Rho-kinase plays an important role in calcium sensitization for vascular smooth muscle (VSMC) contraction and may be involved in the inappropriate coronary vasoconstriction during exercise-induced myocardial ischemia. In this multicenter phase II study, the anti-anginal effect of fasudil, which is metabolized to a specific Rho-kinase inhibitor hydroxyfasudil after oral administration, was examined in patients with stable effort angina. In the phase IIa trial, after a 2-week washout period of anti-anginal drugs, 45 patients received increasing doses of fasudil (5, 10, and 20 mg TID for every 2 weeks). The fasudil treatment significantly prolonged the maximum exercise time and the time to the onset of 1-mm ST segment depression on treadmill exercise test (both p < 0.01), whereas blood pressure and heart rate during exercise were unchanged before and after the treatment. Higher doses of fasudil (20 and 40 mg TID) were subsequently tested in 22 patients in the same manner with similar positive results. In the phase IIb trial, after a 2-week washout period of anti-anginal drugs, 125 patients were assigned, in a double-blind manner, to a 4-week oral treatment with a different dose of fasudil (5, 10, 20, or 40 mg TID) and treadmill exercise test was performed before and after the treatment. Again, both maximum exercise time and time to the onset of 1-mm ST segment depression were prolonged in all groups. A significant dose-response relation was noted across the treatment groups for the exercise tolerance index that was determined by the combined effect of exercise time and ST segment depression (p = 0.006). Fasudil was well tolerated in both trials without any serious adverse reactions. These results suggest the efficacy and adequate safety profile of fasudil, the first drug in a novel class of vasodilators, for the treatment of stable effort angina.

In the health insurance system of Japan, a fee-for-service system has been applied to individual treatment services since 1958. This system involves a structural problem of causing an increase in examination and drug administration. A flat-fee payment system called DPC was introduced in April 2003 to solve the problems of the fee-for-service system. Based on the data of 2003 and 2004, we assessed the impact of DPC in Japan, and obtained the following conclusions: First, the introduction of DPC in Japan could not decrease the absolute value of medical costs; second, the internal efficiency of the institutions was improved, for example, by reducing the mean length of hospitalizations; third, the DPC-based diagnosis classification is considered to be effective for simplifying the medical fee system within the framework of EBM and for providing patients with information; and fourth, after introduction of the DPC, structural problems remain in the flat-fee payment system, such as examination and treatment of low quality, selection of patients and up coding. Its introduction should thus be performed with sufficient caution. We will make greater efforts to establish a better medical fee system by evaluating these problems.

No abstract

Summary:The effects of physical training on hemostatic parameters were evaluated in 56 postmyocardial infarction (MI) patients before and after one month of systematic physical training and in 30 control post-MI patients, who did not undergo such training. There were no significant changes in prothrombin time (PT) and alphal-antitrypsin (alAT) at the beginning and end of the study in either group. Levels of fibrinogen, Factor VIII: C (V1II:C) and von Wildebrand antigen (vWf Ag), and activities of ATIII and plasminogen (Plg) were significantly decreased in the group with physical training (pe 0.09, while values were unchanged in the control group. Hematocrit, platelet counts, and alpha2-plasmin inhibitor (a2PI) activities also decreased in the physical training group (pe 0.05). In contrast, these variables increased in the control group (p ~0 . 0 5 ) .Activated partial thromboplastin time (aP'lT) tended to be prolonged in the group with physical training, while it was shortened in the control group. In a subset of 20 patients with physical training, resting levels of plasmin-a2PI complex (PIC), thrombin-antithrombin I11 complex (TAT), protein-C (P-C:Ag), plasminogen activator inhibitor-1 (PAI-l), VII:C, and P-C activities had significantly decreased after one month of physical training (pc0.05), although tissue plasminogen activator activities remained unchanged. Physical training appeared to sup- press coagulability as indicated by the decrease in fibrinogen, VIII:C, vWf:Ag, VII:C, and TAT, and prolongation of aPTT. The decrease in plasminogen, t-PA:Ag, a2P1, PAI-1, and PIC after physical training may result from the decreased coagulability. In conclusion, physical training appears to induce a suppression of the coagulation system in patients in the recovery phase of MI.

The first use of the BSC to compare hospital performance between China and Japan shows benefits that not only suggests performance improvements in individual hospitals but also reveals effective health factors allowing implementation of valid national health policies.