Cost-effectiveness analysis of minimally invasive surgical treatments for benign prostatic hyperplasia: implications for Japan's public healthcare system.

AIMS: Benign prostatic hyperplasia (BPH) represents a significant public health issue in Japan. This study evaluated the lifetime cost-effectiveness of water vapor energy therapy (WAVE) versus prostatic urethral lift (PUL) for men with moderate-to-severe BPH from a public healthcare payer's perspective in Japan. MATERIALS AND METHODS: A decision analytic model compared WAVE to PUL among males in Japan. Clinical effectiveness and adverse event (AE) inputs were obtained from a systematic literature review. Resource utilization and cost inputs were derived from the Medical Data Vision database and medical service fee national data in Japan. Experts reviewed and validated model input parameters. One-way and probabilistic sensitivity analyses were conducted to determine how changes in the values of uncertain parameters affect the model results. RESULTS: Throughout patients' lifetimes, WAVE was associated with higher quality-adjusted life years (0.920 vs. 0.911 year 1; 15.564 vs. 15.388 lifetime) and lower total costs (¥734,134 vs. ¥888,110 year 1; ¥961,595 vs. ¥1,429,458 lifetime) compared to PUL, indicating that WAVE is a more effective and less costly (i.e. dominant) treatment strategy across all time horizons. Lifetime cost-savings for the Japanese healthcare system per patient treated with WAVE instead of PUL were ¥467,863. The 32.7% cost difference between WAVE and PUL was predominantly driven by lower WAVE surgical retreatment rates (4.9% vs. 19.2% for WAVE vs PUL, respectively, at 5 years) and AE rates (hematuria 11.8% vs. 25.7%, dysuria 16.9% vs. 34.3%, pelvic pain 2.9% vs. 17.9%, and urinary incontinence 0.4% vs. 1.3% for WAVE vs PUL, respectively, at 3 months). Model findings were robust to changes in parameter input values. LIMITATIONS: The model represents a simplification of complex factors involved in resource allocation decision-making. CONCLUSIONS: Driven by lower retreatment and AE rates, WAVE was a cost-effective and cost-saving treatment for moderate-to-severe BPH in Japan compared to PUL, providing better outcomes at lower costs to the healthcare system.

Benign prostatic hyperplasia (BPH) is an important public health issue in Japan, given its high prevalence and potential morbidity in a rapidly aging population. This study compared the clinical and economic outcomes of two minimally invasive surgical treatments for BPH (water vapor energy therapy [WAVE] vs. prostatic urethral lift [PUL]) for patients in Japan. Clinical effectiveness and adverse event (AE) information from published medical literature, and real-world health services and cost data from Japan, were used to estimate the impact of the two treatments. Compared to PUL, WAVE was found to provide better clinical outcomes and quality-of-life for patients whilst costing less to the Japanese healthcare system. Patients treated with WAVE had higher lifetime quality-adjusted life years vs. patients treated with PUL (15.564 vs. 15.388). Lifetime cost-savings for the Japanese healthcare system per patient treated with WAVE instead of PUL were estimated to be ¥467,863. The 32.7% cost difference between WAVE and PUL was predominantly driven by lower retreatment rates for WAVE (surgical retreatment rate was 4.9% vs. 19.2% for WAVE vs. PUL, respectively, at 5 years) and AE rates (AE rates at 3 months for WAVE vs. PUL, respectively, were: hematuria 11.8% vs. 25.7%, dysuria 16.9% vs. 34.3%, pelvic pain 2.9% vs. 17.9%, and urinary incontinence 0.4% vs. 1.3%). These findings provide evidence-based insights for clinicians, payers, and health policymakers to further define the role of WAVE for BPH in Japan.

Cost analysis of leuprorelin acetate in Japanese pre-menopausal breast-cancer patients: comparison between 6-month and 3-month depot formulations.

AIMS: The aim in this study is to evaluate economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot in Japanese pre-menopausal breast cancer patients from a societal perspective. METHODS: The cost analysis was conducted by estimating direct and indirect cost, and intangible costs associated with one 6-month injection compared with two 3-month injections. Claims data were used for the analyses of direct and indirect cost and Medical Fee Schedule Table for direct cost. Discrete choice experiments were conducted by web-based survey to determine the intangible costs. Another web-based survey was also conducted on premenopausal breast cancer patients with injections of leuprorelin acetate, to calibrate the results of discrete choice experiments. RESULTS: The medical costs saved for having one less injection in pre-menopausal breast cancer patients with leuprorelin acetate injection were JPY 6,183. The productivity loss saving was JPY 1,419. An estimation of intangible costs saved for having one less injection of leuprorelin acetate was JPY 58,430, which included the disbenefit due to pain (JPY 8,535), injection site reactions (JPY 44,051), waiting time (JPY 9,595), and subtracting value in medical consultation (JPY 3,751). The total cost saved for having one less injection was JPY 66,032. LIMITATIONS: The respondents from the internet panel provided by a survey company do not necessarily reflect a population of Japanese society. CONCLUSIONS: Leuprorelin acetate 6-month depot demonstrates a higher value than leuprorelin acetate 3-month depot through saving medical costs and loss of productivity, as well as intangible costs saved for having one less injection when treating pre-menopausal breast cancer patients. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

Cost analysis of leuprorelin acetate in Japanese prostate cancer patients: comparison between 6-month and 3-month depot formulations.

AIMS: This study aimed to evaluate the economic value for leuprorelin acetate 6-month depot compared with leuprorelin acetate 3-month depot from a societal perspective in Japanese prostate cancer patients. METHODS: The cost analysis estimated the reduction in direct and indirect costs as well as intangible costs saved by having one less injection. Claims data were used for the analyses of direct and indirect costs reduction. A discrete choice experiment based on a web-based survey estimated the monetary value of the intangible costs for one injection. Another web-based survey of prostate cancer patients, who had received treatment with leuprorelin acetate injections, was carried out to calibrate the results of the discrete choice experiment. RESULTS: Reductions in medical costs and loss of productivity for having one less injection in prostate cancer patients receiving leuprorelin acetate were JPY 5,670 and JPY 1,723, respectively. Intangible costs saved by using a 6-month depot formulation instead of a 3-month depot formulation for the injection of leuprorelin acetate were estimated to be JPY 19,872, including the values for a reduction in pain (JPY 3,131), injection site reactions (JPY 11,545), waiting time (JPY 9,479), and subtracting the value of medical consultation (JPY 4,283). The total cost reduction for having one less injection was JPY 27,265. LIMITATIONS: The respondents from the internet panel provided by a survey company are not necessarily a representative population of Japanese society. CONCLUSIONS: Leuprorelin acetate 6-month depot has an advantage in monetary value in the reduction in medical costs, loss of productivity, and intangible costs for having one less injection in prostate cancer patients compared with leuprorelin acetate 3-month depot. In the costs for treating with leuprorelin acetate, the percentage of intangible costs might not be negligible. The intangible costs will probably be actively evaluated to proceed to patient-centered healthcare in society.

Design of small-size pouch motors for rat gait rehabilitation device.

Recent studies have demonstrated that active gait training can recover voluntary locomotive ability of paralyzed rats. Rehabilitation devices used for studying spinal cord injury to date are usually fixed on a treadmill, but they have been used only slightly for active training. To process active rehabilitation, a wearable, lightweight device with adequate output is needed. Pouch motors, soft pneumatic actuators, are extremely light and have other benefits such as low cost, easy fabrication, and highly customizable design. They can be used to develop active gait rehabilitation devices. However, performance details of different motor designs have not been examined. As described herein, to build a wearable gait assistive device for rat study, we specifically examine how to design small pouch motors with a good contraction ratio and force output. Results show that pouch performance decreases dramatically with size, but better output is obtainable by separation into small 0.8 length-to-width ratio rooms. We used this knowledge to produce an assistive robot suit for gait rehabilitation and to test it with paralyzed rats. Results show that these small pouches can produce sufficient power to control hip joint movements during gait training. They can reveal the potential for new pouch motor applications for spinal cord injury studies.

X-ray phase-contrast computed tomography visualizes the microstructure and degradation profile of implanted biodegradable scaffolds after spinal cord injury.

Tissue engineering strategies for spinal cord repair are a primary focus of translational medicine after spinal cord injury (SCI). Many tissue engineering strategies employ three-dimensional scaffolds, which are made of biodegradable materials and have microstructure incorporated with viable cells and bioactive molecules to promote new tissue generation and functional recovery after SCI. It is therefore important to develop an imaging system that visualizes both the microstructure of three-dimensional scaffolds and their degradation process after SCI. Here, X-ray phase-contrast computed tomography imaging based on the Talbot grating interferometer is described and it is shown how it can visualize the polyglycolic acid scaffold, including its microfibres, after implantation into the injured spinal cord. Furthermore, X-ray phase-contrast computed tomography images revealed that degradation occurred from the end to the centre of the braided scaffold in the 28 days after implantation into the injured spinal cord. The present report provides the first demonstration of an imaging technique that visualizes both the microstructure and degradation of biodegradable scaffolds in SCI research. X-ray phase-contrast imaging based on the Talbot grating interferometer is a versatile technique that can be used for a broad range of preclinical applications in tissue engineering strategies.

Effects of exercise training on nitric oxide synthase in the kidney of spontaneously hypertensive rats.

Exercise training is known to have antihypertensive effects in humans and animals with hypertension, as well as to exhibit renal protective effects in animal models of hypertension and chronic renal failure. However, the mechanisms regulating these effects of exercise training remain unclear. The present study examined the effects of exercise training on nitric oxide synthase (NOS) in the kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Male SHR and WKY rats were randomly divided into a sedentary group and a treadmill exercise group for 8 weeks. Systolic blood pressure (SBP) was measured every 2 weeks by the tail-cuff method and urine and blood samples were collected after the exercise protocol. Nitric oxide synthase activity and protein expression and endothelial (e) NOS phosphorylation in the kidney were examined. Exercise training significantly lowered SBP, decreased urinary albumin excretion, thiobarbituric acid-reactive substances levels and renal NADPH oxidase activity, and increased creatinine clearance in SHR. Exercise training significantly increased plasma and urinary nitrate/nitrite, NOS activity and eNOS and neuronal NOS expression, but decreased eNOS phosphorylation at Ser(1177) and Thr(495) in kidneys of SHR and WKY rats. Renal NOS may be involved in the antihypertensive and renal protective effects of exercise training in SHR.

Disorder of fatty acid metabolism in the kidney of PAN-induced nephrotic rats.

Proteinuria is considered to play an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. Fatty acid-binding albumins are filtered through glomeruli and reabsorbed into proximal tubular epithelial cells (PTECs). However, the role of fatty acid metabolism associated with albuminuria in the development of tubulointerstitial damage remains unclear. Thus, the present study was designed to determine the changes of fatty acid metabolism in the nephrotic kidney. To induce nephrotic syndrome, Sprague-Dawley rats (SDRs) and Nagase analbuminemic rats (NARs) with inherited hypoalbuminemia were treated with a single injection of puromycin aminonucleoside (PAN). In SDRs, PAN treatment induced massive proteinuria and albuminuria and caused tubular damage, apoptosis, and lipid accumulation in PTECs. Among the enzymes of fatty acid metabolism, expressions of medium-chain acyl-CoA dehydrogenase (MCAD) and cytochrome P-450 (CYP)4A significantly decreased in PTECs of PAN-treated SDRs. Expressions of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α and estrogen-related receptor (ERR)α also significantly decreased, without changes in the expression of PPAR-α. In NARs, PAN treatment induced proteinuria but not albuminuria and did not cause tubular damage, apoptosis, or lipid accumulation. Expressions of MCAD, PGC-1α, or ERRα did not change in the kidney cortex of PAN-treated NARs, but the expression of CYP4A significantly decreased. These results indicate that massive albuminuria causes tubular damage and lipid accumulation with the reduction of MCAD, CYP4A, PGC-1α, and ERRα in PTECs.

Atorvastatin upregulates nitric oxide synthases with Rho-kinase inhibition and Akt activation in the kidney of spontaneously hypertensive rats.

OBJECTIVE: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins reduce blood pressure and have beneficial effects in cardiovascular and kidney diseases. The present study examined the effect of chronic treatment with atorvastatin (ATV) on the expression of nitric oxide synthase (NOS) and the activity of Rho-kinase and Akt in the kidney of spontaneously hypertensive rats (SHRs). METHODS: SHRs were treated with ATV for 8 weeks and the SBP was measured. The expressions of endothelial, neuronal and inducible NOS (eNOS, nNOS and iNOS, respectively) proteins in the kidney were examined by immunoblot analysis. The activity of eNOS, Rho-kinase and Akt in the kidney was examined by assessing the phosphorylation of eNOS, ezrin/radixin/moesin (ERM) and Akt, respectively. RESULTS: ATV reduced the SBP without changing the plasma cholesterol levels. ATV increased eNOS expression in the cortex and medulla and nNOS expression in the medulla, whereas it did not affect iNOS expression. Although it upregulated eNOS expression in the kidney, ATV decreased the levels of phosphorylated eNOS in the cortex and did not affect the ratio of phosphorylated eNOS to total eNOS in the medulla. ATV also inhibited Rho-kinase activity and enhanced Akt activity in the kidney of SHRs. CONCLUSION: ATV upregulates eNOS and nNOS expressions with Rho-kinase inhibition and Akt activation in the kidney of SHRs. The renal nitric oxide system, Rho-kinase and Akt may contribute to the antihypertensive and renoprotective effects of statins.