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Digoxin

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101. Digoxin Benefit Varies by Risk of Heart Failure Hospitalization: Applying the Tufts MC HF Risk Model. (Abstract)

Digoxin Benefit Varies by Risk of Heart Failure Hospitalization: Applying the Tufts MC HF Risk Model. Digoxin has been shown to reduce heart failure hospitalizations with a neutral effect on mortality. It is unknown whether there is heterogeneity of treatment effect for digitalis therapy according to predicted risk of heart failure hospitalization.We conducted a post hoc analysis of the Digitalis Investigator Group (DIG) studies, randomized controlled trials of digoxin vs placebo (...) in participants with heart failure and left ventricular ejection fraction ≤45% (main DIG study, n = 6800) or >45% (ancillary DIG study, n = 988). Using a previously derived multistate model to risk-stratify DIG study participants, we determined the differential treatment effect on hospitalization and mortality outcomes. There was a 13% absolute reduction in the risk of any heart failure hospitalizations (39% vs 52%; odds ratio 0.58; 95% confidence interval 0.47-0.71) in the digoxin vs placebo arms

2017 American Journal of Medicine

102. Reply to "Topical ionic contra-viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts". (Abstract)

Reply to "Topical ionic contra-viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts". 29055137 2018 03 25 1468-3083 32 4 2018 Apr Journal of the European Academy of Dermatology and Venereology : JEADV J Eur Acad Dermatol Venereol Reply to 'Topical ionic contra-viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts'. e156-e157 10.1111/jdv.14645 Abdelmaksoud A A Mansoura Dermatology

2017 Journal of the European Academy of Dermatology and Venereology

103. Reply to correspondence 'Topical ionic contra viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts'. (Abstract)

Reply to correspondence 'Topical ionic contra viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts'. 29057503 2018 03 25 1468-3083 32 4 2018 Apr Journal of the European Academy of Dermatology and Venereology : JEADV J Eur Acad Dermatol Venereol Reply to correspondence 'Topical ionic contra-viral therapy comprised of digoxin and furosemide as a potential novel treatment approach for common warts '. e156 10.1111/jdv.14643 van der Kolk T T

2017 Journal of the European Academy of Dermatology and Venereology

104. Effect of Digoxin Use Among Medicaid Enrollees With Atrial Fibrillation. Full Text available with Trip Pro

Effect of Digoxin Use Among Medicaid Enrollees With Atrial Fibrillation. Recently published analysis of contemporary atrial fibrillation (AF) cohorts showed an association between digoxin and increased mortality and hospitalizations; however, other studies have demonstrated conflicting results. Many AF cohort studies did not or were unable to examine racial differences. Our goal was to examine risk factors for hospitalizations and mortality with digoxin use in a diverse real-world AF patient (...) population and evaluate racial differences.We performed a retrospective cohort analysis of claims data for Medicaid beneficiaries, aged 18 to 64 years, with incident diagnosis of AF in 2008 with follow-up until December 31, 2009. We created Kaplan-Meier curves and constructed multivariable Cox proportional hazard models for mortality and hospitalization. We identified 11 297 patients with an incident diagnosis of AF in 2008, of those, 1401 (12.4%) were on digoxin. Kaplan-Meier analysis demonstrated

2017 Circulation. Arrhythmia and electrophysiology

105. Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized for Heart Failure. Full Text available with Trip Pro

Digoxin and 30-Day All-Cause Readmission in Long-Term Care Residents Hospitalized for Heart Failure. Digoxin use has been shown to be associated with a lower risk of 30-day all-cause hospital readmissions in older patients with heart failure (HF). In the current study, we examined this association among long-term care (LTC) residents hospitalized for HF.Of the 8049 Medicare beneficiaries discharged alive after hospitalization for HF from 106 Alabama hospitals, 545 (7%) were LTC residents (...) , of which 227 (42%) received discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 545 patients, were used to assemble a matched cohort of 158 pairs of patients receiving and not receiving digoxin who were balanced on 29 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin among matched patients were estimated using Cox regression models.Matched patients (n = 316) had a mean age of 83 years, 74

2017 Journal of the American Medical Directors Association

106. Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations Full Text available with Trip Pro

Delineating the Role of Various Factors in Renal Disposition of Digoxin through Application of Physiologically Based Kidney Model to Renal Impairment Populations Development of submodels of organs within physiologically-based pharmacokinetic (PBPK) principles and beyond simple perfusion limitations may be challenging because of underdeveloped in vitro-in vivo extrapolation approaches or lack of suitable clinical data for model refinement. However, advantage of such models in predicting clinical (...) observations in divergent patient groups is now commonly acknowledged. Mechanistic understanding of altered renal secretion in renal impairment is one area that may benefit from such models, despite knowledge gaps in renal pathophysiology. In the current study, a PBPK kidney model was developed for digoxin, accounting for the roles of organic anion transporting peptide 4C1 (OATP4C1) and P-glycoprotein (P-gp) in its tubular secretion, with the aim to investigate the impact of age and renal impairment

2017 The Journal of pharmacology and experimental therapeutics

107. Digoxin Plus Trametinib Therapy Achieves Disease Control in BRAF Wild-Type Metastatic Melanoma Patients Full Text available with Trip Pro

Digoxin Plus Trametinib Therapy Achieves Disease Control in BRAF Wild-Type Metastatic Melanoma Patients This is the first prospective study of a combination therapy involving a cardenolide and a MEK inhibitor for metastatic melanoma. Whereas BRAF mutant melanomas can exhibit profound responses to treatment with BRAF and MEK inhibitors, there are fewer options for BRAF wild-type melanomas. In preclinical studies, we discovered that cardenolides synergize with MEK inhibitor to promote (...) the regression of patient-derived xenografts irrespective of BRAF mutation status. We therefore conducted a phase 1B study of digoxin 0.25 mg and trametinib 2 mg given orally once daily in 20 patients with advanced, refractory, BRAF wild-type melanomas. The most common adverse events were rash, diarrhea, nausea, and fatigue. The response rate was 4/20 or 20% with response durations of 2, 4, 6, and 8 months. The disease control rate (including partial responses and stable disease) was 13/20 or 65% of patients

2017 Neoplasia (New York, N.Y.)

108. Digoxin reduces the mutagenic effects of Mitomycin C in human and rodent cell lines Full Text available with Trip Pro

Digoxin reduces the mutagenic effects of Mitomycin C in human and rodent cell lines Digoxin is a drug widely used to treat heart failure and studies have demonstrated its potential as anticancer agent. In addition, digoxin presents the potential to interact with a series of other compounds used in medicine. The aim of the present study was to evaluate in vitro the cytotoxicity, genotoxicity and mutagenicity of digoxin and its potential to interact with the mutagen Mitomycin C (MMC (...) ). The cytotoxicity of digoxin was assessed by employing the MTT method and the comet assay was performed to assess the genotoxicity of this medicine in CHO-K1 and HeLa cell lines. Besides, the cytokinesis-block micronucleus assay was performed to assess the mutagenicity and the antimutagenicity of this drug. The Ames assay was also performed with TA98 and TA100 strains of S. typhimurium. Results showed that digoxin was cytotoxic, genotoxic and mutagenic for HeLa and CHO-K1 cell lines at concentrations many times

2017 Cytotechnology

109. Unmasking the Role of Uptake Transporters for Digoxin Uptake Across the Barriers of the Central Nervous System in Rat Full Text available with Trip Pro

Unmasking the Role of Uptake Transporters for Digoxin Uptake Across the Barriers of the Central Nervous System in Rat The role of uptake transporter (organic anion-transporting polypeptide [Oatp]) in the disposition of a P-glycoprotein (P-gp) substrate (digoxin) at the barriers of central nervous system, namely, the blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), and brain-cerebrospinal fluid barrier (BCSFB), was studied using rat as a preclinical species. In vivo chemical (...) inhibition of P-gp and Oatp was achieved using elacridar and rifampicin, respectively. Our findings show that (1) digoxin had a low brain-to-plasma concentration ratio (B/P) (0.07) in rat; (2) in the presence of elacridar, the B/P of digoxin increased by about 12-fold; (3) rifampicin administration alone did not change the digoxin B/P significantly when compared with digoxin B/P alone; (4) rifampicin administration along with elacridar resulted only in 6-fold increase in the B/P of digoxin; (5) similar

2017 Journal of central nervous system disease

110. Neglected facts in digoxin intoxication Full Text available with Trip Pro

Neglected facts in digoxin intoxication 28616623 2018 11 13 2452-2473 17 2 2017 Jun Turkish journal of emergency medicine Turk J Emerg Med Neglected facts in digoxin intoxication. 79 10.1016/j.tjem.2016.12.001 Serin Sibel Ocak SO Internal Medicine, Istanbul Umraniye Research Hospital, Istanbul, Turkey. eng Journal Article 2017 03 19 Turkey Turk J Emerg Med 101681782 2452-2473 2016 12 12 2016 12 20 2017 6 16 6 0 2017 6 16 6 0 2017 6 16 6 1 epublish 28616623 10.1016/j.tjem.2016.12.001 S2452-2473

2017 Turkish journal of emergency medicine

111. Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects Full Text available with Trip Pro

Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects Semaglutide is a glucagon-like peptide-1 analogue in development for the once-weekly treatment of type 2 diabetes mellitus. Its effect on the rate and extent of absorption of concomitant oral medications (metformin, warfarin, atorvastatin and digoxin) was evaluated in healthy subjects.Subjects received metformin (500 mg twice daily for 3.5 days), warfarin (25 mg, single dose (...) ), atorvastatin (40 mg, single dose) or digoxin (0.5 mg, single dose) before and with subcutaneous semaglutide treatment at steady state (1.0 mg). Lack of drug-drug interaction was concluded if the 90% confidence intervals for the area under the plasma concentration-time curve ratio before and with semaglutide were within a pre-specified interval (0.80-1.25).Overall, metformin, warfarin, atorvastatin and digoxin pharmacokinetics were not affected to a clinically relevant degree with semaglutide co

2017 Clinical pharmacokinetics

112. Selectivity analyses of γ-benzylidene digoxin derivatives to different Na,K-ATPase α isoforms: a molecular docking approach Full Text available with Trip Pro

Selectivity analyses of γ-benzylidene digoxin derivatives to different Na,K-ATPase α isoforms: a molecular docking approach Digoxin and other cardiotonic steroids (CTS) exert their effect by inhibiting Na,K-ATPase (NKA) activity. CTS bind to the various NKA isoforms that are expressed in different cell types, which gives CTS their narrow therapeutic index. We have synthesised a series of digoxin derivatives (γ-Benzylidene digoxin derivatives) with substitutions in the lactone ring (including

2017 Journal of enzyme inhibition and medicinal chemistry

113. Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects Full Text available with Trip Pro

Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters.Five phase 1 single-center, open-label (...) , fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin).OCA showed no substantial suppression/inhibition of S-warfarin, digoxin

2017 Advances in therapy

114. Accidental Intrathecal Administration of Digoxin in an Elderly Male with End-Stage Renal Disease Full Text available with Trip Pro

Accidental Intrathecal Administration of Digoxin in an Elderly Male with End-Stage Renal Disease The systemic effects of digoxin toxicity have been well-known. However, there has been no case citing the effects of intrathecal digoxin in light of end-stage renal disease in the elderly. Here, we report on the case of the successful management of accidental intrathecal digoxin administration in an elderly male with end-stage renal disease.

2017 Case reports in neurological medicine

115. Risk of cancer in patients with heart failure who use digoxin: a 10-year follow-up study and cell-based verification Full Text available with Trip Pro

Risk of cancer in patients with heart failure who use digoxin: a 10-year follow-up study and cell-based verification Heart failure (HF) is the leading cause of death in the world and digoxin remains one of the oldest therapies for HF. However, its safety and efficacy have been controversial since its initial use and there is uncertainty about its long-term efficacy and safety. Recently, the repositioning of cardiac glycosides is to function in anti-tumor activity via multiple working pathways (...) . It is interesting to compare the potential effects of digoxin in clinical patients and cell lines. First, we analyze patient information retrieved from the National Health Insurance Research database of Taiwan between January 1, 2000 and December 31, 2000. This retrospective study included a study cohort (1,219 patients) and a comparison cohort. Our analytical data suggested that patients taking digoxin are at an increased risk of cancers, including breast, liver, and lung cancers, during the 10-year follow-up

2017 Oncotarget

116. Electrocardiographic Changes After Suicidal Digoxin Intoxication in a Healthy Woman Full Text available with Trip Pro

Electrocardiographic Changes After Suicidal Digoxin Intoxication in a Healthy Woman Suicidal digoxin intoxication is a rare clinical entity. Clinical suspicious remains of paramount importance as adequate interpretation of the electrocardiographic changes enable to readily initiate treatment.We describe a case of suicidal attempt after massive digoxin intake that was satisfactory managed with conservative management strategy that involved a close clinical surveillance of the evolving (...) electrocardiographic changes and digoxin serum levels.

2017 The open cardiovascular medicine journal

117. Digoxin Use and Subsequent Clinical Outcomes in Patients With Atrial Fibrillation With or Without Heart Failure in the ENGAGE AF‐TIMI 48 Trial Full Text available with Trip Pro

Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trial, clinical outcomes of patients with atrial fibrillation with and without HF were examined by baseline digoxin use during a median follow-up of 2.8 years. HF was defined at baseline as prior or current clinical stage C or D HF. Of 21 105 patients enrolled, 6327 (30%) were treated with digoxin at baseline. Among patients without HF (n=8981), digoxin use (20%) was independently associated with sudden cardiac death (adjusted (...) hazard ratio, 1.51; 95% CI, 1.10-2.08), with no significant interaction by age, sex, left ventricular ejection fraction, renal function, or concomitant medications (P>0.05 for each). Consistent results were observed using propensity matching (adjusted hazard ratio for sudden cardiac death, 1.90; 95% CI, 1.36-2.65). Among patients with HF (n=12 124), digoxin use (37%) was associated with an increase in all-cause death, cardiovascular death, sudden cardiac death, and death caused by HF/cardiogenic

2017 Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease Controlled trial quality: uncertain

118. Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation Full Text available with Trip Pro

Digoxin reveals a functional connection between HIV-1 integration preference and T-cell activation HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin (...) repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism. Analysis of >400,000 unique integration sites showed that WT virus integrated more frequently than N74D mutant within or near genes susceptible to repression by digoxin and involved in T-cell activation and cell metabolism. Two

2017 PLoS pathogens

119. Digoxin-induced anemia among patients with atrial fibrillation and heart failure: clinical data analysis and drug-gene interaction network Full Text available with Trip Pro

Digoxin-induced anemia among patients with atrial fibrillation and heart failure: clinical data analysis and drug-gene interaction network Digoxin is widely used to treat various heart conditions. In order to clarify the association between digoxin and anemia adverse reaction, we inspected case reports submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015. These reports involved 75618 atrial fibrillation patients and 15699 heart failure patients (...) . Compared to other therapies, digoxin treatment was significantly more likely to be concurrent with anemia adverse reaction among both atrial fibrillation patients (pooled OR = 1.38, 95% CI 1.14-1.68, P-value = 0.001) and heart failure patients (pooled OR =1.50, 95% CI 1.33-1.59-, P =4.27×10-5). We further explored previously published evidences and found 821 human genes directly or indirectly interacting with digoxin. Functional analysis indicated that these genes were significantly enriched

2017 Oncotarget

120. A Rare Case of Digoxin Associated Gingival Overgrowth Full Text available with Trip Pro

A Rare Case of Digoxin Associated Gingival Overgrowth This case report presents a case of drug induced gingival overgrowth in a 28-year-old female patient with history of Coronary Artery Disease (CAD) and was prescribed digoxin in combination with furosemide and acitrom for the same. On clinical examination, the patient presented with severe gingival overgrowth. The volume of enlargement seen did not correlate solely with the diagnosis of inflammatory Gingival Enlargement (GE), hence an added (...) the starting of the medication that is digoxin and manifestation of GO, a causal relationship is likely.

2017 Journal of clinical and diagnostic research : JCDR

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