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Frontiers in Immunology 2023Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and...
BACKGROUND
Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.
OBJECTIVE
This study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.
METHODS
We exploited a rat needle model to investigate digoxin's role in intervertebral disc degeneration . Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects . Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.
RESULTS
Digoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.
CONCLUSION
These findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.
Topics: Humans; Rats; Mice; Animals; Intervertebral Disc Degeneration; NF-kappa B; Digoxin; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Inflammation; LDL-Receptor Related Proteins
PubMed: 37790932
DOI: 10.3389/fimmu.2023.1251517 -
Emergencias : Revista de La Sociedad... Oct 2023
Topics: Humans; Digoxin
PubMed: 37801413
DOI: 10.55633/s3me/E022.2023 -
BMJ Clinical Evidence Nov 2011Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical... (Review)
Review
INTRODUCTION
Atrial fibrillation is a supraventricular tachyarrhythmia characterised by the presence of fast and uncoordinated atrial activation leading to reduced atrial mechanical function. Risk factors for atrial fibrillation include increasing age, male sex, co-existing cardiac and thyroid disease, pyrexial illness, electrolyte imbalance, cancer, and co-existing infection.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral medical treatments to control heart rate in people with chronic (defined as longer than 1 week for this review) non-valvular atrial fibrillation? What is the effect of different treatment strategies (rate versus rhythm) for people with persistent non-valvular atrial fibrillation? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 23 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: beta-blockers (with or without digoxin), calcium channel blockers (with or without digoxin), calcium channel blockers (rate-limiting), digoxin, and rate versus rhythm control strategies.
Topics: Adrenergic beta-Antagonists; Atrial Fibrillation; Calcium Channel Blockers; Cardiovascular Diseases; Digoxin; Humans
PubMed: 22075545
DOI: No ID Found -
British Journal of Clinical Pharmacology Jan 2016
Topics: Atrial Fibrillation; Cardiotonic Agents; Digoxin; Heart Failure; Humans
PubMed: 26390833
DOI: 10.1111/bcp.12791 -
American Journal of Cardiovascular... Sep 2022Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other...
BACKGROUND
Digoxin is indicated for the management of heart failure with reduced ejection fraction and atrial fibrillation. Despite stronger guideline recommendations for other pharmacologic and device therapies, digoxin retains a role in select patients unable to tolerate or refractory to standard therapies. Contemporary utilization of and costs related to digoxin in the United States of America (USA) remain uncharacterized. The objective of this study was to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017.
METHODS
We utilized the Medical Expenditure Panel Survey to estimate trends in digoxin use and expenditures across the USA from 2010 to 2017. The Medical Expenditure Panel Survey is an overlapping panel survey that interviews households in the USA to ascertain their healthcare utilization and expenditures. Complex sampling procedures allow for nationally representative estimates of utilization and expenditures. We report the number of digoxin users and expenditures across key subgroups in 2-year increments from 2010 to 2017.
RESULTS
The number of digoxin users in the USA declined by 47% from 766 users per 100,000 adults in 2010-11 to 402 users per 100,000 adults in 2016-17. While digoxin use declined among women and self-identified White adults, adults living at or below the federal poverty level and those who self-identified as Asian or Hispanic represent an increasing proportion of overall digoxin users. While nationwide digoxin expenditures declined by 26% from 2010-11 to 2012-13, they peaked at $260.3 million in 2014-15 and remained elevated at $188.7 million in 2016-17.
CONCLUSIONS
Despite a nationwide trend towards declining use, digoxin remains prevalent amongst people of Asian and Hispanic descent in the USA. After a spike in cost in 2013, digoxin prices have yet to return to pre-spike levels. The role of digoxin in contemporary heart failure and arrhythmia management will continue to evolve as additional randomized and observational analyses become available.
Topics: Adult; Digoxin; Female; Health Expenditures; Heart Failure; Humans; Patient Acceptance of Health Care; Surveys and Questionnaires; United States
PubMed: 35739347
DOI: 10.1007/s40256-022-00540-x -
International Journal of Environmental... Apr 2021Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of...
Although digoxin is important in heart rate control, the utilization of digoxin is declining due to its narrow therapeutic window. Misdiagnosis or delayed diagnosis of digoxin toxicity is common due to the lack of awareness and the time-consuming laboratory work that is involved. Electrocardiography (ECG) may be able to detect potential digoxin toxicity based on characteristic presentations. Our study attempted to develop a deep learning model to detect digoxin toxicity based on ECG manifestations. This study included 61 ECGs from patients with digoxin toxicity and 177,066 ECGs from patients in the emergency room from November 2011 to February 2019. The deep learning algorithm was trained using approximately 80% of ECGs. The other 20% of ECGs were used to validate the performance of the Artificial Intelligence (AI) system and to conduct a human-machine competition. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of ECG interpretation between humans and our deep learning system. The AUCs of our deep learning system for identifying digoxin toxicity were 0.912 and 0.929 in the validation cohort and the human-machine competition, respectively, which reached 84.6% of sensitivity and 94.6% of specificity. Interestingly, the deep learning system using only lead I (AUC = 0.960) was not worse than using complete 12 leads (0.912). Stratified analysis showed that our deep learning system was more applicable to patients with heart failure (HF) and without atrial fibrillation (AF) than those without HF and with AF. Our ECG-based deep learning system provides a high-accuracy, economical, rapid, and accessible way to detect digoxin toxicity, which can be applied as a promising decision supportive system for diagnosing digoxin toxicity in clinical practice.
Topics: Algorithms; Artificial Intelligence; Deep Learning; Digoxin; Electrocardiography; Humans; Retrospective Studies
PubMed: 33917563
DOI: 10.3390/ijerph18073839 -
Medicine Mar 2016Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed,... (Review)
Review
Digoxin has long been used for rate control in atrial fibrillation (AF); its safety remains controversial.We performed a literature search using MEDLINE (source PubMed, January 1, 1966, to July 31, 2015) and EMBASE (January 1, 1980, to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Pooled effect estimates were obtained by using random-effects meta-analysis.Twenty-two studies involving 586,594 patients were identified. Patients taking digoxin, as compared with those who took no digoxin, experienced an increased risk of death from any cause (RR: 1.29[95% CI 1.16-1.43]), even after reported adjustment for propensity scores (RR: 1.28[95% CI 1.18-1.39]). The risk of death was increased with patients with or without heart failure (RR: 1.12[95% CI 1.02-1.23] and RR: 1.26[95% CI 1.15-1.29], respectively), and patients taking or not taking beta blockers (RR: 1.17 [95% CI 1.06-1.30] and RR: 1.28 [95% CI 1.08-1.51], respectively). Digoxin use was also associated with increased risk of cardiovascular death (RR: 1.32 [95% CI 1.07-1.64]), arrhythmic death (RR: 1.38 [95% CI 1.07-1.79]), and stroke (RR: 1.20 [95% CI 1.004-1.44]). Digoxin treatment is associated with an absolute risk increase of 19 (95% CI 13-26) additional deaths from any cause per 1000 person-years.Digoxin use is associated with a significant increased risk for death from any cause in patients with AF. This finding suggests a need for reconsideration of present treatment recommendations on use of digoxin in AF.
Topics: Atrial Fibrillation; Cause of Death; Digoxin; Humans; Risk; Survival Rate
PubMed: 27015169
DOI: 10.1097/MD.0000000000002949 -
Journal of Clinical Laboratory Analysis Jan 2015Asian, Siberian, and American ginseng are known to interfere with serum digoxin measurements using fluorescence polarization technology, Digoxin II and Digoxin III...
Asian, Siberian, and American ginseng are known to interfere with serum digoxin measurements using fluorescence polarization technology, Digoxin II and Digoxin III assays (Abbott Laboratories, Green oaks, IL) as well as other digoxin assays. Abbott Laboratories more recently launched two new digoxin assays: iDigoxin, a chemiluminescent microparticle immunoassay for application on the ARCHITECT i1000SR and i2000SR immunoassay analyzers, and cDigoxin, a particle-enhanced turbidimetric inhibition immunoassay for application on the ARCHITECT c4000, c8000, and c1600 clinical chemistry analyzers; and we studied potential interferences of ginsengs with these two assays in vitro. When aliquots of drug-free serum pool treated with activated charcoal were supplemented with extracts of various ginsengs, no significant apparent digoxin values were observed. In addition, when aliquots of the digoxin pool prepared from patients taking digoxin were further supplemented with these ginseng extracts and the digoxin values were re-measured, we observed no statistically significant difference in observed digoxin values compared to the original digoxin value of the pool. These results further establish that relatively new digoxin assays for application on the ARCHITECT analyzers that employ specific monoclonal antibodies against digoxin are free from interferences from Asian, Siberian, and American ginseng.
Topics: Anti-Arrhythmia Agents; Chemistry, Clinical; Digoxin; Drug Interactions; False Positive Reactions; Humans; Immunoassay
PubMed: 24659366
DOI: 10.1002/jcla.21714 -
Molecules (Basel, Switzerland) Jun 2021Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12,...
Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3'a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin's cytotoxicity and interactions with Na/K-ATPase. The docking profiles for digoxin and several derivatives and Na/K-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na/K-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na/K-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity.
Topics: Animals; Antineoplastic Agents; Cardiac Glycosides; Cell Proliferation; Digoxin; Humans; Molecular Conformation; Molecular Docking Simulation; Neoplasms; Sodium-Potassium-Exchanging ATPase
PubMed: 34208576
DOI: 10.3390/molecules26123672 -
JACC. Heart Failure May 2016This study was developed to determine contemporary management of digoxin toxicity and clinical outcomes.
OBJECTIVES
This study was developed to determine contemporary management of digoxin toxicity and clinical outcomes.
BACKGROUND
Although the use of digoxin in heart failure management has declined, toxicity remains a prevalent complication.
METHODS
The Premier Perspective Comparative Hospital Database (Premier Inc., Charlotte, North Carolina) was used to retrospectively identify patients diagnosed with digoxin toxicity and/or who received digoxin immune fab (DIF) over a 5-year period (2007 to 2011). DIF was evaluated using treatment date, number of vials administered, and total cost. Clinical outcomes included length of stay (total hospitalization; days after DIF), cost of hospitalization, and in-hospital mortality. Exploratory multivariate analyses were conducted to determine predictors of DIF and effect on length of stay, adjusting for patient characteristics and selection bias.
RESULTS
Digoxin toxicity diagnosis without DIF treatment accounted for 19,543 cases; 5,004 patients received DIF of whom 3086 had a diagnosis of toxicity. Most patients were >65 years old (88%). The predictors of DIF use were urgent/emergent admission, hyperkalemia, arrhythmia associated with digoxin toxicity, acute renal failure, or suicidal intent (odds ratios 1.7, 2.4, 3.6, 2.1, and 3.7, respectively; p < 0.0001 for all). The majority (78%) of DIF was administered on days 1 and 2 of the hospitalization; 10% received treatment after day 7. Digoxin was used after DIF administration in 14% of cases. Among patients who received DIF within 2 days of admission, there was no difference for in-hospital mortality or length of stay compared with patients not receiving DIF.
CONCLUSIONS
Digoxin toxicity diagnoses are clustered in the elderly. One-fifth of cases receive treatment with DIF, most within 2 days of admission. Opportunities exist for improved diagnosis and post-DIF management. Prospective data may be required to assess the impact of DIF on length of stay.
Topics: Aged; Aged, 80 and over; Antidotes; Cardiotonic Agents; Databases, Factual; Digoxin; Female; Heart Failure; Hospital Mortality; Hospitalization; Humans; Immunoglobulin Fab Fragments; Linear Models; Male; Middle Aged; Retrospective Studies
PubMed: 27039127
DOI: 10.1016/j.jchf.2016.01.011