Cost-Effectiveness of Denosumab for the Treatment of Postmenopausal Osteoporosis in South Korea

Background@#Osteoporosis is a progressive skeletal disease associated with an increased risk of bone fracture. This study aimed to estimate the cost-effectiveness of denosumab for osteoporotic fracture prevention compared to bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate) and selective estrogen receptor modulators (raloxifene) in a cohort of postmenopausal women with osteoporosis. @*Methods@#A Markov model was used to evaluate the cost and effectiveness of denosumab versus comparators. The model had a cycle length of 6 months and was run from the age of 68 years to individual patients' lifetime or the age of 100 years. The health states considered in the model were well, hip fracture, vertebral fracture, wrist fracture, other osteoporotic fracture, post-hip fracture, post-vertebral fracture, and death. Recent local data were used as inputs for the model parameters. A discount rate of 4.5% was applied to both costs and outcomes. @*Results@#From the perspective of the healthcare system, denosumab was cost-effective or cost-saving compared to all comparators, considering one unit of Korea's gross domestic product per capita, USA dollar (USD) 34,870. Denosumab was cost-saving compared to ibandronate (oral) and raloxifene. Compared to alendronate, denosumab was cost-effective with an incremental cost-effectiveness ratio (ICER) of USD 767.10 per quality-adjusted life year (QALY). The ICER of denosumab vs. ibandronate IV, risedronate, and zoledronate was USD 685.63, USD 1,469.71, USD 4,668.53 per QALY, respectively. @*Conclusions@#The findings of this analysis suggest that denosumab is a cost-effective therapeutic option for preventing fractures in postmenopausal women with osteoporosis in South Korea.

Pediatric urology in the KJU

No abstract available.

Rapid Increase of Health Care Utilization and Cost due to Benign Prostatic Hyperplasia in Korean Men: Retrospective Population-based Analysis Using the Health Insurance Review and Assessment Service Data

Using the Korean public health insurance database, we analyzed patients diagnosed as benign prostatic hyperplasia (BPH) from 2004 to 2008. Age and year-specific amount and seasonal variation of hospital visits (HV), duration of treatment (DT), the total and per capita amount of insurance payment (TAIP, PCIP) were evaluated. A total of 12,088,995 HV were studied. Total HV increased 1.7 times and DT almost doubled in 2008 compared to those in 2004. HV, DT, and TAIP showed linearly increasing patterns year by year. In a time series analysis, HV increased in winter and demonstrated seasonality in a 12-month cycle. In a Poisson regression analysis, the annual variations of HV, DT, TAIP, and PCIP were different by age groups. In patients older than 40 yr, HV significantly increased 1.10-1.16 times compared to that of the previous year. DT markedly increased in their 60s and 80s patients. The rate of increase in PCIP was steeper in patients 50 yr and older than in the others.Health care utilization due to BPH was rapidly increasing in Korea and it was remarkable in the elderly population. Seasonal variation of HV demonstrated that health care utilization increased in winter.

Rapid Increase of Health Care Utilization and Cost due to Benign Prostatic Hyperplasia in Korean Men: Retrospective Population-based Analysis Using the Health Insurance Review and Assessment Service Data

Using the Korean public health insurance database, we analyzed patients diagnosed as benign prostatic hyperplasia (BPH) from 2004 to 2008. Age and year-specific amount and seasonal variation of hospital visits (HV), duration of treatment (DT), the total and per capita amount of insurance payment (TAIP, PCIP) were evaluated. A total of 12,088,995 HV were studied. Total HV increased 1.7 times and DT almost doubled in 2008 compared to those in 2004. HV, DT, and TAIP showed linearly increasing patterns year by year. In a time series analysis, HV increased in winter and demonstrated seasonality in a 12-month cycle. In a Poisson regression analysis, the annual variations of HV, DT, TAIP, and PCIP were different by age groups. In patients older than 40 yr, HV significantly increased 1.10-1.16 times compared to that of the previous year. DT markedly increased in their 60s and 80s patients. The rate of increase in PCIP was steeper in patients 50 yr and older than in the others.Health care utilization due to BPH was rapidly increasing in Korea and it was remarkable in the elderly population. Seasonal variation of HV demonstrated that health care utilization increased in winter.

Silencing of Heat Shock Protein 27 Expression Accelerates Doxazosin-induced Apoptosis in Prostate Cancer Cell Line PC-3

PURPOSE: Heat shock proteins (HSPs) are highly expressed during stress responses and cellular adaptation to environmental changes. One such protein is HSP27, a 27kDa protein that prevents cell death induced by many pro-apoptotic agents. Therefore, the aim of this study was to investigate the correlation between HSP27 expression and apoptosis induced by doxazosin treatment in prostate cancer cell line PC-3. MATERIALS AND METHODS: RT-PCR, Western blotting, and immunocytochemical staining were performed to determine whether HSP27 mRNA and protein are expressed in PC-3 cells. Next, to investigate the effects of doxazosin on apoptosis and HSP27 protein expression in PC-3 cells, the cells were stained using a TUNEL kit (to detect apoptotic cells) and with HSP27 antibody (to assess HSP27 protein expression) 6, 12, 24, and 48h after treatment with 25microM doxazosin. In addition, to determine whether HSP27 mRNA interference accelerates doxazosin-induced apoptosis of PC-3, we knocked down HSP27 with siRNA and then evaluated the rate of apoptosis after doxazosin treatment. RESULTS: HSP27 mRNA and protein were expressed in PC-3 cells. Furthermore, HSP27 mRNA and protein levels increased until 12 hours after 25microM doxazosin treatment, whereas the rate of apoptosis did not increased dramatically. After 12 hours, HSP27 expression decreased and then apoptosis was accelerated. In addition, siRNA-mediated knockdown of HSP27 induce higher apoptosis rate of PC-3 cells even before 12hrs after doxazosin treatment. CONCLUSIONS: By inhibiting apoptosis, HSP27 expression might play an important role in inhibiting progression to castration-refractory prostate cancer and resistance to anti-cancer treatment.

Expression levels of heat shock protein 27 and cellular FLICE-like inhibitory protein in prostate cancer correlate with Gleason score sum and pathologic stage

PURPOSE: Heat shock protein (HSP) 27 protects the cell by controlling apoptosis and immune reactions, and c-FLIP (cellular-FLICE inhibitory protein) inhibits apoptosis by inhibiting caspase-8 activity. We investigated the relationship of HSP27 and c-FLIP expression to prostate-specific antigen, Gleason score sum (GSS), and pathologic stage. MATERIALS AND METHODS: Samples from 163 patients between May 2004 and April 2010 were analyzed: 83 from patients that had underwent a radical prostatectomy, and 80 from those that underwent transurethral resection of the prostate to alleviate urinary symptoms from benign prostate hyperplasia. c-FLIP and HSP27 expression were observed by immunohistochemistry staining. Samples with less than 5% expression-positive cells were scored as 1, with 5%-50% were scored as 2, and with more than 50% were scored as 3. Local reactions were identified as 0.5 and evaluated. RESULTS: Both the presence of HSP27 within the tumor and the number of cancer cells positive for HSP27 were significantly correlated to GSS and pathologic stage (p<0.001, p=0.001, p<0.001, p<0.001). The same was true for c-FLIP expression (p<0.001). GSS was more highly correlated to HSP27 expression than to c-FLIP expression (r=0.814 for HSP27, r=0.776 for c-FLIP), as was pathologic stage (r=0.592 for HSP27, r=0.554 for c-FLIP). CONCLUSIONS: In prostate cancer, higher GSS and a more advanced pathologic stage were associated with a higher likelihood of having a HSP27-positive tumor and more HSP27-positive tumor cells. HSP27 expression was correlated with GSS and prostate cancer stage. A more advanced pathologic stage corresponded to a higher likelihood of having a c-FLIP-positive tumor and more c-FLIP-positive tumor cells. HSP27 expression had a higher correlation with prostate cancer stage and GSS than c-FLIP expression did.

Experience With Robot-Assisted Laparoscopic Radical Prostatectomy at a Secondary Training Hospital: Operation Time, Treatment Outcomes, and Complications With the Accumulation of Experience

PURPOSE: To investigate the learning curve and outcomes of robot-assisted laparoscopic radical prostatectomy (RALP) performed by a relatively lower volume surgeon at a secondary training hospital. MATERIALS AND METHODS: The medical records and the surgery video recordings of 100 patients who underwent RALP by a single surgeon between March 2010 and January 2013 were reviewed. The first 10 cases were grouped into period 1, cases 11 to 40 into period 2, cases 41 to 70 into period 3, and cases 71 to 100 into period 4. The interval between the operations, the operative time for each step of the surgery, the total console time, and the operative outcomes were investigated. RESULTS: The mean interval between surgeries was 10.6+/-9.3 days. The console time decreased progressively after the first 10 cases and reached under 3 hours after 75 cases. The time taken to begin dissection of the dorsal vein complex, for the division of the bladder neck, for lateral dissection with neurovascular bundle preservation, and for apex dissection decreased significantly with experience, although the time for vesicourethral anastomosis did not. The margin-positive rate of stage T2 patients was 27.4% (20/73), and the transfusion rate was 50% in period 1 patients and 3.3% in period 4 patients. No major complications occurred. CONCLUSIONS: It is difficult to shorten the learning curve of surgeons in secondary training hospitals owing to the smaller number of cases and the irregular surgical intervals. Although the operation time was relatively longer, the surgical outcome and complication rates were comparable with those of surgeons at larger hospitals.

Efficacy of Alfuzosin After Shock Wave Lithotripsy for the Treatment of Ureteral Calculi

PURPOSE: We evaluated the efficacy of alfuzosin for the treatment of ureteral calculi less than 10 mm in diameter after extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A randomized, single-blind clinical trial was performed prospectively by one physician between June 2010 and August 2011. A total of 84 patients with ureteral calculi 5 to 10 mm in diameter were divided into two groups. Alfuzosin 10 mg (once daily) and loxoprofen sodium 68.1 mg (as needed) were prescribed to group 1 (n=41), and loxoprofen sodium 68.1 mg (as needed) only was prescribed to group 2 (n=44). The drug administration began immediately after ESWL and continued until stone expulsion was confirmed up to a maximum of 42 days after the procedure. RESULTS: Thirty-nine of 41 (95.1%) patients in group 1 and 40 of 43 (93.0%) patients in group 2 ultimately passed stones (p=0.96). The number of ESWL sessions was 1.34+/-0.65 and 1.41+/-0.85 in groups 1 and 2, respectively (p=0.33). The patients who required analgesics after ESWL were 8 (19.5%) in group 1 and 13 (30.2%) in group 2 (p=0.31). Visual analogue scale pain severity scores were 5.33+/-1.22 and 6.43+/-1.36 in groups 1 and 2, respectively (p=0.056). The time to stone expulsion in groups 1 and 2 was 9.5+/-4.8 days and 14.7+/-9.8 days, respectively (p=0.005). No significant adverse effects occurred. CONCLUSIONS: The use of alfuzosin in combination with ESWL seems to facilitate stone passage and to reduce the time of stone expulsion but does not affect the stone-free rate.

Effects of Mirodenafil, a Phosphodiesterase-5 Inhibitor, on Female Rat Bladder in a Partial Bladder Outlet Obstruction Model: Physiological and Immunohistochemical Aspects

PURPOSE: We investigated the effects of mirodenafil, a phosphodiesterase-5 inhibitor developed in South Korea, on the female rat bladder in a partial bladder outlet obstruction (BOO) model. MATERIALS AND METHODS: Thirty-six female Sprague-Dawley rats were divided into four groups: the control group, BOO without medication group, BOO with mirodenafil 1 mg/kg group, and BOO with mirodenafil 4 mg/kg group. Mirodenafil was administered orally for 2 weeks after the induction of BOO. Two weeks after BOO, the rats in each group underwent cystometry under urethane anesthesia. After cystometry, the bladder was excised to perform immunohistochemical staining for connexin 43. RESULTS: The three BOO groups showed significant increases in mean bladder weight compared with the control group. Baseline pressure, threshold pressure, and maximum contraction pressure were not significantly different between the four groups. Although the contraction interval was decreased in all BOO groups compared with the control group, it was prolonged in the two groups treated with mirodenafil compared with the untreated BOO group. In the immunohistochemical examination, connexin 43 staining intensity in the lamina propria increased in the three BOO groups compared with the control group. The two groups treated with mirodenafil, however, showed decreased connexin 43 staining compared with the untreated BOO group. CONCLUSIONS: Mirodenafil may increase the contraction intervals of female rat bladders in a partial BOO model. Decreasing bladder overactivity by mirodenafil may be related to intracellular communication mechanisms involving connexin 43.

Effect of Transurethral Resection of the Prostate Based on the Degree of Obstruction Seen in Urodynamic Study

PURPOSE: We retrospectively investigated the effect of transurethral resection of the prostate (TURP) on the basis of the degree of obstruction seen in preoperative urodynamic study in patients with benign prostatic hyperplasia (BPH) who complained of lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: The subjects of this study were 285 patients who were diagnosed with BPH with LUTS and who subsequently underwent TURP. The Abrams-Griffiths number was calculated from the urodynamic results to divide the patients into the following groups: unobstructed, equivocal, and obstructed. There were 26 patients (9.1%) in the unobstructed group, 98 patients (34.4%) in the equivocal group, and 161 patients (56.5%) in the obstructed group. The preoperative and postoperative uroflowmetry, residual urine, International Prostate Symptom Score (IPSS), and quality of life (QoL) score were compared between the three groups to evaluate the outcome of the treatment. RESULTS: The reduction in the IPSS was 14.4 in the obstructed group, which was higher than the reductions of 12.7 in the equivocal group and 9.5 in the unobstructed group, but this difference was not statistically significant (p=0.227). The QoL score was also not significantly different across the three groups (p=0.533). The postoperative maximum flow rate was significantly improved in all three groups. The obstructed group had an improvement of 7.8+/-7.2 mL/s, which was higher than the improvement of 3.7+/-6.2 mL/s in the unobstructed group (p=0.049) but was not significantly different from the improvement of 5.6+/-6.9 mL/s in the equivocal group (p=0.141). CONCLUSIONS: TURP led to an improvement in the maximum flow rate and LUTS even in BPH patients without BOO. Therefore, TURP can be expected to improve LUTS in BPH patients without definite urodynamic obstruction.

Safety and Efficacy of Combined Transrectal Ultrasound-Guided Prostate Needle Biopsy and Transurethral Resection of the Prostate

PURPOSE: This study was conducted to examine whether simultaneous transrectal prostate needle biopsy (TPNB) owing to an increase in prostate-specific antigen (PSA) levels is safe and effective in patients who are scheduled for transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Combined TPNB and TURP was performed in a total of 42 patients aged 60 years and older who had gray-zone PSA values (4-10 ng/ml) and PSA density (PSAD) values of 0.12 and less. The frequencies of fever, sepsis, and epididymitis were assessed after surgery. The diagnostic accuracy was assessed, and the results of histologic examination were evaluated in terms of TPNB or TURP. In addition, the diagnostic accuracy was assessed according to age. RESULTS: Prostate cancer was diagnosed in 6 (14.3%) of the 42 patients: 2 patients were diagnosed with prostate cancer by TPNB only, 3 patients by TURP only, and 1 patient by combined TPNB and TURP. Four (25%) of the 16 patients aged under 70 years and 2 (7.8%) of the 26 patients aged 70 years and older were diagnosed with prostate cancer. Fever was observed in 9 patients (21.4%), 4 (9.5%) of whom had a fever of higher than 38degrees C. The fever normalized the day after surgery in all 9 patients. No septicemia was noted. There were no serious complications related to combined TPNB and TURP. CONCLUSIONS: The results of this study suggest that combined TPNB and TURP may be safe and effective in patients who require TURP.

Clinical and Urodynamic Significance of Morphological Differences in Intravesical Prostatic Protrusion

PURPOSE: The objectives of this study were to evaluate whether morphologic differences correlated with urodynamic and clinical characteristics in patients with benign prostatic hyperplasia (BPH) with intravesical prostatic protrusion (IPP) of trilobar or bilobar adenoma. MATERIALS AND METHODS: Between January 2008 and June 2009, 72 male patients who had undergone transurethral resection (TUR) owing to BPH with IPP were included in this study. They underwent preoperative urodynamic studies, the International Prostate Symptom Score (IPSS)/quality of life (QoL), maximal flow rate (Qmax), post-voiding residual urine volume (PVR), transrectal ultrasonography (TRUS), and serum prostate-specific antigen (PSA) measurement. The patients were classified into 2 groups (the trilobar and bilobar adenoma groups) on the basis of video findings during the TUR operation. RESULTS: The trilobar and bilobar adenoma groups consisted of 37 patients and 35 patients, respectively. The Mean+/-SD IPP, prostate volume (PV), and transition zone volume of the trilobar and bilobar adenoma groups were 11.8+/-5.2 mm and 9.0+/-3.8 mm (p=0.014), 81.1+/-25.8 g and 59.3+/-22.5 g (p<0.001), and 49.6+/-20.6 g and 34.8+/-19.4 g (p=0.003), respectively. The Mean+/-SD PSA, bladder contractility index (BCI), and bladder outlet obstruction index (BOOI) were 4.6+/-2.5 ng/ml and 3.5+/-1.7 ng/ml (p=0.042), 119.8+/-33.4 and 87.7+/-24.4 (p<0.001), and 62.6+/-29.5 and 44.6+/-20.4 (p=0.005), respectively. There were no significant differences in IPSS/QoL, Qmax, PVR, acute urinary retention, or detrusor overactivity in the 2 groups. CONCLUSIONS: IPP has two morphologic types of trilobar or bilobar enlargement. The PV, BOOI, and BCI were significantly smaller in the bilobar adenoma group than in the trilobar adenoma group.

Change in Patients' Perspectives after Education on the Management of Benign Prostatic Hyperplasia

PURPOSE: We assessed patients' understanding of benign prostatic hyperplasia (BPH) and their perspectives on the management of BPH through a questionnaire and evaluated changes in perspective after patient education. MATERIALS AND METHODS: From December 2007 to February 2008, 5 university hospitals participated in the study. A self-administered questionnaire was developed and was completed by patients before and after the patients read the patient's guide. The questionnaire was composed of 22 questions, which were grouped into 4 different categories. The patient's guide was written in everyday words and was based on the American Urological Association patient's guide. RESULTS: A total of 141 patients who visited the urology department for treatment of symptoms suggestive of BPH participated in the survey. Understanding about the statement, "BPH does not progress to become prostate cancer" was increased after reading the patient's guide (35.57%--> 73.87%, p56.7%). Among the desirable effects of drug therapy, the patients' preferences were amelioration of symptoms within a few weeks (51.1%--> 48.9%), reduction in prostate size (18.4%-->24.1%), prevention of acute urinary retention (14.2%-->13.5%), and prevention of prostate surgery (7.8% -->8.5%). The potential side effect of drug therapy that patients were most concerned about was generalized weakness. Patients' reluctance to undergo surgery was increased after reading the patient guide (9.9%-->23.4%, p=0.002). CONCLUSIONS: Patients have considerable misunderstanding about BPH. More efforts should be exercised in patient education and in the development of public education programs. Because patients expect not only rapid symptom improvement but also a reduction in prostate size, physicians should consider these points when treating patients with BPH.