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Exploratory Research in Clinical and... Jun 2024High-alert medication (HAM) is more predictable to cause significant harm to the patient, even when used as intended. The damage related to the HAM lead not only... (Review)
Review
BACKGROUND
High-alert medication (HAM) is more predictable to cause significant harm to the patient, even when used as intended. The damage related to the HAM lead not only suffering to the patient, but also raise the additional costs associated with care.
OBJECTIVE
Evaluate the incidence of drug-related adverse events related to the use of high-alert medications.
METHODS
It was conducted an active search for information through COCHRANE databases, LILACS, SciELO, SCOPUS, PubMed/MEDLINE and WEB OF SCIENCE. The search strategy included the following terms: "Patient safety", "Medication errors" and "Hospital" and "High Alert Medications" or "Dangerous Drugs" in different combinations. Then two reviewers independently conducted a preliminary evaluation of relevant titles, abstracts and finally full-text. Studies quality was evaluated according to PRISMA declaration.
RESULTS
The systematic review evaluated seven articles, which showed that only 11 HAM identified in the literature could have serious events. The most frequently cited were warfarin (22.2%) which progressed from deep vein thrombosis to gangrene, suggesting lower initial doses, followed by cyclophosphamide (22.2%) and cyclosporine (22.2%) which presented invasive fungal infection and death. In addition to these, morphine was compared with its active metabolite (M6G), with M6G causing fewer serious clinical events related to nausea and vomiting, reducing the need for concomitant use of antiemetics.
CONCLUSIONS
The most reported drug classes in the articles included that were related to incidence of drug-related adverse events in use of high-alert medications: morphine, M6G-glucuronide, haloperidol, promethazine, ivabradine, digoxin, warfarin, ximelagatran, cyclophosphamide, cyclosporine, and ATG. The formulate protocols for the use of these medications, with importance placed on evaluating, among the classes, the medication that causes the least harm.
PubMed: 38646469
DOI: 10.1016/j.rcsop.2024.100435 -
Drug Safety May 2024Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug...
BACKGROUND
Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index.
PURPOSE
The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs.
DATA SOURCES
The PubMed and EMBASE databases were searched up to November, 1st 2023.
STUDY SELECTION
We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study.
DATA EXTRACTION
Two authors independently extracted the data.
DATA SYNTHESIS
Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced C and delayed t of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints.
LIMITATIONS
The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction).
CONCLUSIONS
To conclude, reduced C and delayed t of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339 .
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Digoxin; Drug Interactions; Glucagon-Like Peptide 1; Warfarin
PubMed: 38273155
DOI: 10.1007/s40264-023-01392-3 -
Clinical Research in Cardiology :... Jun 2024Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of intravenous beta-blockers in acute atrial fibrillation and flutter is dependent on beta-1 selectivity: a systematic review and meta-analysis of randomised trials.
BACKGROUND
Intravenous beta-blockers are commonly used to manage patients with acute atrial fibrillation (AF) and atrial flutter (AFl), but the choice of specific agent is often not evidence-based.
METHODS
A prospectively-registered systematic review and meta-analysis of randomised trials (PROSPERO: CRD42020204772) to compare the safety and efficacy of intravenous beta-blockers against alternative pharmacological agents.
RESULTS
Twelve trials comparing beta-blockers with diltiazem, digoxin, verapamil, anti-arrhythmic drugs and placebo were included, with variable risk of bias and 1152 participants. With high heterogeneity (I = 87%; p < 0.001), there was no difference in the primary outcomes of heart rate reduction (standardised mean difference - 0.65 beats/minute compared to control, 95% CI - 1.63 to 0.32; p = 0.19) or the proportion that achieved target heart rate (risk ratio [RR] 0.85, 95% CI 0.36-1.97; p = 0.70). Conventional selective beta-1 blockers were inferior for target heart rate reduction versus control (RR 0.33, 0.17-0.64; p < 0.001), whereas super-selective beta-1 blockers were superior (RR 1.98, 1.54-2.54; p < 0.001). There was no significant difference between beta-blockers and comparators for secondary outcomes of conversion to sinus rhythm (RR 1.15, 0.90-1.46; p = 0.28), hypotension (RR 1.85, 0.87-3.93; p = 0.11), bradycardia (RR 1.29, 0.25-6.82; p = 0.76) or adverse events leading to drug discontinuation (RR 1.03, 0.49-2.17; p = 0.93). The incidence of hypotension and bradycardia were greater with non-selective beta-blockers (p = 0.031 and p < 0.001).
CONCLUSIONS
Across all intravenous beta-blockers, there was no difference with other medications for acute heart rate control in atrial fibrillation and flutter. Efficacy and safety may be improved by choosing beta-blockers with higher beta-1 selectivity.
Topics: Humans; Atrial Fibrillation; Atrial Flutter; Randomized Controlled Trials as Topic; Heart Rate; Treatment Outcome; Acute Disease; Adrenergic beta-Antagonists; Adrenergic beta-1 Receptor Antagonists; Administration, Intravenous; Anti-Arrhythmia Agents
PubMed: 37658166
DOI: 10.1007/s00392-023-02295-0 -
Journal of Medicine and Life Apr 2023Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity... (Review)
Review
Cancer is a major public health problem, and chemotherapy plays a significant role in the management of neoplastic diseases. However, chemotherapy-induced cardiotoxicity is a serious side effect secondary to cardiac damage caused by antineoplastic's direct and indirect toxicity. Currently, there are no reliable and approved methods for preventing or treating chemotherapy-induced cardiotoxicity. Understanding the mechanisms of chemotherapy-induced cardiotoxicity may be vital to improving survival. The independent risk factors for developing cardiotoxicity must be considered to prevent myocardial damage without decreasing the therapeutic efficacy of cancer treatment. This systematic review aimed to identify and analyze the evidence on chemotherapy-induced cardiotoxicity, associated risk factors, and methods to decrease or prevent it. We conducted a comprehensive search on PubMed, Google Scholar, and Directory of Open Access Journals (DOAJ) using the following keywords: "doxorubicin cardiotoxicity", "anthracycline cardiotoxicity", "chemotherapy", "digoxin decrease cardiotoxicity", "ATG7 activators", retrieving 59 articles fulfilling the inclusion criteria. Therapeutic schemes can be changed by choosing prolonged infusion application over boluses. In addition, some agents like Dexrazoxane can reduce chemotherapy-induced cardiotoxicity in high-risk groups. Recent research found that Digoxin, ATG7 activators, Resveratrol, and other medical substances or herbal compounds have a comparable effect on Dexrazoxane in anthracycline-induced cardiotoxicity.
Topics: Humans; Resveratrol; Cardiotoxicity; Dexrazoxane; Anthracyclines; Digoxin; Polyketides; Antineoplastic Agents
PubMed: 37305823
DOI: 10.25122/jml-2022-0322 -
BMC Medical Research Methodology Apr 2023Joint modelling combines two or more statistical models to reduce bias and increase efficiency. As the use of joint modelling increases it is important to understand how...
Joint modelling of longitudinal processes and time-to-event outcomes in heart failure: systematic review and exemplar examining the relationship between serum digoxin levels and mortality.
BACKGROUND
Joint modelling combines two or more statistical models to reduce bias and increase efficiency. As the use of joint modelling increases it is important to understand how and why it is being applied to heart failure research.
METHODS
A systematic review of major medical databases of studies which used joint modelling within heart failure alongside an exemplar; joint modelling repeat measurements of serum digoxin with all-cause mortality using data from the Effect of Digoxin on Mortality and Morbidity in Patients with Heart Failure (DIG) trial.
RESULTS
Overall, 28 studies were included that used joint models, 25 (89%) used data from cohort studies, the remaining 3 (11%) using data from clinical trials. 21 (75%) of the studies used biomarkers and the remaining studies used imaging parameters and functional parameters. The exemplar findings show that a per unit increase of square root serum digoxin is associated with the hazard of all-cause mortality increasing by 1.77 (1.34-2.33) times when adjusting for clinically relevant covariates.
CONCLUSION
Recently, there has been a rise in publications of joint modelling being applied to heart failure. Where appropriate, joint models should be preferred over traditional models allowing for the inclusion of repeated measures while accounting for the biological nature of biomarkers and measurement error.
Topics: Humans; Heart Failure; Digoxin; Cohort Studies; Models, Statistical; Research Design; Cardiotonic Agents
PubMed: 37076796
DOI: 10.1186/s12874-023-01918-4 -
PLoS Neglected Tropical Diseases Apr 2023Scorpion envenomation is associated with several complications. One of the most serious complications is the cardiac involvement in the form of myocarditis that remains...
BACKGROUND
Scorpion envenomation is associated with several complications. One of the most serious complications is the cardiac involvement in the form of myocarditis that remains the main reason for mortalities associated with scorpion envenomation. The present review aims to elucidate clinical and paraclinical findings associated with scorpion-related myocarditis, and to explore different management strategies and subsequent outcomes.
METHODS
We searched PubMed, Web of Science, Scopus, and Google Scholar for articles related to keywords of myocarditis associated with scorpion envenomation up to May 1, 2022. Each article was carefully reviewed by two independent researchers. In case of disagreement for inclusion, we sought a third researcher opinion.
RESULTS
A total of 703 cases from 30 case reports and 34 case series were included in our review. Myocarditis associated with scorpion envenomation was usually reported in children presenting with cardiopulmonary symptoms including pulmonary edema (60.7%) and shock or hypotension (45.8%). The most common ECG findings are sinus tachycardia (82%) followed by ST-T changes (64.6%). The management typically included inotropes (especially dobutamine), prazosin, diuretics, nitroglycerine and digoxin, when indicated. Mechanical ventilation was required in 36.7% of the patients. Mortality in confirmed scorpion-related myocarditis cases is estimated at 7.3%. Almost all survived cases showed rapid recovery and improvement in the left ventricular function.
CONCLUSION
Even though myocarditis associated with scorpion envenomation is rare, it remains a serious and in some of cases a fatal consequence of scorpion sting. In case of relative presentations, particularly in envenomed children, diagnosis of myocarditis should be considered. Early screening using serial cardiac markers and echocardiography can guide the treatment. Prompt treatment that focuses on cardiogenic shock and pulmonary edema usually results in a favorable outcome.
Topics: Child; Humans; Animals; Scorpion Stings; Myocarditis; Pulmonary Edema; Dobutamine; Respiration, Artificial; Scorpions
PubMed: 37018229
DOI: 10.1371/journal.pntd.0011219 -
Drugs & Aging Feb 2023Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Drug-drug interactions (DDIs) can lead to medication-related harm, and the older population is at greatest risk. We conducted a systematic review and meta-analysis to estimate DDI prevalence and identify common DDIs in older community-dwelling adults.
METHODS
PubMed and EMBASE were searched for observational studies published between 01/01/2010 and 10/05/2021 reporting DDI prevalence in community-dwelling individuals aged ≥ 65 years. Nursing home and inpatient hospital studies were excluded. Study quality was assessed using the Joanna Briggs Institute critical appraisal tool. Meta-analysis was performed using a random-effects model with logit transformation. Heterogeneity was evaluated using Cochran's Q and I. DDI prevalence and 95% confidence intervals (CIs) are presented. All analyses were performed in R (version 4.1.2).
RESULTS
There were 5144 unique articles identified. Thirty-three studies involving 17,011,291 community-dwelling individuals aged ≥ 65 years met inclusion criteria. Thirty-one studies reported DDI prevalence at the study-participant level, estimates ranged from 0.8% to 90.6%. The pooled DDI prevalence was 28.8% (95% CI 19.3-40.7), with significant heterogeneity (p < 0.10; I = 100%; tau = 2.13) largely explained by the different DDI identification methods. Therefore, 26 studies were qualitatively synthesised and seven studies were eligible for separate meta-analyses. In a meta-analysis of three studies (N = 1122) using Micromedex, pooled DDI prevalence was 57.8% (95% CI 52.2-63.2; I = 69.6%, p < 0.01). In a meta-analysis of two studies (N = 809,113) using Lexi-Interact, pooled DDI prevalence was 30.3% (95% CI 30.2-30.4; I = 6.8%). In a meta-analysis of two studies (N = 947) using the 2015 American Geriatrics Society Beers criteria, pooled DDI prevalence was 16.6% (95% CI 5.6-40.2; I = 97.5%, p < 0.01). Common DDIs frequently involved cardiovascular drugs, including ACE inhibitor-potassium-sparing diuretic; amiodarone-digoxin; and amiodarone-warfarin.
CONCLUSIONS
DDIs are prevalent among older community-dwelling individuals; however, the methodology used to estimate these events varies considerably. A standardised methodology is needed to allow meaningful measurement and comparison of DDI prevalence.
Topics: Humans; Aged; Independent Living; Prevalence; Drug Interactions; Nursing Homes; Skilled Nursing Facilities
PubMed: 36692678
DOI: 10.1007/s40266-022-01001-5 -
Cureus Jul 2022The emergency treatment of atrial fibrillation (AF) involves utilizing two strategies. The first strategy normally involves permitting the atrial fibrillation to... (Review)
Review
An Integrative Comparative Study Between Digoxin and Amiodarone as an Emergency Treatment for Patients With Atrial Fibrillation With Evidence of Heart Failure: A Systematic Review and Meta-Analysis.
The emergency treatment of atrial fibrillation (AF) involves utilizing two strategies. The first strategy normally involves permitting the atrial fibrillation to persevere as the ventricular rate is controlled. The other method involves utilizing anti-arrhythmic drugs in cardioversion and attempting to maintain sinus rhythm. Different pharmacological treatments, including digoxin and amiodarone, have been used to manage AF. A literature review on amiodarone and digoxin in the treatment of AF among patients with heart failure (HF) has shown that both drugs have potential risks. Therefore, we are conducting this systematic review and meta-analysis to compare the effectiveness of amiodarone and digoxin in the treatment of AF among patients with evidence of HF. A literature search of relevant articles was conducted on six electronic databases (PubMed, Web of Science, Medline, ScienceDirect, Cochrane Library, and Google Scholar) from 2000 to 2022. The search yielded seven studies that had met the inclusion criteria. Our meta-analysis of four studies showed that there was no significant difference in the reduction of heart rate after treatment with either amiodarone or digoxin (mean difference (MD): -5.44; 95% confidence interval (CI): -9.53 to -1.34; I = 25%; p = 0.26). On the other hand, the statistical analysis showed that amiodarone had a better effect on the conversion to sinus rhythm than digoxin (63% versus 35%, respectively). Based on evidence from our meta-analysis, the clinical effect of amiodarone and digoxin in the emergency treatment of AF on heart rate control was unclear. However, amiodarone has a significant impact on the restoration of sinus rhythm compared with digoxin and can be considered the first-line drug regimen in conversion to sinus rhythm for AF patients with evidence of heart failure. However, the use of amiodarone and digoxin is complicated by adverse events and all-cause mortality.
PubMed: 35971374
DOI: 10.7759/cureus.26800 -
Frontiers in Pharmacology 2022Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by...
Fetal arrhythmias are common cardiac abnormalities associated with high mortality due to ventricular dysfunction and heart failure, particularly when accompanied by hydrops. Although several types of common fetal tachycardias have been relatively identified medications, such as digoxin, flecainide, and sotalol, there is no first-line drug treatment protocol established for the treatment of various types of fetal tachycardias. We conducted a network meta-analysis using a Bayesian hierarchical framework to obtain a model for integrating both direct and indirect evidence. All tachycardia types (Total group), supraventricular tachycardia (SVT subgroup), atrial flutter (AF subgroup), hydrops subgroup, and non-hydrops subgroup fetuses were analyzed, and five first-line regimens were ranked according to treatment outcomes: digoxin monotherapy (D), flecainide monotherapy (F), sotalol monotherapy (S), digoxin plus flecainide combination therapy (DF), and digoxin plus sotalol combination therapy (DS). Effectiveness and safety were determined according to the cardioversion rate and intrauterine death rate. The pooled data indicated that DF combination therapy was always superior to D monotherapy, regardless of the tachycardia type or the presence of hydrops: Total, 2.44 (95% CrI: 1.59, 3.52); SVT, 2.77 (95% CrI: 1.59, 4.07); AF, 67.85 (95% CrI: 14.25, 168.68); hydrops, 6.03 (95% CrI: 2.54, 10.68); and non-hydrops, 5.06 (95% CrI: 1.87, 9.88). DF and F had a similar effect on control of fetal tachycardias. No significant differences were observed when comparing S, DS with D therapies across the subgroup analyses for the SVT, hydrops, and non-hydrops groups. No significant differences in mortality risks were among the various treatment regimens for the total group. And no significant differences were found in rates of intrauterine death rates at the same cardioversion amount. The flecainide monotherapy and combination of digoxin and flecainide should be considered the most superior therapeutic strategies for fetal tachycardia. (https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=288997), identifier (288997).
PubMed: 35770083
DOI: 10.3389/fphar.2022.935455 -
Drugs & Aging Aug 2022Frailty is highly prevalent in heart failure populations and a major risk factor for adverse drug reactions (ADRs) and adverse drug events (ADEs). This review aimed to...
INTRODUCTION
Frailty is highly prevalent in heart failure populations and a major risk factor for adverse drug reactions (ADRs) and adverse drug events (ADEs). This review aimed to describe the prevalence, causality and severity of ADRs or ADEs from heart failure medications among frail compared with non-frail older adults.
METHODS
A systematic search of CENTRAL, MEDLINE, Embase, Ageline, CINAHL, International Pharmaceutical Abstracts, PsychInfo, Scopus, registries and citations prior to 18 May 2021 was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist. Risk of bias and quality of evidence were assessed. Eligible studies included randomised controlled trials (RCTs) and observational studies of people diagnosed with heart failure, aged ≥ 65 years, with frailty defined by an objective measurement, and reported ADRs/ADEs from/with heart failure medications.
RESULTS
Two reviewers screened 2419 articles; interrater reliability kappa = 0.88. Three observational studies (n = 2596), a secondary analysis of two RCTs (n = 2098) and two cohort studies (n = 498) were included in a narrative synthesis. Frail patients in randomised trials of sacubitril/valsartan, aliskiren, or enalapril had twice the risk of mortality (hazard ratio [HR] 2.09, 1.62-2.71) and hospitalisations (HR 1.82, 1.37-2.41) compared with robust patients, which may reflect responsiveness to medications and/or factors unrelated to medication use. Hospitalisations from falls, tiredness and nausea were probably attributable to digoxin and possibly preventable according to the Naranjo and Hallas scales, respectively.
CONCLUSION
The potential harms from heart failure medications in frail older people are poorly studied and understood. Clinical trials and pharmacovigilance studies should include frailty as a covariate to inform medication optimisation for this vulnerable and growing population.
REGISTRATION
Prospero registration number: CRD 42021253762.
Topics: Aged; Aminobutyrates; Biphenyl Compounds; Drug-Related Side Effects and Adverse Reactions; Frailty; Heart Failure; Humans; Pharmaceutical Preparations; Prevalence
PubMed: 35761118
DOI: 10.1007/s40266-022-00957-8