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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 -
Research in Social & Administrative... Jul 2024To identify trigger tools applied to detect adverse drug events (ADEs) in older people and describe their utility and performance. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To identify trigger tools applied to detect adverse drug events (ADEs) in older people and describe their utility and performance.
METHODS
A systematic review was conducted in the PubMed, Lilacs, and Scopus databases (January 2024). Studies that developed, applied, or validated trigger tools and evaluated their utility and/or performance for detecting ADEs in older people were considered. Direct proportion meta-analyses using the inverse-variance method were performed for prevalence of ADEs and positive predictive value (PPV).
RESULTS
Twenty-four studies (25 publications) were included. Twelve trigger tools were identified, of which six were developed for detecting ADEs in older population, four developed for general population and modified for older people, and two developed for general population. No tools for detecting ADEs in older people receiving palliative care or hospitalized in intensive or surgical care units were found. The performance of triggers was presented through PPV (11.5-71%), negative predictive values (83.3%), and sensitivity (30-94.8%). The overall PPV was 33.3% (95%CI: 32.5-34.2%). Triggers with good performance were changes in plasma levels of digoxin, glucose, and potassium; changes in international normalized ratio; abrupt medication stop; hypotension; and constipation. The prevalence of ADEs ranged from 2.8 to 66%, with overall prevalence of ADEs of 20% (95%CI: 19.3-20.8%). Preventability ranged from 8.4 to 94.4%. Metabolic or electrolyte disturbances induced by diuretics, constipation induced by opioids, and falls and delirium induced by benzodiazepines were the most prevalent ADEs.
CONCLUSION
The trigger tools are flexible and easy to apply, and they can contribute to the detection of ADEs, their associated risk factors, the level of harm, and preventability in different health settings. However, there is no consensus on good or poor values of PPV, which indicate the performance of triggers. Furthermore, there is limited evidence regarding the evaluation of performance through negative predictive value, sensitivity, and specificity.
PROSPERO
CRD42022379893.
Topics: Aged; Humans; Drug-Related Side Effects and Adverse Reactions
PubMed: 38538516
DOI: 10.1016/j.sapharm.2024.03.008 -
European Journal of Clinical... Jun 2024Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of... (Review)
Review
OBJECTIVES
Linezolid is a commonly used antibiotic in the clinical treatment of gram-positive bacterial infections. The impacts of drug interactions on the pharmacokinetics of linezolid are often overlooked. This manuscript aims to review the medications that affect the pharmacokinetics of linezolid.
METHODS
In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we queried the PubMed, Embase, and Cochrane Library for publications from database establishment to November 3, 2023, using the search terms: "Linezolid" and "interaction," or "interact," or "drug-drug interaction," or "co-treatment," or "cotreatment," or "combined," or "combination."
RESULTS
A total of 24 articles were included. Among the reported medication interactions, rifampicin, levothyroxine, venlafaxine, and phenobarbital could reduce the concentration of linezolid; clarithromycin, digoxin, cyclosporine, proton pump inhibitors, and amiodarone could increase the concentration of linezolid, while aztreonam, phenylpropanolamine, dextromethorphan, antioxidant vitamins, and magnesium-containing antacids had no significant effects on linezolid pharmacokinetics. The ratio of mean (ROM) of linezolid AUC in co-treatment with rifampicin to monotherapy was 0.67 (95%CI 0.58-0.77) and 0.63 (95%CI 0.43-0.91), respectively, in 2 studies, and co-treatment with 500 mg clarithromycin to monotherapy was 1.81 (95%CI 1.49-2.13).
CONCLUSIONS
This systematic review found that numerous drugs have an impact on the pharmacokinetics of linezolid, and the purported main mechanism may be that linezolid is the substrate of P-glycoprotein. In clinical practice, it is prudent to pay attention to the changes in linezolid pharmacokinetics caused by interactions. Conducting therapeutic drug monitoring (TDM) is beneficial to improve efficacy and reduce adverse reactions of linezolid.
Topics: Drug Interactions; Linezolid; Humans; Anti-Bacterial Agents
PubMed: 38421436
DOI: 10.1007/s00228-024-03652-2 -
Cardiovascular Drugs and Therapy Feb 2024The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48 h) atrial fibrillation (AF)... (Review)
Review
Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysis.
PURPOSE
The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48 h) atrial fibrillation (AF) is uncertain. We aimed to identify the safest and most effective agent for pharmacologic cardioversion of recent-onset AF in the emergency department.
METHODS
We searched MEDLINE, Embase, and Web of Science from inception to February 21, 2023 (PROSPERO: CRD42018083781). Eligible studies were randomized controlled trials that enrolled adult participants with AF ≤ 48 h, compared a guideline-recommended antidysrhythmic drug with another antidysrhythmic drug or a different formulation of the same drug or placebo and reported specific adverse events. The primary outcome was immediate, serious adverse event - cardiac arrest, sustained ventricular tachydysrhythmia, atrial flutter 1:1 atrioventricular conduction, hypotension, and bradycardia. Additional analyses included the outcomes of conversion to sinus rhythm within 4 h and 24 h. We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effect model and vague prior distribution to calculate odds ratios with 95% credible intervals. We assessed confidence using CINeMA. We used surface under the cumulative ranking curve (SUCRA) to rank agent(s).
RESULTS
The systematic review initially identified 5545 studies. Twenty-five studies met eligibility criteria, and 22 studies (n = 3082) provided data for NMA, which demonstrated that vernakalant (SUCRA = 70.9%) is most likely to be safest. Additional effectiveness NMA demonstrated that flecainide (SUCRA = 89.0%) is most likely to be superior for conversion within 4 h (27 studies; n = 2681), and ranolazine-amiodarone IV (SUCRA 93.7%) is most likely to be superior for conversion within 24 h (24 studies; n = 3213). Confidence in the NMA estimates is variable and limited mostly by within-study bias and imprecision.
CONCLUSIONS
Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4 h; flecainide is definitely among the most effective for cardioversion within 24 h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended.
PubMed: 38324103
DOI: 10.1007/s10557-024-07552-6 -
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 -
Current Problems in Cardiology Feb 2024Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review... (Review)
Review
Association of serum digoxin concentration with morbidity and mortality in patients with atrial fibrillation, heart failure and reduced ejection fraction of 45 % or below.
BACKGROUND
Atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF) are common cardiovascular conditions linked to significant health burdens. This review aims to study the relationship of serum digoxin concentration and mortality and morbidity outcomes in defined population.
METHODS
We conducted a thorough search of databases such as PubMed, Google Scholar, and Cochrane Library, from inception until 20th Aug 2023. Studies that explored the relationship between serum digoxin concentration and mortality, morbidity, or other clinical endpoints in AF and HFrEF patients (ejection fraction ≤45 %) were eligible for inclusion.
RESULTS
The selected studies exhibited a wide range of designs, patient cohorts, and measured outcomes. The association between serum digoxin concentration, mortality and morbidity endpoints like hospitalization rates and cardiovascular events were assessed in these studies. Despite the methodological diversity, our systematic review uncovered consistent trends across the studies, suggesting that elevated serum digoxin concentrations may correlate with higher mortality and morbidity in AF and HFrEF patients.
CONCLUSION
This systematic review emphasizes the need for cautious management of serum digoxin levels in patients with concurrent AF and HFrEF. While digoxin remains a valuable treatment for heart failure, its potential adverse effects on outcomes in this specific patient subgroup call for vigilant monitoring and individualized treatment approaches. Further research is required to elucidate the dose-response relationship and potential confounding factors influencing outcomes associated with serum digoxin concentration in AF and HFrEF patients. Clinicians should consider these findings when making therapeutic decisions to enhance patient care and outcomes.
Topics: Humans; Digoxin; Atrial Fibrillation; Heart Failure; Stroke Volume; Morbidity
PubMed: 38000566
DOI: 10.1016/j.cpcardiol.2023.102218 -
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 -
JACC. Heart Failure Apr 2024Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is).
OBJECTIVES
The authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF.
METHODS
The authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality.
RESULTS
The authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%.
CONCLUSIONS
In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.
Topics: Humans; Angiotensin Receptor Antagonists; Digoxin; Heart Failure; Network Meta-Analysis; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 37656079
DOI: 10.1016/j.jchf.2023.07.014 -
The Annals of Pharmacotherapy Mar 2024To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment. (Review)
Review
OBJECTIVE
To conduct a review of studies evaluating the influence of body size and weight (WT) on the pharmacokinetics (PK) of drugs recommended for heart failure (HF) treatment.
DATA SOURCES
A systematic search of the MEDLINE (1946 to April 2023) and EMBASE (1974 to April 2023) databases was conducted for articles that focused on the impact of WT or body size on the PK of drugs of interest used in HF patients.
STUDY SELECTION AND DATA EXTRACTION
Articles written in English or French related to the aim of our study were retained for analysis.
DATA SYNTHESIS
Of 6493 articles, 20 were retained for analysis. Weight was associated with the clearance of digoxin, carvedilol, enalapril, and candesartan as well as the volume of distribution of eplerenone and bisoprolol. There was no documented direct impact of WT on the PK of furosemide, valsartan, and metoprolol, although these studies were limited or confounded by the small sample size, adjustment of PK factors by WT, or the use of the Cockroff-Gault equation for the evaluation of creatinine clearance, which includes WT.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
This review highlights and summarizes the available data on the importance of WT on the PK of HF treatment.
CONCLUSION
Considering the significant impact of WT on most HF drugs in this review, it may be important to further investigate it in the context of personalized therapy, particularly in patients presenting extreme WTs.
Topics: Humans; Heart Failure; Valsartan; Metoprolol; Carvedilol; Body Size; Adrenergic beta-Antagonists
PubMed: 37338205
DOI: 10.1177/10600280231179484