Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999-2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies-one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics

Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia

Comparative risk of severe hypoglycemia among concomitant users of thiazolidinedione antidiabetic agents and antihyperlipidemics

We conducted high-dimensional propensity score-adjusted cohort studies to examine whether thiazolidinedione use with a statin or fibrate was associated with an increased risk of severe hypoglycemia. We found that concomitant therapy with a thiazolidinedione+fibrate was associated with a generally delayed increased risk of severe hypoglycemia

Antidepressant-Warfarin Interaction and Associated Gastrointestinal Bleeding Risk in a Case-Control Study

Bleeding is the most common and worrisome adverse effect of warfarin therapy. One of the factors that might increase bleeding risk is initiation of interacting drugs that potentiate warfarin. We sought to evaluate whether initiation of an antidepressant increases the risk of hospitalization for gastrointestinal bleeding in warfarin users.Medicaid claims data (1999-2005) were used to perform an observational case-control study nested within person-time exposed to warfarin in those ≥18 years. In total, 430,455 warfarin users contributed 407,370 person-years of warfarin use. The incidence rate of hospitalization for GI bleeding among warfarin users was 4.48 per 100 person-years (95% CI, 4.42-4.55). Each gastrointestinal bleeding cases was matched to 50 controls based on index date and state. Warfarin users had an increased odds ratio of gastrointestinal bleeding upon initiation of citalopram (OR = 1.73 [95% CI, 1.25-2.38]), fluoxetine (OR = 1.63 [95% CI, 1.11-2.38]), paroxetine (OR = 1.64 [95% CI, 1.27-2.12]), amitriptyline (OR = 1.47 [95% CI, 1.02-2.11]). Also mirtazapine, which is not believed to interact with warfarin, increased the risk of GI bleeding (OR = 1.75 [95% CI, 1.30-2.35]).Warfarin users who initiated citalopram, fluoxetine, paroxetine, amitriptyline, or mirtazapine had an increased risk of hospitalization for gastrointestinal bleeding. However, the elevated risk with mirtazapine suggests that a drug-drug interaction may not have been responsible for all of the observed increased risk

Final report of EURAMET.M.G-K3 regional comparison of absolute gravimeters

The regional key comparison of absolute gravimeters, EURAMET.M.G-K3 and the simultaneously organized additional comparison, was held in Germany at the Geodetic Observatory Wettzell of the German Federal Agency for Cartography and Geodesy in the spring of 2018.Here we present the list of the participants who actually performed measurements during the comparison, the data submitted by the operators as well as the results of the determination of the gravity as a function of height at the comparison sites. The measurement strategy is briefly discussed and the results of the data harmonization is documented. Finally, the results of the constrained least squares adjustment are presented including the degrees of equivalence of each gravimeter and the key comparison reference values.Main textTo reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).Export citation and abstract BibTeX RIS

A shortened version of Raven's standard progressive matrices for children and adolescents

Numerous developmental studies assess general cognitive ability, not as the primary variable of interest, but rather as a background variable. Raven's Progressive Matrices is an easy to administer non-verbal test that is widely used to measure general cognitive ability. However, the relatively long administration time (up to 45 min) is still a drawback for developmental studies as it often leaves little time to assess the primary variable of interest. Therefore, we used a machine learning approach - regularized regression in combination with cross-validation - to develop a short 15-item version. We did so for two age groups, namely 9 to 12 years and 13 to 16 years. The short versions predicted the scores on the standard full 60-item versions to a very high degree r = 0.89 (9-12 years) and r = 0.93 (13-16 years). We, therefore, recommend using the short version to measure general cognitive ability as a background variable in developmental studies

Regional comparison of absolute gravimeters, EURAMET.M.G-K2 key comparison

In the framework of the regional EURAMET.M.G-K2 comparison of absolute gravimeters, 17 gravimeters were compared in November 2015. Four gravimeters were from different NMIs and DIs, they were used to link the regional comparison to the CCM.G.K2 by means of linking converter. Combined least-squares adjustments with weighted constraint was used to determine KCRV. Several pilot solutions are presented and compared with the official solution to demonstrate influences of different approaches (e.g. definition of weights and the constraint) on results of the adjustment. In case of the official solution, all the gravimeters are in equivalence with declared uncertainties. == Main text To reach the main text of this paper, click on Final Report [http://www.bipm.org/utils/common/pdf/final_reports/M/G-K2/EURAMET.M.G-K2.pdf] . Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/ [http://kcdb.bipm.org/] . The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA)