Citations

Background— Ambrisentan is a propanoic acid–based, A-selective endothelin receptor antagonist for the once-daily treatment of pulmonary arterial hypertension. Methods and Results— Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Study 1 and 2 (ARIES-1 and ARIES-2) were concurrent, double-blind, placebo-controlled studies that randomized 202 and 192 patients with pulmonary arterial hypertension, respectively, to placebo or ambrisentan (ARIES-1, 5 or 10 mg; ARIES-2, 2.5 or 5 mg) orally once daily for 12 weeks. The primary end point for each study was change in 6-minute walk distance from baseline to week 12. Clinical worsening, World Health Organization functional class, Short Form-36 Health Survey score, Borg dyspnea score, and B-type natriuretic peptide plasma concentrations also were assessed. In addition, a long-term extension study was performed. The 6-minute walk distance increased in all ambrisentan groups; mean placebo-corrected treatment effects were 31 m ( P =0.008) and 51 m ( P <0.001) in ARIES-1 for 5 and 10 mg ambrisentan, respectively, and 32 m ( P =0.022) and 59 m ( P <0.001) in ARIES-2 for 2.5 and 5 mg ambrisentan, respectively. Improvements in time to clinical worsening (ARIES-2), World Health Organization functional class (ARIES-1), Short Form-36 score (ARIES-2), Borg dyspnea score (both studies), and B-type natriuretic peptide (both studies) were observed. No patient treated with ambrisentan developed aminotransferase concentrations >3 times the upper limit of normal. In 280 patients completing 48 weeks of treatment with ambrisentan monotherapy, the improvement from baseline in 6-minute walk at 48 weeks was 39 m. Conclusions— Ambrisentan improves exercise capacity in patients with pulmonary arterial hypertension. Improvements were observed for several secondary end points in each of the studies, although statistical significance was more variable. Ambrisentan is well tolerated and is associated with a low risk of aminotransferase abnormalities.

Total joint arthroplasty (TJA) is implemented primarily for the relief of pain, and secondarily for achieving better function by increasing the joint’s strength and motion. In order to keep health costs low, it is desirable that the TJA achieves and maintains a long-term and secure fixation of the implanted components. Unfortunately, clinical follow-up shows that the prosthetic finger implant components have long-term complications including bone resorption, wear, loosening, and failure of the implant components. Although the mechanism of complications is not fully understood, it is well known that the wear and failure of prostheses are highly related to the mechanical forces or stresses of implant components. It is therefore desirable that reliable 3-D computational finite element analysis (FEA) models can be developed and used for the stress analysis of implants. In this study, the finger proximal interphalangeal (PIP) prosthetic components were analyzed using a nonlinear finite element method. Implant components under different joint flexion angles as well as different forces were studied. The stress distribution on the contact surface of the implant component was obtained. The developed FEA models can be used to examine the contact situations (contact stress, contact region, and stress distribution), which are critical to the wear and potential failure of the implant components. Based on FEA results, the design of the current finger PIP implants can be improved for optimum performance and a long-term fixation.