Summary. Background: Oral anticoagulants, such as dabigatran etexilate, an oral, direct thrombin inhibitor, that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism (VTE) after total knee replacement surgery. Methods: In this randomized, double-blind study, 2076 patients undergoing total knee replacement received dabigatran etexilate, 150 mg or 220 mg once-daily, starting with a half-dose 1-4 h after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery, for 6-10 days. Patients were followed up for 3 months. The primary efficacy outcome was a composite of total VTE (venographic or symptomatic) and mortality during treatment, and the primary safety outcome was the incidence of bleeding events. Results: The primary efficacy outcome occurred in 37.7% (193 of 512) of the enoxaparin group vs. 36.4% (183 of 503) of the dabigatran etexilate 220-mg group (absolute difference, )1.3%; 95% CI, )7.3 to 4.6) and 40.5% (213 of 526) of the 150-mg group (2.8%; 95% CI,)3.1 to 8.7). Both doses were non-inferior to enoxaparin on the basis of the prespecified non-inferiority criterion. The incidence of major bleeding did not differ significantly between the three groups (1.3% vs. 1.5% and 1.3% respectively). No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or followup. Conclusions: Dabigatran etexilate (220 mg or 150 mg) was at least as effective as enoxaparin and had a similar safety profile for prevention of VTE after total knee replacement surgery.
The peripheral nervous system retains a considerable capacity for regeneration. However, functional recovery rarely returns to the preinjury level no matter how accurate the nerve repair is, and the more proximal the injury the worse the recovery. Among a variety of approaches being used to enhance peripheral nerve regeneration are the manipulation of Schwann cells and the use of neurotrophic factors. Such factors include, first, nerve growth factor (NGF) and the other recently identified members of the neurotrophin family, namely, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4/5 (NT-4/5); second, the neurokines ciliary neurotrophic factor (CNTF) and leukemia inhibitory factor (LIF); and third, the transforming growth factors (TGFs)-beta and their distant relative, glial cell line-derived neurotrophic factor (GDNF). In this review article we focus on the roles in peripheral nerve regeneration of Schwann cells and of the neurotrophin family, CNTF and GDNF, and the relationship between these. Finally, we discuss what remains to be understood about the possible clinical use of neurotrophic factors.
The purpose of this study was to investigate strength, fatigability, and activity of upper limb musculature to elucidate the role of muscular imbalance in the pathophysiology of tennis elbow. Sixteen patients clinically diagnosed with tennis elbow, recruited from a university hospital upper limb orthopedic clinic, were compared with 16 control subjects with no history of upper limb musculoskeletal problem, recruited from university students and staff. Muscle strength was measured for grip, metacarpophalangeal, wrist, and shoulder on both sides. Electromyographic activity (RMS amplitude) and fatigue characteristics (median frequency slope) of five forearm and two shoulder muscles were measured during isometric contraction at 50% maximum voluntary contraction. All strength measurements showed dominance difference in C, but none in TE. In tennis elbow compared to controls, hand/wrist and shoulder strength and extensor carpi radialis (ECR) activity were reduced ( p < 0.05), while fatigue was normal. A global upper limb weakness exists in tennis elbow. This may be due to disuse and deconditioning syndrome caused by fear avoidance, and needs to be addressed in prevention and treatment. Activation imbalance among forearm muscles (reduced extensor carpi radialis activity) in tennis elbow, probably due to protective pain-related inhibition, could lead to a widespread upper limb muscle imbalance. ß
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