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Praxis May 2024For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID...
For 7 years we gained experience of how asthma and chronic rhinosinusitis with nasal polyposis respond to biologics. In contrast, it is much less known, how ASA/NSAID intolerance (Widal's disease) behaves under biologicals. We therefore describe the case of a patient with both clinical conditions who reacted with a severe intolerance reaction under perioperative metamizole administration.
Topics: Humans; Nasal Polyps; Asthma, Aspirin-Induced; Sinusitis; Dipyrone; Female; Middle Aged; Asthma; Male; Rhinitis; Anti-Asthmatic Agents; Diagnosis, Differential; Antibodies, Monoclonal, Humanized; Undertreatment
PubMed: 38864100
DOI: 10.23785/PRAXIS.2024.05.005 -
Cureus May 2024We present an atypical case of risedronate-induced chronic fever in an 85-year-old woman with Parkinson's disease, with a dosage regimen of 17.5 mg/week. Our patient had...
We present an atypical case of risedronate-induced chronic fever in an 85-year-old woman with Parkinson's disease, with a dosage regimen of 17.5 mg/week. Our patient had been administered an analgesic/antipyretic drug, acetaminophen, at a rate of 600 mg/day for treatment of a vertebral fracture that occurred relatively frequently, which might have masked the fever caused by risedronate. We noted two clinically significant indications. Firstly, blood test results do not necessarily show the cause of risedronate-induced fever, as white blood cell counts and C-reactive protein levels vary. A simple way to diagnose risedronate-induced fever is to suspend risedronate for a certain period and observe if the patient's fever lowers. Secondly, in general, cases receiving polypharmacy tend to include an analgesic antipyretic agent, which may mask the drug-induced fever. Even in patients with Parkinson's disease whose body temperature is generally unstable due to autonomic nerve system disorder, if they are administered risedronate and experience chronic fever of unknown cause, the possibility of drug fever may be considered. This study concludes that risedronate-induced chronic fever, as observed in our case, represents a rare phenomenon, and it may be necessary to reconsider treatment methods for osteoporosis.
PubMed: 38864058
DOI: 10.7759/cureus.60117 -
Upsala Journal of Medical Sciences 2024Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses...
BACKGROUND
Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
METHODS
A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
RESULTS
Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
CONCLUSION
Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.
Topics: Humans; Hypnotics and Sedatives; Analgesics; Male; Female; Middle Aged; Aged; Intensive Care Units; Prospective Studies; Adult; Midazolam; Critical Care; Dexmedetomidine; Fentanyl; Critical Illness; Propofol; Clonidine; Ketamine; Morphine; Aged, 80 and over; Dose-Response Relationship, Drug; Thiopental; Acetaminophen
PubMed: 38863729
DOI: 10.48101/ujms.v129.10560 -
BMC Infectious Diseases Jun 2024Sepsis is a life-threatening disease accompanied by disorders of the coagulation and immune systems. P2Y12 inhibitors, widely used for arterial thrombosis prevention and...
BACKGROUND
Sepsis is a life-threatening disease accompanied by disorders of the coagulation and immune systems. P2Y12 inhibitors, widely used for arterial thrombosis prevention and treatment, possess recently discovered anti-inflammatory properties, raising potential for improved sepsis prognosis.
METHOD
We conducted a retrospective analysis using the data from Medical Information Mart for Intensive Care-IV database. Patients were divided into an aspirin-alone group versus a combination group based on the use of a P2Y12 inhibitor or not. Differences in 30-day mortality, length of stay (LOS) in intensive care unit (ICU), LOS in hospital, bleeding events and thrombotic events were compared between the two groups.
RESULT
A total of 1701 pairs of matched patients were obtained by propensity score matching. We found that no statistically significant difference in 30-day mortality in aspirin-alone group and combination group (15.3% vs. 13.7%, log-rank p = 0.154). In addition, patients received P2Y12 inhibitors had a higher incidence of gastrointestinal bleeding (0.5% vs. 1.6%, p = 0.004) and ischemic stroke (1.7% vs. 2.9%, p = 0.023), despite having a shorter LOS in hospital (11.1 vs. 10.3, days, p = 0.043). Cox regression showed that P2Y12 inhibitor was not associated with 30-day mortality (HR = 1.14, 95% CI 0.95-1.36, p = 0.154).
CONCLUSION
P2Y12 inhibitors did not provide a survival benefit for patients with sepsis 3 and even led to additional adverse clinical outcomes.
Topics: Humans; Male; Female; Sepsis; Aspirin; Retrospective Studies; Propensity Score; Aged; Middle Aged; Purinergic P2Y Receptor Antagonists; Length of Stay; Intensive Care Units; Treatment Outcome; Aged, 80 and over; Platelet Aggregation Inhibitors
PubMed: 38862910
DOI: 10.1186/s12879-024-09421-x -
BMJ (Clinical Research Ed.) Jun 2024To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess the effect of different antiplatelet strategies on clinical outcomes after coronary artery bypass grafting.
DESIGN
Five year follow-up of randomised Different Antiplatelet Therapy Strategy After Coronary Artery Bypass Grafting (DACAB) trial.
SETTING
Six tertiary hospitals in China; enrolment between July 2014 and November 2015; completion of five year follow-up from August 2019 to June 2021.
PARTICIPANTS
500 patients aged 18-80 years (including 91 (18.2%) women) who had elective coronary artery bypass grafting surgery and completed the DACAB trial.
INTERVENTIONS
Patients were randomised 1:1:1 to ticagrelor 90 mg twice daily plus aspirin 100 mg once daily (dual antiplatelet therapy; n=168), ticagrelor monotherapy 90 mg twice daily (n=166), or aspirin monotherapy 100 mg once daily (n=166) for one year after surgery. After the first year, antiplatelet therapy was prescribed according to standard of care by treating physicians.
MAIN OUTCOME MEASURES
The primary outcome was major adverse cardiovascular events (a composite of all cause death, myocardial infarction, stroke, and coronary revascularisation), analysed using the intention-to-treat principle. Time-to-event analysis was used to compare the risk between treatment groups. Multiple post hoc sensitivity analyses examined the robustness of the findings.
RESULTS
Follow-up at five years for major adverse cardiovascular events was completed for 477 (95.4%) of 500 patients; 148 patients had major adverse cardiovascular events, including 39 in the dual antiplatelet therapy group, 54 in the ticagrelor monotherapy group, and 55 in the aspirin monotherapy group. Risk of major adverse cardiovascular events at five years was significantly lower with dual antiplatelet therapy versus aspirin monotherapy (22.6% 29.9%; hazard ratio 0.65, 95% confidence interval 0.43 to 0.99; P=0.04) and versus ticagrelor monotherapy (22.6% 32.9%; 0.66, 0.44 to 1.00; P=0.05). Results were consistent in all sensitivity analyses.
CONCLUSIONS
Treatment with ticagrelor dual antiplatelet therapy for one year after surgery reduced the risk of major adverse cardiovascular events at five years after coronary artery bypass grafting compared with aspirin monotherapy or ticagrelor monotherapy.
TRIAL REGISTRATION
NCT03987373ClinicalTrials.gov NCT03987373.
Topics: Humans; Coronary Artery Bypass; Platelet Aggregation Inhibitors; Female; Male; Middle Aged; Ticagrelor; Aspirin; Aged; Follow-Up Studies; Adult; Aged, 80 and over; Drug Therapy, Combination; Adolescent; Postoperative Complications; Treatment Outcome; Young Adult; China; Dual Anti-Platelet Therapy
PubMed: 38862179
DOI: 10.1136/bmj-2023-075707 -
BMJ (Clinical Research Ed.) Jun 2024
Topics: Humans; Coronary Artery Bypass; Platelet Aggregation Inhibitors; Dual Anti-Platelet Therapy; Aspirin; Clopidogrel
PubMed: 38862159
DOI: 10.1136/bmj.q1083 -
Stroke Jul 2024The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The atherosclerotic sources of embolism are a significant contributor to embolic stroke of undetermined source (ESUS). However, there is limited evidence for the efficacy of intensive dual antiplatelet therapy for ESUS. We conducted an investigation to determine whether gene-directed dual antiplatelet therapy could reduce the risk of recurrent stroke in patients with ESUS.
METHODS
CHANCE-2 (Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events-II) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial that objectively compared ticagrelor plus aspirin and clopidogrel plus aspirin in patients with minor stroke or transient ischemic attack who carried loss-of-function alleles in China. All study participants were classified into ESUS and non-ESUS groups for the prespecified exploratory analysis. Cox proportional hazards models were used to assess the interaction of the state of ESUS with the effects of dual antiplatelet therapy with ticagrelor-aspirin versus clopidogrel-aspirin, adjusting for sociodemographic and clinical factors.
RESULTS
The subgroup analysis comprised 5796 participants (90.4% of the total 6412 participants) in the CHANCE-2 trial, with a median age of 64.9 years (range, 57.0-71.4 years), of whom 1964 (33.9%) were female. These participants underwent diffusion-weighted imaging as part of the study protocol. After systematic evaluation, 15.2% of patients (881/5796) were deemed to have ESUS. The incidence of stroke recurrence in patients with ESUS was found to be 5.6% in the ticagrelor-aspirin group and 9.2% in the clopidogrel-aspirin group (hazard ratio, 0.57 [95% CI, 0.33-0.99]; =0.04). In patients without ESUS, the respective incidence rates were 5.6% and 7.5% (hazard ratio, 0.72 [95% CI, 0.58-0.90]; <0.01). The value was 0.56 for the treatment × ESUS status interaction effect.
CONCLUSIONS
In this prespecified exploratory analysis, ticagrelor with aspirin was superior to clopidogrel with aspirin for preventing stroke at 90 days in patients with acute ischemic stroke or transient ischemic attack who carried loss-of-function alleles and were classified as ESUS.
REGISTRATION
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04078737.
Topics: Humans; Middle Aged; Female; Male; Platelet Aggregation Inhibitors; Aged; Clopidogrel; Aspirin; Ticagrelor; Double-Blind Method; Dual Anti-Platelet Therapy; Embolic Stroke; Cytochrome P-450 CYP2C19; Stroke
PubMed: 38860396
DOI: 10.1161/STROKEAHA.124.046834 -
Journal of the American Heart... Jun 2024Coronary artery calcium testing using noncontrast cardiac computed tomography is a guideline-indicated test to help refine eligibility for aspirin in primary prevention....
Carotid Ultrasound-Based Plaque Score for the Allocation of Aspirin for the Primary Prevention of Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Atherosclerosis Risk in Communities Study.
BACKGROUND
Coronary artery calcium testing using noncontrast cardiac computed tomography is a guideline-indicated test to help refine eligibility for aspirin in primary prevention. However, access to cardiac computed tomography remains limited, with carotid ultrasound used much more often internationally. We sought to update the role of aspirin allocation in primary prevention as a function of subclinical carotid atherosclerosis.
METHODS AND RESULTS
The study included 11 379 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) and ARIC (Atherosclerosis Risk in Communities) studies. A harmonized carotid plaque score (range, 0-6) was derived using the number of anatomic sites with plaque from the left and right common, bifurcation, and internal carotid artery on ultrasound. The 5-year number needed to treat and number needed to harm as a function of the carotid plaque score were calculated by applying a 12% relative risk reduction in atherosclerotic cardiovascular disease (ASCVD) events and 42% relative increase in major bleeding events related to aspirin use, respectively. The mean age was 57 years, 57% were women, 23% were Black, and the median 10-year ASCVD risk was 12.8%. The 5-year incidence rates (per 1000 person-years) were 5.5 (4.9-6.2) for ASCVD and 1.8 (1.5-2.2) for major bleeding events. The overall 5-year number needed to treat with aspirin was 306 but was 2-fold lower for individuals with carotid plaque versus those without carotid plaque (212 versus 448). The 5-year number needed to treat was less than the 5-year number needed to harm when the carotid plaque score was ≥2 for individuals with ASCVD risk 5% to 20%, whereas the presence of any carotid plaque demarcated a favorable risk-benefit for individuals with ASCVD risk >20%.
CONCLUSIONS
Quantification of subclinical carotid atherosclerosis can help improve the allocation of aspirin therapy.
Topics: Humans; Aspirin; Female; Male; Middle Aged; Primary Prevention; Plaque, Atherosclerotic; Carotid Artery Diseases; Aged; Risk Assessment; United States; Platelet Aggregation Inhibitors; Carotid Arteries; Ultrasonography; Risk Factors; Ethnicity; Aged, 80 and over; Ultrasonography, Carotid Arteries
PubMed: 38860391
DOI: 10.1161/JAHA.123.034718 -
Drug Metabolism and Disposition: the... Jun 2024Acetaminophen (APAP) is the most used non-prescription drug throughout the world. At therapeutic doses, APAP has potent analgesic and antipyretic effects. The efficacy...
Acetaminophen (APAP) is the most used non-prescription drug throughout the world. At therapeutic doses, APAP has potent analgesic and antipyretic effects. The efficacy and safety of APAP are influenced by multi-factorial processes that are dependent upon dosing, namely frequency and total dose. APAP poisoning by repeated ingestion of supratherapeutic doses, depletes glutathione (GSH) stores in liver and other organs capable of metabolic bioactivation, leading to hepatocellular death due to exhausted antioxidant defenses. Numerous genes, encompassing transcription factors and signaling pathways, have been identified as playing pivotal roles in APAP toxicity, with the liver being the primary organ studied due to its central role in APAP metabolism and injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) and its array of downstream responsive genes are crucial in counteracting acetaminophen APAP toxicity. Nrf2, along with its negative regulator Kelch-like ECH-associated protein 1 (Keap1), plays a vital role in regulating intracellular redox homeostasis. This regulation is significant in modulating the oxidative stress, inflammation, and hepatocellular death induced by APAP. In this review, we provide an updated overview of the mechanisms through which Nrf2 activation and signaling critically influence the threshold for developing APAP toxicity. We also describe how genetically modified rodent models for Nrf2 and related genes have been pivotal in underscoring the significance of this antioxidant response pathway. While Nrf2 is a primary focus, the article comprehensively explores other genetic factors and related pathways that contribute to APAP toxicity, thereby providing a holistic understanding of the genetic landscape influencing susceptibility to this condition. This review scrutinizes the genetic elements and signaling pathways underlying acetaminophen (APAP)-induced liver toxicity, with a focus on the crucial protective role of the transcription factor NRF2. This review also delves into the genetic intricacies influencing APAP safety and potential liver harm and it emphasizes the need for deeper insight into the molecular mechanisms of hepatotoxicity, especially the interplay of NRF2 with other pathways.
PubMed: 38857948
DOI: 10.1124/dmd.124.001282 -
Cytokine Aug 2024Kawasaki disease (KD) is a vasculitis of unknown etiology in children aged under 5 years. Coronary arterial aneurysm (CAA) is the major complication of KD. It is no...
BACKGROUND
Kawasaki disease (KD) is a vasculitis of unknown etiology in children aged under 5 years. Coronary arterial aneurysm (CAA) is the major complication of KD. It is no longer though to be a self-limiting disease because its cardiovascular sequelae might persist into adulthood. NLRP3 is a key protein of the NLRP3 inflammasome that participates in sterile inflammatory disease. This study investigated the serum levels of NLRP3 in patients with KD at different stages to explore the relationships between serum NLRP3 and clinical parameters.
METHODS
A total of 247 children enrolled in this study. There were 123 patients in the acute stage of KD, and 93 healthy children made up the healthy control (HC) group. Among the acute KD patients, 52 had coronary arterial aneurysm (KD-CAA) and 71 did not (KD-NCAA). 36 patient samples were collected after IVIG and aspirin treatment. Additionally, 29 patients were in the cardiovascular sequelae stage. Enzyme-linked immunosorbent assay was used to measure serum NLRP3 levels in all subjects.
RESULTS
Serum NLRP3 was elevated in the KD group and was even higher in the KD-CAA subgroup than in the KD-NCAA subgroup of acute-stage patients. Serum NLRP3 declined when the patients were treated with IVIG and aspirin, but during the convalescent (coronary sequelae) stage, serum NLRP3 re-increased. Serum NLRP3 was higher in the ≥ 6-mm-coronary-arterial-diameter group than that the < 6-mm-diameter group. The ROC curve of serum NLRP3 indicated its utility in the prediction of both KD and KD-CAA.
CONCLUSIONS
NLRP3 may be involved in the development of KD and CAA in children with KD. Targeting NLRP3 might mitigate CAA, thereby reducing the risk of cardiovascular events in adulthood.
Topics: Humans; Mucocutaneous Lymph Node Syndrome; NLR Family, Pyrin Domain-Containing 3 Protein; Male; Female; Coronary Aneurysm; Child, Preschool; Biomarkers; Infant; Child; Aspirin; Immunoglobulins, Intravenous
PubMed: 38857561
DOI: 10.1016/j.cyto.2024.156667