Symptom Assessment of Candidates for Sacral Neuromodulation Therapy With Urologic and Colorectal Conditions: Time for a Holistic Approach? Results and Findings From a Prospective Single-Center Study.

OBJECTIVES: Sacral neuromodulation (SNM) has evolved as a therapeutic intervention for various pelvic floor dysfunctions. However, the traditional approach primarily assesses discipline-specific symptoms, potentially overlooking holistic symptom improvement. We aimed to investigate whether a more comprehensive evaluation of pelvic floor symptoms enhances the assessment of SNM's test phase. MATERIAL AND METHODS: A prospective single-center trial (Optimization of Lower Urinary Tract Symptoms study) assessed SNM efficacy from March 2018 to December 2021 in patients from the urology department (UD) and colorectal surgery department (CRD) with a follow-up of 12 months. Objective and subjective outcomes were examined using diaries and patient-reported outcome measures. Statistical analyses were conducted to determine predictive factors for treatment success, expressed by the patient global impression of change. SPSS 29.0 was used. RESULTS: A total of 85 participants were included, displaying concomitant pelvic floor symptoms. After the first phase, significant improvements on all pelvic floor domains questionnaires were seen for both patients from UD and those from CRD. Although improvements were observed in bladder and bowel diaries, the traditional criteria for success (≥50% improvement in diary variables) did not consistently correlate with the patients' global impression of change. The absolute reductions in bother sum scores from multiple domains were significant predictors for the patients' global impression of change, outperforming discipline-specific assessments. Patients from UD benefit from both a urologic and pelvic pain symptom evaluation, and those from CRD, from both a urologic and bowel symptom evaluation. CONCLUSIONS: SNM shows positive effects across various pelvic floor domains, even beyond the primary intended indication of implantation. The rather rigid approach of patient selection of discipline-specific symptoms alone can be questioned. A more comprehensive evaluation encompassing various pelvic floor symptoms with the emphasis on subjective outcome measures could enhance SNM's efficacy assessment during the test phase. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05313984.

The cost of lifelong LUTS-A systematic literature review.

BACKGROUND: Lower urinary tract symptoms (LUTS) are highly prevalent and very bothersome. To support the best possible allocation of health care resources and to avoid unnecessary expenditures, it is important to understand and quantify the wide-ranging health care costs affecting people suffering from LUTS. We aimed at creating a foundation for exploring the cost of LUTS. METHOD: In this systematic literature review, we explored the costs of illness of the LUTS umbrella. We used the online literature review tool Silvi.ai for transparent decision-making and literature management. RESULTS: A total of 1821 original articles were screened. Forty had explored the cost of illness of a LUTS disease since 2013. The studies were conducted in 18 countries. A number of different study designs were applied, including both retrospective and prospective studies. In total, seven LUTS indications were explored. None of them focused on lifelong LUTS. None of them were conducted in infants or children. Eighty-two percent were conducted in adults and 18% in frail elderly. Most cost of illness studies focused on the cost of hospitalization and use of medicine. CONCLUSION: We have created the groundwork for understanding the cost of LUTS illness. To fully understand the cost of illness of lifelong LUTS, the main gap in research is to investigate the cost of LUTS in infants and children.

Introductory editorial: Lifelong LUTS, a matter of transition?

INTRODUCTION: The EPIC study has highlighted the prominence of nocturia as a crucial symptom of overactive bladder (OAB), intertwining OAB and nocturia with bladder, kidney, and brain functions. METHODS: Expert opinion, review. RESULTS: To truly comprehend lower urinary tract symptoms (LUTS), we must delve into the interactions among these three systems, alongside their circadian rhythms. CONCLUSION: The perception of LUTS is a result of the intricate interplay between bladder, brain, and kidney function, which may evolve across a lifetime due to the (dys)functionality of these organs.

Lifelong LUTS: Understanding the bladder's role and implications across transition phases, a comprehensive review.

INTRODUCTION: Lower urinary tract symptoms (LUTSs) are a diverse array of urinary and pelvic dysfunctions that can emerge from childhood, extend through adulthood, and persist into older age. This narrative review aims to provide a comprehensive perspective on the continuum of LUTS and shed light on the underlying mechanisms and clinical implications that span across the lower urinary tract. METHODS: A panel of five experts from Belgium, the Netherlands, India, Denmark, and the United States participated in an intensive research to explore and pinpoint existing insights into the lifelong concept of LUTS, particularly at the pelvic level. The experts reviewed the existing literature and held a webinar to discuss their findings. RESULTS: Childhood LUTS can persist, resolve, or progress into bladder underactivity, dysfunctional voiding, or pain syndromes. The Lifelong character can be explained by pelvic organ cross-talk facilitated through complex neurological and nonneurological interactions. At the molecular level, the role of vasopressin receptors in the bladder's modulation and their potential relevance to therapeutic strategies for LUTS are explored. Frailty emerges as a parallel concept to lifelong LUTS, with a complex and synergistic relationship. Frailty, not solely an age-related condition, accentuates LUTS severity with insufficient evidence regarding the effectiveness and safety profile of the available therapeutic modalities. CONCLUSION: Understanding lifelong LUTSs offers insights into genetic, anatomical, neurological, and molecular mechanisms. Further research could identify predictive biomarkers, elucidate the role of clinically translatable elements in pelvic cross-talk, and uncover molecular signatures for personalized management.

Exploring lifelong overactive bladder: Transitions, evidence, and clinical implications; A modified Delphi process.

INTRODUCTION: Overactive bladder (OAB) is a prevalent urological condition characterized by urinary urgency, with or without urgency urinary incontinence, accompanied by increased daytime frequency and nocturia. However, the current definition of OAB lacks a specified time frame, hindering our understanding of the temporal aspects and transitions that occur within the OAB spectrum. METHODS: A modified Delphi study was conducted in three rounds, involving a panel of international experts in functional urology, urogynaecology, geriatrics, transitional medicine, and pediatric urology. The study took place between February 2023 and June 2023 and employed two sequential rounds of online surveys, followed by a final hybrid group discussion session in June 2023. RESULTS: The Delphi process resulted in a consensus definition of lifelong OAB as a persistent and continuous condition that may manifest differently from birth and evolve over time, with varying levels of clinical perception. The course of its progression is influenced by transition periods and modifying factors, mainly anatomical, hormonal, and psychosocial/stressors. Three main transition periods were identified: achievement of daytime continence, adulthood to elderly, and transition to frail elderly. The panel also considered the therapeutic and diagnostic implications of lifelong OAB, as well as future research prospects in terms of importance and feasibility. CONCLUSIONS: Future longitudinal research is needed to develop this concept and further identify transitions and temporal dynamics.

Is the insomnia phenotype the common denominator in LUTS during transition periods? An expert NOPIA research group review.

AIMS: As people age, sleep stages and characteristics transition over time, but sleep deficits can profoundly impact health and cognitive functioning. Chronic sleep deprivation is linked to impaired attention and productivity, weakened immunity, increased risk of cardiovascular disease, obesity, and mental health disorders. Insomnia, obstructive sleep apnea syndrome, hormonal changes, nocturia, neurological disorders, and life events interfere with sleep patterns and some are linked to lower urinary tract symptoms (LUTS). This NOPIA symposium on Lifelong LUTS aimed to analyze the literature on associations between sleep and LUTS, generate ideas for future research, and explore whether there is support for the concept of lifelong LUTS in relation to changes in sleep throughout the lifespan. METHODS: An international panel of experts took part in an online meeting addressing the role of lifelong LUTS in relationship to sleep and the brain organized by the NOPIA research group. The manuscript summarizes existing literature, hypotheses, future research ideas, and clinical recommendations. RESULTS: Insomnia, sleep fragmentation, hyperarousal, and sensory processing disorders emerged as potential factors in the relationship between sleep and LUTS. Insomnia is often a persistent factor and may have been the initial symptom; however, it is often unrecognized and/or unaddressed in healthcare settings. By recognizing insomnia as a primary driver of various health issues, including nocturia, transitional care aims to address root causes and underlying problems earlier to initiate appropriate treatment. CONCLUSIONS: A multidisciplinary approach with collaboration between healthcare professionals from various disciplines, such as urology, sleep medicine, gynecology, pediatrics, and geriatrics, is needed and should include validated measurements such as the insomnia severity index and sleep and voiding diaries. Ensuring ongoing follow-up and monitoring through transitional care is crucial for individuals with persistent sleep problems and LUTS, allowing issues that arise or fluctuate over the lifespan to be addressed.

First uninterrupted sleep period in children and adolescents with nocturnal enuresis: Added value in diagnosis and follow-up during therapy.

BACKGROUND: The first uninterrupted sleep period (FUSP, time up to the first episode of enuresis/nocturia after falling asleep) is a frequently investigated parameter in adults with nocturia, as it correlates with quality of life. However, it has not been included in pediatric enuresis studies. AIM: Investigate FUSP, circadian renal water and sodium handling, as well as sleep quality before and after desmopressin therapy in enuresis. MATERIALS AND METHODS: We conducted a post hoc analysis of a prospective study in 30 treatment-naïve children with enuresis who underwent a video-polysomnography and a 24-h urine concentration profile before and after 6 months of desmopressin therapy. We analyzed FUSP, periodic limb movements in sleep (PLMS), and arousal indexes and their correlations with the urinary parameters. RESULTS: Sixteen children with a mean age of 10.9 ± 3.1 years had full registrations and were included in this subanalysis. After therapy, FUSP was significantly longer (p < 0.001), and the PLMS index was lower (p = 0.023). Significant differences in the circadian rhythm of diuresis (night/day diuresis, p = 0.041), nocturnal urinary osmolality (p = 0.009), and creatinine (p = 0.001) were found, demonstrating the increase of urinary concentration overnight by desmopressin, as well as a significant antidiuretic effect (diuresis [p = 0.013] and diuresis rate (p = 0.008). There was no correlation between the difference of FUSP, PLMS index, and urinary parameters. Nevertheless, despite this study being underpowered, there are indications of a correlation between nocturnal diuresis and diuresis rate. RESULTS: Our results support the need for further research regarding FUSP in children with enuresis, in accordance with nocturia studies in adults, as this parameter could be valuable in the follow-up and evaluation of therapeutic strategies for enuresis.

From nocturnal awakenings to nocturnal voiding: the relationship between insomnia and nocturia - a systematic review.

INTRODUCTION: The aim of this study was to systematically evaluate relevant literature regarding 1) the prevalence of nocturia in patients with insomnia; 2) sleep characteristics of insomniacs with and without nocturia; 3) interventions for the treatment of insomnia and their effect on nocturia. EVIDENCE ACQUISITION: A systematic review of literature was performed through EMBASE, MEDLINE, CLINICALTRIALS.GOV and CENTRAL databases up until November 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. From the identified reports, 11 studies were retained, of which 7 were eligible for meta-analysis. Bias assessment was performed using the ROBINS tools as per the Cochrane collaboration guidelines. EVIDENCE SYNTHESIS: A total of 5396 older adults were included in the meta-analysis. The pooled estimate of the OR was 1.958 (95% CI: 1.609-2.384) for nocturia in patients with insomnia based on 7 studies in a random effects model with nonsignificant heterogeneity (I2=50.83%, P=0.06). Wake after sleep onset (WASO) was longer in people with insomnia and nocturia compared to those without and sleep efficiency (SE) declined. Interventions with melatonin, diet and behavioral therapy were beneficial on nocturia frequency in insomniacs. A limiting factor of our analysis was the scarcity of available data, potentially causing an important selection bias. CONCLUSIONS: The overall odds for nocturia in older adults is higher in patients with insomnia than those without and is associated with worse sleep outcomes. Interventions for treating insomnia such as melatonin, behavioral therapy and diet show beneficial results on nocturnal voiding frequency. We advocate for further research in which uniform definitions and questionnaires are used. Routine screening for nocturia in patients with insomnia could be beneficial to maximize sleep quality improvement.

How should we assess the cardiovascular system in patients presenting with bothersome nocturia? ICI-RS 2023.

AIMS: The link between nocturia and cardiovascular disease (CVD) is frequently discussed in literature, yet the precise nature of this relationship remains poorly characterized. The existing literature was reviewed in order to address issues concerning the origin, diagnosis, management, and implications of the co-occurrence of CVD and nocturia. METHODS: This review summarizes literature and recommendations regarding the link between CVD and nocturia discussed during a think-tank meeting held at the 2023 International Consultation on Incontinence-Research Society. RESULTS: Cardiovascular disorders are often underestimated contributors to nocturia, with various potential mechanisms influencing nighttime urination, such as impact on fluid retention, atrial natriuretic peptide, and glomerular filtration rate. The redistribution of fluid from leg edema in supine position can lead nocturnal polyuria (NP). Additionally, sleep disturbances due to nocturia in itself may lead to CVD through an increase in blood pressure, insulin resistance, and inflammation. Disrupted circadian rhythms (e.g., in sleep pattern and urine production) were identified as critical factors in most etiologies of nocturia, and their contribution is deemed imperative in future research and treatment approaches, particularly in the aging population. NP can be detected through a simple bladder diary and can even be used to distinguish cardiac from noncardiac causes of nocturia. For the treatment of NP, desmopressin can be effective in select patients, however, caution and close monitoring is warranted for those with CVD due to increased risk of side effects. CONCLUSIONS: Gaps were identified in the available evidence and clear cut recommendations were put forth for future research. It is essential to gain a deeper understanding of the mechanisms linking nocturia and CVD to develop optimal management strategies.

The role of renal circadian biorhythms in lifelong LUTS.

INTRODUCTION: This article delves into the intricate relationship between kidney function, diuresis, and lower urinary tract symptoms (LUTS) throughout the transitions of the human lifespan. It explores circadian regulation of urine production, maturation of renal function from birth to adulthood, and effects of aging on kidney function and LUTS. The complex connections between these factors are highlighted, offering insights into potential interventions and personalized management strategies. METHODS: An international panel of seven experts engaged in online discussions, focusing on kidney function, diuresis, and LUTS throughout life. This manuscript summarizes expert insights, literature reviews, and findings presented during a webinar and subsequent discussions. RESULTS: Renal function undergoes significant maturation from birth to adulthood, with changes in glomerular filtration rate, diuresis, and tubular function. A circadian rhythm in urine production is established during childhood. Adolescents and young adults can experience persistent enuresis due to lifestyle factors, comorbidities, and complex physiological changes. In older adults, age-related alterations in kidney function disrupt the circadian rhythm of diuresis, contributing to nocturnal polyuria and LUTS. CONCLUSION: The interplay between kidney function, diuresis, and LUTS is crucial in understanding lifelong urinary health. Bridging the gap between pediatric and adult care is essential to address enuresis in adolescents and young adults effectively. For older adults, recognizing the impact of aging on renal function and fluid balance is vital in managing nocturia. This holistic approach provides a foundation for developing innovative interventions and personalized treatments to enhance quality of life for individuals with LUTS across all stages of life.

Laying the foundation for enhancing safety of desmopressin in older people: Validation of capillary blood sodium levels.

PURPOSE: We aim to make desmopressin a safe treatment option for (older) patients at risk for hyponatremia, by introducing a new way of sodium monitoring. The goal is to reduce the risk of hyponatremia, enhance patient safety and ultimately introduce self-monitoring of sodium levels. The first step in the aforementioned is to validate capillary sodium. MATERIALS AND METHODS: 100 randomly selected patients admitted to the urology department received a single finger prick to collect capillary blood (250 µl) in a lithium-heparin tube. Each patient acted as its own control for the capillary and venous blood sample. Venous and capillary plasma sodium were analyzed by indirect ion-selective electrode measurement. The primary outcome was the agreement between capillary and venous sodium measurements, measured by the intra-class correlation coefficient (ICC). RESULTS: One hundred paired blood samples were obtained of which four were excluded. There was no significant statistical difference observed between venous and capillary sodium (-0.23 mmol/L, p = 0.374). The ICC for single measures between capillary and venous sodium was 0.82 (95% confidence interval 0.75-0.88). Inter-method differences analyzed by a Bland-Altman plot and a Passing-Bablock regression did not reveal a statistically significant difference between both groups. CONCLUSIONS: We demonstrated that venous and capillary sodium levels are interchangeable, taken into account the inter- and intravariability between analyses. We provided the first step towards a simple and safe solution for frequent sodium monitoring through a minimal invasive capillary blood collection. The results are of direct clinical relevance to safely use desmopressin in (older) patients at risk.

The Influence of Salt Sensitivity Phenotype on Sodium Excretion and Diuresis: A Chrononutrition Pilot Study.

Background: Chrononutrition studies on interaction of diet/nutrients on endogenous circadian clocks and meal timing on metabolic homeostasis may be of importance in the management of nocturnal polyuria (NP), owing to loss of circadian rhythm in nighttime urination. Dietary salt restriction is an increasingly popular lifestyle recommendation for NP patients. Aim: This study aims to evaluate the effect of an acute salt load on diuresis and to study the phenomenon of salt sensitivity. Methodology. Young, healthy men (n = 21, fasted and sober) ingested 500 ml of water on the control day and 8 g and 12 g of salt with water (500 ml) on two other days. Blood and urine samples were collected at 0 hrs, 2 hrs, and 4 hrs and voided volumes were recorded. Diuresis, serum and urine osmolality, sodium, potassium, urea, and creatinine were measured. Salt sensitivity was determined based on the rate of sodium excretion. Results: Compared to 8 g, ingestion of 12 g of salt significantly increased diuresis after 4 hrs. Pure water load induced fast diuresis, whereas salt and water load initially reduced diuresis and promoted late increase in diuresis. The total voided volume was significantly lower in the salt sensitive individuals. Conclusion: Taken together, salt sensitivity profile and type and time of fluid intake are important considerations to build effective personalized lifestyle recommendations for NP patients, which needs further investigation.

OAB supraspinal control network, transition with age, and effect of treatment: A systematic review.

OBJECTIVE: In light of a better understanding of supraspinal control of nonneurogenic overactive bladder (OAB), the prevalence of which increases with age, functional imaging has gained significant momentum. The objective of this study was to perform a systematic review on the transition of supraspinal control of OAB with age, the effect of therapeutic modalities, and a coordinate-based meta-analysis of all neuroimaging evidence on supraspinal OAB control in response to bladder filling. METHODOLOGY: We performed a systematic literature search of all relevant libraries in November 2021. The coordinates of brain activity were extracted from eligible neuroimaging studies to perform an activation likelihood estimation (ALE) meta-analysis. RESULTS: A total of 16 studies out of 241 were selected for our systematic review. Coordinates were extracted from five experiments involving 70 patients. ALE meta-analysis showed activation of the insula, supplementary motor area, dorsolateral prefrontal cortex, anterior cingulate gyrus, and temporal gyrus with a transition of activation patterns with age, using a threshold of uncorrected p < 0.001. Among young patients, neuroplasticity allows the activation of accessory circuits to maintain continence, as in the cerebellum and temporoparietal lobes. Anticholinergics, pelvic floor muscle training, sacral neuromodulation, and hypnotherapy are correlated with supraspinal changes attributed to adaptability and possibly a substratum of an intrinsic supraspinal component. The latter is better demonstrated by a resting-state functional connectivity analysis, a promising tool to phenotype OAB with recent successful models of predicting severity and response to behavioral treatments. CONCLUSION: Future neuroimaging studies are necessary to better define an OAB neurosignature to allocate patients to successful treatments.