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Current Opinion in Clinical Nutrition... Mar 2024Unintentional intoxication comprises a major chunk of all intoxications. Most patients are in the pediatric age group with another set of patients being the elderly.... (Review)
Review
PURPOSE OF REVIEW
Unintentional intoxication comprises a major chunk of all intoxications. Most patients are in the pediatric age group with another set of patients being the elderly. Substances found to cause accidental intoxication vary from country to country and even within different regions of a country. Frequent reviews of current literature are needed to be abreast of trends.
RECENT FINDINGS
Prescription drugs and household chemicals are major culprits when it comes to accidental intoxication. Acetaminophen, digoxin and metformin are some of the prominent prescription drugs frequently associated with unintentional intoxications. Increasingly alcohol based hand sanitizers are becoming an important etiology of these events, following their increased usage during the COVID-19 pandemic. Pattern recognition to identify class of intoxicant and supportive care including prevention of further absorption and increased excretion are cornerstones of therapy. Antidote when available should be used promptly.
SUMMARY
Knowledge about current epidemiology of accidental intoxications, toxidrome pattern recognition and appropriate antidote usage beside adequate and timely supportive care help in successful management of the unfortunate victim of accidental intoxication.
Topics: Humans; Child; Aged; Antidotes; Pandemics; Ethanol; Metformin
PubMed: 38260945
DOI: 10.1097/MCO.0000000000001013 -
Emergencias : Revista de La Sociedad... Oct 2023
Topics: Humans; Digoxin
PubMed: 37801413
DOI: 10.55633/s3me/E022.2023 -
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 -
Critical Care Medicine Sep 2023To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.
OBJECTIVES
To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.
DESIGN
Multicenter, prospective, inception cohort study.
SETTING
Forty-four ICUs in 12 countries in four geographical regions.
SUBJECTS
Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99).
CONCLUSIONS
In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.
Topics: Adult; Humans; Atrial Fibrillation; Cohort Studies; Prospective Studies; Incidence; Risk Factors; Intensive Care Units
PubMed: 37078722
DOI: 10.1097/CCM.0000000000005883 -
JACC. Heart Failure Apr 2024Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is).
OBJECTIVES
The authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF.
METHODS
The authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality.
RESULTS
The authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%.
CONCLUSIONS
In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.
Topics: Humans; Angiotensin Receptor Antagonists; Digoxin; Heart Failure; Network Meta-Analysis; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 37656079
DOI: 10.1016/j.jchf.2023.07.014 -
The Canadian Journal of Cardiology Nov 2023
Topics: Humans; Digoxin; Atrial Fibrillation; Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Heart Rate
PubMed: 37453646
DOI: 10.1016/j.cjca.2023.07.013 -
Therapie 2024Drug-induced hyperglycemia and diabetes have negative and potentially serious health consequences but can often be unnoticed. (Review)
Review
BACKGROUND
Drug-induced hyperglycemia and diabetes have negative and potentially serious health consequences but can often be unnoticed.
METHODS
We reviewed the literature searching Medline database for articles addressing drug-induced hyperglycemia and diabetes up to January 31, 2023. We also selected drugs that could induce hyperglycemia or diabetes according official data from drug information databases Thériaque and Micromedex. For each selected drug or pharmacotherapeutic class, the mechanisms of action potentially involved were investigated. For drugs considered to be at risk of hyperglycemia or diabetes, disproportionality analyses were performed using data from the international pharmacovigilance database VigiBase. In order to detect new pharmacovigilance signals, additional disproportionality analyses were carried out for drug classes with more than 100 cases reported in VigiBase, but not found in the literature or official documents.
RESULTS
The main drug classes found to cause hyperglycemia are glucocorticoids, HMG-coA reductase inhibitors, thiazide diuretics, beta-blockers, antipsychotics, fluoroquinolones, antiretrovirals, antineoplastic agents and immunosuppressants. The main mechanisms involved are alterations in insulin secretion and sensitivity, direct cytotoxic effects on pancreatic cells and increases in glucose production. Pharmacovigilance signal were found for a majority of drugs or pharmacological classes identified as being at risk of diabetes or hyperglycemia. We identified new pharmacovigilance signals with drugs not known to be at risk according to the literature or official data: phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, sodium oxybate, biphosphonates including alendronic acid, digoxin, sartans, linosipril, diltiazem, verapamil, and darbepoetin alpha. Further studies will be needed to confirm these signals.
CONCLUSIONS
The risks of induced hyperglycemia vary from one drug to another, and the underlying mechanisms are multiple and potentially complex. Clinicians need to be vigilant when using at-risk drugs in order to detect and manage these adverse drug reactions. However, it is to emphasize that the benefits of appropriately prescribed treatments most often outweigh their metabolic risks.
Topics: Humans; Adverse Drug Reaction Reporting Systems; Diabetes Mellitus; Hyperglycemia; Pharmacovigilance; Drug-Related Side Effects and Adverse Reactions; Databases, Factual
PubMed: 37985310
DOI: 10.1016/j.therap.2023.09.010 -
European Journal of Emergency Medicine... Dec 2023There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus... (Review)
Review
There are currently no universally accepted guidelines for the management of digoxin toxicity. In the absence of clinical practice guidelines, a set of consensus recommendations for management of digoxin toxicity in the clinical setting were developed through a modified Delphi approach. The recommendations highlight the importance of early recognition of signs of potentially life-threatening toxicity that requires immediate treatment with digoxin-specific antibodies. The consensus identifies a straightforward approach to dosing immune antibody fragments according to the presence or absence of signs of life-threatening toxicity. Supportive measures and management of specific signs of toxicity are also covered.
Topics: Humans; Digoxin; Consensus; Drug-Related Side Effects and Adverse Reactions
PubMed: 37650725
DOI: 10.1097/MEJ.0000000000001065 -
JACC. Clinical Electrophysiology May 2024
PubMed: 38842976
DOI: 10.1016/j.jacep.2024.04.013 -
Cardiovascular Drugs and Therapy Aug 2023Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a... (Review)
Review
PURPOSE
Publishe d decades after several randomized controlled trials (RCT) demonstrating decreased hospitalizations and no effect on all-cause mortality with digoxin use, a series of meta-analyses linking digoxin treatment and mortality have contributed to a narrower application of this medication for the management of heart failure (HF) and atrial fibrillation (AF). Given the conflicting data from the earlier RCTs and more recent meta-analyses, there is a growing polarization among providers for and against the use of digoxin in managing these conditions.
METHODS
To help close this divide, we provide a perspective on the literature with special attention to the quality of both older and more recent studies on this subject.
RESULTS
The data from the highest quality studies we have, RCTs, suggest that digoxin use in patients with HF and/or AF is associated with improvement in several areas of outcomes including functional capacity, symptom management, reduced hospitalizations, fewer deaths due to HF, and treatment of refractory chronic heart failure with rEF, and may even have overall mortality benefit when serum digoxin concentrations are within therapeutic range. These effects are more pronounced in patients with EF < 25% and NYHA Class II-IV and at highest risk for hospitalization.
CONCLUSION
As the risk of confounding factors was minimized by the study design, the likelihood that positive outcomes were identified with digoxin use increased. Clinicians and researchers need further adequately designed and powered RCTs exploring the connection between digoxin therapy and mortality, hospitalizations, and symptom management.
Topics: Humans; Digitalis; Randomized Controlled Trials as Topic; Digoxin; Heart Failure; Atrial Fibrillation
PubMed: 34748147
DOI: 10.1007/s10557-021-07287-8