International Continence Society (ICS) report on the terminology for nocturia and nocturnal lower urinary tract function.

INTRODUCTION: The terminology for nocturia and nocturnal lower urinary tract function is reviewed and updated in a clinically and practically-based consensus report. METHODS: This report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardisation Steering Committee (SSC). All relevant definitions were updated on the basis of research over the last 16 years since the publication of the first nocturia standardization document in 2002. An extensive process of 16 rounds of internal and external reviews was involved to examine each definition exhaustively, with decision-making by collective opinion (consensus). RESULTS: A clinically-based terminology report for nocturia and nocturnal lower urinary tract function, encompassing five key definitions divided into signs and symptoms has been developed. Clarity and user-friendliness have been key aims to make it interpretable by healthcare professionals and allied healthcare practitioners involved in the care of individuals with nocturnal lower urinary tract function. CONCLUSION: A consensus-based terminology report for nocturia and nocturnal lower urinary tract function has been produced to aid clinical practice and research.

ICS educational module: Cystometry in children.

AIMS: To introduce the standard procedure of cystometry and interpretation of the results in children. METHODS: The literature on cystometry in children in PubMed for the last 20 years was reviewed. The updated knowledge regarding indication, preparation, technique, and interpretation of cystometry in children were summarized. RESULTS: Filling cystometry is the core content of a paediatric urodynamic study. In this section, the technique for performing cystometry is introduced in details. Emphasis is placed on correctly setting up the equipment according to ICS and ICCS guidelines, using appropriate terminology, providing indications for its performance with specific considerations for children, and proper interpretation of results. CONCLUSIONS: Cystometry can be used in children including newborn to evaluate lower urinary tract dysfunction.

Adolescents with nocturnal enuresis and daytime urinary incontinence-How can pediatric and adult care be improved-ICI-RS 2015?

AIMS: Nocturnal enuresis (NE) and daytime urinary incontinence (DUI) are common in adolescents. The aim of this paper was to review studies on prevalence, clinical symptoms and associated risk factors and to formulate recommendations for assessment and treatment. MATERIALS AND METHODS: A systematic Scopus search was performed and relevant publications were selected. The topic was discussed during the ICI-RS meeting in 2015. RESULTS: One to two percent of older adolescents are affected by NE and 1% by DUI. NE and DUI are associated with multiple risk factors such as fecal incontinence and constipation, obesity, chronic illness, and psychological impairment. Chronic treatment-resistant, relapsing and new-onset cases can occur. Adolescent NE and DUI can be treated by a multidisciplinary team according to pediatric principles. Additional treatment components have been developed for adolescents. Transition from pediatric to adult services is frequently disorganized. CONCLUSIONS: Incontinence in adolescents is a neglected research topic and clinical care is often suboptimal. As adolescents are seen by both pediatric and adult services, alignment and harmonization of diagnostic and therapeutic principles is needed. Also, an organized transition process is recommended to improve care for adolescent patients. Neurourol. Urodynam. 36:843-849, 2017. © 2017 Wiley Periodicals, Inc.

Is testosterone important in LUT function in men and women? ICI-RS 2015.

AIM: This review article is a collaborative report based upon the Authors' presentations and Group discussion on the role of testosterone (T) in the male and female lower urinary tract (LUT) which took place at the 6th International Consultation on Incontinence Research Society's (ICI-RS) annual meeting, in Bristol, UK (September 8-10, 2015). METHODS: It comprises overviews and opinions on both the current state of knowledge of the role of T in LUT function and dysfunction in both sexes. RESULTS: Results from animal studies suggest that T treatment may be beneficial for disorders of the LUT in women including urinary incontinence and pelvic organ prolapse. The need for clinical studies to evaluate the effect of T treatment in peri- and post-menopausal women, taking into account the type of applied androgen, the application form, timing and dosage, is especially emphasized. In males, findings on the impact of T on the male external urethral sphincter underscores that there is still much to learn about its role in male LUT physiology. The important topic of the use of T therapy in the treatment of enuresis in the young, both sexes, is also discussed. The importance of understanding the steroidogenic pathways linking T with estradiol is discussed as being of paramount importance in researching the unique actions of T in the LUT. CONCLUSION: The overall conclusion is that further research into the role of T in LUT function and dysfunction across genders and age groups (young to old) is extremely important. Neurourol. Urodynam. 36:859-862, 2017. © 2017 Wiley Periodicals, Inc.

No immediate effect on urodynamic parameters during transcutaneous electrical nerve stimulation (TENS) in children with overactive bladder and daytime incontinence-A randomized, double-blind, placebo-controlled study.

AIM: To evaluate the immediate effect on natural fill urodynamic parameters and bladder function during transcutaneous electrical nerve stimulation (TENS) in children with overactive bladder (OAB) and daytime urinary incontinence (DUI). MEETHODS: In this double-blind, placebo-controlled study, 24 children with severe OAB and DUI (mean age 8.5 ± 1.2 years) underwent 48-h natural fill urodynamics. After 24 h of baseline investigation, the children were randomized to either active continuous TENS (n = 12) or placebo TENS (n = 12) over the sacral S2-S3 outflow. The urodynamic recordings were analyzed manually for three different bladder contraction patterns resulting in a void. The number of bladder contractions not leading to a void was also calculated. Maximum voided volume (MVV) and average voided volume (AVV) were identified for both the baseline and the intervention day. RESULTS: We found that TENS had no immediate objective effect on bladder capacity. The difference (before minus after treatment) in MVV/EBC in the active TENS group = 0.03 ± 0.23 versus placebo TENS group = -0.01 ± 0.10 (P = 0.61). Also, there was no significant difference in the proportion of different bladder contraction types between the two groups. TENS did not significantly influence the number of bladder contractions not leading to a void. Results are presented as mean ± SD. CONCLUSION: There is no immediate objective effect of TENS on bladder activity assessed by natural fill urodynamics in children with OAB and DUI.

Vagotomy and subsequent risk of Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) may be caused by an enteric neurotropic pathogen entering the brain through the vagal nerve, a process that may take over 20 years. We investigated the risk of PD in patients who underwent vagotomy and hypothesized that truncal vagotomy is associated with a protective effect, whereas superselective vagotomy has a minor effect. METHODS: We constructed cohorts of all patients in Denmark who underwent vagotomy during 1977-1995 and a matched general population cohort by linking Danish registries. We used Cox regression to compute hazard ratios (HRs) for PD and corresponding 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Risk of PD was decreased in patients who underwent truncal (HR = 0.85; 95% CI = 0.56-1.27; follow-up of >20 years: HR = 0.58; 95% CI: 0.28-1.20) compared to superselective vagotomy. Risk of PD was also decreased after truncal vagotomy when compared to the general population cohort (overall adjusted HR = 0.85; 95% CI: 0.63-1.14; follow-up >20 years, adjusted HR = 0.53; 95% CI: 0.28-0.99). In patients who underwent superselective vagotomy, risk of PD was similar to the general population (HR = 1.09; 95% CI: 0.84-1.43; follow-up of >20 years: HR = 1.16; 95% CI: 0.80-1.70). Statistical precision of risk estimates was limited. Results were consistent after external adjustment for unmeasured confounding by smoking. INTERPRETATION: Full truncal vagotomy is associated with a decreased risk for subsequent PD, suggesting that the vagal nerve may be critically involved in the pathogenesis of PD.

Fundamentals and clinical perspective of urethral sphincter instability as a contributing factor in patients with lower urinary tract dysfunction--ICI-RS 2014.

AIMS: Urethral pathophysiology is often neglected in discussions of bladder dysfunction. It has been debated whether "urethral sphincter instability," referred to based on observed "urethral pressure variations," is an important aspect of overactive bladder syndrome (OAB). The purpose of this report is to summarize current urethral pathophysiology evidence and outline directions for future research based on a literature review and discussions during the ICI-RS meeting in Bristol in 2014. METHODS: Urethral pathophysiology with a focus on urethral pressure variation (UPV) was presented and discussed in a multidisciplinary think tank session at the ICI_R meeting in Bristol 2014. This think tank session was based on collaboration between physicians and basic science researchers. RESULTS: Experimental animal studies or studies performed in clinical series (predominantly symptomatic women) provided insights into UPV, but the findings were inconsistent and incomplete. However, UPV is certainly associated with lower urinary tract symptoms (likely OAB), and thus, future research on this topic is relevant. CONCLUSIONS: Future research based on adequately defined clinical (and urodynamic) parameters with precisely defined patient groups might shed better light on the cause of OAB symptoms. Further fundamental investigation of urethral epithelial-neural interactions via the release of mediators should enhance our knowledge and improve the management of patients with OAB.

Bladder function development and its urodynamic evaluation in neonates and infants less than 2 years old.

AIMS: To understand the function development of bladder and its evaluation in neonates and infants less than 2 years old. METHODS: Literature on neonatal and infant bladder function development and urodynamic evaluation were collected and reviewed. RESULTS: Normal range of bladder volume, pressure during voiding and other parameters in neonates and infants less than 2 years old is far from set up, making interpretation of UDS findings difficult. This review provides insight into the bladder development process and problems of the lower urinary tract in this age group with special emphasis on the urodynamic evaluation. CONCLUSIONS: Further animal and human studies will increase our understanding of bladder development leading toward mature function. UDS are still important in providing information for early bladder dysfunction in newborns and infants.

Risk factors of nocturia (two or more voids per night) in Chinese people older than 40 years.

AIMS: To explore the risk factors of nocturia in Chinese inhabitants aged ≥40 years. METHODS: A randomized, community-based, cross-sectional study was performed on 10,160 inhabitants ≥40 years old in mainland China, via a stratified sampling approach. A questionnaire, including socio-demographics, lifestyle factors and medical history, was completed. Nocturia was defined as a threshold of two or more voids per night. Differences in prevalence between age and gender groups were ascertained by the chi-squared test. Gender-related factors were evaluated by multivariate logistic regression analysis. P < 0.05 was considered to be statistically significant. RESULTS: Data on 9,637 (94.9%) people aged 59.6 ± 9.7 years qualified for final statistical analysis. The overall prevalence of nocturia was 31.7% (3,053/9,637), and this increased with age (P < 0.001). Nocturia was significantly associated with cardiovascular disease and overactive bladder symptom score (OABSS) (P < 0.05), while sporting activities were protective (P < 0.001). Diabetes mellitus (DM) was significantly correlated with nocturia in men (P < 0.05), whereas hypertension was correlated with nocturia in women (P < 0.05). No correlation was found between nocturia and education level, occupation, civil status, tea consumption, body mass index (BMI), female birth history, and International Prostate Symptom Score. CONCLUSIONS: In Chinese people aged ≥40 years, nocturia is associated with aging, OABSS, cardiovascular disease, hypertension, and DM. Sporting activities are negatively associated with nocturia.

Transcutaneous Electrical Nerve Stimulation Increases Rectal Activity in Children.

OBJECTIVES: Neurostimulation is increasingly used in treating bladder and bowel dysfunction, but its effect on rectal motility is obscure. The aim of the study was to evaluate the acute effect of transcutaneous electrical nerve stimulation (TENS) on rectal motility in children with overactive bladder (OAB). METHODS: In this double-blind placebo-controlled study in 20 children with OAB (mean age 8.6 ±â€Š1.8 years; 7 girls), 48-hour urodynamic monitoring including rectal manometry was performed. After 24-hours of baseline investigation without stimulation the children were randomised to either active TENS (n = 10) or placebo (n = 10). Surface electrodes were placed over the sacral bone. The exterior of active and placebo stimulators was identical. Starting in the morning, the children received either continuous TENS stimulation or placebo until bedtime. Rectal contractions were defined as pressure runs exceeding 5 cm H2O and lasting ≥3 minutes. RESULTS: At baseline there was no significant difference in proportion of time with rectal contractions in the 2 groups (TENS group median 31% [range 12%-66%] vs placebo group median 31% [range 10%-66%]; P = 0.75); however, on the day of stimulation there was more time with rectal contractions in the group receiving TENS (median 51% [range 25%-78%]) compared with placebo (median 32% [range 4%-68%]; P = 0.02). Also, there was an increase in time with rectal contractions in the TENS group (P = 0.007) but not in the placebo group (P = 0.39). The night after the TENS was disabled, rectal activity in both groups returned to baseline level. CONCLUSIONS: TENS acutely increases time with rectal contractions in children undergoing urodynamic investigation. The effect disappears when the stimulator is turned off.

Age-related changes in expression in renal AQPs in response to congenital, partial, unilateral ureteral obstruction in rats.

Previously we demonstrated that neonatally induced partial unilateral ureteral obstruction (PUUO) in rats is associated with changes in the abundance of renal acid-base transporters that were paralleled by reduction in renal functions dependent on the severity and duration of obstruction. The aim of the present study was to identify whether changes in renal aquaporin abundance are age-dependent. Semiquantitative immunoblotting and immunohistochemistry were used to examine the changes in abundance of AQP1, AQP2, p-S256AQP2 (AQP2 phosphorylated at consensus site Ser(256)) and AQP3 in the kidneys of rats with neonatally induced PUUO within the first 48 h of life, and then monitored for 7 or 14 weeks. Protein abundance of AQP2 and AQP3 increased in both obstructed and non-obstructed kidneys 7 weeks after induction of neonatal PUUO (PUUO-7W). In contrast, AQP1 and AQP2 protein abundance in the obstructed kidney were reduced after 14 weeks of PUUO (PUUO-14W). Importantly, pS256-AQP2 protein abundance was reduced in obstructed kidneys of both PUUO-7W and PUUO-14W. Immunohistochemistry confirmed the persistent pS256-AQP2 downregulation in both PUUO-7W and PUUO-14W rats. The study shows that the protein abundance of AQP1, AQP2, and AQP3 in the obstructed kidney is increased in PUUO-7W, which may be a compensatory phenomenon and reduced in PUUO-14W rats suggesting a time-/age-dependent dysregulation in response to PUUO. pS256-AQP2 protein abundance is reduced consistent with obstruction-induced direct effects in the apical part of the collecting duct principal cells in response to PUUO.

Melamine-related urinary stones in 195 infants and young children: clinical features within 2 years of follow-up.

OBJECTIVE: To summarize the clinical features and follow-up, the effects of melamine-tainted milk powder (MMP) consumption on kidney and body growth in children who suffered from melamine-related urinary stones (MUS) 2 years earlier were checked. MEASUREMENTS: Body height and weight, kidney and bladder morphology monitored by ultrasound, urinalysis and renal function were recorded. Plain abdominal radiography was performed for differential diagnosis. The first follow-up was carried out at 15 months and the second 2 years later for patients who showed any abnormality at the first follow-up. Two hundred age- and gender-matched cohorts were included. RESULTS: All cases received conservative treatment in hospital. Fifteen months of follow-up was successfully carried out in 167 cases. 91 children had residual MUS at the time of discharge, 58 MUS disappeared completely, 25 dissolved partially, 1 increased in size, and 7 did not change. At 2 years of follow-up, the residual stones all disappeared except for 1 case; the patient who showed a delayed development with regard to height caught up at 24 months of follow-up. CONCLUSIONS: Conservative treatment shows a high effectiveness in cases with residual MUS. Consumption of MMP with timely treatment did not demonstrate an evident impact on kidney and bladder although body height is slightly affected in a few cases.

A conversation on how animal experimental studies allies with translational medicine.

Basis science research in pediatric urology studies physiological questions in animal models to provide new data on how to treat patients. We sat down with Jens-Christian Djurhuus to discuss both practical and philosophical questions on how to best perform basic science research. Initial questions such as "What type of questions are best studied in animal models?" and "Which animal model should I use?" help us answer the basic question of "What is a good research topic?". To take advantage of his experience leading a research team, we went on to discuss "How do you lead a research team?" and "How do we make sure that basic science research translates to clinical practice?". As research funding becomes scarce, we thank Professor Djurhuus for his insights on how to focus basic science research on relevant topics that are easily translatable to the care of children.

Gender-dependent bladder response to one-day bladder outlet obstruction.

BACKGROUND: Development of bladder fibrosis, loss of compliance, and voiding dysfunction are among the severe consequences of various lower urinary conditions, for example, bladder outlet obstruction (BOO), neurogenic bladder, and radiotherapy to the pelvic area. The bladder remodelling results in significant changes in bladder function and architecture, and may ultimately be deleterious for kidney function. The molecular signals underlying pathologic bladder remodelling, as well as the impact of gender, remain poorly understood. OBJECTIVE: To investigate the bladder remodelling after one day BOO, whether the remodelling is different between different bladder sections, and whether genders may affect the remodelling. STUDY DESIGN: Thirty male and 30 female C57BL/6NRj mice were randomly divided into Control, Sham and BOO groups with ten mice per group. A 24-h total urethral obstruction was performed at the proximal urethra. Histological changes were observed via H&E, trichrome and immunohistochemistry staining. Harvested bladders were divided into upper and lower sections for analysis. Protein and gene expression were detected by Western blotting and qPCR. RESULTS: No significant changes in bladder wall thickness were observed following BOO, while increased bladder mass after BOO was found in female mice only. We detected FN and ⍺-SMA upregulation in the male upper bladder segment. Female BOO mice bladders showed increased α-SMA expression in both bladder segments, but no difference of FN was observed in either bladder segments. BOO-induced upregulation of TGF-ß and Gremlin were detected in both male and female bladders, while downregulation of BMP-7 was detected only in male bladders. Furthermore, phosphorylation of both SMAD2/3 and SMAD1/5/9 were increased in male bladders following BOO, whereas female mice exhibited increased pSMAD2/3 in the upper and increased pSMAD1/5/9 in the lower bladder segment. CONCLUSIONS: Our data indicate that some specific proteins and growth factors were detected as early alterations of tissue which may lead to fibrosis. In addition, the males tended to have more pronounced response than females. However, the causes and consequences of the findings need to be further investigated.

Excess diuresis and natriuresis during acute sleep deprivation in healthy adults.

The transition from wakefulness to sleep is associated with a pronounced decline in diuresis, a necessary physiological process that allows uninterrupted sleep. The aim of this study was to assess the effect of acute sleep deprivation (SD) on urine output and renal water, sodium, and solute handling in healthy young volunteers. Twenty young adults (10 male) were recruited for two 24-h studies under standardized dietary conditions. During one of the two admissions, subjects were deprived of sleep. Urine output, electrolyte excretions, and osmolar excretions were calculated. Activated renin, angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic peptide were measured in plasma, whereas prostaglandin E(2) and melatonin were measured in urine. SD markedly increased the diuresis and led to excess renal sodium excretion. The effect was more pronounced in men who shared significantly higher diuresis levels during SD compared with women. Renal water handling and arginine vasopressin levels remained unaltered during SD, but the circadian rhythm of the hormones of the renin-angiotensin-aldosterone system was significantly affected. Urinary melatonin and prostaglandin E(2) excretion levels were comparable between SD and baseline night. Hemodynamic changes were characterized by the attenuation of nocturnal blood pressure dipping and an increase in creatinine clearance. Acute deprivation of sleep induces natriuresis and osmotic diuresis, leading to excess nocturnal urine production, especially in men. Hemodynamic changes during SD may, through renal and hormonal processes, be responsible for these observations. Sleep architecture disturbances should be considered in clinical settings with nocturnal polyuria such as enuresis in children and nocturia in adults.

Timer watch assisted urotherapy in children: a randomized controlled trial.

PURPOSE: We evaluated the effect of timer watch treatment in addition to standard urotherapy in children with overactive bladder and daytime urinary incontinence. MATERIALS AND METHODS: A total of 60 children with daytime urge incontinence were included in the study. Following a 4-week run-in period of standard urotherapy children were randomized to 12 weeks of standard urotherapy with or without a timer watch. Incontinence episodes were registered and 48-hour bladder diaries were obtained before randomization, and at weeks 1, 11 and 12. Long-term response was evaluated at 7 months. RESULTS: Two children became continent during the run-in period. Before intervention children in the timer group were slightly more wet than children in the standard urotherapy group (median 7 [IQR 25% to 75% 6 to 7] vs 6 [3 to 7] wet days per week, p <0.05). Following 12 weeks of standard urotherapy children randomized to timer assisted urotherapy had significantly fewer wet days per week (median 2, IQR 25% to 75% 0 to 5) vs those undergoing standard urotherapy alone (5, 2.75 to 6.75, p <0.01). In the timer group 18 children (60%) achieved a greater than 50% decrease in incontinence episodes, compared to only 5 (18%) treated without timer assistance. Nine patients (30%) in the timer group and no child in the standard urotherapy group achieved complete daytime continence. The timer increased compliance with the timed voiding regimen. At 7 months of followup 60% of children in the timer group were still continent in the daytime. CONCLUSIONS: A programmable timer watch significantly improves the effect of standard urotherapy. When using the timer watch as a supplement to standard urotherapy 60% of the children obtained complete and sustainable daytime continence.

Increased nocturnal blood pressure in enuretic children with polyuria.

PURPOSE: We investigated the association between nocturnal blood pressure and urine production in children with enuresis. MATERIALS AND METHODS: A total of 39 consecutive children with a mean age of 9.8 years (range 6.2 to 14.9) with monosymptomatic nocturnal enuresis completed a bladder diary, including 2 weeks of basic documentation and 2 with desmopressin titration from 120 to 240 microg sublingually. Arterial blood pressure was measured every 30 minutes during 24 hours and during 4 additional nights using an ambulatory blood pressure monitor. Furthermore, 10 healthy children were recruited into the study who completed a bladder diary for 5 days while measuring arterial blood pressures with documentation of all intake and voided volumes. RESULTS: Patients with nocturnal polyuria had significantly higher nocturnal mean arterial pressure than patients without polyuria and controls (p <0.05). Furthermore, a positive correlation was seen between nocturnal urine output and nocturnal mean arterial pressure (r = 0.32, p <0.001). Nocturnal urine output was significantly higher during wet nights than dry nights (p <0.001). However, no significant difference was found in mean arterial pressure between wet and dry nights. CONCLUSIONS: Nocturnal mean arterial pressure was significantly higher in children with enuresis with polyuria than in children without polyuria. There was a significant positive correlation between average nocturnal mean arterial pressure and nocturnal urine volume in the whole study. The association between nocturnal blood pressure and urine volume, and the role of blood pressure should be investigated in a larger group of children with enuresis who have nocturnal polyuria.

24-hour rectal manometry for overactive bladder.

PURPOSE: We describe prolonged rectal manometry used to characterize rectal motor activity patterns and possible rectum-bladder interaction during defecation and micturition in children with nonneuropathic overactive bladder. MATERIALS AND METHODS: We evaluated 10 children with a mean +/- SD age of 9.7 +/- 1.3 years with overactive bladder who underwent urodynamics and 24-hour rectal manometric recording. All records were analyzed visually. Rectal contractions were defined as pressure runs exceeding 5 cm H(2)O and lasting longer than 5 seconds. RESULTS: Three rectal motility patterns were noted in all children, including 1) slow tonic pressure waves with a frequency of 3 to 12 per hour, b) rectal motor complexes with a frequency of 3 to 10 per minute and c) single contractions 10 to 30 seconds in duration. The median nocturnal duration of rectal motor complexes was longer than that during the day (16.3 minutes, range 10.8 to 18.8 vs 11.0, range 8.9 to 12.6, p <0.05). As a percent of time, median total contraction time was greater at night than during the day (51.9%, range 42.6% to 56.9% vs 30.6%, range 19.4% to 49.3%, p <0.05). Characteristic rectal activity was seen during defecation and voiding but no bladder-rectum interaction was detected. CONCLUSIONS: We identified 3 rectal motility patterns in all children with overactive bladder. Like the upper gastrointestinal tract, the rectum shows some periodic motor activity, which is more frequent at night. No association was observed between bladder and rectal activity during micturition and defecation.