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EBioMedicine May 2024Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called...
BACKGROUND
Active surveillance pharmacovigilance is an emerging approach to identify medications with unanticipated effects. We previously developed a framework called pharmacopeia-wide association studies (PharmWAS) that limits false positive medication associations through high-dimensional confounding adjustment and set enrichment. We aimed to assess the transportability and generalizability of the PharmWAS framework by using medical claims data to reproduce known medication associations with Clostridioides difficile infection (CDI) or gastrointestinal bleeding (GIB).
METHODS
We conducted case-control studies using Optum's de-identified Clinformatics Data Mart Database of individuals enrolled in large commercial and Medicare Advantage health plans in the United States. Individuals with CDI (from 2010 to 2015) or GIB (from 2010 to 2021) were matched to controls by age and sex. We identified all medications utilized prior to diagnosis and analysed the association of each with CDI or GIB using conditional logistic regression adjusted for risk factors for the outcome and a high-dimensional propensity score.
FINDINGS
For the CDI study, we identified 55,137 cases, 220,543 controls, and 290 medications to analyse. Antibiotics with Gram-negative spectrum, including ciprofloxacin (aOR 2.83), ceftriaxone (aOR 2.65), and levofloxacin (aOR 1.60), were strongly associated. For the GIB study, we identified 450,315 cases, 1,801,260 controls, and 354 medications to analyse. Antiplatelets, anticoagulants, and non-steroidal anti-inflammatory drugs, including ticagrelor (aOR 2.81), naproxen (aOR 1.87), and rivaroxaban (aOR 1.31), were strongly associated.
INTERPRETATION
These studies demonstrate the generalizability and transportability of the PharmWAS pharmacovigilance framework. With additional validation, PharmWAS could complement traditional passive surveillance systems to identify medications that unexpectedly provoke or prevent high-impact conditions.
FUNDING
U.S. National Institute of Diabetes and Digestive and Kidney Diseases.
Topics: Humans; Clostridium Infections; Case-Control Studies; Pharmacovigilance; Male; Gastrointestinal Hemorrhage; Female; Aged; Clostridioides difficile; Middle Aged; Anti-Bacterial Agents; United States; Risk Factors; Adult; Aged, 80 and over
PubMed: 38653188
DOI: 10.1016/j.ebiom.2024.105130 -
Health Science Reports Apr 2024Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health,...
BACKGROUND AND AIM
Obesity affects nearly 650 million adults worldwide, and the prevalence is steadily rising. This condition has significant adverse effects on cardiovascular health, increasing the risk of hypertension, coronary artery disease, heart failure, and atrial fibrillation (AF). While anticoagulation for obese patients with AF is a well-established therapy for the prevention of thromboembolism, the safety and efficacy of different anticoagulants in this specific population are not well explored. This meta-analysis aimed to compare direct oral anticoagulants (DOAC) to vitamin K antagonists in obese populations with AF.
METHODS
The PRISMA guidelines were followed for this meta-analysis, registered in PROSPERO (CRD42023392711). PubMed, PubMed Central, Embase, Cochrane Library, and Scopus databases were searched for relevant articles from inception through January 2023. Two independent authors screened titles and abstracts, followed by a full-text review in Covidence. Data were extracted in Microsoft Excel and analyzed using RevMan v5.4 using odds ratio as an effect measure.
RESULTS
Two thousand two hundred fifty-nine studies were identified from the database search, and 18 were included in the analysis. There were statistically significant reductions in the odds of ischemic and hemorrhagic stroke in the DOAC group compared with the VKA group (OR 0.70, CI 0.66-0.75) and (OR 0.47, CI 0.35-0.62), respectively. In addition, the DOAC group exhibited lower odds of systemic embolism (OR 0.67, CI 0.54-0.83), major bleeding (OR 0.62, CI 0.54-0.72), and composite outcome (OR 0.72, CI 0.63-0.81).
CONCLUSION
Based on the findings from this meta-analysis, DOACs demonstrate superior safety and efficacy in obese patients with AF compared with VKAs. These results may have significant implications for guiding anticoagulation strategies in this patient population.
PubMed: 38650729
DOI: 10.1002/hsr2.2044 -
The American Journal of Case Reports Apr 2024BACKGROUND We present a case of metachronous cardiac and intramuscular metastases in a patient with a known history of radical nephroureterectomy for upper-tract...
BACKGROUND We present a case of metachronous cardiac and intramuscular metastases in a patient with a known history of radical nephroureterectomy for upper-tract urothelial carcinoma (UTUC). CASE REPORT A 58-year-old man had a history of metachronous renal pelvis urothelial carcinoma with prior left radical nephroureterectomy. He was also diagnosed with malignancy-associated deep vein thrombosis (DVT) and was on rivaroxaban. He presented at an oncology follow-up consult with shortness of breath and right scapular lump. CT scan revealed a soft-tissue mass at the surgical bed suspicious for local recurrence, as well as intracardiac hypodensities and intramuscular nodules in the right latissimus dorsi and right adductor muscles. The intracardiac hypodensities were located in the left atrial appendage and inter-atrial septum. Given that the patient had a history of DVT and in a pro-thrombotic state, differentials for the intracardiac densities included intracardiac thrombi or metastases. The intramuscular hypodensities were rim-enhancing. Given that the patient was on rivaroxaban, differentials included hematomas or metastases. As there was no overlying bruising and the lesions remained unchanged in size clinically, they were treated as metastases. The patient was treated with clexane but re-presented with worsening of shortness of breath and palpitations. CT scan showed increased size of intracardiac lesions, suggesting no response to anticoagulation, and therefore were likely metastatic in nature. He completed a 2-year course of IV pembrolizumab and was in complete remission. CONCLUSIONS Our case highlights the importance of this clinically challenging scenario when patients with known malignancy and on anticoagulation present with cardiac or musculoskeletal symptoms. Though these patients are at risk of thrombus and haematoma, cardiac and intramuscular metastasis should be considered, as the prognosis is guarded.
Topics: Humans; Male; Middle Aged; Nephroureterectomy; Heart Neoplasms; Muscle Neoplasms; Carcinoma, Transitional Cell; Kidney Neoplasms; Neoplasms, Second Primary; Venous Thrombosis; Tomography, X-Ray Computed
PubMed: 38650318
DOI: 10.12659/AJCR.942864 -
Clinical and Applied... 2024Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though... (Review)
Review
Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.
Topics: Humans; Administration, Oral; Anticoagulants; Drug Monitoring; Factor Xa Inhibitors; Blood Coagulation Tests
PubMed: 38650302
DOI: 10.1177/10760296241241524 -
Frontiers in Veterinary Science 2024Rivaroxaban, a specific factor Xa inhibitor and commonly utilized anticoagulant, has been known to cause hepatotoxicity and liver failure in humans. Although rivaroxaban...
Rivaroxaban, a specific factor Xa inhibitor and commonly utilized anticoagulant, has been known to cause hepatotoxicity and liver failure in humans. Although rivaroxaban is frequently used in veterinary medicine, hepatotoxicity has not been previously reported in dogs. The current case report describes a dog that developed severe hepatopathy following rivaroxaban administration for a large right pulmonary artery thrombus. An estimated 6-year-old spayed female mixed-breed dog developed anorexia and lethargy 9 days after rivaroxaban administration began. Subsequent labwork revealed severe hepatocellular hepatopathy, and rivaroxaban was discontinued. Additional diagnostics did not reveal an underlying etiology, although hepatic cytology could be consistent with a toxic injury. The hepatopathy and clinical signs improved after rivaroxaban was discontinued. The time to onset, type of hepatopathy, and time to resolution were all similar to those reported for human cases. This case provides precedence to advocate for improved and closer monitoring of dogs receiving factor Xa inhibitors. In cases of suspected hepatotoxicity with no other identifiable cause, a risk-benefit analysis should be performed, and discontinuation of rivaroxaban administration or alternative anticoagulant medications should be considered.
PubMed: 38638638
DOI: 10.3389/fvets.2024.1364677 -
Cureus Mar 2024Pemphigus vulgaris is a chronic autoimmune disease of the skin caused by the production of autoantibodies targeting desmogleins 1 and 3 usually presenting in individuals...
Pemphigus vulgaris is a chronic autoimmune disease of the skin caused by the production of autoantibodies targeting desmogleins 1 and 3 usually presenting in individuals with an average age of onset of approximately 40 years. A 35-year-old obese, diabetic woman presented with fluid-filled lesions over her body for three months along with erosions and painful ulcers in her mouth and genital area for two months. Based on clinical and histopathological studies, the patient was diagnosed as a case of pemphigus vulgaris. She was started on conventional treatment with oral corticosteroids followed by pulse therapy and mycophenolate mofetil. Rituximab infusion was scheduled but could not be administered due to elevated D-dimer values. The patient underwent screening for deep vein thrombosis (DVT) and received subcutaneous enoxaparin and oral rivaroxaban. She developed severe sepsis for which she was treated with systemic antibiotics. She subsequently developed acute renal failure and underwent hemodialysis. The patient's clinical condition further deteriorated, which necessitated therapeutic plasma exchange (TPE). Collagen, colloidal silver, and silicone foam dressings were done to hasten wound healing. Two distinct approaches were employed to eliminate the pseudomembrane on the wounds. One portion was treated with hydrogen peroxide (HO), while the other was with hyaluronidase. The hyaluronidase treatment resulted in considerable improvement of the lesions. Intravenous immunoglobulin (IVIG) infusion was scheduled. However, the treatment could not be administered as the patient succumbed to death due to pulmonary thromboembolism (PTE) secondary to DVT.
PubMed: 38633948
DOI: 10.7759/cureus.56357 -
Risk Management and Healthcare Policy 2024This study aims to conduct a comprehensive cost-effectiveness comparison between novel oral anticoagulants (NOACs) and warfarin in Chinese patients with left ventricular...
PURPOSE
This study aims to conduct a comprehensive cost-effectiveness comparison between novel oral anticoagulants (NOACs) and warfarin in Chinese patients with left ventricular thrombosis (LVT). By incorporating the impact of volume-based procurement (VBP) policy for pharmaceuticals in China, this analysis intends to provide crucial insights for informed healthcare decision-making.
PATIENTS AND METHODS
A Markov model was employed to simulate the disease progression of LVT over a 54-week time horizon, using weekly cycles and six mutually exclusive health states. The model incorporated transition probabilities between health states calculated based on clinical trial data and literature sources. Various cost and utility parameters were also included. Additionally, a series of sensitivity analyses were conducted to address parameter variations and associated uncertainties.
RESULTS
The study finding suggest that from the perspective of Chinese healthcare, the majority of brand-name drug (BND) NOACs generally lack cost-effectiveness when compared to warfarin. However, when considered the VBP policy, NOACs, particularly rivaroxaban, prove to be more cost-effective than warfarin. Rivaroxaban provided an additional 0.0304 quality-adjusted life years (QALYs) per patient and reduced overall medical costs by 9095.73 CNY, resulting in an incremental cost-effectiveness ratio (ICER) of -298,786.20 CNY/QALY. Sensitivity analysis indicated a 78.4% probability of any NOACs being more cost-effective compared to warfarin. However, specifically considering NOACs under the VBP policy, the likelihood of them being more cost-effective approached 90%.
CONCLUSION
Taking into account Chinese pharmaceutical procurement policies, the findings highlight the superior efficacy of NOACs, especially rivaroxaban, in enhancing both the quality of life and economic benefits for Chinese LVT patients. NOACs present a more cost-effective treatment option, improving patient quality of life and healthcare cost efficiency compared to warfarin.
PubMed: 38633670
DOI: 10.2147/RMHP.S454463 -
Frontiers in Pediatrics 2024Direct Oral Anticoagulants (DOACs) typically exhibit a predictable pharmacokinetic and pharmacodynamic response at a fixed dose, not necessitating monitoring under...
Direct Oral Anticoagulants (DOACs) typically exhibit a predictable pharmacokinetic and pharmacodynamic response at a fixed dose, not necessitating monitoring under standard conditions. Yet, in specific clinical scenarios that can impair it, like Congenital Nephrotic Syndrome (CNS) or Short Bowel Syndrome (SBS) due to absorption issues, anti-thrombin III (AT-III) deficiency and non-selective proteinuria, adjusting the dosage to achieve appropriate plasma concentrations could prove beneficial. We report a 3-month-old female with catheter-related jugular thrombosis affected by CNS concomitant to SBS and failure of both treatments with heparin and warfarin, that was switched to dose-adjusted pediatric rivaroxaban. Rivaroxaban was adjusted to reach peak levels between 189 and 419 ng/ml and the lower trough levels between 6 and 87 ng/ml. Increasing doses were needed due to SBS related malabsorption but a complete permeabilization of the vein was achieved without bleeding complications. The use of anti-Xa adjusted rivaroxaban could be an alternative to improve anticoagulation and secondary thromboprophylaxis in pediatric patients SBS and an option to children with CNS.
PubMed: 38633324
DOI: 10.3389/fped.2024.1385065 -
Journal of Cardiothoracic Surgery Apr 2024Patients requiring coronary artery bypass grafting (CABG) are often loaded with antithrombotic drugs (AT) and are at an increased risk for perioperative bleeding...
BACKGROUND
Patients requiring coronary artery bypass grafting (CABG) are often loaded with antithrombotic drugs (AT) and are at an increased risk for perioperative bleeding complications. Active AT removal by a hemoadsorption cartridge integrated in the cardiopulmonary bypass circuit is increasingly used in this setting to reduce bleeding, and herein we describe the extension of this application in patients on AT undergoing off-pump coronary artery bypass (OPCAB).
METHODS
Ten patients (80% male; mean age: 67.4 ± 9.2years) were treated with ticagrelor (eight patients), rivaroxaban and ticagrelor (one patient), and rivaroxaban (one patient) prior to OPCAB surgery. AT's were discontinued one day before surgery in nine patients and on the day of surgery in one patient, and all patients were also on aspirin. The cohort mean EuroSCORE-II was 2.9 ± 1.5%. A hemoadsorption cartridge was integrated into a dialysis device (n=4) or a stand-alone apheresis pump (n=6) periprocedural, for a treatment time of 145 ± 33 min. Outcome measures included bleeding according to Bleeding Academic Research Consortium (BARC)-4 and 24-hour chest-tube-drainage (CTD).
RESULTS
Mean operation time was 184 ± 35 min. All patients received a left internal thoracic artery with a mean of 2.3 ± 0.9 total grafts. One patient had a BARC-4 bleeding event and there were no surgical re-explorations for bleeding. Mean 24-hours CTD was 680 ± 307mL. During follow-up of 19.5 ± 17.0 months, none of the patients died or required further reinterventions. No device-related adverse events were reported.
CONCLUSIONS
Hemoadsorption via a stand-alone apheresis pump during OPCAB surgery was feasible and safe. This innovative and new approach showed favorable bleeding rates in patients on antithrombotic drugs requiring bypass surgery.
Topics: Humans; Male; Middle Aged; Aged; Female; Coronary Artery Bypass, Off-Pump; Fibrinolytic Agents; Ticagrelor; Rivaroxaban; Coronary Artery Bypass; Treatment Outcome
PubMed: 38632635
DOI: 10.1186/s13019-024-02772-1 -
European Heart Journal May 2024
PubMed: 38630622
DOI: 10.1093/eurheartj/ehae227