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Archives of Dermatological Research Jun 2024There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
There are many therapeutic modalities for plantar warts, however treating it remains challenging. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide were observed to be effective and safe, however no comparison study between them was done. Our study was conducted to evaluate the efficacy of both therapies in the treatment of plantar warts. 90 adult patients with multiple recalcitrant plantar warts were included in our study. They were randomly allocated to one of three groups; combined digoxin and furosemide, 5-fluorouarcil, or normal saline group. Fortnightly injections were done into all studied warts till complete clearance or up to 5 sessions. Warts were evaluated clinically and dermoscopically. Clinical response was reported in 24 patients (80%) of the combined digoxin and furosemide group with 40% complete response and in 24 patients (80%) of the 5-fluorouarcil group with 33.3% complete response. No statistically significant difference was observed between the two groups concerning efficacy and safety. Intralesional injection of 5-fluorouarcil and combined digoxin and furosemide are nearly equivalent in efficacy and safety for plantar wart treatment. Dermoscopy helps to take the truthful judgment about complete clearance of warts.
Topics: Humans; Furosemide; Male; Female; Adult; Warts; Digoxin; Injections, Intralesional; Treatment Outcome; Prospective Studies; Young Adult; Middle Aged; Drug Therapy, Combination; Adolescent; Dermoscopy; Flucytosine
PubMed: 38878078
DOI: 10.1007/s00403-024-03014-z -
JACC. Clinical Electrophysiology May 2024Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated...
BACKGROUND
Some studies have shown digoxin use to be associated with adverse outcomes, including increased mortality. There are limited data on whether digoxin use is associated with increased risk of ventricular tachycardia/ventricular fibrillation (VT/VF) in heart failure patients with an implantable cardioverter-defibrillator (ICD).
OBJECTIVES
This study sought to assess whether digoxin use is associated with increased risk of VT/VF in patients with heart failure with reduced ejection fraction with a primary prevention ICD in landmark clinical trials.
METHODS
The study cohort consisted of patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in 4 landmark MADIT trials (Multicenter Automatic Defibrillator Implantation Trials). We employed propensity score quintile stratification for treatment with digoxin as well as additional multivariable adjustment to assess the risk of digoxin vs no-digoxin therapy for the endpoints of first and recurrent VT/VF and all-cause mortality. The proportional hazards regression models for arrhythmia-specific endpoints incorporated adjustments for the competing risk of death.
RESULTS
At baseline, 1,155 of 4,499 patients were on digoxin (26%). After propensity score quintile stratification, patients prescribed digoxin were shown to exhibit a statistically significant 48% increased risk of VT/VF (P < 0.001), 42% increased risk of the composite of VT/VF or death (P < 0.001), and a 37% increased risk of all-cause mortality (P = 0.006). Digoxin use was also associated with increased risk of appropriate ICD shocks (HR: 1.91; P < 0.001) and with increased burden of VT/VF events (HR: 1.46; P = 0.001).
CONCLUSIONS
Our findings suggests that digoxin use is associated with ventricular tachyarrhythmia and death in heart failure with reduced ejection fraction patients with an ICD.
PubMed: 38878014
DOI: 10.1016/j.jacep.2024.03.042 -
Cardiovascular Drugs and Therapy Jun 2024New onset atrial fibrillation (NOAF) is a common occurrence after transcatheter aortic valve replacement (TAVR) and portends a poorer prognosis. The optimal strategy for...
BACKGROUND
New onset atrial fibrillation (NOAF) is a common occurrence after transcatheter aortic valve replacement (TAVR) and portends a poorer prognosis. The optimal strategy for managing NOAF in this population is uncertain.
METHODS
This retrospective cohort study utilized deidentified patient data from the TriNetX Research Network. Patients with TAVR and NOAF were stratified into a rhythm control cohort if they were treated with antiarrhythmics, received AF ablation, or underwent cardioversion within 1 year of AF diagnosis. A rate control cohort was similarly defined by the absence of rhythm control strategies and treatment with a beta blocker, calcium channel blocker, or digoxin. After 1:1 propensity score matching, the Kaplan-Meier survival analysis and Cox proportional hazard ratios (HRs) were used to compare outcomes at 7 years of follow-up.
RESULTS
We identified 569 patients in each cohort following propensity matching. At 7 years, the primary composite outcome of all-cause death, myocardial infarction, cerebrovascular accident, and heart failure hospitalization was not significantly different between the rhythm and rate control cohorts (HR 0.99, 95% CI 0.83-1.18). The individual components of the primary outcome in addition to all-cause hospitalization were also similar between the groups.
CONCLUSIONS
Similar outcomes were seen among patients receiving an early rhythm or rate control strategy to manage NOAF after TAVR. The attenuated benefits of an early rhythm control strategy observed in this setting may be due to the overall high burden of comorbidities and advanced age of these patients.
PubMed: 38869743
DOI: 10.1007/s10557-024-07577-x -
Clinical Laboratory Jun 2024Therapeutic drug monitoring (TDM) involves the measurement of drug concentrations in serum, plasma, whole blood, or other biologic fluids. This study focused on...
BACKGROUND
Therapeutic drug monitoring (TDM) involves the measurement of drug concentrations in serum, plasma, whole blood, or other biologic fluids. This study focused on evaluating the TDM requests of a city hospital over a period of one year, retrospectively.
METHODS
The study retrospectively analyzed TDM requests for carbamazepine, cyclosporine-A, digoxin (DIGOX), lithium (LITH), methotrexate (MTX), phenitoin, tacrolimus, and valproic acid (VALP) from June 1, 2022, to June 1, 2023. Parameters such as the age and the gender of patients, the requesting departments, the measurement results, and the turnaround time (TAT) were assessed. Drug concentrations below the reference values were classified as subtherapeutic, whereas concentrations above the reference values were considered supratherapeutic.
RESULTS
In total, 10,913 drug concentration measurement records were analyzed. The gender distribution was 51.6% male and 48.4% female. Pediatric samples comprised 6.2% and elderly samples 8.6% of the total. Notably, DIGOX, LITH, and VALP levels showed a significant correlation with age (p = < 0.0001, p = < 0.0001, and p = 0.0002, respectively). TAT was maintained at 360 minutes (6 hours) for all tests.
CONCLUSIONS
The study found significant correlations between age and DIGOX, LITH, and VALP levels. TDM plays a critical role in the elderly population, necessitating careful management of these drugs.
Topics: Humans; Drug Monitoring; Male; Female; Retrospective Studies; Middle Aged; Adult; Aged; Child; Adolescent; Young Adult; Child, Preschool; Hospitals, Urban; Infant; Aged, 80 and over; Infant, Newborn; Age Factors
PubMed: 38868874
DOI: 10.7754/Clin.Lab.2024.231223 -
Journal of Medical Case Reports Jun 2024Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by...
BACKGROUND
Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a potentially life-threatening clinical condition characterized by bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia. It constitutes a vicious circle in which the accumulation of pharmacologically active compounds and hyperkalemia lead to hemodynamic instability and heart failure.
CASE PRESENTATION
A 66-year-old Caucasian female patient was admitted to the emergency department presenting with fatigue and bradycardia. Upon examination, the patient was found to be anuric and hypotensive. Laboratory investigations revealed metabolic acidosis and hyperkalemia. Clinical evaluation suggested signs of digoxin toxicity, with serum digoxin concentrations persistently elevated over several days. Despite the implementation of antikalemic measures, the patient's condition remained refractory, necessitating renal dialysis and administration of digoxin immune fab.
CONCLUSION
Bradycardia, renal failure, atrioventricular (AV) node blocking, shock, and hyperkalemia syndrome is a life-threatening condition that requires prompt management. It is important to also consider potential coexisting clinical manifestations indicative of intoxication from other pharmacological agents. Specifically, symptoms associated with the accumulation of drugs eliminated via the kidneys, such as digoxin. These manifestations may warrant targeted therapeutic measures.
Topics: Humans; Female; Aged; Digoxin; Hyperkalemia; Bradycardia; Renal Dialysis; Renal Insufficiency; Anti-Arrhythmia Agents; Syndrome; Acidosis; Shock; Atrioventricular Block; Immunoglobulin Fab Fragments
PubMed: 38851740
DOI: 10.1186/s13256-024-04600-5 -
JACC. Clinical Electrophysiology May 2024
PubMed: 38842976
DOI: 10.1016/j.jacep.2024.04.013 -
Drugs - Real World Outcomes Jun 2024Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily....
BACKGROUND
Digoxin is a widely prescribed drug for congestive heart failure and atrial fibrillation. Digoxin has a narrow therapeutic index and toxicity can develop quite easily. Digoxin immune fab (DIF) is an effective treatment for toxicity, however there are limited studies characterizing its impact on clinical outcomes in real-world clinical practice.
OBJECTIVES
The aim of this study was to identify factors and healthcare outcomes associated with digoxin immune fab (DIF) treatment in patients with confirmed/suspected digoxin toxicity.
METHODS
An IRB-approved retrospective chart review of digoxin toxic patients (2011-2020) presenting at an academic healthcare system was conducted. Demographic and clinical data were collected. Patients were stratified by DIF treatment versus non-DIF treatment. DIF utilization patterns (appropriate, use when not indicated, or underutilized) were determined using pre-defined criteria. Severe digoxin toxicity was defined as having one or more of the following: mental status disturbances, antiarrhythmic therapy, acute renal impairment or dehydration, serum digoxin concentration (SDC) > 4 ng/mL, or serum K+ > 5 mEq/mL. Logistic multivariable regression analysis evaluated factors associated with DIF use. All statistical analyses were performed in R version 4.1.
RESULTS
Data from 96 patients (non-DIF treated group = 49; DIF treated group = 47) were analyzed. DIF was used appropriately in 70 patients (73%), underutilized in 19 (20%), and administered to 7 (7%) patients when it was not indicated. Several clinical parameters differentiated the DIF from the non-DIF group (p < 0.05) including higher mean SDC (3.41 ± 1.63 vs 2.87 ± 1.17), higher mean potassium (5.33 ± 1.48 vs 4.55 ± 0.87), more toxicity severity (85% vs 49%), and more likely to require cardiac pacing (26% vs 4%). Digoxin toxicity resolved sooner in the DIF group (coefficient - 0.702, 95% CI - 1.137 to - 0.267) (p < 0.01) and they had shorter intensive care unit lengths of stay (12.4 ± 20.3 vs 24.4 ± 28.7 days; p = 0.018). The all-cause mortality rate in patients appropriately managed with DIF therapy versus those patients where DIF was underutilized was 11% and 21%, respectively.
CONCLUSIONS
Based on our study population, DIF therapy appears to be beneficial in limiting duration of toxicity and intensive care unit lengths of stay in digoxin toxic patients. Although DIF was appropriately utilized in most cases, there was a relatively high proportion of cases in which DIF treatment was either underutilized or not indicated.
PubMed: 38839728
DOI: 10.1007/s40801-024-00435-0 -
Journal of the American Geriatrics... Jun 2024The use of potentially inappropriate medications (PIMs) is associated with increased risk of hospitalizations and emergency room visits and varies by racial and ethnic...
BACKGROUND
The use of potentially inappropriate medications (PIMs) is associated with increased risk of hospitalizations and emergency room visits and varies by racial and ethnic subgroups. Medicare's nationwide medication therapy management (MTM) program requires that Part D plans offer an annual comprehensive medication review (CMR) to all beneficiaries who qualify, and provides a platform to reduce PIM use. The objective of this study was to assess the impact of CMR on PIM discontinuation in Medicare beneficiaries and whether this differed by race or ethnicity.
METHODS
Retrospective cohort study of community-dwelling Medicare Part D beneficiaries ≥66 years of age who were eligible for MTM from 2013 to 2019 based on 5% Medicare fee-for-service claims data linked to the 100% MTM data file. Among those using a PIM, MTM-eligible CMR recipients were matched to non-recipients via sequential stratification. The probability of PIM discontinuation was estimated using regression models that pooled yearly subcohorts accounting for within-beneficiary correlations. The most common PIMs that were discontinued after CMR were reported.
RESULTS
We matched 24,368 CMR recipients to 24,368 CMR non-recipients during the observation period. Median age was 74-75, 35% were males, most were White beneficiaries (86%-87%), and the median number of PIMs was 1. In adjusted analyses, CMR receipt was positively associated with PIM discontinuation (adjusted relative risk [aRR]: 1.26, 95% CI: 1.20-1.32). There was no evidence of differential impact of CMR by race or ethnicity. The PIMs most commonly discontinued after CMR were glimepiride, zolpidem, digoxin, amitriptyline, and nitrofurantoin.
CONCLUSIONS
Among Medicare beneficiaries who are using a PIM, CMR receipt was associated with PIM discontinuation, suggesting that greater CMR use could facilitate PIM reduction for all racial and ethnic groups.
PubMed: 38826070
DOI: 10.1111/jgs.19013 -
Current Problems in Cardiology May 2024Atrial fibrillation (AF) is common, but there are limited data to guide selection of rate control medications (RCM). Reasons for selection are multivariable, and the... (Review)
Review
Atrial fibrillation (AF) is common, but there are limited data to guide selection of rate control medications (RCM). Reasons for selection are multivariable, and the impact on outcomes is unknown. We investigated prescribing patterns of RCM among patients with AF. Using a nationwide database, we identified 135,927 patients with AF. We stratified by baseline presence of heart failure with reduced ejection fraction (HFrEF) and examined prescription rates of RCM as a function of clinical variables. We also evaluated associations with clinical outcomes. Beta blockers (BB) were most commonly prescribed (44.6%), then calcium channel blockers (CCB) (14.0%) and digoxin (8.6%). Patients prescribed BB were more likely male (45.6% vs 43.4%, p < 0.0001), patients prescribed CCB were less likely male (12.0% vs 16.3%, p < 0.0001). There were higher rates of HF hospitalization (HFH) among females and those with Medicaid. Randomized trials are needed to define optimal choice of RCM.
PubMed: 38823526
DOI: 10.1016/j.cpcardiol.2024.102669 -
British Journal of Clinical Pharmacology May 2024Common genetic variations in the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. In a previous study, we observed an...
AIMS
Common genetic variations in the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. In a previous study, we observed an association between the rs10494366 variant of this gene and an increased QT-interval shortening in digoxin users. As QT-interval shortening is a risk factor for sudden cardiac death (SCD), in this study, we investigated whether the association between digoxin use and risk of SCD differs in participants with different NOS1AP rs10494366 genotypes.
METHODS
We included 11 377 individuals from the prospective population-based cohort of the Rotterdam Study. We used Cox proportional hazard regression analysis with digoxin as time-dependent exposure to estimate the associations between current digoxin use and the risk of SCD among different rs10494366 genotype groups in the adjusted models. We also studied whether such an association was dose-dependent, comparing high dosage (≥ 0.250 mg), moderate dosage (0.125 mg ≤ dose< 0.250 mg) and low dosage (< 0.125 mg) digoxin users with non-users.
RESULTS
The median baseline age of the total study population was 62 (interquartile range [IQR] 58-71) years. The cumulative incidence of SCD was 4.1% (469 cases), and among them, 74 (15.7%) individuals were current digoxin users at the time of death, during a median follow-up of 11.5 (IQR 6.5-17) years. Current digoxin users had an increased risk of SCD (multivariable adjusted model hazard ratio [HR]: 3.07; 95% confidence interval [CI]: 2.38-3.98), with no significant differences between the three genotype groups. The adjusted HRs were 4.03 [95% CI: 1.98-8.21] in the minor homozygous GG, 3.46 [95% CI: 2.37-5.04] in the heterozygous TG and 2.56 [95%CI: 1.70-3.86] in the homozygous TT genotype groups. Compared to low- and moderate-dose, high-dose digoxin users with GG genotype had the highest risk of SCD (HR: 5.61 [95% CI: 1.34-23.47]).
CONCLUSIONS
Current use of digoxin is associated with a significantly increased risk of SCD. The NOS1AP gene rs10494366 variant did not modify the digoxin-associated risk of SCD in a population of European ancestry.
PubMed: 38822495
DOI: 10.1111/bcp.16130