin, clotting factor concentrates or tranexamic acid) to prevent bleeding was described in 100% (30/30) of EA procedures and in 4% (24/661) of hysterectomies. Bleeding complications despite prophylaxis were described in 13% (3/24) of hysterectomies vs 0% (0/30) in EA.
CONCLUSION
VWD women often seem to experience bleeding complications during hysterectomy and all women with VWD received preprocedural hemostatic agents during EA, indicating potential under- and overdosing of current prophylactic strategies. Prospective studies are needed to determine the optimal (pre)operative strategy for gynecological surgical procedures in women with VWD.
Topics: Female; Humans; Hemorrhage; Menorrhagia; Prospective Studies; Tranexamic Acid; von Willebrand Diseases; von Willebrand Factor
PubMed: 37716881
DOI: 10.1016/j.blre.2023.101131 -
Harm Reduction Journal Oct 2023Providing sterile drug smoking materials to people who use drugs can prevent the acquisition of infectious diseases and reduce overdose risk. However, there is a lack of... (Review)
Review
BACKGROUND
Providing sterile drug smoking materials to people who use drugs can prevent the acquisition of infectious diseases and reduce overdose risk. However, there is a lack of understanding of how these practices are being implemented and received by people who use drugs globally.
METHODS
A systematic review of safer smoking practices was conducted by searching PubMed, PsycInfo, Embase for relevant peer-reviewed, English-language publications from inception or the availability of online manuscripts through December 2022.
RESULTS
Overall, 32 peer-reviewed papers from six countries were included. 30 studies exclusively included people who use drugs as participants (n = 11 people who use drugs; generally, n = 17 people who smoke drugs, n = 2 people who inject drugs). One study included program staff serving people who use drugs, and one study included staff and people who use drugs. Sharing smoking equipment (e.g., pipes) was reported in 25 studies. People who use drugs in several studies reported that pipe sharing occurred for multiple reasons, including wanting to accumulate crack resin and protect themselves from social harms, such as police harassment. Across studies, smoking drugs, as opposed to injecting drugs, were described as a crucial method to reduce the risk of overdose, disease acquisition, and societal harms such as police violence. Ten studies found that when people who use drugs were provided with safer smoking materials, they engaged in fewer risky drug use behaviors (e.g., pipe sharing, using broken pipes) and showed improved health outcomes. However, participants across 11 studies reported barriers to accessing safer smoking services. Solutions to overcoming safer smoking access barriers were described in 17 studies and included utilizing peer workers and providing safer smoking materials to those who asked.
CONCLUSION
This global review found that safer smoking practices are essential forms of harm reduction. International policies must be amended to help increase access to these essential tools. Additional research is also needed to evaluate the efficacy of and access to safer smoking services, particularly in the U.S. and other similar countries, where such practices are being implemented but have not been empirically studied in the literature.
Topics: Humans; Cocaine-Related Disorders; Crack Cocaine; Substance-Related Disorders; Narration; Harm Reduction; Drug Overdose; Smoking; Substance Abuse, Intravenous
PubMed: 37891658
DOI: 10.1186/s12954-023-00875-x -
The Journal of Dermatological Treatment Dec 2024Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing... (Review)
Review
Methotrexate is an off-label therapy for atopic dermatitis. A lack of consensus on dosing regimens poses a risk of underdosing and ineffective treatment or overdosing and increased risk of side effects. This systematic review summarizes the available evidence on dosing regimens.A literature search was conducted, screening all randomized controlled trials (RCTs) and guidelines published up to 6 July 2023, in the MEDLINE, Embase, and Cochrane Library databases.Five RCTs and 21 guidelines were included. RCTs compared methotrexate with other treatments rather than different methotrexate dosing regimens. The start and maintenance doses in RCTs varied between 7.5-15 mg/week and 14.5-25 mg/week, respectively. Despite varied dosing, all RCTs demonstrated efficacy in improving atopic dermatitis signs and symptoms. Guidelines exhibited substantial heterogeneity but predominantly proposed starting doses of 5-15 mg/week for adults and 10-15 mg/m/week for children. Maintenance doses suggested were 7.5-25 mg/week for adults and 0.2-0.7 mg/kg/week for children. One guideline suggested a test dose and nearly half advised folic acid supplementation.This systematic review highlights the lack of methotrexate dosing guidelines for atopic dermatitis. It identifies commonly recommended and utilized dosing regimens, serving as a valuable resource for clinicians prescribing methotrexate off-label and providing input for an upcoming consensus study.
Topics: Adult; Child; Humans; Methotrexate; Dermatitis, Atopic
PubMed: 38124505
DOI: 10.1080/09546634.2023.2292962 -
Europace : European Pacing,... Oct 2023Limited real-world data show that rivaroxaban following dosage criteria from either ROCKET AF [20 mg/day or 15 mg/day if creatinine clearance (CrCl) < 50 mL/min]... (Meta-Analysis)
Meta-Analysis
Comparisons of effectiveness and safety between on-label dosing, off-label underdosing, and off-label overdosing in Asian and non-Asian atrial fibrillation patients treated with rivaroxaban: a systematic review and meta-analysis of observational studies.
AIMS
Limited real-world data show that rivaroxaban following dosage criteria from either ROCKET AF [20 mg/day or 15 mg/day if creatinine clearance (CrCl) < 50 mL/min] or J-ROCKET AF (15 mg/day or 10 mg/day if CrCl < 50 mL/min) is associated with comparable risks of thromboembolism and bleeding with each other in patients with non-valvular atrial fibrillation (NVAF). We are aimed to study whether these observations differ between Asian and non-Asian subjects.
METHODS AND RESULTS
A systematic review and meta-analysis with random effects was conducted to estimate the aggregate hazard ratio (HR) and 95% confidence interval (CI) using PubMed and MEDLINE databases from 8 September 2011 to 31 December 2022 searched for adjusted observational studies that reported relevant clinical outcomes of NVAF patients receiving rivaroxaban 10 mg/day if CrCl > 50 mL/min, on-label dose rivaroxaban eligible for ROCKET AF or J-ROCKET AF, and rivaroxaban 20 mg/day if CrCl < 50 mL/min. Effectiveness and safety endpoints were compared between ROCKET AF and J-ROCKET AF dosing regimen in Asian and non-Asian subjects, separately. Also, risks of events of rivaroxaban 10 mg/day despite of CrCl > 50 mL/min and rivaroxaban 20 mg/day despite of CrCl < 50 mL/min were compared to that of 'ROCKET AF/J-ROCKET AF dosing'. Sensitivity analyses were performed by sequential elimination of each study from the pool. The meta-regression analysis was performed to explore the influence of potential factors on the effectiveness and safety outcomes. Eighteen studies involving 67 571 Asian and 54 882 non-Asian patients were included. Rivaroxaban following J-ROCKET AF criteria was associated with comparable risks of thromboembolism in the Asian subgroup, whereas rivaroxaban following J-ROCKET AF criteria was associated with higher risks of all-cause mortality (HR:1.30; 95% CI:1.05-1.60) compared with that of ROCKET AF criteria in the non-Asian population. There were no differences in risks of major bleeding between rivaroxaban following J-ROCKET AF vs. ROCKET AF criteria either in the Asian or non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism (HR:1.64; 95% CI:1.28-2.11) but lower risk of major bleeding (HR:0.72; 95% CI:0.57-0.90) compared with eligible dosage criteria. The use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse clinical outcomes in the risks of thromboembolism (HR:1.32; 95% CI:1.09-1.59), mortality (HR:1.33; 95% CI:1.10-1.59), and major bleeding (HR:1.26; 95% CI:1.03-1.53) compared with eligible dosage criteria. The pooled results were generally in line with the primary effectiveness and safety outcomes by removing a single study at one time. Meta-regression analyses failed to detect the bias in most potential patient characteristics associated with the clinical outcomes.
CONCLUSION
Rivaroxaban dosing regimen following J-ROCKET criteria may serve as an alternative to ROCKET AF criteria for the Asian population with NVAF, whereas the dosing regimen following ROCKET AF criteria was more favourable for the non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism but a lower risk of major bleeding, while use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse outcome in most clinical events.
Topics: Humans; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Off-Label Use; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome; Warfarin; Observational Studies as Topic
PubMed: 37738425
DOI: 10.1093/europace/euad288