BackgroundNeonicotinoids, which are novel pesticides, have entered into usage around the world because they are selectively toxic to arthropods and relatively non-toxic to vertebrates. It has been suggested that several neonicotinoids cause neurodevelopmental toxicity in mammals. The aim was to establish the relationship between oral intake and urinary excretion of neonicotinoids by humans to facilitate biological monitoring, and to estimate dietary neonicotinoid intakes by Japanese adults.Methodology/Principal FindingsDeuterium-labeled neonicotinoid (acetamiprid, clothianidin, dinotefuran, and imidacloprid) microdoses were orally ingested by nine healthy adults, and 24 h pooled urine samples were collected for 4 consecutive days after dosing. The excretion kinetics were modeled using one- and two-compartment models, then validated in a non-deuterium-labeled neonicotinoid microdose study involving 12 healthy adults. Increased urinary concentrations of labeled neonicotinoids were observed after dosing. Clothianidin was recovered unchanged within 3 days, and most dinotefuran was recovered unchanged within 1 day. Around 10% of the imidacloprid dose was excreted unchanged. Most of the acetamiprid was metabolized to desmethyl-acetamiprid. Spot urine samples from 373 Japanese adults were analyzed for neonicotinoids, and daily intakes were estimated. The estimated average daily intake of these neonicotinoids was 0.53–3.66 μg/day. The highest intake of any of the neonicotinoids in the study population was 64.5 μg/day for dinotefuran, and this was <1% of the acceptable daily intake.

BackgroundOral anticoagulants (OACs) can help prevent stroke in patients with nonvalvular atrial fibrillation (NVAF). The aim of this study was to characterize the use of OACs other than direct thrombin inhibitors (DTIs) for NVAF.MethodsPatients with NVAF taking antithrombotics other than DTIs were enrolled in this cross-sectional study. Patient demographics and medication history were collected, and the patients were classified as taking antiplatelet monotherapy (AP), anticoagulant monotherapy (AC), or combination therapy (AP+AC). OAC users were also stratified as naïve (N; initiated within 6 months), switcher (S; switched within 6 months), or prevalent user (P; continued for >6 months).ResultsA total of 3053 patients (AP, 216; AC, 2381; AP+AC, 456) from 268 sites were enrolled from 2012 to 2013. Significant differences were observed in CHADS2 scores (AP/AC/AP+AC: 2.0/2.1/2.7, P<0.0001), angina complications (20.1/8.6/32.1, P<0.0001), myocardial infarction (5.1/2.8/18.1, P<0.0001), prothrombin time–international normalized ratio (PT–INR) (−/2.00/1.94, P=0.0350), and others. There were 2831 OAC users (N, 328; S, 213; P, 2290). Significant differences were observed in history of bleeding (N/S/P: 2.4/9.4/4.5, P<0.001), PT–INR (1.83/2.01/2.00, P<0.0001), and others.ConclusionsPatients taking AP+AC had higher CHADS2 scores than those taking an AP or AC alone. Additionally, the combination therapy (AP+AC) was preferred in patients with cardiovascular comorbidity. Changes in AC regimens were not influenced by CHADS2 scores or complications but influenced by history of bleeding. These characteristics were thus identified as major factors affecting the selection of antithrombotic regimens other than DTIs in patients with NVAF.

Introduction Following approval of dabigatran and other antithrombotics in Japan, few studies have specifically evaluated the clinical characteristics of patients prescribed these antithrombotics for nonvalvular atrial fibrillation (NVAF) in real-world practice. Methods We conducted a descriptive analysis of data from two real-world studies [J-dabigatran surveillance and Japanese study on current Anticoagulation therapies for Patients with nonvalvular Atrial Fibrillation (JAPAF); conducted at sites common to both studies] to determine the characteristics of patients with NVAF initiated on dabigatran etexilate [110 mg twice daily (BID; DE110) or 150 mg BID (DE150)], warfarin, rivaroxaban, or antiplatelets as their first antithrombotic treatment. Inferential statistical analyses were not performed, and no statistical hypothesis was tested. Results Data for 1270 and 3011 eligible patients from the J-dabigatran surveillance (DE110, 976; DE150, 273) and JAPAF study (warfarin, 82.5%; rivaroxaban, 10.3%; antiplatelets, 21%), respectively, were extracted. In the J-dabigatran surveillance, 31.8% (full cohort, 28.1%) of patients had been switched from warfarin to dabigatran. Among patients prescribed DE110/DE150, 41.4%/57.5% and 41.5%/18.7% of patients had low-to-intermediate risk for ischemic stroke (CHADS 2 score of 0 or 1) and high risk for bleeding (HAS-BLED score ≥ 3), respectively. Similarly, 33.7%/41.3%/40.2% and 48.7%/42.6%/75.7% of patients taking warfarin/rivaroxaban/antiplatelets had a CHADS 2 score of 0 or 1 and HAS-BLED score ≥ 3, respectively. Dabigatran was favored in patients with creatinine clearance > 50 ml/min. Conclusions In Japan, physicians who attempt stroke prevention in patients with atrial fibrillation choose appropriate anticoagulant treatment, taking into consideration the individual patient backgrounds as well as the features of each antithrombotic agent. Trial Registration ClinicalTrials.gov Identifier, NCT01491178 and University Hospital Medical Information Network (UMIN) Clinical Trial Registry Identifier, UMIN000009644. Funding Nippon Boehringer Ingelheim Co., Ltd. Plain Language Summary Plain language summary available for this article.