The factor xa inhibitor edoxaban for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

INTRODUCTION: With the rising prevalence of nonvalvular atrial fibrillation (NVAF) in the general population, the development of new drugs for prevention of thromboembolic events is essential. Non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to present a number of advantages over conventionally used agents, such as predictable pharmacokinetics and no requirement for continuous anticoagulant monitoring. The most recently approved NOAC for the NVAF indication is edoxaban. Several subgroup analyses from the edoxaban phase III ENGAGE AF-TIMI 48 trial have now been published, alongside meta-analysis data comparing the four currently approved NOACs. Consequently, an updated review of the literature is merited. Areas covered: A PubMed search using the terms 'edoxaban', 'non-vitamin K antagonist oral anticoagulant', 'ENGAGE AF-TIMI 48', and 'atrial fibrillation' was performed and results screened for the most relevant English language publications. The market position, pharmacological profile, clinical efficacy, safety and tolerability of edoxaban are presented and discussed. Expert commentary: Edoxaban has been shown to have an efficacy similar or superior to that of warfarin, with a potentially lower risk of major bleeding and predictable, dose-dependent pharmacology. In order to clarify its position within the NOAC market, head-to-head comparative studies are required.

The value of biochemical markers in predicting a perforation in acute appendicitis.

BACKGROUND: Acute appendicitis is the most common surgical diagnosis of abdominal pain. Perforated appendicitis can result in increased morbidity and mortality. Identifying a perforation early can reduce the impact on the patient. Bilirubin, C-reactive protein (CRP) and white cell count (WCC) have been shown to indicate perforation in appendicitis. This study aimed to identify whether these biochemical markers can be used to identify if patients are suitable for either a conservative or surgical approach. METHODS: A retrospective post hoc analysis of all appendicectomies over a 6-year period investigating the association between preoperative bilirubin, CRP, WCC, and neutrophil count and the histological findings of either the presence or lack of a perforation. RESULTS: One thousand two hundred seventy-one patients had appendicitis, 154 (12.12%) of which were perforated upon histological examination. All biochemical markers were significantly higher in perforation (P < 0.001). The greatest sum of sensitivity and specificity of CRP was at 34.6 mg/L (sensitivity 78.57%, specificity 63.01%), and for bilirubin was at 21.5 µmol/L (sensitivity 62.96%, specificity 88.31%). Combining CRP and bilirubin improved sensitivity and specificity, but this was reduced by further incorporating WCC and neutrophils. Logistic regression analysis identified CRP as the most sensitive marker of perforation (odds ratio (OR) = 1.064 (1.043-1.085) ) (P < 0.001), with bilirubin (OR = 1.005 (1.003-1.008) ) also significant (P < 0.001) for a 1-unit increase. CONCLUSION: Bilirubin and CRP are markers of perforation in appendicitis, but are not accurate enough to be diagnostic. In a patient with high clinical suspicion of acute appendicitis, a raised CRP and bilirubin suggests that a patient is not suitable for conservative treatment.

Molecular analysis of peroxisome proliferation in the hamster.

Three novel P450 members of the cytochrome P450 4A family were cloned as partial cDNAs from hamster liver, characterised as novel members of the CYP4A subfamily, and designated CYP4A17, 18, and 19. Hamsters were treated with the peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, methylclofenapate (MCP) or Wy-14,643, and shown to develop hepatomegaly and induction of CYP4A17 RNA, and concomitant induction of lauric acid 12- hydroxylase. This treatment also resulted in hypolipidaemia, which was most pronounced in the VLDL fraction, with up to 50% reduction in VLDL-triglycerides; by contrast, blood cholesterol concentration was unaffected by this treatment. These data show that hamster is highly responsive to induction of CYP4A by peroxisome proliferators. To characterise the molecular basis of peroxisome proliferation, the hamster PPARalpha was cloned and shown to encode a 468-amino-acid protein, which is highly similar to rat and mouse PPARalpha proteins. The level of expression of hamster PPARalpha in liver is intermediate between mouse and guinea pig. These results fail to support the hypothesis that the level of PPARalpha in liver is directly responsible for species differences in peroxisome proliferation.