Improvement of medication adherence for desmopressin by adjusting the prescription dosage in male patients with overactive bladder: A claims database analysis.

OBJECTIVES: Desmopressin is widely used for nocturia in patients with nocturnal polyuria. We investigated the continuation rate and adherence for desmopressin in patients with overactive bladder and nocturia using a claims database and evaluated factors that improved adherence. METHODS: Patients with nocturia in a Japanese claims database who started desmopressin between September 2019 and July 2021 were evaluated. Drug persistence was assessed using the Kaplan-Meier method for initial prescription of desmopressin. The proportion of days covered (PDC) was also evaluated among patients with prescription persistence. Multivariate analysis was performed using logistic regression analysis to identify factors predicting adherence to desmopressin. RESULTS: The study included 72,888 patients entered into Japan Medical Data Center (JMDC) database between September 2019 and July 2021. For the 236 patients prescribed desmopressin formulations, mean prescription duration was 114 days. Among the total cases, 90 (38.1%) cases were prescribed only once, mean PDC was 0.60, and the number of high-adherence patients (PDC ≥ 0.80) was 108 (45.8%). Desmopressin prescription doses were fixed in 216 patients and adjusted in 20 patients. Multivariate analysis identified prescription dose adjustment for desmopressin as significantly associated with high PDC. CONCLUSION: Desmopressin showed a 38% dropout rate after the first dose. However, high medication continuation and high medication adherence rates (PDC) could be maintained with prescription adjustments. Careful patient monitoring and appropriate adjustment of the desmopressin dosage appear to be important factors in improving nocturia.

Effect of Pharmacotherapy for Overactive Bladder on the Incidence of and Factors Related to Urinary Tract Infection: A Systematic Review and Meta-analysis.

PURPOSE: The aim of this meta-analysis was to investigate the effect of pharmacotherapy for overactive bladder on the pathogenesis of urinary tract infection. MATERIALS AND METHODS: A comprehensive search was performed in MEDLINE and the Cochrane Library using terms for overactive bladder, antimuscarinic agents, and beta 3-adrenoceptor agonists. The primary end point was the emergence of urinary tract infection after pharmacotherapy for overactive bladder. The secondary end point was the emergence of urinary retention, dysuria, and/or increased residual urine volume after overactive bladder treatment. Meta-analyses were conducted using random-effects models. RESULTS: A total of 35,939 patients in 33 trials (29 trials of antimuscarinic agents vs placebo, and 9 trials of beta 3-adrenoceptor agonists vs placebo) that included patients with overactive bladder were identified. At 1-3 months after treatment, the incidence of urinary tract infections was statistically significantly higher in the patients treated with antimuscarinic agents (RR: 1.23, 95% CI: 1.04, 1.45; P = .013) than in the placebo control group. The incidence of urinary tract infections was not increased in the patients treated with beta 3-adrenoceptor agonists (RR: 1.04, 95% CI: 0.76, 1.42; P = .796). Antimuscarinic agents also statistically significantly increased the risks of urinary retention, dysuria, and/or increased residual urine volume (RR: 2.88, 95% CI: 1.79, 4.63; P < .001), whereas beta 3-adrenoceptor agonists did not (RR: 1.26, 95% CI: 0.38, 4.14; P = .708). CONCLUSIONS: This meta-analysis showed that antimuscarinic agents statistically significantly increased the incidences of urinary tract infection and lower urinary tract symptoms and dysfunction, but beta 3-adrenoceptor agonists did not. To prevent urinary tract infection emergence, beta 3-adrenoceptor agonists might be safer than antimuscarinic agents.

Bayesian Optimization-Assisted Screening to Identify Improved Reaction Conditions for Spiro-Dithiolane Synthesis.

Bayesian optimization (BO)-assisted screening was applied to identify improved reaction conditions toward a hundred-gram scale-up synthesis of 2,3,7,8-tetrathiaspiro[4.4]nonane (1), a key synthetic intermediate of 2,2-bis(mercaptomethyl)propane-1,3-dithiol [tetramercaptan pentaerythritol]. Starting from the initial training set (ITS) consisting of six trials sampled by random screening for BO, suitable parameters were predicted (78% conversion yield of spiro-dithiolane 1) within seven experiments. Moreover, BO-assisted screening with the ITS selected by Latin hypercube sampling (LHS) further improved the yield of 1 to 89% within the eight trials. The established conditions were confirmed to be satisfactory for a hundred grams scale-up synthesis of 1.

Efficacy of the opened legs position for protecting against postoperative rhabdomyolysis after robot-assisted radical prostatectomy: A propensity score-matched analysis of perioperative outcomes.

OBJECTIVES: The aim of the present study was to clarify the relationships of intraoperative surgical position with the incidence of postoperative rhabdomyolysis and with postoperative renal function to safely perform robot-assisted radical prostatectomy. METHODS: The participants in the present study were 276 consecutive patients who underwent robot-assisted radical prostatectomy at our institutions between 2013 and 2020; 130 cases were performed in the opened legs position and 146 cases in the lithotomy position with a steep 23°-25° head-down position. Rhabdomyolysis was defined as creatine kinase values greater than 1000 IU/L. Propensity score matching including age, body mass index, the presence of comorbidities, preoperative creatine kinase, preoperative estimated glomerular filtration rate, and prostate-specific antigen was performed, resulting in a matched cohort of 146 patients (opened legs position group n = 73; lithotomy position group n = 73). RESULTS: After propensity score matching, creatine kinase values on the first day after surgery were significantly lower in the opened legs position group than in the lithotomy position group (opened legs position group: lithotomy position group = 246.9 ± 114.9 IU/L: 558.2 ± 114.9 IU/L, P = 0.034). There were significantly fewer patients diagnosed with postoperative rhabdomyolysis in the opened legs position group (opened legs position group: lithotomy position group = 0% (0/73): 9.6% (7/73), P < 0.001). In addition, fluid replacement volume was significantly less in the opened legs position group (opened legs position group: lithotomy position group = 5747 ± 180 mL: 6349 ± 0176 mL, P = 0.018). CONCLUSIONS: To prevent rhabdomyolysis after surgery, robot-assisted radical prostatectomy should be performed in the opened legs position.

The effect of ß3-adrenoceptor gene polymorphisms on lower urinary tract function in males.

PURPOSE: To clarify the role of Trp64Arg polymorphisms of the gene encoding the ß3-adrenoceptor for lower urinary tract function in males, the present study investigated the association between the Trp64Arg polymorphisms and lower urinary tract symptoms (LUTS) and function. METHODS: This prospective observational study included patients who underwent robot-assisted radical prostatectomy. Before surgery, blood samples were collected, and analyses of ß3-adrenoceptor gene polymorphism were performed using the real-time polymerase chain reaction. The present cohort was divided into patients with wild type (Trp64Trp) and with variant type (Trp64Arg + Arg64Arg), and LUTS and lower urinary tract function before surgery were compared between them. RESULTS: Wild type was found in 247 patients, with variant type in 129. There were no significant differences in LUTS between the two groups. Residual urine volume (PVR) (wild type: variant type = 47 ± 53 mL: 58 ± 77 mL, P = 0.04) and voiding time on uroflowmetry (wild type: variant type = 29 ± 15 s: 33 ± 17 s, P = 0.04) were significantly increased in the variant type. CONCLUSION: The Trp64Arg variant of the ß3-adrenoceptor gene significantly increased PVR and voiding time in men. However, it was not significantly associated with the emergence of LUTS. Thus, since the effect of ß3-adrenoceptor gene polymorphisms on the genitourinary organs might be weak, whether men possess the Trp64Arg variant of the ß3-adrenoceptor gene might not critically affect urinary quality of life, but modestly affect the lower urinary tract function.

Comprehensive approach for preserving cavernous nerves and erectile function after radical prostatectomy in the era of robotic surgery.

A nerve-sparing procedure during robot-assisted radical prostatectomy has been considered one of the most important techniques for preserving postoperative genitourinary function. The reason is that adequate nerve-sparing procedures could preserve both erectile function and lower urinary tract function after surgery. When a nerve-sparing procedure is carried out, the cavernous nerves themselves cannot be visualized, despite the magnified viewing field during robot-assisted radical prostatectomy. Thus, nerve-sparing procedures have been considered challenging operations, even now. However, because not all surgeons have carried out a sufficient number of nerve-sparing procedures, the development of new nerve-sparing procedures or new methods for mapping the cavernous nerves is required. Recently, various new operative techniques, for example, Retzius-sparing robot-assisted radical prostatectomy, transvesical robot-assisted radical prostatectomy and retrograde release of neurovascular bundle technique during robot-assisted radical prostatectomy, have been developed. In addition, new surgical devices, for example, biological/bioengineering solutions for cavernous nerve protection and devices for identifying the cavernous nerves during radical prostatectomy, have developed to preserve the cavernous nerves. In contrast, limitations or problems in preserving cavernous nerves and postoperative erectile function have become apparent. In particular, the recovery rate of erectile function, the positive surgical margin rate at the site of nerve-sparing and the indications for nerve sparing have become obvious with the accumulation of much evidence. Furthermore, predictive factors for postoperative erectile function after nerve-sparing procedures have also been clarified. In this article, the importance of a comprehensive approach for early recovery of erectile function in the robot-assisted radical prostatectomy era is discussed.

Estimating the mitigation effect of Tokai earthquake measures on housing damage: a counterfactual approach.

This paper evaluates the mitigation effect of Tokai earthquake measures on housing damage using a counterfactual approach. It focuses on those measures that stimulate ex-ante investment in disaster prevention in the supposedly affected area, including earthquake-proof retrofitting and improved housing construction; the effect of the measures on housing losses is estimated monetarily. The study compares factual disaster damage computed using a real distribution of houses with counterfactual damage to a hypothetical housing distribution that would occur if the measures were not implemented. The key findings are: (i) the disaster mitigation effects of Tokai earthquake measures on housing amount to approximately JPY 18 billion (USD 0.18 billion) for Yamanashi Prefecture and JPY 0.26 trillion (USD 2.6 billion) for Shizuoka Prefecture, which would be at the centre of the event; (ii) a before-after comparison biases estimates of the mitigation effect; and (iii) statistically, the measures do not mitigate the housing damage predicted for an earthquake in Tokai.

[A Case of Metastatic Peripheral T-cell Lymphoma of the Central Nervous System During the Perinatal Period].

The diagnosis of malignant tumors during pregnancy is not uncommon; the incidence is one per six thousand pregnancies. However, the diagnosis of malignant lymphoma-especially T-cell lymphoma-during pregnancy is extremely rare. Thus, the early detection and management of T-cell lymphoma necessitates difficult decision-making. A 30-year-old woman developed consciousness disturbance on postpartum day three. Because brain MRI showed multiple edematous lesions in both hemispheres, vasculitis or encephalitis was initially suspected, and diagnostic therapy was initiated with the administration of steroids. One month later, the patient suddenly developed a subarachnoid hemorrhage followed by acute hydrocephalus. Emergent ventricular drainage and lesion biopsy were simultaneously performed. Based on the findings, the patient was diagnosed with peripheral T-cell lymphoma not otherwise specified(PTCL-NOS). Laboratory findings indicated Epstein-Barr virus(EBV)infection. Moreover, the same diagnosis was supported by breast and bone marrow biopsies. Thus, the brain lesions were presumed to be metastatic in nature. The prognosis of PTCL-NOS is severely poor in pregnant women as diagnosis is delayed owing to limitations of radiological examinations and because symptoms can be confused with those of other diseases or hyperemesis gravidarum. Additionally, the alteration of immunotolerance in association with pregnancy and EBV infection might have influenced the aggressive features of this case. When a pregnant woman presents with neurological symptoms, malignant lymphoma should be considered when making a differential diagnosis.

Uniformity Study of Two-Functional Luminescent Dyes Adsorbed over an Anodized Aluminum Coating for Motion-Capturing Pressure- and Temperature-Sensitive Paint Imaging.

The pressure- and temperature-sensitive paint (PSP/TSP) technique, for steady-state and unsteady-state measurements, is becoming widespread. However, unsteady quantitative measurement is still difficult because non-uniform distribution of the probes over a test model may cause errors in the results. We focus on the dipping method that applies two luminophores into a binding material to improve sensitivity uniformity over a model surface. A bullet-shaped axisymmetric test model with motion-capturing TSP was used to evaluate the sensitivity uniformity, and three dipping methods (static, convectional, and rotational) were examined. The average peak ratios in the longitudinal direction were 1.17-1.46 for static, 1.38-1.51 for convectional, and 1.42-1.45 for rotational dipping. The standard deviations in the transverse direction were the smallest for rotational (0.022-0.033), relative to static (0.086-0.104), and convectional (0.044-0.065) dipping.

Zebrafish xenotransplantation model for cancer stem-like cell study and high-throughput screening of inhibitors.

Xenotransplantation studies are important tools for studying cancer biology, especially for assaying tumor cell malignancy and providing cancer information in vivo. Cancer stem-like cells (CSCs) have been identified in many cancer types to drive tumor growth and recurrence, from "keeping" to "keep" resistant to chemotherapy and radiation therapy. In this study, we developed the xenotransplantation of CSCs derived from the leukemia and solid tumor cell lines using the zebrafish models. In adult zebrafish, we investigated that the xenografted leukemia stem cells (LSCs) from K562 cells could proliferate in vivo and keep the cancer property by re-transplantation. As for the solid tumor, these CSCs from DU145 cells (human prostate cancer) and HepG2 cells (human liver cancer) could form the tumor mass and even metastasis after xenotransplantation. In addition, the zebrafish embryos with CSC xenotransplantation could evaluate docetaxel in vivo efficiently and be available to screen the novel inhibitors by high-throughput manner. In summary, these zebrafish xenotransplantation models devote a good platform for the CSC mechanism investigation and anti-CSC inhibitor screening.

[A case of repeated shunt malfunctions with eosinophilic meningitis caused by silicone allergy].

The ventricular-peritoneal shunt for hydrocephalus is a well-known and established method but is sometimes complicated by shunt malfunction due to several causes. Eosinophilic meningitis is a rare disease, but has occasionally been reported as a cause of shunt malfunction. Here, we report the case of a 74-year-old woman with repeated shunt malfunction and eosinophilic meningitis due to a silicone allergy. Originally, the patient received a ventricular-peritoneal shunt for normal pressure hydrocephalus secondary to subarachnoid hemorrhage. However, shunt malfunction was identified 6 weeks later, and the first shunt revision was performed using a new shunt system from a different company. Further evaluation to identify the cause of the shunt malfunction revealed no abnormal findings, except for eosinophilia in the serum and cerebrospinal fluid. A second shunt malfunction was identified 16 weeks after the first shunt revision. We therefore concluded that eosinophilic meningitis caused by a silicone allergy might be the real culprit and a second shunt revision was performed using a silicone "extracted" tube. Since then, the patient's course has been free from shunt malfunction. In this case, the serum and cerebrospinal fluid eosinophilia were useful markers for identifying the cause of repeated shunt malfunctions. The silicone "extracted" tube may be helpful for diagnosis and therapy.

Utilizing a Guiding Catheter to Improve Endovascular Therapy Outcomes for Acute Vertebrobasilar Artery Occlusion in Patients with Tortuous Vessels.

Objective Stable and swift placement of a guiding catheter in endovascular therapies for acute vertebrobasilar artery occlusion is often difficult because of the tortuous bends of the vertebral or subclavian artery especially in older people. The use of a delivery assist guiding catheter (DAGC) shortens the time with stable support to deliver a therapeutic treatment catheter to the target lesions. Herein, we reported the clinical and radiographic outcomes in endovascular therapies utilizing the DAGC for acute vertebrobasilar artery occlusions in actual clinical settings. Materials and Methods Between January 2018 and December 2021, 33 consecutive patients (males, 20[60.6%]; median age, 78 years) using a DAGC for acute vertebrobasilar artery occlusion were analyzed retrospectively. Reperfusion was graded using postinterventional angiograms based on the "thrombolysis in cerebral infarction" (TICI) classification. Furthermore, the time from puncture to recanalization and the rate of effective recanalization achievement were investigated. Results Effective recanalization with TICI 2b or 3 was achieved in 28 (84.8%) patients, and the median time from puncture to recanalization was only 44 minutes, despite the high rate of older patients in our cohort. In contrast, asymptomatic intracranial hemorrhage as a complication was observed in only 3 (9.1%) patients. Conclusion The DAGC contributes to the shortening of recanalization time and improves the outcomes of endovascular therapies for acute vertebrobasilar artery occlusion.

The Mayo Adhesive Probability Score as a Predictor of Postoperative Renal Function in Robot-assisted Partial Nephrectomy.

Background/Aim: The aim of this study was to evaluate the Mayo Adhesive Probability (MAP) score as a predictor of split renal function deterioration after robot-assisted partial nephrectomy (RAPN). Patients and Methods: A total of 30 patients who underwent RAPN were identified retrospectively. The parameters evaluated included patient characteristics, tumor diameter, MAP score, warm ischemic time (WIT), and renal function. Split renal function was evaluated using Tc-99m DTPA renal scintigraphy before and six months after surgery. Univariate and multivariate logistic regression analyses were performed. Results: Nine patients (30.0%) showed more than 90% preservation of split renal function on the operated side. The MAP score (p=0.015), cT1b tumor (p=0.0002), and WIT (p=0.044) were associated with preservation of split renal function six months after surgery on univariate analysis. The MAP score was the strongest predictor of preservation of split renal function six months after surgery on multivariable analysis (p=0.007). On receiver-operating characteristic (ROC) curve analysis, the MAP score (cutoff value 3.0; p=0.01) was a significant predictor of split renal function six months after surgery. Conclusion: The MAP score was significantly associated with postoperative split renal function six months after RAPN on the operated kidney side. The MAP score is useful for predicting split renal function after RAPN.

Factors related to nocturia-specific quality of life in renal transplantation patients.

OBJECTIVES: Patients following renal transplantation (RTX) may experience nocturia exacerbation due to polyuria and reduced bladder capacity, thereby impacting the specific quality of life (QOL) associated with nocturia. The present study aims to investigate factors associated with the deterioration of nocturia-specific QOL in RTX patients. METHODS: The study cohort comprised 59 consecutive patients who had undergone successful RTX. Nocturia-related QOL questionnaires (N-QOL) were employed to evaluate the specific QOL related to nocturia. The Bother/Concern and Sleep/Energy domains of the N-QOL were also assessed. The primary outcome measure was to explore factors related to the aggravation of nocturia-specific QOL in patients post-RTX. RESULTS: The mean nocturia frequency post-RTX was 1.3 ± 1.0. Univariate and multivariate analyses revealed a significant reduction in the Bother/Concern domain score associated with increased nocturia (p = .042). Aging significantly decreased the total N-QOL score and the Sleep/Energy domain score (p = .001 and .0002, respectively). Prolonged duration after RTX significantly reduced the scores of both the Sleep/Energy domain and the Bother/Concern domain (p = .018 and .037, respectively). However, the duration of dialysis prior to RTX was not significantly associated with the total score or subdomains of N-QOL. CONCLUSIONS: Nocturia-specific QOL affected not only the nocturia itself, but also aging and the prolonged duration after RTX. Thus, comprehensive approaches to the RTX patients were needed to improve the Nocturia-specific QOL in RTX patients.

Identification of risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis-transurethral resection of bladder tumor.

BACKGROUND: Oral 5-aminolevulinic acid for transurethral resection of bladder tumor reduces bladder cancer recurrence compared with standard white-light transurethral resection of bladder tumor. However, data regarding risks of adverse events with this drug are unclear. The aim of the present study was to identify risk factors associated with oral 5-aminolevulinic acid induced adverse events in photodynamic diagnosis-transurethral resection of bladder tumor. METHODS: We studied 104 cases of 5-aminolevulinic acid-photodynamic diagnosis-transurethral resection of bladder tumor from October 2021 to April 2023, administering 20 mg/kg 5-aminolevulinic acid orally at least 2 h pre-surgery. Four major adverse events associated with 5-aminolevulinic acid were selected to identify risk factors for their occurrence, including perioperative hypotension, nausea and/or vomiting, photosensitivity, and liver dysfunction. Univariate and multivariate analyses were conducted to identify the risk factors of those adverse events. RESULTS: Perioperative hypotension (11.5 %), nausea and/or vomiting (37.5 %) photosensitivity (31.7 %), and liver dysfunction (51.9 %) were observed. Multivariate analyses revealed that spinal anesthesia was associated with hypotension (p = 0.02), whereas advanced age (p < 0.01) and higher body mass index (p < 0.01) were associated with nausea and/or vomiting. Also, male sex (p < 0.01) and longer operative time (p = 0.01) were associated with photosensitivity, and renin-angiotensin system inhibitors use was associated with postoperative liver dysfunction (p < 0.01). CONCLUSIONS: For elderly male obese patients taking renin-angiotensin system inhibitors, particular attention is needed during the perioperative period of photodynamic diagnosis-transurethral resection of bladder tumor under spinal anesthesia due to the higher risk of onset of the adverse events involved in oral administration of 5-aminolevulinic acid.

[A case of HELLP syndrome resulting in eclampsia with non-aneurysmal subarachnoid hemorrhage].

It is known that hemorrhagic stroke at the perinatal period are caused by specifics conditions like eclampsia as well as by the existing abnormal vessels. We treated a case of HELLP syndrome resulting in eclampsia with non-aneurysmal, convexity subarachnoid hemorrhage. A 34-year-old female, who had been pointed out to have a high level of urinal protein at the 37th week, was seen in the emergency department because of severe headache, vomiting and respiratory discomfort. Her systolic blood pressure was over 190mmHg, and caesarean section was selected. On the way to the operating room, she had a generalized convulsion with loss of consciousness. The delivery was carried out. The CT immediately after the caesarean section revealed faint and localized subarachnoid hemorrhage in the bilateral convexity areas. Additionally, the FLAIR image of MRI demonstrated increased intensity in the bilateral cerebellar hemispheres, basal ganglion and subcortical area, suggesting vasogenic edema. The patient had a good clinical course and the abnormal signal of MRI also recovered by treatment with oral iron and zinc. Here, we report a speculation for the mechanism of this case and precautions against stroke in the perinatal period.