'Nocturomics': transition to omics-driven biomarkers of nocturia, a systematic review and future prospects.

OBJECTIVE: To systematically review studies that investigated different biomarkers of nocturia, including omics-driven biomarkers or 'Nocturomics'. MATERIALS AND METHODS: PubMed® , Scopus® , and Embase® were searched systematically in May 2022 for research papers on biomarkers in physiological fluids and tissues from patients with nocturia. A distinction was made between biomarkers or candidates discovered by omics techniques, referred to as omics-driven biomarkers, and classical biomarkers, measured by standard laboratory techniques and mostly thought from pathophysiological hypothesis. RESULTS: A total of 13 studies with 18 881 patients in total were included, eight of which focused on classical biomarkers including: atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-reactive protein (CRP), aldosterone, and melatonin. Five were 'Nocturomics', including one that assessed the microbiome and identified 27 faecal and eight urinary bacteria correlated with nocturia; and four studies that identified candidate metabolomic biomarkers, including fatty acid metabolites, serotonin, glycerol, lauric acid, thiaproline, and imidazolelactic acid among others. To date, no biomarker is recommended in clinical practice. Nocturomics are in an embryonic phase of conception but are developing quickly. Although candidate biomarkers are being identified, none of them are yet validated on a large sample, although some preclinical studies have shown a probable role of fatty acid metabolites as a possible biomarker of circadian rhythm and chronotherapy. CONCLUSION: Further research is needed to validate biomarkers for nocturia within the framework of a diagnostic and therapeutic precision medicine perspective. We hope this study provides a summary of the current biomarker discoveries associated with nocturia and details future prospects for omics-driven biomarkers.

The association between nocturia, hormonal symptoms and bladder parameters in women: an observational study.

OBJECTIVE: Postmenopausal nocturia is poorly understood. This study aimed to identify hormonal and lifestyle factors associated with nocturia and to understand the relative contribution of altered urine production and bladder storage dysfunction in women. DESIGN, SETTING, POPULATION AND METHODS: Women ≥40 years presenting to public continence services were enrolled in a cross-sectional study. A total of 153 participants completed a hormone status questionnaire, a validated nocturia causality screening tool and a 3-day bladder diary. Descriptive statistics and logistic regression models for nocturia severity and bladder diary parameters were computed. RESULTS: Overall, 91.5% reported nocturia, 55% ≥2 /night. There was a difference of 167.5 ml (P < 0.001) in nocturnal urine volume between women with nocturia ≥2 (median 736 ml) versus less often (517 ml). Significant predictors of self-reported disruptive nocturia were age (odds ratio [OR] 1.04, 95% CI 1.002-1.073) and vitamin D supplementation (OR 2.33, 95% CI 1.11-4.91). Nocturnal polyuria was significantly more common with nocturia ≥2 compared with less frequent nocturia (P < 0.002). Exercise for 150 minutes a week was protective for nocturnal polyuria (OR 0.22, P = 0.001). Nocturia index >1.3 was significantly predicted by age (OR 1.07, P < 0.001), regular exercise (OR 0.41, P = 0.036), day flushes (OR 4.00, P = 0.013) and use of vitamin D (OR 2.34, P = 0.043). Maximum voided volumes were significantly lower with nocturia ≥2 versus less often (night: 268 ml versus 350 ml; day: 200 ml versus 290 ml). CONCLUSIONS: Bothersome nocturia in postmenopausal women is associated with changes to both nocturnal diuresis and bladder storage. Regular physical activity, prolapse reduction and oestrogen replacement may be adjunctive in managing bothersome nocturia in women.

Effectiveness of acupuncture for nocturia: A protocol for systematic review and meta-analysis.

BACKGROUND: Nocturia is a common and highly troubled lower urinary tract symptom, which has a wide range of effects. About 33% of patients with lower urinary tract symptoms have been affected by nocturia. Nocturia is mainly manifested as the increase of urination frequency and urine volume at night. It has been proved that acupuncture can reduce the symptoms of nocturia and regulate bladder function in Western countries. Acupuncture may be a promising choice for the treatment of nocturia. METHODS: RCTs of acupuncture for nocturia will be searched in the relevant database, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure Wanfang Database, Chinese Biomedical Literature Database, and Chinese Scientific Journal Database. The studies of electronic searches will be exported to EndNote V.9.1 software. We will run meta-analyses using the Review Manager (RevMan) V.5.3 software. Any disagreement will be solved in consultation with a third reviewer. RESULTS: Our study aims to explore the efficacy of acupuncture for nocturia and to provide up-to-date evidence for clinical of nocturia. CONCLUSION: The conclusion of this study will provide evidence for the efficacy of acupuncture treatment of nocturia. INPLASY REGISTRATION NUMBER: INPLASY202130100.

Treatment for overactive bladder: A meta-analysis of transcutaneous tibial nerve stimulation versus percutaneous tibial nerve stimulation.

BACKGROUND: We aim to compare the safety and effectiveness of transcutaneous tibial nerve stimulation (TTNS) versus percutaneous tibial nerve stimulation (PTNS) in treating overactive bladder. METHODS: A systematical search on PubMed, Embase, clinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials from January 1, 1999 to November 1, 2020 was performed. The primary outcomes were the changes in a 3-day voiding diary. Quality of life scores were also evaluated. Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was applied to conduct all statistical analyses. RESULTS: A total of 4 trials (2 randomized controlled trials, 1 retrospective study, and 1 before-after study) with 142 patients were eventually enrolled. Compared with PTNS, TTNS had a similar performance in the voiding frequency in 24 hours (mean difference [MD] = -0.65, 95% confidence interval [CI]: -1.35 to 0.05, P = .07), the number of urgency episodes in 24 hours (MD = 0.13, 95% CI: -0.36 to 0.62, P = .60), the number of incontinence episodes in 24 hours (MD = 0.01, 95% CI: -0.13 to 0.14, P = .93), as well as in the nocturia frequency (MD = -0.14, 95% CI: -0.52 to 0.24, P = .47). Moreover, comparable results were observed regarding HRQL scores (P = .23) and incontinence quality of life scores (P = .10) in both groups. The total complication rate in the current study was 2.1% (3/142). No adverse events were identified in the TTNS group. CONCLUSION: Current data supported that TTNS is as effective as PTNS for the treatment of overactive bladder, moreover, with no reported adverse events. However, the evidence is low-grade and well-designed prospective studies with a large sample size are warranted to verify our findings.

Development of an overactive bladder assessment tool (BAT): A potential improvement to the standard bladder diary.

AIMS: To develop a comprehensive patient-reported bladder assessment tool (BAT) for assessing overactive bladder (OAB) symptoms, bother, impacts, and satisfaction with treatment. METHODS: Subjects were consented and eligibility was confirmed by a recruiting physician; subjects were then scheduled for in-person interviews. For concept elicitation and cognitive interviews, 30 and 20 subjects, respectively, were targeted for recruitment from US sites. All interviews were conducted face-to-face, audio-recorded, transcribed verbatim, anonymized, and analyzed using a qualitative data analysis software program. A draft BAT was created based on the results of the concept elicitation interviews and further revised based on cognitive interviews as well as feedback from an advisory board of clinical and patient-reported outcome (PRO) experts. RESULTS: Nocturia, daytime frequency, and urgency were reported by all subjects (n = 30, 100.0%), and incontinence was reported by most subjects (n = 25, 83.3%). The most frequently reported impacts were waking up to urinate (n = 30, 100.0%), embarrassment/shame (n = 24, 80.0%), stress/anxiety (n = 23, 76.7%), and lack of control (n = 23, 76.7%). Following analysis, item generation, cognitive interviews, and advisory board feedback, the resulting BAT contains four hypothesized domains (symptom frequency, symptom bother, impacts, and satisfaction with treatment) and 17 items with a 7-day recall period. CONCLUSIONS: The BAT has been developed in multiple stages with input from both OAB patients and clinical experts following the recommended processes included in the FDA PRO Guidance for Industry. Once fully validated, we believe it will offer a superior alternative to use of the bladder diary and other PROs for monitoring OAB patients in clinical trials and clinical practice.

Medical Treatment of Nocturia in Men with Lower Urinary Tract Symptoms: Systematic Review by the European Association of Urology Guidelines Panel for Male Lower Urinary Tract Symptoms.

CONTEXT: The treatment of nocturia is a key challenge due to the multi-factorial pathophysiology of the symptom and the disparate outcome measures used in research. OBJECTIVE: To assess and compare available therapy options for nocturia, in terms of symptom severity and quality of life. EVIDENCE ACQUISITION: Medical databases (Embase, Medline, Cochrane Systematic Reviews, Cochrane Central) were searched with no date restriction. Comparative studies were included which studied adult men with nocturia as the primary presentation and lower urinary tract symptoms including nocturia or nocturnal polyuria. Outcomes were symptom severity, quality of life, and harms. EVIDENCE SYNTHESIS: We identified 44 articles. Antidiuretic therapy using dose titration was more effective than placebo in relation to nocturnal voiding frequency and duration of undisturbed sleep; baseline serum sodium is a key selection criterion. Screening for hyponatremia (< 130 mmol/l) must be undertaken at baseline, after initiation or dose titration, and during treatment. Medications to treat lower urinary tract dysfunction (α-1 adrenergic antagonists, 5-α reductase inhibitors, phosphodiesterase type 5inhibitor, antimuscarinics, beta-3 agonist, and phytotherapy) were generally not significantly better than placebo in short-term use. Benefits with combination therapies were not consistently observed. Other medications (diuretics, agents to promote sleep, nonsteroidal anti-inflammatories) were sometimes associated with response or quality of life improvement. The recommendations of the Guideline Panel are presented. CONCLUSIONS: Issues of trial design make therapy of nocturia a challenging topic. The range of contributory factors relevant in nocturia makes it desirable to identify predictors of response to guide therapy. Consistent responses were reported for titrated antidiuretic therapy. For other therapies, responses were less certain, and potentially of limited clinical benefit. PATIENT SUMMARY: This review provides an overview of the current drug treatments of nocturia, which is the need to wake at night to pass urine. The symptom can be caused by several different medical conditions, and measuring its severity and impact varies in separate research studies. No single treatment deals with the symptom in all contexts, and careful assessment is essential to make suitable treatment selection.