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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 -
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 -
Theranostics 2024Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene...
Acetaminophen (APAP) overdosing is a major cause of acute liver failure worldwide and an established model for drug-induced acute liver injury (ALI). While studying gene expression during murine APAP-induced ALI by 3'mRNA sequencing (massive analysis of cDNA ends, MACE), we observed splenic mRNA accumulation encoding for the neutrophil serine proteases cathepsin G, neutrophil elastase, and proteinase-3 - all are hierarchically activated by cathepsin C (CtsC). This, along with increased serum levels of these proteases in diseased mice, concurs with the established phenomenon of myeloid cell mobilization during APAP intoxication. In order to functionally characterize CtsC in murine APAP-induced ALI, effects of its genetic or pharmacological inhibition were investigated. We report on substantially reduced APAP toxicity in CtsC deficient mice. Alleviation of disease was likewise observed by treating mice with the CtsC inhibitor AZD7986, both in short-term prophylactic and therapeutic protocols. This latter observation indicates a mode of action beyond inhibition of granule-associated serine proteases. Protection in CtsC knockout or AZD7986-treated wildtype mice was unrelated to APAP metabolization but, as revealed by MACE, realtime PCR, or ELISA, associated with impaired expression of inflammatory genes with proven pathogenic roles in ALI. Genes consistently downregulated in protocols tested herein included , , and . Moreover, , a positive regulator of the toll-like receptor/interferon-axis, was reduced by targeting CtsC. This work suggests CtsC as promising therapeutic target for the treatment of ALI, among others paradigmatic APAP-induced ALI. Being also currently evaluated in phase III clinical trials for bronchiectasis, successful application of AZD7986 in experimental APAP intoxication emphasizes the translational potential of this latter therapeutic approach.
Topics: Animals; Acetaminophen; Cathepsin C; Mice; Chemical and Drug Induced Liver Injury; Mice, Inbred C57BL; Mice, Knockout; Male; Disease Models, Animal
PubMed: 38855187
DOI: 10.7150/thno.96092 -
Cureus May 2024Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the...
Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.
PubMed: 38854268
DOI: 10.7759/cureus.59874 -
BMJ Paediatrics Open Jun 2024Neural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited...
Determinants of neural tube defect among newborns admitted to neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, Southern Ethiopia: a case-control study.
BACKGROUND
Neural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited attention. In Ethiopia, the estimated number of neural tube defect cases was significantly higher. So, identifying factors contributing to it would be significant for planning risk reduction and preventive strategies. Therefore, identifying the possible determinants was aimed at this study.
METHODS
A hospital-based, unmatched case-control study was conducted on 104 cases and 208 controls selected from neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, southern Ethiopia from December 2021 to November 2022. All neural tube defect cases were included consecutively and controls were selected by using a simple random sampling method. Data were collected using interviewer-administered semistructured questionnaires. Data analysis was done by using SPSS V.25. Binary logistic regression was used, and variables with a p value less than 0.25 in bivariate analysis were entered into the multivariable logistic regression model. An adjusted OR with a 95% CI was estimated, and finally, variables that show a level of p value less than 0.05 in multivariable analysis were declared statistically significant.
RESULT
After controlling confounders, factors such as unplanned pregnancy 2.20 (95% CI 1.20 to 4.041), history of abortions 2.09 (95% CI 1.19 to 3.67), khat chewing 6.67 (95% CI 2.95 to 15.06), antipyretic and analgesic medications 2.87 (95% CI 1.47 to 5.56) and, being a female neonate 2.11 (95% CI 1.21 to 3.67) were significantly associated with a neural tube defect.
CONCLUSION
This study has identified some determinants of neural tube defects. Hence, the behavioural, medical and obstetrical conditions of mothers need serious evaluation in the prepregnancy period. So, improving preconception counselling and prenatal care practices would have a significant role in reducing the risk of neural tube defects.
Topics: Humans; Ethiopia; Female; Case-Control Studies; Infant, Newborn; Intensive Care Units, Neonatal; Hospitals, Teaching; Male; Pregnancy; Neural Tube Defects; Adult; Risk Factors; Young Adult
PubMed: 38844382
DOI: 10.1136/bmjpo-2023-002235