Warfarin use and risk of knee and hip replacements

Background Identification of modifiable risk factors and treatments for osteoarthritis (OA) are needed. Warfarin, a vitamin K antagonist, causes fetal and animal model skeletal abnormalities. Vitamin K insufficiency has been associated with OA, but whether warfarin is also detrimental to OA is not known. Methods We conducted a nested case-control study using a UK general practitioner electronic medical records database. We identified cases of knee or hip replacement (KR or HR) from among adults with atrial fibrillation newly prescribed either warfarin or direct oral anticoagulants (DOACs). Cases were matched with four controls by age and sex. We assessed the relation of warfarin compared with DOAC use to risk of joint replacement using conditional logistic regression. We also evaluated different durations of warfarin use. Results We identified 857 subjects with KR or HR (cases), of whom 64.6% were warfarin users, and 3428 matched controls, of whom 56.1% were warfarin users (mean age 75, 47% female). Warfarin users had a 1.59 times higher risk of joint replacement thanDOAC users (adjusted OR 1.59, 95% CI 1.31 to 1.92). Longer duration of warfarin use was associated with higher risk of joint replacement in comparison with <1 year of warfarin use. Conclusion Warfarin, a vitamin K antagonist, was associated with greater risk of KR and HR (an indicator for end-stage knee OA) than DOAC use, supporting the importance of adequate vitamin K functioning in limiting OA progression

Primary prevention of myocardial infarction in rheumatoid arthritis using aspirin:A case-crossover study and a propensity score-matched cohort study

Objective.Subjects with rheumatoid arthritis (RA) are at higher risk of developing cardiovascular disease, which is their leading cause of death. Conflicting evidence exists regarding the efficacy of aspirin (ASA) as primary prevention. We evaluated whether a protective association exists between ASA and myocardial infarction (MI) in RA subjects.Methods.In the United Kingdom, persons age ≥ 60 years receive free ASA by prescription and 75% of use is by prescription. Subjects ≥ 60 years with RA in the population-based The Health Improvement Network database constituted our study population. We excluded patients with history of MI, angina, stroke, peripheral vascular disease, or coronary artery procedures. Our main outcome was the occurrence of fatal and nonfatal MI. We performed a case-crossover study with each subject contributing a hazard period and a control period 90 days prior to the MI. In addition, to minimize confounding by indication, a propensity score (PS)–matched cohort study was performed, considering all patients with RA with an incident prescription of low-dose ASA as our exposed group.Results.We did not find a protective effect in the case-crossover study (OR 1.83, 95% CI 0.71–4.71), with 55 subjects exposed in the hazard period and 44 in the control period. Similarly, among 1836 subjects included in the PS-matched cohort study (918 ASA users and 918 ASA non-users), we did not find a protective effect of low ASA on MI (HR 1.39, 95% CI 0.87–2.23).Conclusion.We did not find a protective effect of ASA on MI in patients with RA when used as primary prophylaxis.</jats:sec

Relation of NSAIDs, DMARDs, and TNF Inhibitors for Ankylosing Spondylitis and Psoriatic Arthritis to Risk of Total Hip and Knee Arthroplasty.

ObjectiveAnkylosing spondylitis (AS) and psoriatic arthritis (PsA) often affect the hip and/or knee. If effective, treatments might reduce risk of total hip or total knee arthroplasty (THA/TKA). We evaluated risk of THA/TKA related to use of medical therapies in AS/PsA.MethodsWe conducted a nested case-control study using 1994-2018 data from the OptumLabs Data Warehouse, which includes deidentified medical and pharmacy claims, laboratory results, and enrollment records for commercial and Medicare Advantage enrollees. Among those with AS/PsA, THA/TKA cases were matched up to 4 controls by sex, age, AS/PsA diagnosis, diagnosis year, insurance type, obesity, and prior THA/TKA. We assessed AS/PsA treatment 6 months prior to THA/TKA, including disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibitors (TNFi), alone or in combination, stratified by nonsteroidal antiinflammatory drug (NSAID) use. We evaluated the relation of treatment to risk of THA/TKA using conditional logistical regression with adjustment for confounders.ResultsAmong 16,748 adults with AS, there were 444 THA/TKA cases and 1613 matched controls. Among 34,512 adults with PsA, there were 1003 cases and 3793 controls. Adjusted ORs for treatment category and THA/TKA ranged from 0.60 to 1.92; however, none were statistically significant. Results were similarly null in several sensitivity analyses.ConclusionOdds of THA/TKA were not reduced with any combinations of NSAIDs, DMARDs, or TNFi among persons with AS or PsA. Given current utilization patterns in this population of US adults with AS and PsA, these medical therapies did not appear to be associated with less end-stage peripheral joint damage

Ocean state estimation from hydrography and velocity observations during EIFEX with a regional biogeochemical ocean circulation model

In the European Iron Fertilization Experiment (EIFEX), the iron hypothesis was tested by an open ocean perturbation experiment. The success of EIFEX owes to the applied experimental strategy; namely to use the closed core of a mesoscale eddy for the iron injection. This strategy not only allowed tracking the phytoplankton bloom within the fertilized patch of mixed-layer water, but also allowed the export of biologically fixed carbon to the deep ocean to be quantified. In this present study, least-squares techniques are used to fit a regional numerical ocean circulation model with four open boundaries to temperature, salinity, and velocity observations collected during EIFEX. By adjusting the open boundary values of temperature, salinity and velocity, an optimized model is obtained that clearly improves the simulated eddy and its mixed layer compared to a first guess representation of the cyclonic eddy. A biogeochemical model, coupled to the optimized circulation model, simulates the evolution of variables such as chlorophyll a and particular organic carbon in close agreement with the observations. The estimated carbon export, however, is lower than the estimates obtained from observations without numerical modeling support. Tuning the sinking parameterization in the model increases the carbon export at the cost of unrealistically high sinking velocities. Repeating the model experiment without adding iron allows more insight into the effects of the iron fertilization. In the model this effect is about 40% lower than in previous estimates in the context of EIFEX. The likely causes for these discrepancies are potentially too high remineralization, inaccurate representation of the bloom-termination in the model, and ambiguity in budget computations and averaging. The discrepancies are discussed and improvements are suggested for the parameterization used in the biogeochemical model components