Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs ...are limited.
To compare rates of GIB among apixaban, dabigatran, and rivaroxaban.
Nationwide population-based cohort study.
Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland.
New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019.
Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression.
In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio HR, 1.42 95% CI, 1.04 to 1.93) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 CI, 1.00 to 2.24) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 CI, 1.01 to 1.94) or dabigatran (HR, 2.04 CI, 1.17 to 3.55). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses.
Unmeasured confounding and small subgroup analyses.
Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.
Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland.
Previous observational studies have yielded conflicting results on whether medication adherence differs between patients receiving warfarin and direct oral anticoagulants (DOACs). Importantly, no ...study has adequately accounted for warfarin dosing being continuously modified based on INR values while dosing of DOACs is fixed. We aimed to compare non-adherence between new users of apixaban, dabigatran, rivaroxaban and warfarin in a population-based cohort.
New users of apixaban, dabigatran, rivaroxaban and warfarin from 2014 to 2019 living in the Icelandic capital area were included. Non-adherence was defined as proportion of days covered below 80%. Inverse probability weighting was used to yield balanced study groups and non-adherence was compared using logistic regression. Factors associated with non-adherence were estimated using multivariable logistic regression.
Overall, 1266 patients received apixaban, 247 dabigatran, 1566 rivaroxaban and 768 warfarin. The proportion of patients with non-adherence ranged from 10.5% to 16.7%. Dabigatran was associated with significantly higher odds of non-adherence compared with apixaban (OR 1.57, 95% CI 1.21 to 2.04, p<0.001), rivaroxaban (OR 1.45, 95% CI 1.12 to 1.89, p=0.005) and warfarin (OR 1.63, 95% CI 1.23 to 2.15, p<0.001). The odds of non-adherence were similar for apixaban, rivaroxaban and warfarin. Apart from the type of oral anticoagulants (OACs) used, female sex, hypertension, history of cerebrovascular accident and concomitant statin use were all independently associated with lower odds of non-adherence.
Dabigatran was associated with higher odds of non-adherence compared with other OACs. Non-adherence was similar between apixaban, rivaroxaban and warfarin users. Female sex and higher comorbidity were associated with better medication adherence.
Some of the longest and most comprehensive marine ecosystem monitoring programs were established in the Gulf of Alaska following the environmental disaster of the Exxon Valdez oil spill over 30 years ...ago. These monitoring programs have been successful in assessing recovery from oil spill impacts, and their continuation decades later has now provided an unparalleled assessment of ecosystem responses to another newly emerging global threat, marine heatwaves. The 2014-2016 northeast Pacific marine heatwave (PMH) in the Gulf of Alaska was the longest lasting heatwave globally over the past decade, with some cooling, but also continued warm conditions through 2019. Our analysis of 187 time series from primary production to commercial fisheries and nearshore intertidal to offshore oceanic domains demonstrate abrupt changes across trophic levels, with many responses persisting up to at least 5 years after the onset of the heatwave. Furthermore, our suite of metrics showed novel community-level groupings relative to at least a decade prior to the heatwave. Given anticipated increases in marine heatwaves under current climate projections, it remains uncertain when or if the Gulf of Alaska ecosystem will return to a pre-PMH state.
While overall gastrointestinal bleeding (GIB) rates have been extensively compared between warfarin and direct oral anticoagulants (DOACs), it is still unclear whether upper and lower GIB rates ...differ between these types of drugs. This study aimed to compare upper and lower GIB rates between warfarin and DOACs in a nationwide cohort.
Data on all patients in Iceland who received a prescription for oral anticoagulation from 2014 to 2019 were collected and their personal identification numbers linked to the electronic medical record system of the National University Hospital of Iceland and the 4 regional hospitals in Iceland. Inverse probability weighting was used to yield balanced study groups and rates of overall, major, upper, and lower GIB were compared using Cox regression. All GIB events were manually confirmed by chart review.
Warfarin was associated with higher rates of upper GIB (1.7 events per 100 person-years vs 0.8 events per 100 person-years; hazard ratio HR, 2.12; 95% confidence interval CI, 1.26-3.59) but similar rates of lower GIB compared with DOACs. Specifically, warfarin was associated with higher rates of upper GIB compared with apixaban (HR, 2.63; 95% CI, 1.35-5.13), dabigatran (5.47; 95% CI, 1.87-16.05), and rivaroxaban (HR, 1.74; 95% CI, 1.00-3.05). Warfarin was associated with higher rates of major GIB compared with apixaban (2.3 events per 100 person-years vs 1.5 events per 100 person-years; HR, 1.79; 95% CI, 1.06-3.05), but otherwise overall and major GIB rates were similar in warfarin and DOAC users.
Warfarin was associated with higher rates of upper but not overall or lower GIB compared with DOACs. Warfarin was associated with higher rates of major GIB compared with apixaban.
Background
Although epistaxis is one of the most common side effects of oral anticoagulation, it is unclear whether epistaxis rates vary between different oral anticoagulants (OAC).
Objective
To ...compare rates of clinically relevant epistaxis between OAC.
Methods
Epistaxis event rates were compared between new users of apixaban, dabigatran, rivaroxaban, and warfarin in a nationwide population‐based cohort study over a 5‐year study period, 2014–2019. Data was collected from the Icelandic Medicine Registry and the five major hospitals in Iceland. Inverse probability weighting (IPW) was used to yield balanced baseline characteristics, and epistaxis rates were compared using Kaplan–Meier survival estimates and Cox regression.
Results
During the study period, 2098 patients received apixaban, 474 dabigatran, 3106 rivaroxaban, and 1403 warfarin. In total, 93 patients presented with clinically relevant epistaxis, including 11 (12%) major epistaxis events and one fatal epistaxis episode. Furthermore, seven patients (9%) with non‐major epistaxis later presented with major bleeding during the follow‐up period. Warfarin use was associated with higher rates of epistaxis compared to apixaban (2.2 events per 100‐person years (events/100‐py) vs. 0.6 events/100‐py, hazard ratio HR 4.22, 95% confidence interval CI 2.08–8.59, p < 0.001), rivaroxaban (2.2 events/100‐py vs. 1.0 events/100‐py, HR 2.26, 95% CI 1.28–4.01, p = 0.005), and dabigatran (2.2 events/100‐py vs. no events, HR n/a, p < 0.001).
Conclusion
Warfarin treatment was associated with higher rates of clinically relevant epistaxis compared to direct oral anticoagulants.
Previous studies have reported that related human couples tend to produce more children than unrelated couples but have been unable to determine whether this difference is biological or stems from ...socioeconomic variables. Our results, drawn from all known couples of the Icelandic population born between 1800 and 1965, show a significant positive association between kinship and fertility, with the greatest reproductive success observed for couples related at the level of third and fourth cousins. Owing to the relative socioeconomic homogeneity of Icelanders, and the observation of highly significant differences in the fertility of couples separated by very fine intervals of kinship, we conclude that this association is likely to have a biological basis.
COnstraint-Based Reconstruction and Analysis (COBRA) methods are widely used for genome-scale modeling of metabolic networks in both prokaryotes and eukaryotes. Due to the successes with metabolism, ...there is an increasing effort to apply COBRA methods to reconstruct and analyze integrated models of cellular processes. The COBRA Toolbox for MATLAB is a leading software package for genome-scale analysis of metabolism; however, it was not designed to elegantly capture the complexity inherent in integrated biological networks and lacks an integration framework for the multiomics data used in systems biology. The openCOBRA Project is a community effort to promote constraints-based research through the distribution of freely available software.
Here, we describe COBRA for Python (COBRApy), a Python package that provides support for basic COBRA methods. COBRApy is designed in an object-oriented fashion that facilitates the representation of the complex biological processes of metabolism and gene expression. COBRApy does not require MATLAB to function; however, it includes an interface to the COBRA Toolbox for MATLAB to facilitate use of legacy codes. For improved performance, COBRApy includes parallel processing support for computationally intensive processes.
COBRApy is an object-oriented framework designed to meet the computational challenges associated with the next generation of stoichiometric constraint-based models and high-density omics data sets.
http://opencobra.sourceforge.net/
Over the past decade, a growing community of researchers has emerged around the use of constraint-based reconstruction and analysis (COBRA) methods to simulate, analyze and predict a variety of ...metabolic phenotypes using genome-scale models. The COBRA Toolbox, a MATLAB package for implementing COBRA methods, was presented earlier. Here we present a substantial update of this in silico toolbox. Version 2.0 of the COBRA Toolbox expands the scope of computations by including in silico analysis methods developed since its original release. New functions include (i) network gap filling, (ii) (13)C analysis, (iii) metabolic engineering, (iv) omics-guided analysis and (v) visualization. As with the first version, the COBRA Toolbox reads and writes systems biology markup language-formatted models. In version 2.0, we improved performance, usability and the level of documentation. A suite of test scripts can now be used to learn the core functionality of the toolbox and validate results. This toolbox lowers the barrier of entry to use powerful COBRA methods.
Altered metabolism in cancer cells has been viewed as a passive response required for a malignant transformation. However, this view has changed through the recently described metabolic oncogenic ...factors: mutated isocitrate dehydrogenases (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) that produce oncometabolites that competitively inhibit epigenetic regulation. In this study, we demonstrate in silico predictions of oncometabolites that have the potential to dysregulate epigenetic controls in nine types of cancer by incorporating massive scale genetic mutation information (collected from more than 1,700 cancer genomes), expression profiling data, and deploying Recon 2 to reconstruct context-specific genome-scale metabolic models. Our analysis predicted 15 compounds and 24 substructures of potential oncometabolites that could result from the loss-of-function and gain-of-function mutations of metabolic enzymes, respectively. These results suggest a substantial potential for discovering unidentified oncometabolites in various forms of cancers.
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