Study protocol for the Heads-Up trial: a phase II randomized controlled trial investigating head-up tilt sleeping to alleviate orthostatic intolerance in Parkinson's Disease and parkinsonism.

BACKGROUND: In persons with Parkinson's Disease (PD) or certain forms of atypical parkinsonism, orthostatic hypotension is common and disabling, yet often underrecognized and undertreated. About half of affected individuals also exhibit supine hypertension. This common co-occurrence of both orthostatic hypotension and supine hypertension complicates pharmacological treatments as the treatment of the one can aggravate the other. Whole-body head-up tilt sleeping (HUTS) is the only known intervention that may improve both. Evidence on its effectiveness and tolerability is, however, lacking, and little is known about the implementability. METHODS: In this double-blind multicenter randomized controlled trial (phase II) we will test the efficacy and tolerability of HUTS at different angles in 50 people with PD or parkinsonism who have both symptomatic orthostatic hypotension and supine hypertension. All participants start with one week of horizontal sleeping and subsequently sleep at three different angles, each maintained for two weeks. The exact intervention will vary between the randomly allocated groups. Specifically, the intervention group will consecutively sleep at 6°, 12° and 18°, while the delayed treatment group starts with a placebo angle (1°), followed by 6° and 12°. We will evaluate tolerability using questionnaires and compliance to the study protocol. The primary endpoint is the change in average overnight blood pressure measured by a 24-hour ambulatory blood pressure recording. Secondary outcomes include orthostatic blood pressure, orthostatic tolerance, supine blood pressure, nocturia and various other motor and non-motor tests and questionnaires. DISCUSSION: We hypothesize that HUTS can simultaneously alleviate orthostatic hypotension and supine hypertension, and that higher angles of HUTS are more effective but less tolerable. The Heads-Up trial will help to clarify the effectiveness, tolerability, and feasibility of this intervention at home and can guide at-home implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551377; Date of registration: September 22, 2022.

Menopausal stages and overactive bladder symptoms in middle-aged women: A cross-sectional study.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

Efficacy and safety of desmopressin in nocturia and nocturnal polyuria control of neurological patients: A systematic review and meta-analysis.

PURPOSE: Evidence on the efficacy of desmopressin in nocturia in patients with neurological diseases is still very limited except for multiple sclerosis (MS). Our aim was to evaluate the efficacy and safety of desmopressin treatment on nocturia in patients with underlying neurological diseases. METHODS: Studies were identified by electronic search of PubMed, Embase, Cochrane, CINAHL, and Google Scholar databases. Studies were considered if they provided information on the effectiveness and safety of desmopressin (1-desamino-8-d-arginine vasopressin, or DDAVP) in the treatment of nocturia and their participants had acquired neurological pathology. Two researchers independently extracted the articles using specified datasets, such as quality-of-study indicators. Statistical meta-analysis was carried out using Review Manager (RevMan) 5.4 statistical software (Cochrane Collaboration). RESULTS: Of a total of 1042 articles in the initial search, 14 studies were included. Most of the published papers were related to MS (n = 7), two were on spinal cord injury, and other conditions were neural tube defect, myelodysplasia, Parkinson's disease, stroke, and multiple system atrophy. Overall, a total of 200 patients (mostly females) were enrolled. Thirteen studies evaluated the intranasal formulation of desmopressin and one study evaluated oral desmopressin. A significant decrease in nocturia episodes was reported in seven studies evaluating this topic. An increase in the maximum hours of uninterrupted sleep was reported in the three studies in which this outcome was assessed. A significant reduction in the volume of nocturnal incontinence was found in one study. Three studies were eligible to include in the meta-analysis. The results showed that desmopressin compared to placebo, significantly reduced nighttime urination (mean difference: -0.75, 95% CI: -1.10 to -0.41; p < 0.00001). The rate of adverse events ranged from 0% to 68.42%. The critical appraisal results for all trials showed that most of the studies had low or moderate quality. CONCLUSIONS: Our results emphasized desmopressin's safety and efficacy in reducing nocturia episodes, with transient adverse effects on neurological patients. However, the data were achieved from low or medium-quality trials, and further well-designed randomized controlled trials are needed.

The relationships between blood lead levels and nocturia prevalence in adults: A retrospective study.

PURPOSE: The purpose of this study was to examine the association between blood lead levels and the prevalence of nocturia in American adults. METHODS: We analyzed data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2020, focusing on individuals aged 20 years or older (n = 11,919). Blood lead levels were categorized into two groups (<2 µg/dL and ≥2 µg/dL), and the presence of nocturia was assessed based on questionnaire responses. We used multivariable logistic regression models to explore the association between blood lead levels and nocturia while adjusting for various covariates, including sex, ratio of family income to poverty (RIP), lipid profile, age, body mass index (BMI), race, citizenship, sleep trouble, diabetes, and hypertension. To verify whether certain covariates influence blood lead levels and the risk of nocturia, we conducted subgroup analyses. RESULTS: Of the study participants, 31.70% reported experiencing nocturia. Individuals with higher blood lead levels (≥2 µg/dL) exhibited a higher likelihood of experiencing nocturia compared to those with lower levels (<2 µg/dL) in all three models (Model 1: OR 1.46, 95% CI 1.29-1.66, p < 0.0001; Model 2: OR 1.25, 95% CI 1.09-1.44, p = 0.002; Model 3: OR 1.22, 95%CI 1.06-1.41, p = 0.01). Subgroup analyses revealed that factors such as age, sex, sleep trouble, diabetes, hypertension, BMI, RIP, and race did not affect the association between blood lead levels and the risk of nocturia (P for interaction >0.05). CONCLUSIONS: This study reported the correlation between blood lead levels and nocturia. We found that compared to blood lead levels below 2 µg/dL, when lead levels reached or exceeded 2 µg/dL, the risk of nocturia occurrence increased by 22%. CLINICAL TRIAL REGISTRATION: This study is based on existing data from a public database and not from a specific clinical trial; hence, clinical registration information is not provided.

The relationship between arthritis and nocturia among adults under 60: A cross-sectional study based on National Health and Nutrition Examination Survey.

OBJECTIVE: This study aims to investigate how arthritis, including osteoarthritis and rheumatoid arthritis, affects the incidence of nocturia in adults aged 20-59. METHODS: This study utilized data from the National Health and Nutrition Examination Survey from 2005 to 2020, involving 18 745 adults aged 20-59. Arthritis, including osteoarthritis and rheumatoid arthritis, was considered as the exposure factor, with nocturia as the outcome variable. We first compared the baseline characteristics of individuals with and without nocturia. The impact of arthritis on nocturia was assessed using weighted multivariate logistic regression models. To ensure the stability of the results, propensity score matching analysis and subgroup analyses were conducted. RESULTS: The incidence of nocturia was approximately 22.31%, and the incidence of arthritis was about 15.32% (2871/18 745), with osteoarthritis accounting for 35.49% (1019/2871) and rheumatoid arthritis accounting for 20.20% (580/2871). Adjusted multivariate logistic regression analysis revealed that the risk of nocturia was increased by arthritis (odds ratio [OR] = 1.45, 95% confidence interval [CI]: 1.28-1.65, p < 0.0001), including osteoarthritis (OR = 1.45, 95% CI: 1.18-1.78, p < 0.001) and rheumatoid arthritis (OR = 1.51, 95% CI: 1.14-2.00, p = 0.004). After propensity score matching using nearest neighbor methods at a 1:1 ratio, this relationship still exists. Subgroup analyses showed no significant differences in the interactions between arthritis and the risk of nocturia across various factors, such as age, family income to poverty ratio, education level, body mass index, smoking status, hypertension, and diabetes. However, significant differences were observed across different sex groups and sleep trouble groups. CONCLUSIONS: This study revealed that arthritis, including osteoarthritis and rheumatoid arthritis, increased the risk of nocturia in adults under the age of 60.

Lower urinary tract symptoms in young-middle aged males with a diagnosis of obstructive sleep apnea syndrome.

BACKGROUND: The aim of the current study is to measure the prevalence and the potential role of International Prostate Symptom Score (IPSS) score as a predictor of obstructive sleep apnea syndrome (OSAS) in male experienced lower urinary tract symptoms (LUTS). METHODS: A cross-sectional web-based Italian survey was administered via Google Forms between July 17 and October 31, 2022. The urinary functioning was measured through the IPSS questionnaire. Specifically, we considered symptoms occurring more than "about half the time" (score ≥ 3) as bothering symptoms. Multivariable logistic regression models (LRMs) adjusting for age, body mass index (BMI), International Index of Erectile Function-5, IPSS, and hypertension were fitted to predict OSAS in the cohort of men responding to the survey and experiencing LUTS. RESULTS: Overall, 58 (24.4%) patients had a confirmed diagnosis of OSAS. The overall median IPSS was 5 (inter quartile range [IQR]: 3-8), respectively. According to IPSS items, 24 (10%), 44 (18.4%), 12 (5%), 12 (5%), 12 (5%), 11 (4.6%), 63 (26.4%) patients exhibit incomplete bladder emptying, urinary frequency, intermittency, urgency, weak stream, straining, nocturia with a score ≥ 3, respectively. After multivariable LRMs predicting the developing OSAS, age (odds ratio [OR]: 1.09, p < 0.001), BMI (OR:1.12, p < 0.001) and IPSS total score (OR:1.08, p = 0.02) were independent predicting factors. CONCLUSION: This analysis revealed that the IPSS total score, age, and BMI are independent predictors of OSAS in males. In this context, the use of IPSS in daily practice could be helpful in assessing the LUTS presence and in supporting physicians to identify a hidden sleep apnea condition.

The association between different levels of depression and overactive bladder: A cross-sectional study of the 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND: There is growing evidence of a possible correlation between depression and overactive bladder (OAB). However, few studies have classified depression according to its severity. Whether there is an association between different levels of depression and OAB symptoms remains unclear. METHODS: Participants with complete information about depression, OAB, and covariates in the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were included in this study. Depression symptoms were assessed by the Patient Health Questionnaire-9. OAB symptoms were evaluated by the Overactive Bladder Symptom Score. Weighted multivariate logistic regression models were applied to analyze the relationship between depression and OAB. RESULTS: A total of 30 359 participants were included in this study, consisting of 6245 OAB patients and 24 114 non-OAB participants. The multivariate logistic regression suggested depression independently correlated with OAB (odds ratio [OR] = 2.764, 95% confidence interval [CI] = 2.429-3.146, p < 0.001). Further, mild (OR = 2.355, 95% CI = 2.111-2.627, p < 0.001), moderate (OR = 3.262, 95% CI = 2.770-3.841, p < 0.001), and moderately severe to severe depression (OR = 3.927, 95% CI = 3.246-4.752, p < 0.001) were all associated with OAB. Additionally, depression was also correlated with urgency urinary incontinence (OR = 2.249, 95% CI = 1.986-2.548, p < 0.001) and nocturia (OR = 2.166, 95% CI = 1.919-2.446, p < 0.001). CONCLUSION: This study indicated different levels of depression, even mild depression, were independent risk factors for OAB. Given the frequent coexistence and potential interactions between depression and OAB, clinicians should be aware of the importance of assessing both physical and psychological symptoms in these patients. Early diagnosis and holistic treatment may improve the treatment outcomes, particularly for those suffering from both conditions.

The relationship between nocturia and suicidal ideation: A study on The National Health and Nutrition Survey data.

OBJECTIVES: The focus of this research was to explore any potential link between nocturia and the risk of suicidal ideation. METHODS: Drawing from the National Health and Nutrition Survey, data relating to 25 241 participants was scrutinized. This included 13 421 individuals identifying as male and 11 820 individuals identifying as female. Participants provided information on nocturia and suicidal ideation via self-completed questionnaires. To determine if nocturia was independently related to suicidal ideation, a multivariable logistic regression analysis was employed. Analyses were also undertaken separately for adult males and females. RESULTS: It was found that around 3.5% of participants had experienced suicidal ideation. The results indicated that nocturia increased the risk for suicidal ideation in all adult groups (odds ratio [OR] = 1.67, 95% confidence interval[CI]: 1.37-2.03, p < 0.0001), including both males (OR = 1.91, 95% CI: 1.38-2.65, p < 0.001) and females (OR = 1.48, 95% CI: 1.158-1.90, p = 0.002). The risk for suicidal ideation increased with the severity of nocturia, with significant trends observed in adult males (p for trend = 0.04) and adult females (p for trend = 0.01). Additionally, subgroup examination showed a significant interaction between nocturia and educational level in adult males (p for interaction = 0.03). Among adult females, a noteworthy interaction was observed between nocturia and body mass index (p for interaction = 0.02). CONCLUSION: The research uncovered a connection between nocturia and an elevated risk of suicidal ideation.

Association between nighttime urinary frequency and clinical outcomes in Japanese patients with ulcerative colitis.

INTRODUCTION: Nocturia is a common symptom of lower urinary tract syndrome (LUTS). In previous studies, a close association between LUTS and colorectal inflammation has been reported. However, evidence regarding the association between nighttime urinary frequency and ulcerative colitis (UC) is limited. Herein, we investigated the association between nighttime urinary frequency and clinical outcomes of UC. METHODS: We surveyed 287 Japanese patients with UC. A self-administered questionnaire was used to collect the information on the variables studied. Patients were divided into three groups based on nighttime urinary frequency: (1) no voids, (2) one void, and (3) two or more voids. The assessment of clinical outcomes was based on mucosal healing (MH) and clinical remission (CR). The association between nighttime urinary frequency and prevalence of MH and CR was evaluated using multivariate logistic regression analyses. RESULTS: The prevalence of one nighttime frequency and two or more nighttime frequency in this cohort was 35.5% and 26.8%, respectively. The percentage of MH and CR was 24.7% and 59.2%, respectively. Two or more nighttime frequency (adjusted odds ratio [OR]: 0.31, 95% confidence interval [CI]: 0.13-0.73) was independently and inversely associated with MH. In nonelderly patients (<70 years) and patients in CR, an association between two or more nighttime frequency and MH remained significant (non-elderly: adjusted OR: 0.27, 95% CI: 0.09-0.72 and only CR: adjusted OR: 0.34, 95% CI: 0.12-0.90). CONCLUSION: Nighttime urinary frequency was independently and inversely associated with MH in Japanese patients with UC. Nighttime urinary frequency may serve as a complementary physical sign of MH in patients with UC.

Electroencephalography-based investigation of the effects of oral desmopressin on improving slow-wave sleep time in nocturnal polyuria patients (the DISTINCT study): A single-arm, open-label, single-assignment trial.

AIMS: To investigate changes in subjective and objective sleep quality after desmopressin administration in patients with nocturia due to nocturnal polyuria (NP) using electroencephalography (EEG) and the Pittsburgh sleep quality index (PSQI). METHODS: Twenty male patients (≥65 years old) with NP participated in this study. The inclusion criteria were nocturnal frequency ≥ 2, NP index (NPi) ≥ 0.33, first uninterrupted sleep period (FUSP) ≤ 2.5 h, serum sodium concentration ≥ 135 mEq/L, and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2. Participants were given 50 µg of desmopressin to be taken orally once daily before bed. The primary endpoint was the change in the duration of slow-wave sleep (nonrapid eye movement sleep stages 3 and 4), as evaluated by EEG 28 days from the baseline. The visual analog scale (VAS) was used as an additional indicator of sleep quality. RESULTS: Analysis of data from 15 participants (median age: 74.0 [70.5, 76.0] years) revealed that from before to after desmopressin administration, significant decreases occurred in the median nocturnal frequency (3.0 [2.0, 4.0] to 1.5 [1.0, 2.0]) and NPi (0.445 [0.380, 0.475] to 0.360 [0.250, 0.430]). Furthermore, FUSP was significantly prolonged from 120.0 (94.0, 150.0) min to 210.0 (203.8, 311.3) min. Although the VAS scores improved, slow-wave sleep duration and the PSQI global score showed no significant differences (68.50 [47.50, 75.50] and 48.00 [38.00, 66.50]; 5.0 [5.0, 10.0] and 7.0 [5.0, 9.0] min, respectively). CONCLUSION: Oral administration of 50 µg desmopressin improved nocturnal frequency and FUSP in older individuals with NP but did not significantly enhance sleep quality. In older adults, decreased nighttime urinary frequency may enhance quality of life; however, its influence on objective sleep quality may be limited.

Transition in enuresis patients: Identifying the gaps and opportunities for the future.

BACKGROUND: Nocturnal enuresis is generally considered a children's condition, yet it may persist 1%-2% in adolescence and early adulthood. Refractory patients often demand follow-up by multidisciplinary teams, which is only restricted to some of the expert tertiary centers. However, there are no standardized transition programs/guidelines when follow-up must be passed from pediatric to adult healthcare providers. AIM, MATERIALS & METHODS: To investigate this issue, we conducted a literature search on enuresis transition, which resulted in no articles. We, therefore, proceeded in a rescue search strategy: we explored papers on transition programs of conditions that may be related and/or complicated by enuresis, nocturia, or other urinary symptoms (chronic diseases, CKD, bladder dysfunction, kidney transplant, neurogenic bladder). RESULTS: These programs emphasize the need for a multidisciplinary approach, a transition coordinator, and the importance of patient and parent participation, practices that could be adopted in enuresis. The lack of continuity in enuresis follow-up was highlighted when we investigated who was conducting research and publishing on enuresis and nocturia. Pediatric disciplines (50%) are mostly involved in children's studies, and urologists in the adult ones (37%). DISCUSSION: We propose a stepwise approach for the transition of children with enuresis from pediatric to adult care, depending on the clinical subtype: from refractory patients who demand more complex, multidisciplinary care and would benefit from a transition coordinator up to children/young adults cured of enuresis but who persist in having or present lower urinary tract symptoms (LUTS)/nocturia later on. In any case, the transition process should be initiated early at the age of 12-14 years, with adequate information to the patient and parents regarding relapses or LUTS/nocturia occurrence and of the future treating general practitioner on the enuresis characteristics and comorbidities of the patient.

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.

Association between TV and/or video time and nocturia in adults: An analysis of the National Health and Nutrition Examination Survey.

AIMS: This study aimed to examine the correlation between television (TV) and/or video viewing time and the occurrence of nocturia in adults. METHODS: An analysis of data from the National Health and Nutrition Examination Survey for 2011-2016 was conducted, involving 13 294 adults aged 20 and older. The main outcome was specified as nocturia, which refers to the requirement of urinating two or more times during the night. Initially, baseline characteristics were contrasted between individuals with and without nocturia. The effects of TV and/or video viewing time on nocturia were further explored using multivariable logistic regression models. To acknowledge the variation in baseline data regarding the prevalence of nocturia, subgroup analyses were performed. RESULTS: Adjusted multivariate analysis revealed that individuals in the group with the longest TV and/or video viewing time had a significantly 48% higher risk of experiencing nocturia compared to those with the shortest TV and/or video viewing time. The results of subgroup analyses revealed no significant differences in the interaction tests between TV and/or video viewing time and nocturia. CONCLUSIONS: Our research showed that individuals who spent 5 or more hours a day watching TV and/or videos were significantly more likely to develop nocturia.

Associations between waist circumference and nocturia in adults: National health and nutrition examination survey 2005-2020.

BACKGROUND: The relationship between waist circumference and nocturia has not been previously studied. This study investigated the association between waist circumference and the occurrence of nocturia in adults. METHODS: We analyzed data from the National Health and Nutrition Examination Survey covering 2005-2020, encompassing 6287 adults aged ≥20. Nocturia was defined as the need to urinate two or more times during the night. First, we compared baseline characteristics between the nocturia and non-nocturia groups. Subsequently, we used multivariate logistic regression analysis to investigate the relationship between waist circumference and nocturia prevalence. We also employed restricted cubic spline analysis to study the potential nonlinear correlation between waist circumference and the prevalence of nocturia. Recognizing the baseline data's heterogeneity based on nocturia prevalence, we conducted subgroup analyses according to age, sex, body mass index (BMI), and ethnicity. RESULTS: Our findings indicated that females, individuals aged ≥50, citizens, Non-Hispanic Black, those with lower education levels (high school or less), higher BMIs, lower family income-to-poverty ratios, higher waist circumference, hypertension, and diabetes were more likely to experience nocturia. Compared with individuals in the lowest waist circumference quartile (Q1), those in the higher quartiles (Q4) exhibited an increased risk of nocturia in Model 1 (Q4, OR:2.00, 95% CI:1.64, 2.45, p < 0.0001). These results remained consistent after adjusting for covariates in models 2 and 3. A restricted cubic spline analysis suggested a linear association between waist circumference and nocturia (P for nonlinearity = 0.066). Subgroup analyses based on age, sex, BMI, and ethnicity revealed no significant differences in the interaction tests between waist circumference and nocturia (P for interaction = 0.437, 0.331, 0.121, and 0.889, respectively), indicating that these baseline characteristics did not influence the association. CONCLUSIONS: Our findings indicated an association between increased waist circumference and a higher prevalence of nocturia. Knowledge of this association reinforces the importance of lifestyle modifications in maintaining a healthy waist circumference and informs public health strategies to address other potential risk factors for nocturia.

The association between testosterone deficiency and nocturia: Insights from The National Health and Nutrition Examination Survey data set.

AIMS: To examine the association between testosterone deficiency (TD) and nocturia in males, with specific attention to age and cardiovascular disease (CVD) comorbidity. METHODS: This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2016, assessing 6137 adult male participants. TD was defined by a serum total testosterone (TT) concentration less than 300 ng/dL. Nocturia was determined based on participants' responses to a standard NHANES question regarding the frequency of urination during the night. RESULTS: The study observed a significant association between TD and nocturia (adjusted odds ratio [95% confidence interval] = 1.211 [1.060-1.384], p = 0.005). Moreover, a U-shape pattern was noted in the relationship between serum TT concentration and the relative odds of nocturia. Subgroup analysis revealed a robust correlation between TD and nocturia in those over 60 years old, and those with hypertension, dyslipidemia, and CVDs. CONCLUSION: Our findings suggest a positive correlation between TD and nocturia, particularly among elderly individuals with CVD. This association underscores the potential therapeutic significance of addressing TD in the management of nocturia. Furthermore, longitudinal studies are needed to establish a causal relationship between TD and nocturia.

Prevalence of Sleep CALM nocturia factors in a male veteran population.

INTRODUCTION: Nocturia is a complex and multifactorial condition, associated with several genitourinary abnormalities as well as a host of conditions beyond the urinary tract, and thus often poses a significant diagnostic challenge in real-world practice. Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications, the so-called "Sleep C.A.L.M." factors, are five common causes of nocturia requiring judicious evaluation according to current consensus guidelines. This study aims to assess the prevalence of the Sleep C.A.L.M. factors in a nocturia clinical population. METHODS: Retrospective analysis of frequency-volume charts from men with ≥2 nocturnal voids as well as concurrent demographic, clinical, and medical history data to identify patients with each of the Sleep C.A.L.M. FACTORS: Comorbidities and medications were classified as a single group. RESULTS: A total of 213 subjects met the criteria for inclusion (median age 68.0 [63.5-75.5] years). The prevalence of 1) sleep disorders, 2) comorbidities and/or medication use, 3) actions (i.e., modifiable behaviors/lifestyle factors), and 4) lower urinary tract dysfunction was 31%, 31%, 19%, and 41%, respectively. Among included participants, 73% were found to have at least 1 Sleep C.A.L.M. factor, and 33% had multiple Sleep C.A.L.M. FACTORS: Results were similar upon stratification by age and nocturnal polyuria status. CONCLUSIONS: The Sleep C.A.L.M. factors are highly common among nocturia patients in the clinical urology setting. Although many of these factors are strongly associated with advanced age in community-based nocturia study samples, they appear common even among younger men in a nocturia patient population; the differential effect of age and individual Sleep C.A.L.M. factors on nocturia pathophysiology requires further investigation.

NITES, a nocturnal bladder score to aid diagnosis during the transition to older age care.

BACKGROUND: As adults transition to older age, bothersome nocturnal lower urinary tract symptoms (LUTS) become common. There is need for a reliable assessment metric to detect and measure specific symptoms. OBJECTIVE: To subject the nocturnal LUTS score for older individuals, Nocturia, Incontinence, Toileting and Enuresis Symptom Score (NITES), to psychometric analysis. MATERIAL AND METHODS: Factor analysis of the metric was conducted with completed questionnaires from 151 older individuals who were either admitted to a tertiary hospital or attending an outpatient continence clinic. Test re-test reliability involved 18 older community dwelling individuals attending a Geriatrician clinic completing the metric at two timepoints separated by at least 1 week. Intra-class correlation coefficients were determined for reliability of each factor and item. RESULTS: The NITES metric was completed by 98 hospitalized older individuals and 53 attending a continence clinic (mean age 83.2 years [SD 7.0]). Factor analysis demonstrated that one item had a floor effect and two items had poor endorsement. After test re-test reliability analysis, a further three items were removed: one due to poor correlation between timepoints and two demonstrating inadequate internal consistency. The final NITES metric is comprised of three factors: Sleep 4-items, Incontinence 4-items, and Personal Bother 2-items. A 4-item short form for symptom screening was extracted from the longer measure. CONCLUSION: The final NITES metric is a 10-item questionnaire with an embedded 4-item short symptom screen. It has utility utilized to detect nocturnal bladder symptoms in both community dwelling and hospitalized older adults.

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.

A better understanding of basic science may help our management of LUTS/LUTD in older persons with nocturnal polyuria and nocturia: ICI-RS 2024.

AIMS: To discuss the role of autocrine/paracrine signaling of urothelial arginine vasopressin (AVP) on mammalian bladder capacities and micturition thresholds, impact of distension on water/urea reabsorption from the bladder, review of the literature to better characterize the central/peripheral effects of AVP, desmopressin (dAVP) toxicity, and urine biomarkers of nocturia. METHODS: This review summarizes discussions during an International Consultation on Incontinence-Research Society 2024 think tank with respect to the role of urothelial AVP in aged individuals with nocturnal polyuria, impact of solute and water reabsorption by the bladder on uninterrupted sleep, central effects of AVP, pharmacological basis of dAVP toxicity, and biomarkers in nocturia/lower urinary tract dysfunction (LUTD) with neurological diseases. RESULTS: Consensus recognized AVP function and pathways in the central nervous system (CNS), pre-proAVP localized using immunohistochemistry in bladder sections from adult/aged noncancerous human punch biopsies and rodent bladder sections is likely to accelerate the systemic uptake of water and urea from the bladder of anesthetized mice instilled with 3H-water and 14C-urea. Mechanisms for charged and uncharged solutes and water transport across the bladder, mechanism of dAVP toxicity, and utility of urine biomarkers in those with neurological diseases/nocturia were determined from literature reviews. CONCLUSION: Pre-proAVP is present in human/rodent bladders and may be involved in water reabsorption from bladder that prevents the sensation of fullness for uninterrupted sleep in healthy adults. The mechanism of action of AVP in the CNS was discussed, as was electrolyte/water transport across the bladder, the basis for dAVP toxicity, and feasibility of urine biomarkers to identify nocturia/LUTD with neurological diseases.

Posterior Tibial Nerve Stimulation With versus Without Mirabegron: A Randomized Controlled Trial.

INTRODUCTION AND HYPOTHESIS: To compare change in urgency urinary incontinence episodes (UUIEs) in women undergoing posterior tibial nerve stimulation (PTNS) plus mirabegron versus PTNS plus placebo for the treatment of refractory urgency urinary incontinence (UUI). The primary hypothesis was that combination therapy is superior to monotherapy. METHODS: A randomized controlled trial was performed in individuals identifying as female aged ≥ 18 years with UUI symptoms refractory to second-line treatment or who could not tolerate antimuscarinic medications. Both participants and providers were blinded to medication treatment allocation. Participants were randomized (1:1) to PTNS plus mirabegron or PTNS plus placebo. Participants completed a 3-day bladder diary prior to and after 12-week treatment. Validated symptom distress and impact questionnaires were obtained pre- and post-treatment. The primary outcome was change in mean number of UUIEs on a 3-day bladder diary pre- versus post-treatment between arms. Primary and secondary outcomes were analyzed via sample t tests. RESULTS: Fifty-four subjects were randomized, mean ± SD baseline age 56.2±15.6 years and body mass index 35.0±9.4 (kg/m2); no differences were noted in any clinical-demographic characteristics. There was a significant difference between arms in mean pre- to post-treatment UUIEs, 9.4±3.9, mirabegron versus 5.3±5.5, placebo (p=0.007). Significant differences were found pre- compared with post-treatment in urinary frequency, Overactive Bladder Questionnaire Short Form Symptom Bother and Symptom Health-Related Quality of Life scores. CONCLUSIONS: In subjects undergoing PTNS treatment for refractory UUI and OAB-wet symptoms, the addition of a ß-3 agonist produced significant improvement in both objective and subjective overactive bladder symptom outcomes compared with PTNS plus placebo.