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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 -
Farmacia Hospitalaria : Organo Oficial... Nov 2022To resume the available literature about digoxin population pharmacokinetic studies in elderly patients. To identify the pathophysiological changes in this...
OBJECTIVE
To resume the available literature about digoxin population pharmacokinetic studies in elderly patients. To identify the pathophysiological changes in this subpopulation with clinical implications on digoxin pharmacokinetics.
METHOD
A systematic review was performed regarding the population pharmacokinetic studies in elderly patients receiving digoxin. Pub-Med, ISI Web of Science, SCOPUS and Science Direct were used to identify the articles with the descriptors ("Digoxin"[Mesh]) AND ("Pharmacokinetics"[Mesh]) AND ("Aged"[Mesh] OR "Elderly"[Mesh]), followed by a manual search.
RESULTS
Nine studies were found and reviewed, five of them carried out in Asian patients. NONMEM was used for pharmacokinetic analysis of digoxin blood levels, being mostly described by a one-compartment model. Serum creatinine, body weight and concomitant administration of calcium channel blockers are the covariates that most frequently influence digoxin pharmacokinetics in elderly patients.
CONCLUSIONS
Elderly people present pathophysiological changes with influence on the pharmacokinetics of many drugs. The covariates with most influence on digoxin pharmacokinetics should be considered when adjusting this drug dosage in elder patients to achieve optimum health benefits and prevent possible side effects.
Topics: Humans; Aged; Digoxin; Creatinine; Patients
PubMed: 36520576
DOI: No ID Found -
Current Drug Targets 2023One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
One of the major indications for digoxin use is the treatment of heart failure (HF). Although the clinical application of digoxin in long-term outcomes in patients with HF and reduced ejection fraction (HFrEF) patients is well explained, the association between digoxin therapy and outcomes in patients with HF and preserved ejection fraction (HFpEF) is not very clear.
OBJECTIVES
The aim of this study was to show the clinical efficacy of digoxin on long-term outcomes in subjects with HFpEF.
METHODS
PubMed, Embase, Scopus and Web of Science (ISI) electronic databases were searched until May 2021 to obtain relevant studies. The primary outcome was all-cause mortality attributed to treatment with digoxin. The secondary outcomes were "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".
RESULTS
Seven studies with more than 23000 patients with HFpEF, of which more than 4900 were treated with digoxin, fulfilled the eligibility criteria and were included in this meta-analysis. Treatment with digoxin was associated with a neutral effect on all-cause mortality (HR 1.04, 95 % CI 0.91-1.20, I2 = 57.9 %), all-cause hospitalization (HR 0.97, 95 % CI 0.88-1.07, I2 = 0.0 %), HFhospitalization (HR 0.96, 95 % CI 0.90-1.02, I2 = 41.4 %), and all-cause mortality or HFhospitalization (HR 1.07, 95 % CI 0.91-1.26, I2 = 81.2 %). In subgroup meta-analyses based on ejection fraction (EF), treatment with digoxin did not significantly alter these outcomes in each subset of patients.
CONCLUSION
The results of this meta-analysis suggest that digoxin does not have any significant effect on long-term outcomes of HFpEF patients, including "all-cause mortality", "all-cause hospitalization", "hospitalization because of HF" and "all-cause mortality or hospitalization of HF".
Topics: Humans; Digoxin; Heart Failure; Hospitalization; Prognosis; Stroke Volume; Treatment Outcome; Cardiotonic Agents
PubMed: 36065922
DOI: 10.2174/1389450123666220906093058 -
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 -
British Journal of Anaesthesia May 2022New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart... (Review)
Review
BACKGROUND
New onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically unwell patients. NOAF can lead to worsening haemodynamic compromise, heart failure, thromboembolic events, and increased mortality. The aim of this systematic review and narrative synthesis is to evaluate the non-pharmacological and pharmacological management strategies for NOAF in critically unwell patients.
METHODS
Of 1782 studies, 30 were eligible for inclusion, including 4 RCTs and 26 observational studies. Efficacy of direct current cardioversion, amiodarone, β-adrenergic receptor antagonists, calcium channel blockers, digoxin, magnesium, and less commonly used agents such as ibutilide are reported.
RESULTS
Cardioversion rates of 48% were reported for direct current cardioversion; however, re-initiation of NOAF was as high as 23.4%. Amiodarone was the most commonly reported intervention with cardioversion rates ranging from 18% to 96% followed by β-antagonists with cardioversion rates from 40% to 92%. Amiodarone was more effective than diltiazem (odds ratio [OR]=1.91, P=0.32) at cardioversion. Short-acting β-antagonists esmolol and landiolol were more effective compared with diltiazem for cardioversion (OR=3.55, P=0.04) and HR control (OR=3.2, P<0.001).
CONCLUSION
There was significant variation between studies with regard to the definition of successful cardioversion and heart rate control, making comparisons between studies and interventions difficult. Future RCTs comparing individual anti-arrhythmic agents, in particular magnesium, amiodarone, and β-antagonists, and studying the role of anticoagulation in critically unwell patients are required. There is also an urgent need for a core outcome dataset for studies of new onset atrial fibrillation to allow comparisons between different anti-arrhythmic strategies.
CLINICAL TRIAL REGISTRATION
PROSPERO CRD42019121739.
Topics: Adult; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Diltiazem; Electric Countershock; Humans; Magnesium
PubMed: 34916053
DOI: 10.1016/j.bja.2021.11.016 -
JACC. Heart Failure Feb 2022This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study sought to estimate and compare the aggregate treatment benefit of pharmacological therapy for heart failure (HF) with reduced ejection fraction.
BACKGROUND
The estimated treatment effects of various combinations of contemporary HF medical therapies are not well characterized.
METHODS
We performed a systematic network meta-analysis, using MEDLINE/EMBASE and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between January 1987 and January 2020. We included angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers (BB), mineralocorticoid receptor antagonists (MRAs), digoxin, hydralazine-isosorbide dinitrate, ivabradine, angiotensin receptor-neprilysin inhibitors (ARNi), sodium glucose cotransporter-2 inhibitors (SGLT2i), vericiguat, and omecamtiv-mecarbil. The primary outcome was all-cause death. We estimated the life-years gained in 2 HF populations (BIOSTAT-CHF [BIOlogy Study to TAilored Treatment in Chronic Heart Failure] and ASIAN-HF [Asian Sudden Cardiac Death in Heart Failure Registry]).
RESULTS
We identified 75 relevant trials representing 95,444 participants. A combination of ARNi, BB, MRA, and SGLT2i was most effective in reducing all-cause death (HR: 0.39; 95% CI: 0.31-0.49); followed by ARNi, BB, MRA, and vericiguat (HR: 0.41; 95% CI: 0.32-0.53); and ARNi, BB, and MRA (HR: 0.44; 95% CI: 0.36-0.54). Results were similar for the composite outcome of cardiovascular death or first hospitalization for HF (HR: 0.36; 95% CI: 0.29-0.46 for ARNi, BB, MRA, and SGLT2i; HR: 0.44; 95% CI: 0.35-0.56 for ARNi, BB, MRA, and omecamtiv-mecarbil; and HR: 0.43; 95% CI: 0.34-0.55 for ARNi, BB, MRA, and vericiguat). The estimated additional number of life-years gained for a 70-year-old patient on ARNi, BB, MRA, and SGLT2i was 5.0 years (2.5-7.5 years) compared with no treatment in secondary analyses.
CONCLUSIONS
In patients with HF with reduced ejection fraction, the estimated aggregate benefit is greatest for a combination of ARNi, BB, MRA, and SGLT2i.
Topics: Aged; Angiotensin Receptor Antagonists; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Network Meta-Analysis; Stroke Volume
PubMed: 34895860
DOI: 10.1016/j.jchf.2021.09.004