Many healthcare resources have been and continue to be allocated to the management of patients with COVID-19. Therefore, the ongoing care of patients receiving oral anticoagulation with warfarin is ...likely to be compromised amid this unprecedented crisis. This article discusses a stepwise algorithm for the management of outpatient warfarin therapy. Alternative management strategies are presented and discussed, including alternative pharmacological therapy options and self-monitoring. Our algorithm aims to help clinicians safely optimize the treatment of patients requiring anticoagulation therapy in the context of the global response to the current pandemic.
Objective
Through predictable pharmacokinetics—including a convenient fixed-dose regimen, direct oral anticoagulants (DOACs) are preferred over previous treatments in anticoagulation for various ...indications. However, the association between higher body weight and the risk of adverse consequences is not well studied among DOAC users. We aim to explore the association of body weight and adverse clinical outcomes in DOAC users.
Methods
A total of 97,413 anonymised DOAC users in a tertiary care setting were identified following structured queries on the electronic health records (EHRs) to extract the feature-rich anonymised dataset. The prepared dataset was analysed, and the features identified with machine learning (ML) informed the adjustments of covariates in the multivariate regression analysis to examine the association. Kaplan–Meier analysis was performed to evaluate the mortality benefits of DOACs.
Results
Among DOAC users, the odds of adverse clinical outcomes, such as clinically relevant non-major bleeding (CRNMB), ischaemic stroke, all-cause mortality, and prolonged hospital stay, were lower in patients with overweight, obesity, or morbid obesity than in patients with normal body weight. The odds of ischaemic stroke (OR 0.42, 95% CI: 0.36–0.88,
p
= 0.001) and all-cause mortality (OR 0.87, 95% CI: 0.81–0.95,
p
= 0.001) were lower in patients with morbid obesity than in patients with normal body weight. In the Kaplan–Meier analysis, apixaban was associated with a significantly lower rate of mortality overall and in obesity and overweight subgroups than other DOACs (
p
< 0.001). However, rivaroxaban performed better than apixaban in the morbid obesity subgroup (
p
< 0.001).
Conclusion
This study shows the positive effects of DOAC therapy on clinical outcomes, particularly in patients with high body weight. However, this still needs validation by further studies particularly among patients with morbid obesity.
The clinical outcomes of direct oral anticoagulant (DOAC) dosage regimens in morbid obesity are uncertain due to limited clinical evidence. This study seeks to bridge this evidence gap by identifying ...the factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients.
A data-driven observational study was carried out using supervised machine learning (ML) models with a dataset extracted from electronic health records and preprocessed. Following 70%:30% partitioning of the overall dataset via stratified sampling, the selected ML classifiers (e.g., random forest, decision trees, bootstrap aggregation) were applied to the training dataset (70%). The outcomes of the models were evaluated against the test dataset (30%). Multivariate regression analysis explored the association between DOAC regimens and clinical outcomes.
A sample of 4,275 morbidly obese patients was extracted and analysed. The decision trees, random forest, and bootstrap aggregation classifiers achieved acceptable (excellent) values of precision, recall, and F1 scores in terms of their contribution to clinical outcomes. The length of stay, treatment days, and age were ranked highest for relevance to mortality and stroke. Among DOAC regimens, apixaban 2.5 mg twice daily ranked highest for its association with mortality, increasing the mortality risk by 43% (odds ratio OR 1.430, 95% confidence interval CI 1.181-1.732, p = 0.001). On the other hand, apixaban 5 mg twice daily reduced the odds of mortality by 25% (OR 0.751, 95% CI 0.632-0.905, p = 0.003) but increased the odds of stroke events. No clinically relevant non-major bleeding events occurred in this group.
Data-driven approaches can identify key factors associated with clinical outcomes following the dosing of DOACs in morbidly obese patients. This will help design further studies to explore well tolerated and effective DOAC doses for morbidly obese patients.
There is limited evidence to support definite clinical outcomes of direct oral anticoagulant (DOAC) therapy in chronic kidney disease (CKD). By identifying the important variables associated with ...clinical outcomes following DOAC administration in patients in different stages of CKD, this study aims to assess this evidence gap.
An anonymised dataset comprising 97,413 patients receiving DOAC therapy in a tertiary health setting was systematically extracted from the multidimensional electronic health records and prepared for analysis. Machine learning classifiers were applied to the prepared dataset to select the important features which informed covariate selection in multivariate logistic regression analysis.
For both CKD and non-CKD DOAC users, features such as length of stay, treatment days, and age were ranked highest for relevance to adverse outcomes like death and stroke. Patients with Stage 3a CKD had significantly higher odds of ischaemic stroke (OR 2.45, 95% Cl: 2.10-2.86; p = 0.001) and lower odds of all-cause mortality (OR 0.87, 95% Cl: 0.79-0.95; p = 0.001) on apixaban therapy. In patients with CKD (Stage 5) receiving apixaban, the odds of death were significantly lowered (OR 0.28, 95% Cl: 0.14-0.58; p = 0.001), while the effect on ischaemic stroke was insignificant.
A positive effect of DOAC therapy was observed in advanced CKD. Key factors influencing clinical outcomes following DOAC administration in patients in different stages of CKD were identified. These are crucial for designing more advanced studies to explore safer and more effective DOAC therapy for the population.
This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced ...data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach-if implemented in clinical practice-could optimise dosing for the DOACs for better safety and efficacy.
Background
Increasing evidence for the use of the aspirin in patients undergoing an orthopaedic surgery for venous thromboembolism prophylaxis has led to a change in the national guidelines ...substituting anticoagulants with aspirin. Little is known about the impact of such substitution on real-world outcomes from clinical practice.
Objective
The study was designed to examine clinical outcomes associated with the use of aspirin and apixaban.
Setting
Two large-scale general hospitals in West Yorkshire region of England.
Method
A 1-year observational study among adults who underwent elective knee replacements and received venous thromboembolism prophylaxis within the first 14 days post replacements.
Main outcome measure
The incidence of postoperative venous thromboembolism, leaking wounds during the hospital stay, and 30-day any readmission for the two drugs.
Results
A total of 420 patients were included. There was a significant drop in apixaban prescribing (from 80.37 to 10.51%) and increase in aspirin use (from 19.02 to 81.71%) after the implementation of the revised guidelines. There were 52 (12.38%) cases of leaking wound, 16 (3.81%) cases of postoperative venous thromboembolism, 45 (10.71%) cases of 30-day readmission and no case of 30-day major bleeding. The leaking wounds and 30-day readmissions were almost twice more frequent in obese compared to non-obese patients. Multivariate logistic regression found an increased risk of leaking wound with apixaban and postoperative venous thromboembolism and 30-day readmission with aspirin use but the differences were not statistically significant.
Conclusion
The results suggest aspirin to be as effective as apixaban in preventing venous thromboembolism and readmission. Apixaban usage decreased with a corresponding increase in Aspirin use. The impact of obesity and length of hospital stay need further investigations.
A comparison of warfarin monitoring service models Hasan, Syed Shahzad; Sunter, Wendy; Ahmed, Nadia ...
Research in social & administrative pharmacy/Research in social and administrative pharmacy,
October 2019, 2019-10-00, 20191001, Volume:
15, Issue:
10
Journal Article
Peer reviewed
Open access
Warfarin-related knowledge and patient satisfaction with warfarin monitoring services are generally high with respect to anticoagulation-related care received. Providing a cost-effective warfarin ...monitoring service while improving warfarin-related knowledge, patient safety and satisfaction can be challenging.
To compare ‘post and dose' service offered by the Calderdale Royal Hospital (CRH) and ‘face-to-face’ service offered by Huddersfield Royal Infirmary (HRI) in terms of costs of service delivery, patient satisfaction, warfarin-related knowledge and safety indicators.
A cross-sectional sample of 160 patients on long-term warfarin therapy from anticoagulation (outpatient) clinics at CRH and HRI using interviewer-administered data collection form. International Normalized Ratio (INR), Time in Therapeutic Range (TTR) and Variance Growth Rate (VGR) values of last 12 months and the data on costs of service delivery, knowledge and satisfaction were collected.
Patients monitored at HRI had higher mean VGR value (0.35 ± 0.62 vs. 0.17 ± 0.17, p = 0.092) and slightly lower mean TTR (68.70 ± 19.43 vs. 69.63 ± 17.71, p = 0.756) compared with CRH patients. Patients monitored in ‘post and dose’ were estimated at a price of £11.06 per patient per visit and each patient in face-to-face service only cost £9.70 per visit. Patients monitored at HRI had marginally higher overall knowledge score (65.22 ± 23.29 vs. 60.31 ± 20.93, p = 0.165) and overall satisfaction score (15.59 ± 3.16 vs. 15.05 ± 3.10, p = 0.279) compared with CRH patients. A positive and significant correlation was found between patients' knowledge and patient satisfaction (r = +0.327, p = 0.001).
Although, HRI provided monitoring service at a slightly lower cost than CRH, patients monitored at CRH had better anticoagulation control and favourable indicators. Warfarin-related knowledge needs to be improved to achieve further improvement in quality of warfarin use.
Data pertaining to a 1982 birth cohort from Matlab, Bangladesh, are analysed to test the thesis that excess female mortality in the first months of life arises from deliberate and selective behaviour ...by parents. This selectivity has strategic value for family welfare in a society which is both rigidly patriarchal and increasingly competitive. The findings suggest that sex-differentials are emerging in the neo-natal and early infant months, substantially earlier than reported for a 1973 cohort from the same area. In addition, birth order affects differential mortality. Whereas the presence of same-sex siblings is associated with decreased mortality for males, aged 0-54 months, it is associated with increased mortality for females, regardless of socio-economic status. More significantly, excess female neonatal and early infant mortality is associated with the presence of older sisters. These findings support the thesis that early excess female mortality is selective and strategic.
Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause ...human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.
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