Estimated prospects of demand and supply of urologists in Korea over the next 10 years.

PURPOSE: This study aimed to provide the basic data needed to estimate future urologist supply and demand by applying various statistical models related to healthcare utilization. MATERIALS AND METHODS: Data from multiple sources, including the Yearbook of Health and Welfare Statistics, Korean Hospital Association, Korean Medical Association, and the Korean Urological Association, were used for supply estimation. Demand estimation incorporated data on both clinical and non-clinical urologists, along with future population estimates. In-and-out moves and demographic methods were employed for supply estimation, while the Bureau of Health Professions model was utilized for demand estimation. Supply estimation assumptions included fixed resident quotas, age-specific death rates, migration rates, and retirement age considerations. Demand estimation assumptions included combining clinical and nonclinical urologist demands, adjusting population size for age-related healthcare usage variations. Urologist productivity was determined by adjusting productivity levels to 100%, 90%, and 80% of the base year based on actual clinical practice volumes. RESULTS: Estimations of both demand and supply consistently indicate an oversupply of urologists until 2025, followed by an expected shortage by 2035 owing to increased deaths and retirements attributed to the aging urologist population. This shortage becomes more pronounced when employing more reliable models, such as logit or ARIMA (autoregressive integrated moving average), underscoring the growing need for urologists in the future. CONCLUSIONS: All estimation models estimated an oversupply of urologists until 2025, transitioning to a deficit due to reduced supply thereafter. However, considering potential unaccounted factors, greater effort is needed for accurate predictions and corresponding measures.

Scoring system to evaluate meaningful fecal impaction in patients with lower urinary tract dysfunction with simple radiography (KUB).

PURPOSE: The management of bowel bladder disorder (BBD) has only been indicated for subjective constipation without objective evidence. We attempted to highlight the radiological findings in patients with BBD and construct a scoring system to identify patients with BBD prior to treatment. MATERIALS AND METHODS: Forty-five patients with lower urinary tract dysfunction (LUTD) received polyethylene glycol for 2 months before bladder medication for LUTD. Based on partial response to LUTD following treatment, we divided the patients into LUTD-fecal impaction (FI) and LUTD not attributed to FI (LUTD-NFI) groups. Pre/post-treatment kidney, ureter, and bladder (KUB) were compared with respect to several radiographic parameters. Items with significant changes after treatment were included in the scoring system. The accuracy and inter-rater agreement were also evaluated. RESULTS: Cecal dilation, descending colon dilation, fecal quality, and overall haziness were found to undergo significant changes after laxative treatment. We assigned 0 to 2 points for each item, with a total score of 8. Receiver operating characteristic curve analysis revealed a cutoff value of 5 between LUTD-FI and LUTD-NFI, with 79% sensitivity and 88% specificity. The scoring system was instructed to six doctors who were unaware of it and was then tested on previous patients, which showed a substantial concordance rate (κ=0.79, p<0.05). CONCLUSIONS: Fecal scoring system based on KUB was beneficial in identifying children with LUTD attributed to FI. This may provide an opportunity to obtain objective FI data as an alternative to subjective assessment of constipation.

Role of urinary N-acetyl-beta-D-glucosaminidase in predicting the prognosis of antenatal hydronephrosis.

PURPOSE: Urinary biomarkers are known to be able to diagnose renal damage caused by obstruction at an early stage. We evaluated the usefulness of urine N-acetyl-beta-D-glucosaminidase (NAG) to determine the prognosis of antenatal hydronephrosis. MATERIALS AND METHODS: From January 2019 to December 2021, a retrospective study was performed on patients with grade 3 or 4 hydronephrosis. We analyzed the ultrasonographic findings and the urinary NAG/Cr ratio between the laparoscopic pyeloplasty (LP) group and active surveillance (AS) group. RESULTS: A total of 21 children underwent LP for ureteropelvic junction (UPJ) obstruction and 14 children underwent AS. The mean age at the time of examination was 3.7 months (1.7-7.5 months) in the LP and 5.2 months (0.5-21.5 months) in the AS (p=0.564). The mean anteroposterior pelvic diameter was 30.0 mm (15.0-49.0 mm) in the LP and 16.7 mm (9.0-31.3 mm) in the AS (p=0.003). The mean renal parenchymal thickness was 2.6 mm (1.2-3.7 mm) in the LP and 3.8 mm (2.9-5.5 mm) in the AS (p=0.017). The urinary NAG/Cr ratio was 26.1 IU/g (9.8-47.4 IU/g) in the LP and 11.1 IU/g (2.6-18.1 IU/g) in the AS (p=0.003). After LP, the urinary NAG/Cr ratio was significantly reduced to 10.4 IU/g (3.4-14.2 IU/g) (p=0.023). CONCLUSIONS: The urinary NAG/Cr ratio, one of the biomarkers of acute renal injury, is closely related to the degree of hydronephrosis. Therefore, it may be useful to determine whether to perform surgery on the UPJ obstruction and to predict the prognosis.

Effect of Preoperative Androgen Stimulation on Penile Size and Postoperative Complication Rate in Patients with Hypospadias: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically review and evaluate the beneficial effects of preoperative androgen stimulation (PAS) on penile length, glans width, and postoperative complications in patients with hypospadias using meta-analysis. MATERIALS AND METHODS: A comprehensive search of the published literature between 1980 and 2022 was done on PubMed, Embase, Google Scholar, Scopus, Web of Science, and Proquest. Studies of patients with 5-alpha reductase deficiency, differentiation sex disorder, or micro-penis without hypospadias were excluded. The full-text screening, quality assessment, and data acquisition were done independently by two reviewers. Meta-analysis was done to quantify the penile growth and postoperative complications. RESULTS: The initial literature search yielded 2,389 records, wherein 32 studies were eligible for the systematic review and meta-analysis. Preoperative testosterone stimulation increased the penile length and glans width by 9.34 mm (95% CI: 6.71-11.97) and 3.26 mm (95% CI: 2.50-4.02), respectively. A longer penis at the baseline led to greater length gain following treatment (1 mm longer at the baseline was likely to gain 0.5 mm more). However, the increase in penile length was not associated with the severity of hypospadias. While the treatment did not affect the overall complication rate, the postoperative fistula risk was lower in those receiving PAS (RR=0.52, 95% CI: 0.30-0.91, p=0.02). CONCLUSIONS: The beneficial effects of PAS on increasing the penile length and glans width were again confirmed. More gain of penile length was expected in the larger penis at baseline. There are no reported increased postoperative complications in association with PAS.

Preoperative Videourodynamic Study Is Helpful in Predicting Long-term Postoperative Voiding Function in Asymptomatic Patients With Closed Spinal Dysraphism.

PURPOSE: Controversy exists regarding the role preoperative urodynamic study for asymptomatic closed spinal dysraphism as it has failed to reveal the benefit in surgical decision and expectation of urological outcomes. We explore the relationship between preoperative videourodynamic study and postoperative urological outcomes after toilet training completed, focusing on their capability of spontaneous voiding. METHODS: We retrospectively reviewed the data of 181 patients who underwent preventive spinal cord untethering and followed at least till the completion of toilet training. Before untethering, patients underwent preoperative videourodynamic study. Postoperative voiding function was evaluated in 3 phases: (1) till postoperative 6 months, (2) till the completion of toilet training, and (3) 2 years after toilet training. Changing distribution of emptying pattern at each period was described. Also, relevance to preoperative urodynamic parameters on spontaneous voiding and urinary continence after toilet training was assessed. RESULTS: Spinal lipoma and low lying conus were found in 145 (80%) and 128 patients (70.7%), respectively. Spontaneous voiding was found in 125 (69.1%), 164 (90.6%), and 162 patients (89.5%) at postoperative 6 months, till the toilet training, and 2 years after toilet training, respectively. Videourodynamics helped to clarify the presence of vesicourethral synergy. This was correlated with spontaneous voiding at postoperative 6 months and better urinary continence after 2 years of toilet training. CONCLUSION: Eventual spontaneous voiding was achieved till toilet training in 90% patients following preventive untethering. Those showing preoperative vesicourethral synergy was associated with faster achievement of spontaneous voiding and better urinary continence when they enter elementary school.

Can portable ultrasound bladder scanner be applied to young children less than three years old?

INTRODUCTION: The bladder scanner (BS), a portable ultrasound device specialized in bladder volume measurement, has been developed and applied to clinical assessment of postvoid residual urine, which is a requisite in evaluating patients with voiding dysfunction. However, experiences in the application of the BS to the pediatric population remain limited despite commonly encountered reluctance to catheterization. This prospective observational study aimed to evaluate the correlation and accuracy of the newly developed pediatric module of the BS (BioCon-900) in measuring bladder volume in children 0-6 years old. MATERIALS AND METHODS: This study included 29 patients scheduled to undergo preventive untethering for their spinal dysraphism. When they undergo cystometry for the confirmation of normal neurologic function, bladder volume was measured by BS when recorded volume infusion reached each quartile of the age-adjusted estimated bladder capacity (EBC). The difference (bias) between measured and infused volume was expressed as a percentage of EBC (%EBC). The correlation coefficient and the Bland-Altman plot were obtained to determine the discriminating power and accuracy, respectively. The acceptable limit was set as 30%EBC. RESULTS: A strong correlation between the measured and infused volume (r = 0.95, P < 0.001) was found for the entire age range. This excellent correlation remained comparable between children less than three years and the older ones. Bladder volume tended to be overestimated, and the mean bias was 33 ± 22.3%EBC, and it became higher with increasing quartiles. The accuracy was acceptable in all ranges of measurement in the older group and first and second quartiles in the younger one. DISCUSSION: We have first evaluated the potential use of BS in 0-3 years old children and compared the results with 4-6-year-old children in whom the accuracy of BS has been demonstrated. The strong point of our study was the inclusion of data spanning all quartiles of bladder volume. The use of infused volume as reference enabled us to assess the accuracy in a more precise way than the use of ultrasound. Despite the good discriminating power, the accuracy was not acceptable in higher quartiles in the younger group. If the trend of overestimation especially higher volume, could be understood prior to measurement, it would be helpful to assume the real val. CONCLUSIONS: The children's module in BS showed excellent discriminating power and generally acceptable accuracy in more than four-year-old children. This may lose accuracy in higher quartiles among less than three years old children.

A preliminary study of shear-wave elastography for the evaluation of varicocele in adolescents and young adults.

PURPOSE: The purpose of this study was to use shear-wave elastography (SWE) to assess testicular stiffness changes during the Valsalva maneuver in adolescents and young adults with varicocele, to compare these changes according to clinical severity, and to evaluate the role of SWE in the diagnosis of varicocele. METHODS: This study included patients undergoing testicular ultrasonography for the diagnosis of varicocele or for post-varicocelectomy follow-up between June 2016 and February 2017. Fifty-four testicles of 27 consecutive patients (mean age, 15.9 years) were classified by clinical grade (grade 0-3). Using SWE, mean testicular stiffness (Emean) was measured at rest and during the Valsalva maneuver. The correlations between multiple ultrasonographic parameters (volume asymmetry, Emean at rest, and absolute and percentage changes in Emean during the Valsalva maneuver) and clinical grade were assessed using the Spearman correlation test. RESULTS: The Emean at rest was similar across clinical grades. During the Valsalva maneuver, increased testicular stiffness was frequently observed in patients with grade 2 or 3 varicocele but rarely observed in those with grade 0 or 1 varicocele. The changes in Emean were positively correlated with the clinical grade (all P<0.001), whereas the Emean at rest and volume asymmetry were not (all P>0.05). CONCLUSION: A transient, reversible increase in testicular stiffness during the Valsalva maneuver was observed in adolescents with high-grade varicocele, and the degree of stiffness change was correlated with the clinical grade. Stiffness change identified using SWE during the Valsalva maneuver is a potential surrogate indicator of venous congestion.

Endoscopic Botulinum Toxin Injection for Refractory Enuresis Based on Urodynamic Assessment.

PURPOSE: This study aimed to determine the urodynamic characteristics of refractory enuresis and explored whether those characteristics can be managed through differential endoscopic injections with botulinum toxin. METHODS: In total, 27 patients with nonmonosymptomatic enuresis who showed no response after conservative treatment for more than 12 months were included. The patients then underwent a videourodynamic study and received a differential endoscopic injection of botulinum toxin on the same day. Reduced capacity, detrusor overactivity, and bladder neck widening were the 3 major abnormal findings assessed during the filling phase, while sphincter hyperactivity was the only abnormality assessed during the emptying phase. An intravesical or intrasphincteric injection of botulinum toxin was attempted according to the videourodynamic study findings. Follow-up was conducted at 1, 3, 6, and 12 months after treatment. RESULTS: The median age was 10 years (range, 7-31 years). Although 19 and 8 patients had a preoperative diagnosis of overactive bladder or dysfunctional voiding, respectively, the urodynamic diagnosis was different in more than half of the patients. Those showing detrusor overactivity benefited from intravesical botulinum toxin injection, whereas those with only sphincter hyperactivity benefited from both intravesical and intrasphincteric injections. Treatment resistance to botulinum toxin seemed to be attributable to bladder neck widening. Time had no apparent effect on efficacy, which persisted 6 months after the injection. More than 80% of the patients maintained the benefits of the injection after 1 year. CONCLUSION: Videourodynamic studies were useful for identifying the reasons underlying refractory nonmonosymptomatic enuresis and helpful for determining the appropriate site of botulinum toxin injection.

Ultrasonographic cystometry for neurogenic bladder using elastography.

AIM: Ultrasound shear wave elastography (SWE) has been used to measure elasticity (Young's modulus: YM) in solid organs. It was reported to show a better correlation with intravesical pressure (Pves) than with compliance, supporting its potential use in noninvasive cystometry. Contrariwise, conceptually, YM should be more correlated with compliance than with Pves. To optimize the potential use of YM as a noninvasive urodynamic study, the relationship between YM, Pves, and compliance was reassessed in this study. METHOD: YM was serially measured using SWE along with bladder filling. To overcome problems inherent to current compliance measurements, modified dynamic compliance was developed from cystometry by a locally weighted scatter plot smoothing algorithm. Then it was matched with YM from SWE. YM was also correlated with Pves. Furthermore, to understand the nature of YM, which was measured by ultrasound, the bladder wall's modulus, which was the mathematical assessment of YM derived from cystometric data, was also calculated and compared. RESULTS: Thirty-two neurogenic bladder patients were included in this study. YM correlated with Pves (r = .72, p < .0001) better than with modified dynamic compliance (r = -0.43, p < .0001). The correlation of YM with Pves was even higher than that with the calculated bladder wall's modulus (r = .52, p < .0001). CONCLUSION: YM measured by SWE associates with Pves better than with compliance, confirming the results of previous studies. SWE reflects the integration of both the holding capability of the bladder wall and urine rather than either of one, implying its potential utilization in noninvasive cystometry.

Treatment of lower urinary tract dysfunction facilitates awakening and affects the cure rate in patients with nonmonosymptomatic enuresis.

PURPOSE: Poor awakening in patients with enuresis has been assumed to be an adaptation to the chronic influence of arousal stimuli like lower urinary tract dysfunction (LUTD). This study aimed to examine the effect of controlling LUTD on improvement of awakening and cure of enuresis. MATERIALS AND METHODS: Data for 119 enuretic patients with overactive bladder were retrospectively analyzed. The patients received urotherapy, laxatives, and anticholinergic agents. LUTD symptoms and enuresis were regularly monitored every 3 months. History of waking up because of bedwetting (ability to awaken, AA) was used as a surrogate marker of arousal and was graded at baseline and every 3 months of treatment. Changing distribution of each grade of AA was associated with other LUTD symptoms. Multivariate analysis was applied to understand whether the lack of improvement in AA might harbor any prognostic implications regarding cure of enuresis. RESULTS: Decreasing number of LUTD with treatment corresponded to increasing number of better AA. Enuresis was resolved completely in 88 patients in a median time of 7 months. Failure to show even single episode of awakening before bedwetting within 6 months of treatment and persistent daytime incontinence were identified as risk factors for treatment resistance until 18 months of treatment. CONCLUSIONS: Controlling LUTD symptoms in the management of nonmonosymptomatic enuresis was crucial for not only the treatment of enuresis but also for allowing the patients to obtain better arousal. AA tended to improve subsequent to bladder control and may contribute to the cure of enuresis.

The Effect of Global Surgery Fellowship for Tertiary Hospital Professionals from Myanmar: Current Issues and Future Challenges.

OBJECTIVE: As the surgical burden of diseases grows higher than ever, the development of skilled surgeons and surgery teams is of fundamental importance. However, there is scarce evidence of the effectiveness of surgical training programs. Our study aims to evaluate the effectiveness of a global surgery fellowship program. DESIGN: In 2018, Myanmar subspecialty surgeons were trained for a 3-month in tertiary hospital of Korea. We evaluated the reactions, learning, and transfer of the 11 trainees using Kirkpatrick's Evaluation Model. SETTING: Myanmar and Korean tertiary hospital. PARTICIPANTS: Eleven participants of fellowship from Myanmar. RESULTS: Participants' overall reaction scores were 4.45 ± 0.52 out of 5.00. Regarding overall competency, the trainees assessed themselves as at an "advanced beginner level" (3.63 ± 1.38 out of 10.00) at the beginning and at a "competent level" (5.40 ± 1.70 out of 10.00) after the training (p for difference = 0.014). The trainees stated that their transfer in clinical practice was between "quite applicable" and "I am very sure that I can do this" (3.39 ± 0.61 out of 4.00). Their transfer in education was second, ranked around "quite applicable" (3.21 ± 0.77 out of 4.00), and their transfer in research was last and ranked "applicable, but just a little" (2.81 ± 0.67 out of 4.00). However, in our online survey, native and foreign trainers had mixed opinions about the transfer of training and were not entirely confident in the trainees' competency. Trainees felt that there were multifactorial challenges for transfer and cited infrastructure, facilities, human resources, perioperative care, and financing. CONCLUSIONS: Surgical trainees reported high-level satisfaction and increased knowledge after training. However, further onsite surgical experiences are necessary for a successful transfer to the real setting. Challenges for such transfers were multifactorial, and surgical care must be systemically strengthened.

Changes in attention variables in those who treated with anticholinergic agents for nonmonosymptomatic enuresis.

Purpose: Brain dysfunction related to areas regarding attention and arousal may occur not only in patients with attention-deficit/hyperactivity disorder (ADHD) but also in patients with enuresis and daytime symptoms. This study aimed to investigate changes in computerized comprehensive attention tests (CATs), a psychometric test for ADHD when patients with nonmonosymptomatic enuresis (NME) were treated with anticholinergic agents. Materials and Methods: Thirty patients with NME featuring overactive bladder were prospectively enrolled. They were treated with 5 mg of solifenacin to control daytime symptoms. Using CATs, patients were evaluated during 12 weeks of treatment. Four subtests of attention (visual and auditory selective attention, sustained attention, and flanker tests) were measured. For each subtest, four domains (omission error, commission error, response time [RT], and standard deviation of RT) were assessed. Results: Only one domain of the flanker test was in the deficient range at baseline. The presence of urge incontinence affected follow-up results on the sustained attention tests. Treatment with anticholinergic agents did not significantly affect attention variables but changes in several variables were correlated with bladder symptoms and enuresis. Conclusions: Minimal baseline defects in attention function were seen in patients with NME. Follow-up results for some attention variables were affected by daytime symptoms and enuresis. These results suggest that altered brain function in enuretic patients influences improvement in both attention and bladder function.

Do junctional neural tube defect and segmental spinal dysgenesis have the same pathoembryological background?

INTRODUCTION: Junctional neural tube defect (JNTD) is a recently introduced form of congenital spinal dysraphism that is characterized by functional disconnection between the primary and secondary neural tubes. The upper and lower cords appeared to be connected by a non-functioning band-like structure. JNTD is suspected to arise from a developmental error not corresponding to either primary or secondary neurulation, but rather between the two neurulation processes. On the other hand, segmental spinal dysgenesis (SSD) is an older entity of spinal anomalies in which a segment of the spine and spinal cord does not develop properly. The anomaly had been noted for the bony abnormality, as it is the most prominent feature. Based on the recent encounter of two cases resembling both entities, we sought the possibility that the two diseases may have the same pathoembryogenesis. METHODS AND RESULTS: Based on the impression that the two entities share important features, we compared the details of the two anomalies. First, our two recently encountered cases of JNTD were described. Second, previous reports of SSD were comprehensively reviewed. The two cases had the essential anomaly of the neural structures satisfying the definition of JNTD, as well as the elaborate spinal deformity as seen in SSD. In the previous literature on SSD, it was recognized that in addition to the bone anomaly, disconnected spinal cord was present. Hence, the two entities seem to have many similar clinical and neuroimaging features. The dysgenic spinal level is similar, and the disconnection between the primary and secondary neural tubes is found in the two diseases. The two neural tubes are connected by a band-like structure, with severe stenosis of the spinal canal at the level of the band. Both entities show segmental anomalies of the vertebrae in the thoracolumbar region, especially in the posterior element. Although the extent of shared features seems high, the previously suggested hypothetical pathoembryogenesis of SSD did not involve the process of junctional neurulation. We suggest that SSD shares the same origin as JNTD, and the bony abnormality may be a secondary phenomenon to the core error during neural tube development. CONCLUSIONS: We propose that JNTD and SSD may be the same entity, originating from an error during junctional neurulation. As there is controversy regarding the treatment strategy for both entities, unified accumulation of clinical experience and analysis may help improve the management of patients.

Erratum: Correction of Error in Result: Urological Problems in Patients with Menkes Disease.

This corrects the article on e4 in vol. 1, PMID: 30618512.

Urological Problems in Patients with Menkes Disease.

BACKGROUND: Menkes disease (MD) is a rare X-linked hereditary multisystemic disorder that is caused by dysfunction of copper metabolism. Patients with MD typically present with progressive neurodegeneration, some connective tissue abnormalities, and characteristic "kinky" hair. In addition, various types of urological complications are frequent in MD because of underlying connective tissue abnormalities. In this study, we studied the clinical features and outcomes of MD, focusing on urological complications. METHODS: A total of 14 unrelated Korean pediatric patients (13 boys and 1 girl) with MD were recruited, and their phenotypes and genotypes were analyzed by retrospective review of their medical records. RESULTS: All the patients had early-onset neurological deficit, including developmental delay, seizures, and hypotonia. The girl patient showed normal serum copper and ceruloplasmin levels as well as milder symptoms. Mutational analysis of the ATP7A gene revealed 11 different mutations in 12 patients. Bladder diverticula was the most frequent urological complication: 8 (57.1%) in the 14 patients or 8 (72.7%) in the 11 patients who underwent urological evaluation. Urological imaging studies were performed essentially for the evaluation of accompanying urinary tract infections. Four patients had stage II chronic kidney disease at the last follow-up. CONCLUSION: Urologic problems occurred frequently in MD, with bladder diverticula being the most common. Therefore, urological imaging studies and appropriate management of urological complications, which may prevent or reduce the development of urinary tract infections and renal parenchymal damage, are required in all patients with MD.

Effects of combined growth hormone and testosterone treatments in a rat model of micropenis.

Although it is well known that penile growth is dependent on androgens, few clinical studies have reported successful treatment of micropenis with testosterone, likely due to concerns regarding the efficacy and safety of prolonged testosterone use. Thus, we assessed the synergenic effects of growth hormone (GH) treatments with and without testosterone on phallic growth in a rat model of micropenis. Fifty Sprague-Dawley rats were assigned to control (C), microphallus (MP), testosterone (T), GH (G) and GH plus testosterone (GT) treatment groups, and microphallus was induced by secondary hypogonadism. Pre-pubertal treatments with testosterone, GH or the combination were initiated from 7 days after birth and were maintained until 12 weeks of age. To assess the efficacy of treatments, phallic dimensions were determined and histological markers of cavernosal integrity were evaluated. Skeletal and gonadal safety profiles of the treatments were then assessed according to right tibial lengths and testicular weights, respectively. No monotreatments normalised penile dimensions, whereas combination treatments led to complete restoration. The combination treatment also prevented decreases in histological indicators of cavernosal integrity, including smooth muscle actin and collagen III expression levels and fat globule accumulation and sinusoidal density. These synergenic effects of GH treatments on penile growth may follow changes in androgen receptor expression levels and were accompanied by decreased testicular volume losses. Although the physiological conditions of phallic growth differ between humans and rats, this proof-of-concept study provides a strategy for circumventing the problems of testosterone monotherapy for human micropenis.

Identification of the primary determining factor(s) governing the oral absorption of edaravone in rats.

This study was performed to determine the primary factor(s) governing the oral absorption of edaravone, a novel anti-oxidant for the treatment of amyotrophic lateral sclerosis, in rats. While the aqueous solubility of edaravone widely varied depending on the vehicle used, the oral bioavailability of the drug was not low when it was adequately solubilized, as evidenced by the fact that the oral exposure was high (in terms of the absolute bioavailability of 50-90%) at all dose ranges (i.e., 0.5-27 mg/kg) under solubilized conditions in rats. The sum of the in vitro clearance values for edaravone, 12.7 mL/(min × kg), obtained from metabolic stability studies with tissue-homogenates from the rat liver, kidney, intestine, and with the rat plasma, was found to be virtually identical to the systemic clearance of the drug in rats. It was noted that the liver represented over 83.9% of the total elimination with a hepatic extraction ratio of approximately 0.137, indicative of the minor role of hepatic first pass metabolism in the systemic absorption of edaravone after its oral administration. In studies with Ussing chamber with rat intestinal segments and Madin-Darby canine kidney (MDCKII) cells, edaravone was found to be highly permeable (i.e., Papp over 10 × 10-6 cm/s), and appeared to be a substrate for rat P-glycoprotein (P-gp; estimated Km of 421 µM). In contrast, however, the drug did not appear to be a substrate for human P-gp in transport studies with MDCKII-hMDR1 cells. Collectively, these observations suggest that the primary determining factor for the intestinal absorption of edaravone is its solubilization in vehicle/intestinal fluids, rather than permeability, pre-systemic first-pass metabolism, or efflux transport. Considering the fact that the newly approved indication of the drug would require prolonged administration, probably via oral administration, the findings reported herein provide relevant information regarding its use.

Time Course of Treatment for Primary Enuresis With Overactive Bladder.

PURPOSE: To characterize the course of treatment for nonmonosymptomatic enuresis with overactive bladder (OAB) in a real clinical setting. METHODS: Data from 111 OAB patients with moderate to severe enuresis were analyzed. The baseline analysis included a questionnaire, voiding diary, uroflowmetry with postvoid residual urine measurement, and plain abdominal radiography of the kidneys, ureters, and bladder (KUB). Following standard urotherapy for 1 month, anticholinergic medication was administered with or without laxatives. Desmopressin was added if there was a partial response to OAB. Patients were followed every 3 months to evaluate the status of OAB and enuresis. Multivariate analysis was performed to identify predictors associated with the lack of complete response (CR) in enuresis at 12 months. RESULTS: Following 12 months of treatment, 64% and 88% of patients experienced at least partial response in enuresis and OAB, respectively. Urgency improved more quickly than enuresis, supporting the need to address daytime symptoms before enuresis. Seventy-nine patients (71%) had fecal impaction on KUB and/or subjective constipation. The combination of anticholinergics with either laxatives or desmopressin fared better than anticholinergics alone. Daytime incontinence and anticholinergics- only treatment were associated with a lack of CR during 12 months of treatment. CONCLUSIONS: The data confirmed the validity of addressing OAB before treating enuresis. The results of this study also highlight the need to address fecal impaction. Patients should be counseled about the need for a prolonged course of treatment before starting treatment. Anticholinergics should be accompanied with either desmopressin or laxatives for better control of enuresis.

New bulking agent for the treatment of vesicoureteral reflux: Polymethylmethacrylate/dextranomer.

Purpose: The aim of this study was to report preliminary results of endoscopic treatment of vesicoureteral reflux in children with a single injection of a new bulking agent, cross-linked dextran and polymethylmethacrylate mixture. Materials and Methods: We performed a single-center, single surgeon, prospective, off-label study using polymethylmethacrylate/dextranomer to treat vesicoureteral reflux. All patients underwent endoscopic injection, followed by renal ultrasound and voiding cystourethrogram at 3 months postoperatively to identify de novo or worsening hydronephrosis and vesicoureteral reflux correction (to Grade 0 or I). Results: Eighteen patients underwent injection of polymethylmethacrylate/dextranomer at our institution between April 2013 and December 2013. Ten were males and eight were females, with a median age of 58 months (range, 6 months to 5 years). Vesicoureteral reflux was unilateral in three patients and bilateral in 15, for a total of 33 renal refluxing units. Vesicoureteral reflux was Grade I in one renal refluxing unit, Grade II in 12, Grade III in 16, and Grade IV in four. Mean injected volume was 0.86 mL. Reflux was corrected in 23 renal refluxing units (69.7%) according to the 3-month voiding cystourethrogram. Complications included urinary retention in one patient. Mild pyelectasis was noted in one patient at 3 months, which spontaneously resolved 3 months later. Conclusions: Our short-term data show that polymethylmethacrylate/dextranomer injection can be used to treat vesicoureteral reflux with comparable efficacy to other substances currently used and a low rate of complications. Long-term follow-up is required to confirm the usefulness of this material in treating vesicoureteral reflux.