Comparison of mirabegron and vibegron for clinical efficacy and safety in female patients with overactive bladder: a multicenter prospective randomized crossover trial.

PURPOSE: To compare the efficacy and safety of mirabegron and vibegron in female OAB patients. METHODS: We conducted a multicenter, prospective, randomized crossover study of female patients with OAB. The patients were assigned to Group MV (mirabegron for 8 weeks, followed by vibegron for 8 weeks) or group VM (vibegron for 8 weeks, followed by mirabegron for 8 weeks). The primary endpoint was the change in OABSS from baseline, and the secondary endpoint was the change in FVC parameters. After completion of the study, each patient was asked which drug was preferable. RESULTS: A total of 83 patients were enrolled (40 and 43 in groups MV and VM, respectively). At 8th and 16th week, 33 and 29 in Group MV and 34 and 27 in Group VM continued to receive the treatment. The change in PVR was not significantly different between treatment with mirabegron and vibegron. The changes in OABSS, nighttime frequency, mean, and maximum voided volume were similar between mirabegron and vibegron. The mean change in the daytime frequency was greater in the vibegron than in the mirabegron. Of the 56 patients, 15 (27%) and 30 (53%) preferred mirabegron and vibegron, respectively. The remaining 11 patients (20%) showed no preference. The change in the urgency incontinence score during vibegron was better in patients who preferred vibegron to mirabegron. CONCLUSION: The efficacies of mirabegron and vibegron in female patients was similar. The patients' preference for vibegron could depend on the efficacy of vibegron for urgency incontinence.

Risk Factors for Poor Pain Control after Opioid Switching from Oxycodone Tablet to Fentanyl Patch.

Pain control becomes poor in some cases after opioid switching from oxycodone tablet (OXC) to fentanyl patch (FP). However, fewer studies on risk factors have been reported. In this study, we surveyed the states of pain control (PC) and opioid administration, patient background, laboratory test values, and concomitant drugs retrospectively in 86 patients switching from OXC to FP between June 2010 and April 2018 in Mazda Hospital and Hiroshima Prefectural Hospital. The subjects were divided into 2 groups based on the median number of days to the initial dose increase after switching to FP. Between the early (<7.5 d) and late (≥7.5 d) increase groups, a significant difference was noted in the presence or absence of liver metastasis (LM), concomitant drugs with a high protein binding rate (CDHPBR), and the state of PC before and after switching to FP (p < 0.05). Binary logistic regression analysis showed the presence of CDHPBR, absence of LM, and poor PC after switching were risk factors for early dose increase (presence of CDHPBR: odds ratios (OR), 3.30, 95% confidence interval (CI), 1.09-9.98; presence of LM: OR, 0.31, 95% CI, 0.10-0.93; good PC: OR, 0.23, 95% CI, 0.07-0.79, respectively). The initial dose increase after switching to FP was earlier in patients with CDHPBR and/or without LM than those without CDHPBR and with LM (p < 0.05, log-rank test). It was suggested that the analgesic effect of FP after switching from OXC is likely to be insufficient in patients treated with CDHPBR and patients without LM.

Factors Influencing the Appearance of Oxaliplatin-Induced Allergy.

Several studies reported that the administration of oxaliplatin often induced allergy, but few studies have analyzed the pathogenesis. In this study, we examined the relationship between the incidence of allergy and status of oxaliplatin administration, patient background, laboratory data, or combined drugs. The subjects were 144 patients with colorectal or gastric cancer in whom oxaliplatin administration was started and completed between 2010 and 2016. They were divided into 2 groups: allergy and non-allergy groups. We extracted important factors influencing its appearance using multivariate analysis, and analyzed items of which the influence was suggested, using receiver operating characteristic (ROC) analysis. In 11 patients (7.6%), allergy appeared. The median frequency of appearance was 9 times (range: 5-13), being similar to that previously reported. On multivariate analysis, albumin (Alb) was extracted as an important factor. The cut-off value of Alb for the risk of allergy was 4.1 g/dL. An increase in the number of protein conjugates may have increased the risk of functioning as a hapten. Furthermore, the results suggested that the more frequency of oxaliplatin administration might increase the incidence of allergy, although it was not extracted as an important factor. In addition to young and female patients, as previously indicated, careful follow-up may be necessary for those with an Alb level of ≥4.1 g/dL especially after the 6th course.

Investigation of Risk Factors Affecting Lactate Levels in Japanese Patients Treated with Metformin.

Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia. 290 outpatients receiving various doses of metformin at our hospital were enrolled between March and July 2014. Serum electrolytes, Cre (creatinine), BUN (blood urea nitrogen), UA (uric acid), HbA1c (hemoglobin A1c), and lactate levels were investigated. Lactate levels did not significantly differ between the elderly (≥75 years) and non-elderly (<75 years) groups. Patients in the elderly group had a significantly lower daily metformin dose and estimated glomerular filtration rate (eGFR), compared with the non-elderly group (both p<0.005). Between with and without hyperlactemia groups, no significant differences were observed in either Cre or age. On the other hand, patients with hyperlactemia had a significantly higher dose of metformin than those without hyperlactemia (p<0.05). In this study, we found that old age and mildly impaired kidney function were not associated with increased lactate levels, and that a higher dose of metformin may be an independent risk factor for elevated lactate levels in Japanese patients.

[Clinical significance of cystoscopy in transrectal prostate biopsy].

The clinical significance of cystoscopy in patients with benign prostatic hyperplasia or prostate cancer remains open to discussion. We have always performed cystoscopy with prostate biopsy and have discovered bladder cancer in some patients. The present study investigated the clinical significance of performing cystoscopy with prostate biopsy. Subjects were 458 patients who underwent cystoscopy and ultrasound-guided transrectal prostate biopsy from January 1998 to December 2004. Mean age of subjects was 71.3 years (range, 52-93 years). Prostate biopsy was performed modified Eskews systematic 5-region prostate biopsy (12 core). Some abnormalities were found in 43 of the 458 patients (9.3%). Among these 43 patients, bladder cancer was found in 11 patients (2.4%), and transurethral resection bladder tumor (TUR-Bt) was performed on all 11 patients. Pathological staging of bladder cancer was pT1 and G2 in all cases. Bladder stones were seen in 13 patients (2.8%), benign bladder tumor in 5 patients (1.1%), urethral polyp in 7 patients (1.5%), urethral stenosis in 6 patients (1.3%) and ureteral stones associated with ureterocele in 1 patient (0.2%). Appropriate examinations and treatments were performed for all cases. Cystoscopy may be needed at the time of prostate biopsy because: the above-mentioned abnormalities were first discovered on cystoscopy; and the frequency of bladder cancer was 2.4% for the total patient population, and endoscopic surgery was performed.

[A case of erythropoietin-producing renal cell carcinoma with polycythemia].

The patient was a 46-year-old man with gross hematuria and left lumbar pain. Computed tomography revealed a large left renal tumor with hemorrhage. Serological examination revealed polycythemia and a high erythropoietin level. After left radical nephrectomy, polycythemia and serologically high level of erythropoietin disappeared. Histopathological findings showed renal cell carcinoma composed of spindle cells. Based on the above mentioned clinical course, we diagnosed this case as erythropoietin-producing renal cell carcinoma with polycythemia. It is suggested that erythropoietin not only causes polycythemia but also stimulates proliferation of the tumor, because the majority of erythropoietin-producing renal cell carcinomas have been reported to be highly advanced. This patient had no evidence of disease one year after the operation.

[Epidemiological characteristics of urolithiasis in Okhotsk coast area in Hokkaido].

An epidemiological study of 422 stone-formers who visited our hospital from 1997 to 2001 was conducted. The mean annual prevalence and incidence of both upper and lower urinary tract stones were higher than what was found in a nationwide urolithiasis survey carried out in Japan in 1995. The incidence of upper and lower urinary tract stones was 90.8% and 9.2%, respectively. The frequency of lower urinary tract stones was higher than that found in the previously mentioned nationwide study. The male-to-female ratio of upper and lower urinary tract stones was 1.68:1 and 2.25:1, respectively. The frequency in females was higher in this study than that found in the nationwide survey. The peak age for incidence of upper urinary tract stones is 50s in males and females. In the treatment of upper urinary tract stones, ureteroscopic lithotripsy was carried out more often than shock wave lithotripsy (SWL), because our hospital had no SWL device. Many endoscopic lithotripsy procedures were performed to treat stones located in the lower urinary tract. Of the upper urinary tract stones 83.7% were composed of calcium, the incidence of uric acid stones was high (6.6%), whereas the incidence of infectious stones was low (1.9%). For lower urinary tract stones, the frequency of infectious stones was high (52.6%). In the present study, the epidemiological features were as follows: high annual prevalence and incidence, high frequency of lower urinary tract stones, high frequency in females, many endoscopic treatment procedures and high frequency of uric acid stones in the upper urinary tract.

Relation between technetium 99m-methoxyisobutylisonitrile accumulation and multidrug resistance protein in the parathyroid glands.

Technetium 99m ((99m)Tc)-methoxyisobutylisonitrile (MIBI) scintigraphy has been reported to be a useful method for visualizing the parathyroid glands for the diagnosis of hyperparathyroidism. Some drug metabolism transporters, such as p-glycoprotein (P-GP) or multidrug resistance-associated protein (MRP), are believed to be involved with one mechanism of (99m)Tc-MIBI accumulation in the parathyroid glands. We analyzed the expression of P-GP and MRP in 40 parathyroid glands from eight patients with primary hyperparathyroidism and six patients with secondary hyperparathyroidism using an immunohistochemical procedure. These patients underwent (99m)Tc-MIBI scintigraphy and thallium 201 ((201)Tl)/(99m)Tc subtraction scintigraphy preoperatively. We investigated the relation between the scintigraphic images and the expression of P-GP and MRP. The positive findings of (99m)Tc-MIBI accumulation in the hyperfunctioning parathyroids were increased significantly. There was a significant difference between the expression of P-GP and the (99m)Tc-MIBI scintigraphy findings. High expression of P-GP in parathyroid cells resulted in the negative image of (99m)Tc-MIBI, and low or no expression of P-GP made the image positive. There was no significant difference between the expression of MRP and the (99m)Tc-MIBI scintigraphic imaging. The (99m)Tc-MIBI image was also related to the weight of the parathyroid glands but not to the type of the parathyroid cells. Based on these clinical findings, we can hypothesize that P-GP functions as a drug transporter not only for chemotherapeutic agents but also for (99m)Tc-MIBI.