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Tokushima-shi, Japan

Takai S.,Teikyo University | Akagi M.,Kinki University | Crawford B.,Adelphi Values | Ichinohe S.,Iwate Medical University | And 5 more authors.
Value in Health Regional Issues

Objectives: Venous thromboembolism (VTE) is the most frequent complication following major orthopaedic surgery (MOS). Although studies in Western populations have demonstrated significantly higher costs for patients with VTE versus those without VTE after MOS, there is a paucity of such data in Japan. This study was conducted to understand the costs and VTE rates in Japanese patients. Methods: Data were extracted from a hospital claims database. MOS was defined as total hip replacement, total knee replacement, or hip fracture repair. Subjects who underwent more than one MOS during the same admission were excluded. Identified VTE cases were matched on a 1:2 matching scheme on the basis of surgery type, hospital, and date of surgery (±6 months). The primary outcome was the difference in 90-day costs. Secondary outcomes included differences in total 6-month costs postsurgery and average length and cost of initial hospital stay. Results: The 90-day cumulative VTE incidence was 0.774%, with 94% of the cases occurring within 30 days postsurgery. Total 90-day costs were significantly higher in patients with VTE (difference of 864,153 Japanese yen [US $10,538]). Average length of stay was longer for patients with VTE (66 days vs. 42 days). Costs incurred by patients with VTE were on average much higher than those incurred by patients without VTE throughout 5 months postsurgery. Conclusions: The development of a VTE in patients undergoing MOS results in a 1.5-fold increase in the length of stay and a 1.7-fold increase in 90-day costs. Findings indicate that the avoidance of VTEs through more effective prophylaxis will help to reduce the economic burden associated with MOS. © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Source

Nishisho T.,Tokushima University | Hanaoka N.,Inayama Hospital | Miyagi R.,Tokushima University | Sakai T.,Oe Kyodo Hospital | And 5 more authors.

Giant cell tumor of bone is a locally aggressive tumor with a high local recurrence rate. Several adjuvant therapies have been employed to reduce the recurrence rate, but their effectiveness remains controversial. The authors attempted local administration of zoledronic acid, a nitrogen-containing bisphosphonate that strongly inhibits bone resorption, as an adjuvant treatment for histologically proven giant cell tumor of bone in 5 patients at their institution. After biopsy, 4 patients were treated with local administration of zoledronic acid with artificial bone and 1 was treated with zoledronic acid without artificial bone. Histologic response to the treatment was evaluated with surgically resected specimens. The 4 patients treated with artificial bone showed local control, with histologic tumor necrosis rates of 90%, 90%, 50%, and 10%. Magnetic resonance imaging showed poor gadolinium enhancement, and histologic examination after local zoledronic acid treatment showed tumor necrosis. One patient without artificial bone showed no histologic tumor necrosis and had local recurrence in soft tissue 18 months after tumor resection. A 3-week waiting period between biopsy and zoledronic acid treatment appears reasonable from the histological study. Complication of this therapy was delayed wound healing and it occurred in 2 cases. Taken together, this case series suggests that local administration of zoledronic acid with artificial bone is a potential adjuvant therapy for giant cell tumor of bone. On the other hand, effective local administration of zoledronic acid requires some bone matrix, including artificial bone. Campanacci's grading is important for predicting the effect of local administration of zoledronic acid. Source

Soeki T.,Tokushima University | Kitani M.,Kagawa Prefectual Shirotori Hospital | Kusunose K.,Tokushima University | Yagi S.,Tokushima University | And 6 more authors.
Hypertension Research

Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin-angiotensin system inhibitor were randomly assigned to a cilnidipine (n18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2′-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties. © 2012 The Japanese Society of Hypertension All rights reserved. Source

Sato M.,Tokushima University | Muguruma N.,Tokushima University | Nakagawa T.,Tokushima University | Okamoto K.,Tokushima University | And 11 more authors.
Cancer Science

The antitumor activity of pladienolide B, a novel splicing inhibitor, against gastric cancer is totally unknown and no predictive biomarker of pladienolide B efficacy has been reported. We investigated the antitumor activity of pladienolide B and its derivative on gastric cancer cell lines and primary cultured cancer cells from carcinomatous ascites of gastric cancer patients. The effect of pladienolide B and its derivative on six gastric cancer cell lines was investigated using a MTT assay and the mean IC50 values determined to be 1.6 ± 1.2 (range, 0.6-4.0) and 1.2 ± 1.1 (range, 0.4-3.4) nM, respectively, suggesting strong antitumor activity against gastric cancer. The mean IC50 value of pladienolide B derivative against primary cultured cells from 12 gastric cancer patients was 4.9 ± 4.7 nM, indicative of high antitumor activity. When 18 SCID mice xenografted with primary cultured cells from three patients were administered the pladienolide B derivative intraperitoneally, all tumors completely disappeared within 2 weeks after treatment. Histological examination revealed a pathological complete response for all tumors. In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed. When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B. In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction. The pladienolide B and its derivative showed very high anti-tumor activity against various gastric cancer cell lines and primary cultured gastric cancer cells from carcinomatous ascites in vitro and in a xenograft model. The mechanism of the anti-tumor activity of pladienolide B involves splicing impairment and apoptosis induction. © 2013 The Authors. Source

Matsuda K.,Red Cross | Kawata I.,Anan Kyoei Hospital | Abe R.,Oe Kyodo Hospital | Kitamura Y.,Tokushima University | And 4 more authors.
Practica Oto-Rhino-Laryngologica

We examined the effect of oral administration of beraprost sodium, a derivative of prostaglandin I2 (PGI2) in patients with sudden deafness as a salvage treatment after failure of initial systemic steroid therapy with prostaglandin El. We then compared them with those of mecobalamin, a derivative of vitamin B12. A significant improvement in the average hearing level was obtained in patients who received beraprost sodium for 12 weeks, but not in patients who received mecobalamin. The hearing levels at 125 Hz, 250 Hz, 500 Hz and 8000 Hz significantly improved after the salvage treatment of beraprost sodium over those of mecobalamin. These findings suggested that oral administration of the PGI2 derivative could be utilized as a salvage treatment for refractory sudden deafness after failure of initial steroid therapy. Source

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