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The American Journal of Emergency... Jul 2024Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status... (Observational Study)
Observational Study
BACKGROUND
Digoxin poisonings are relatively common and potentially fatal, requiring immediate therapeutic intervention, with special attention to the patient's hemodynamic status and the presence of electrocardiographic and electrolytic disturbances.
OBJECTIVE
To identify factors associated with seven-day and thirty-day mortality in digoxin poisoning.
DESIGN, SETTINGS AND PARTICIPANTS
A retrospective, observational, multicenter study was conducted across 15 Hospital Emergency Departments (HED) in Spain. All patients over 18 years of age who presented to participating HEDs from 2015 to 2021 were included. The inclusion criteria encompassed individuals meeting the criteria for digoxin poisoning, whether acute or chronic.
OUTCOMES MEASURE AND ANALYSIS
To identify independent factors associated with 7-day and 30-day mortality, a multivariate analysis was conducted. This analysis included variables of clinical significance, as well as those exhibiting a trend (p < 0.1) or significance in the bivariate analysis.
MAIN FINDINGS
A total of 658 cases of digoxin poisoning were identified. Mortality rates were 4.5% (30 patients) at seven days and 11.1% (73 patients) at thirty days. Regarding 7-day mortality, the mean age of deceased patients was comparable to survivors (84.7 (8.9) vs 83.9 (7.9) years; p = ns). The multivariate analysis revealed that factors independently associated with 7-day mortality encompassed the extent of dependence assessed by the Barthel Index (BI 60-89 OR 0.28; 95% CI 0.10-0.77; p = 0.014 and BI>90 OR 0.22; 95% CI 0.08-0.63; p = 0.005), the identification of ventricular arrhythmias (OR 1.34; 95% CI 1.34-25.21; p = 0.019), and the presence of circulatory (OR 2.84; 95% CI 1.19-6.27; p = 0.019) and neurological manifestations (OR 2.67; 95% CI 1.13-6.27; p = 0.025). Factors independently associated with 30-day mortality encompassed extent of dependence (BI 60-89 OR 0.37; 95% CI 0.20-0.71; p = 0.003 and BI>90 OR 0.18; 95% CI 0.09-0.39; p < 0.001) and the identification of circulatory (OR 2.13; 95% CI 1.10-4.15; p = 0.025) and neurological manifestations (OR 2.39; 95% CI 1.25-3.89; p = 0.006).
CONCLUSIONS
The study identifies the degree of dependency assessed by the Barthel Index and the presence of cardiovascular and neurological symptoms as independent predictors of both 7-day and 30-day mortality. Additionally, the detection of ventricular arrhythmia is also an independent factor for 7-day mortality.
Topics: Humans; Female; Digoxin; Male; Retrospective Studies; Aged; Aged, 80 and over; Spain; Emergency Service, Hospital; Risk Factors; Middle Aged
PubMed: 38713933
DOI: 10.1016/j.ajem.2024.04.048 -
The Journal of the Royal College of... Aug 1977All patients being prescribed digoxin in a general practice were examined and the serum urea, creatinine, electrolytes, and digoxin concentrations were...
All patients being prescribed digoxin in a general practice were examined and the serum urea, creatinine, electrolytes, and digoxin concentrations were determined.Sixty-six patients were identified (0.73 per cent of the practice population). After excluding six, whose tablet-taking was unreliable, it was found that two patients had serum digoxin levels above the usually accepted upper limit and a total of 23 patients (38 per cent of the digoxin takers) had some alteration made to their dose, including eight whose digoxin was stopped. We believe that serum digoxin estimations are useful in determining the optimum dose of digoxin in general practice.
Topics: Adult; Aged; Child; Digoxin; Drug Administration Schedule; Electrolytes; Female; Humans; Kidney Function Tests; Male; Medical Audit; Middle Aged
PubMed: 616833
DOI: No ID Found -
Tidsskrift For Den Norske Laegeforening... Nov 2016
Topics: Anti-Arrhythmia Agents; Digitoxin; Digoxin; Drug Substitution; Humans; Norway; Practice Guidelines as Topic
PubMed: 27830897
DOI: 10.4045/tidsskr.16.0810 -
European Review For Medical and... Aug 2023This study aimed to investigate the effect of digoxin on mortality and rehospitalization in heart failure with reduced ejection fraction (HFrEF) patients. Heart failure...
OBJECTIVE
This study aimed to investigate the effect of digoxin on mortality and rehospitalization in heart failure with reduced ejection fraction (HFrEF) patients. Heart failure is a clinical syndrome that requires frequent rehospitalization and has a high mortality. This study aimed to investigate the effect of digoxin on mortality and rehospitalization in patients with heart failure with reduced ejection fraction.
PATIENTS AND METHODS
The study included 326 patients with HFrEF that were hospitalized for decompensation between September 2014 and January 2016. The patients were divided into two groups: digoxin users and a control group. The study's endpoints were cardiovascular death and rehospitalization after 24-month long-term follow-ups.
RESULTS
Rehospitalization was lower in patients taking digoxin (25% vs. 47%, p = 0.001). The mean age of patients taking digoxin (n: 78) was 63.7 ± 12.4 years, among which 64% were males. The mean age of the control group was 65.4 ± 11.8 years, among which 74% were males. However, there was no difference in mortality between the two groups (34% vs. 45%, p = 0.10). While Kaplan-Meier curves revealed no significant differences between mortality rates in the groups (log-rank p = 0.508), a statistical difference was found between the groups in rehospitalization rates (log-rank p = 0.013). A multiple linear regression analysis revealed that smoking (HR: 1.97, CI: 1.24-3.11, p = 0.004), systolic blood pressure (HR: 0.983, CI: 0.974-0.992, p < 0.001), atrial fibrillation (HR: 2.09, CI: 1.17-3.72, p = 0.012), C-reactive protein (CRP) (HR: 1.009, CI: 1.003-1.015, p = 0.004), beta-blockers (HR: 0.891, CI: 0.799-0.972, p = 0.009), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (HR: 0.778, CI: 0.641-0.956, p < 0.001), mineralocorticoid receptor antagonists (HR: 0.41, CI:0.26-0.65, p < 0.001), and digoxin use (HR: 0.59, CI: 0.43-0.80, p = 0.001) are independent predictors of rehospitalization in patients with HFrEF.
CONCLUSIONS
Our results show that digoxin use does not affect mortality in HFrEF patients. However, rehospitalization decreased in patients taking digoxin in HFrEF.
Topics: Male; Humans; Middle Aged; Aged; Female; Heart Failure; Digoxin; Stroke Volume; Atrial Fibrillation; Prognosis
PubMed: 37606130
DOI: 10.26355/eurrev_202308_33294 -
Clinical Therapeutics May 2021Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in...
PURPOSE
Dronedarone may increase digoxin plasma levels through inhibition of P-glycoprotein. Using real-world data, we evaluated the risk of digitalis intoxication in concomitant users of dronedarone and digoxin compared digoxin-alone users.
METHODS
We used the Clinformatics DataMart, a US claims database, to identify adult patients with atrial fibrillation (AF) or atrial flutter (AFL) who concomitantly used dronedarone and digoxin and those who used digoxin alone between July 2009 and March 2016. Digitalis intoxication during follow-up until March 2016 was ascertained using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Adjusted hazard ratios (HR) for digitalis intoxication in concomitant users versus users of digoxin alone were estimated, controlling for age, sex, cohort entry year, number of medical encounters for AF or AFL, history of congestive heart failure, diabetes, hypertension, stroke, myocardial infarction, renal failure, use of drugs interacting with digoxin, and digoxin dose.
FINDINGS
Overall, 524 concomitant users and 32,459 users of digoxin alone were identified, among which 3 and 301 events of digitalis intoxication occurred during follow-up, respectively. Incidence rates were 17.25 and 9.17 cases per 1000 person-years, respectively. The adjusted HR for digitalis intoxication in concomitant users versus users of digoxin alone was 1.56 (95% CI, 0.50-4.88; P = 0.45). When digitalis intoxication was defined by ICD-9-CM and ICD-10-CM codes accompanied by laboratory testing for digoxin/digitoxin or hospitalization within 30 days, no events occurred in the concomitant users and 40 events occurred in the users of digoxin alone (incidence rate of 1.22 cases per 1000 person-years).
IMPLICATIONS
Concomitant use of dronedarone and digoxin was uncommon in this study, and no significant increase in the risk of digitalis intoxication with concomitant use was found.
Topics: Adult; Atrial Fibrillation; Atrial Flutter; Digitalis; Digoxin; Dronedarone; Humans
PubMed: 33888353
DOI: 10.1016/j.clinthera.2021.03.014 -
Cleveland Clinic Journal of Medicine Sep 2006Digoxin has been the cornerstone of the treatment of heart failure for more than 2 centuries. Now that newer therapies have been introduced that reduce the mortality... (Review)
Review
Digoxin has been the cornerstone of the treatment of heart failure for more than 2 centuries. Now that newer therapies have been introduced that reduce the mortality rate in heart failure and recent trials have failed to prove the same for digoxin, its use has significantly decreased. But a careful review of the multiple pharmacologic actions of digoxin and closer analysis of the results of recent trials suggest that digoxin may in fact continue to be an effective treatment for heart failure.
Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans
PubMed: 16970134
DOI: 10.3949/ccjm.73.9.821 -
Nature Apr 2011CD4(+) T helper lymphocytes that express interleukin-17 (T(H)17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also...
CD4(+) T helper lymphocytes that express interleukin-17 (T(H)17 cells) have critical roles in mouse models of autoimmunity, and there is mounting evidence that they also influence inflammatory processes in humans. Genome-wide association studies in humans have linked genes involved in T(H)17 cell differentiation and function with susceptibility to Crohn's disease, rheumatoid arthritis and psoriasis. Thus, the pathway towards differentiation of T(H)17 cells and, perhaps, of related innate lymphoid cells with similar effector functions, is an attractive target for therapeutic applications. Mouse and human T(H)17 cells are distinguished by expression of the retinoic acid receptor-related orphan nuclear receptor RORγt, which is required for induction of IL-17 transcription and for the manifestation of T(H)17-dependent autoimmune disease in mice. By performing a chemical screen with an insect cell-based reporter system, we identified the cardiac glycoside digoxin as a specific inhibitor of RORγt transcriptional activity. Digoxin inhibited murine T(H)17 cell differentiation without affecting differentiation of other T cell lineages and was effective in delaying the onset and reducing the severity of autoimmune disease in mice. At high concentrations, digoxin is toxic for human cells, but non-toxic synthetic derivatives 20,22-dihydrodigoxin-21,23-diol and digoxin-21-salicylidene specifically inhibited induction of IL-17 in human CD4(+) T cells. Using these small-molecule compounds, we demonstrate that RORγt is important for the maintenance of IL-17 expression in mouse and human effector T cells. These data indicate that derivatives of digoxin can be used as chemical templates for the development of RORγt-targeted therapeutic agents that attenuate inflammatory lymphocyte function and autoimmune disease.
Topics: Animals; Autoimmune Diseases; Autoimmunity; Cell Differentiation; Cell Line; Digoxin; Drosophila; Humans; Interleukin-17; Mice; Nuclear Receptor Subfamily 1, Group F, Member 3; Th17 Cells; Transcription, Genetic
PubMed: 21441909
DOI: 10.1038/nature09978 -
The Prostate Jan 2014Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. Preclinical studies...
PURPOSE
Digoxin is a commonly used medication for heart failure and cardiac arrhythmias that has recently been suggested as a novel chemotherapeutic agent. Preclinical studies of prostate cancer (PCa) have shown anti-tumor activity with digoxin. We explore the relationship between use of digoxin and PCa risk.
METHODS
Data from a population-based case-control study of incident cases aged 35-74 years at PCa diagnosis in 2002-2005 in King County, Washington were available. Controls were identified by random digit dialing and frequency matched by age. Use of digoxin was determined from in-person questionnaires regarding medical and prescription history. The relationship of digoxin use with PCa risk was evaluated with logistic regression.
RESULTS
One thousand one cases of PCa and 942 controls were analyzed. The prevalence of digoxin use in controls was 2.7%, and use was positively correlated with age. In multivariate analysis adjusting for age, race, PSA screening, and family history of PCa, digoxin use was associated with a reduction in the odds ratio of PCa (OR 0.58, 95% CI: 0.30-1.10). Among those with ≥3 PSA tests over the preceding 5 years (546 cases, 380 controls), digoxin use was associated with a stronger reduction of PCa risk (OR 0.44, 95% CI: 0.20-0.98).
CONCLUSION
These data indicate digoxin use may be associated with a reduction in risk of PCa. Given the potential mechanisms by which digoxin may exert an anti-neoplastic effect and other recent studies showing a negative association between digoxin use and PCa, further research is warranted.
Topics: Adult; Aged; Cardiovascular Diseases; Case-Control Studies; Digoxin; Humans; Male; Middle Aged; Population Surveillance; Prostatic Neoplasms; Risk Factors
PubMed: 24318956
DOI: 10.1002/pros.22733 -
International Journal of Biological... 2014Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The... (Review)
Review
Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and target-based screening assays. With the successful clinical introduction of a number of non-cancer drugs for cancer treatment, drug repositioning now became a powerful alternative strategy to discover and develop novel anticancer drug candidates from the existing drug space. In this review, recent successful examples of drug repositioning for anticancer drug discovery from non-cancer drugs will be discussed.
Topics: Antineoplastic Agents; Computational Biology; Digoxin; Drug Repositioning; Itraconazole; Nelfinavir; Nitroquinolines
PubMed: 25013375
DOI: 10.7150/ijbs.9224 -
Pharmacological Reports : PR 2011The interest in digoxin has recently increased due to the expanding knowledge regarding endogenous cardiac glycosides and a potential oncological application of this...
The interest in digoxin has recently increased due to the expanding knowledge regarding endogenous cardiac glycosides and a potential oncological application of this drug. Hydrogen sulfide (H(2)S), a crucial co-modulator of various physiological processes, is involved in the pathophysiology of different disorders and may be useful in the treatment of some diseases. The interaction between cardiac glycosides and H(2)S is unknown. The aim of the study is to assess the influence of digoxin on H(2)S tissue concentrations in mouse brain, heart and kidney. Thirty male BALB/c mice were given intraperitoneal injections of digoxin at 0.5 mg/kg body weight (b.w.) per day (group D1, n = 10) or 1 mg/kg b.w. per day (group D2, n = 10). The control group (n = 10) received physiological saline. Free H(2)S tissue concentrations were measured via the Siegel spectrophotometric modified method. There was a significant, progressive increase in the H(2)S concentrations for both the low and high digoxin doses in the brain (7.7% and 8.5%, respectively), heart (by 6.0% and 22.1%, respectively) and kidney (by 7.6% and 13.0%, respectively). This report shows that digoxin administration is followed by an increase in the free H(2)S concentrations in mouse brain, heart and kidney tissues.
Topics: Animals; Brain; Cardiotonic Agents; Digoxin; Dose-Response Relationship, Drug; Heart; Hydrogen Sulfide; Injections, Intraperitoneal; Kidney; Male; Mice; Mice, Inbred BALB C; Myocardium; Spectrophotometry
PubMed: 22180368
DOI: 10.1016/s1734-1140(11)70645-4