Safety and efficacy of direct oral anticoagulants across body mass index groups in patients with venous thromboembolism: a retrospective cohort design.

Current literature on the safety and efficacy of direct oral anticoagulants (DOACs) in patients of extreme weights are limited, however, they are still being prescribed in these populations. The objective of this study is to describe the safety and efficacy of DOAC therapy in patients of extreme weights for the treatment of venous thromboembolism (VTE) using body mass index (BMI) groups. A multi-site, retrospective cohort design at four hospitals was performed. Patients who experienced an initial VTE between November 2012 and August 2017 and placed on a DOAC were included. Patients were defined as: extremely obese (EO) if BMI ≥ 40 kg/m2, obese if BMI 30-39.9 kg/m2, normal/overweight if BMI 18.5-29.9 kg/m2, and underweight if BMI < 18.5 kg/m2. The primary efficacy outcome of recurrent VTE and primary safety outcome of major bleeding (MB) within 12 months were compared between weights. Univariate statistical tests and multivariate logistic regression analyses were performed. Rates of recurrent VTE showed no significant differences (p = 0.58) across groups; 7.8% (11/142) EO, 4.7% (18/383) obese, 5.2% (27/517) normal/overweight, and 5.9% (1/17) underweight. Proportions of MB were overall significantly different (p = 0.026); 6.3% (9/142) EO, 10.4% (40/383) obese, 10.1% (52/517) normal/overweight, and 29.4% (5/17) underweight. EO and obese patients had similar odds of MB compared to normal/overweight (OR 0.61, 95% CI [0.29, 1.26] and OR 1.04, 95% CI [0.67, 1.61]). Underweight patients showed larger odds of MB compared to normal/overweight (OR 3.73, 95% CI [1.26, 11.0]). This study found that recurrence of VTE was not associated with BMI. However, the proportions of major bleeding were statistically different among the BMI categories.

A novel model for neuroendocrine toxicology: neurobehavioral effects of BPA exposure in a prosocial species, the prairie vole (Microtus ochrogaster).

Impacts on brain and behavior have been reported in laboratory rodents after developmental exposure to bisphenol A (BPA), raising concerns about possible human effects. Epidemiological data suggest links between prenatal BPA exposure and altered affective behaviors in children, but potential mechanisms are unclear. Disruption of mesolimbic oxytocin (OT)/vasopressin (AVP) pathways have been proposed, but supporting evidence is minimal. To address these data gaps, we employed a novel animal model for neuroendocrine toxicology: the prairie vole (Microtus ochrogaster), which are more prosocial than lab rats or mice. Male and female prairie vole pups were orally exposed to 5-µg/kg body weight (bw)/d, 50-µg/kg bw/d, or 50-mg/kg bw/d BPA or vehicle over postnatal days 8-14. Subjects were tested as juveniles in open field and novel social tests and for partner preference as adults. Brains were then collected and assessed for immunoreactive (ir) tyrosine hydroxylase (TH) (a dopamine marker) neurons in the principal bed nucleus of the stria terminalis (pBNST) and TH-ir, OT-ir, and AVP-ir neurons in the paraventricular nucleus of the hypothalamus (PVN). Female open field activity indicated hyperactivity at the lowest dose and anxiety at the highest dose. Effects on social interactions were also observed, and partner preference formation was mildly inhibited at all dose levels. BPA masculinized principal bed nucleus of the stria terminalis TH-ir neuron numbers in females. Additionally, 50-mg/kg bw BPA-exposed females had more AVP-ir neurons in the anterior PVN and fewer OT-ir neurons in the posterior PVN. At the 2 lowest doses, BPA eliminated sex differences in PVN TH-ir neuron numbers and reversed this sex difference at the highest dose. Minimal behavioral effects were observed in BPA-exposed males. These data support the hypothesis that BPA alters affective behaviors, potentially via disruption of OT/AVP pathways.