Implementing the new oral anticoagulants into the hospital formulary

The new oral anticoagulants may prove to be one of most significant innovations in clinical practice in the past 60 years. Apixaban and rivaroxaban are direct inhibitors of Factor Xa, while dabigatran inhibits Factor IIa. The predictable pharmacological profile of these new agents allows physicians to prescribe these drugs without the need for routine coagulation monitoring, which is the mainstay of warfarin therapy. In addition, these new agents have not been shown to have any food interactions and minimal drug–drug interactions, interactions are limited to the p‐glycoprotein (p‐Gp) transporter or cytochrome P450 (CYP450) system, each drug is unique in its drug interaction profile, as will be discussed below. These unique pharmacokinetics profiles may usher in for clinicians a new era of managing thromboembolic disorders. In this article, the pharmacology of these new oral anticoagulants will be reviewed along with the major clinical trials evaluating the use of these agents for thromboembolic prophylaxis in patients undergoing total hip and knee arthroplastic surgery, the treatment of venous thromboembolic disorders and stroke prevention in atrial fibrillation. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.     

Human temporomandibular joint and myofascial pain biochemical profiles: a case-control study

Neurobiological mechanisms of human musculoskeletal pain are poorly understood. This case-control study tested the hypothesis that biomarkers within temporomandibular muscle and joint disorders (TMJD) subjects' masseter muscles or temporomandibular joint (TMJ) synovial fluid correlate with plasma biomarker concentrations. Fifty subjects were recruited and categorized into TMJD cases (n=23) and pain-free controls (n=27) at the University of Minnesota School of Dentistry. Prior to specimen collection, pain intensity and pressure pain threshold masseter muscles and the TMJs were assessed. We collected venous blood; biopsied masseter muscle; and sampled TMJ synovial fluid on the subjects' side of maximum pain intensity. We assayed these tissues for the presence of nerve growth factor (NGF), bradykinin (BK), leukotreine B(4) (LTB(4) ) and prostaglandin E(2) (PGE(2) ), F(2) -isoprostane (F(2) I) and substance P (SP). The data was analyzed using Spearman Correlation Coefficients. We found that only plasma concentrations of bradykinin statistically correlated with synovial fluid concentrations (ρ=-0·48, P=0·005), but no association was found between pain intensities. The data suggests that biomarkers used to assess TMJD need to be acquired in a site-specific manner. We also discovered that F(2) I concentrations were associated with muscle pain intensity and muscle pressure pain threshold (PTT) (β=0·4, 95%CI: 0·03-0·8) and joint PPT (β=0·4, 95%CI: 0·07-0·8) suggesting that muscle oxidative stress is involved in myofascial pain and that F(2) -I may be a biomarker for myofascial pain.     

Exercise during energy restriction mitigates bone loss but not alterations in estrogen status or metabolic hormones

Summary

Energy restriction causes bone loss, increasing stress fracture risk. The impact of exercise during energy restriction on bone and endocrine factors is examined. Exercise with energy restriction did not influence endocrine factors, but did mitigate some bone loss seen with energy restriction in sedentary rats.

Introduction

Chronic dietary energy restriction (ER) leads to bone loss and increased fracture risk. Strictly controlled trials of long-term ER with and without vigorous exercise are required to determine whether exercise loading can counterbalance ER-induced bone loss. The aim of this current project is to elucidate the impact of exercise and ER on bone mass, estrogen status, and metabolic hormones.

Methods

Twenty-four virgin female Sprague-Dawley rats (n?=?8/group) were divided into three groups—ad libitum fed?+?exercise (Adlib?+?EX), 40 % energy restricted?+?exercise (ER?+?EX), and 40 % energy restricted?+?sedentary (ER?+?SED). Energy availability between ER groups was equal. Treadmill running was performed 4 days/week at 70 % VO_2max for 12 weeks.

Results

Fat and lean mass and areal bone mineral density (aBMD) were lower after 12 weeks (p?<?0.05) for ER?+?EX vs Adlib?+?EX, but ER?+?EX aBMD was higher than ER?+?SED (p?<?0.0001). Serum leptin and a urinary estrogen metabolite, estrone-1-glucuronide (E1G), were lower at week 12 (p?=?0.0002) with ER, with no impact of exercise. Serum insulin-like growth factor I (IGF-I) declined (p?=?0.02) from baseline to week 12 in both ER groups. ER?+?EX exhibited higher cortical volumetric bone mineral density (vBMD) at the midshaft tibia (p?=?0.006) vs ER?+?SED.

Conclusion

Exercise during ER mitigated some, but not all, of the bone loss observed in sedentary ER rats, but had little impact on changes in urinary E1G and serum IGF-I and leptin. These data highlight the importance of both adequate energy intake and the mechanical loading of exercise in maintaining bone mass.