Beyond Surgery: Navigating Postoperative Care for Cauda Equina Syndrome Through a Scoping Review.

OBJECTIVE: Cauda equina syndrome (CES) is a serious neurological injury that can result in permanent disability. Our objective was to review the evidence for rehabilitation strategies for CES in a scoping review. METHODS: A scoping review of the literature to identify rehabilitation strategies and their outcomes was performed. The search strategy used was: (Cauda equina syndrome) AND (treatment OR management OR intervention OR physio* OR bladder* OR neuro* OR stem cell OR repair OR rehab*) AND ("post?operat* OR post?surgical OR surgery"). MEDLINE, CINHAL, Prospero, Cochrane, ClinicalTrials.gov, EMBASE, Web of Science, PEDro, and eThos were searched. RESULTS: Eight studies of rehabilitation for CES were identified which assessed general rehabilitation, active rehabilitation in a spinal cord injury unit, multidisciplinary team involvement and follow-up, spinal manipulation, spinal cord stimulation and sacral nerve stimulation. Outcome measures used were inconsistent, study quality was low, and it was difficult to draw conclusions regarding the effectiveness of rehabilitation strategies. CONCLUSION: Despite the risk of devastating injury and a recent GIRFT pathway recommending rehabilitation post CES surgery, there is very limited literature on rehabilitation for CES. Future high-quality rehabilitation trials following CES surgery are needed to guide treatment decisions and optimise post-surgical outcomes.

Innovating Indwelling Catheter Design to Counteract Urinary Tract Infection.

BACKGROUND AND OBJECTIVE: Bacteriuria is anticipated in long-term indwelling catheter (IDC) use, and urinary tract infections (UTIs) and related issues are common. Defence mechanisms against infection are undermined by the presence of a Foley catheter, and adjustments to design could influence UTI risk. METHODS: We reviewed the various aspects of IDCs and ureteric stent designs to discuss potential impact on UTI risk. KEY FINDINGS AND LIMITATIONS: Design adaptations have focussed on reducing the sump of undrained urine, potential urinary tract trauma, and bacterial adherence. Experimental and computational studies on ureteral stents found an interplay between urine flow, bacterial microcolony formation, and accumulation of encrusting particles. The most critical regions for biofilm and crystal accumulation are associated with low shear stress. The full drainage system is the functioning unit, not just the IDC in isolation. This means reliably keeping the drainage system closed and considering whether a valve is preferred to a collection bag. Other developments may include one-way valves, obstacles to "bacterial swimming", and ultrasound techniques. Preventing or clearing IDC blockage can exploit access via the lumen or retaining balloon. Progress in computational fluid dynamics, energy delivery, and soft robotics may increase future options. Clinical data on the effectiveness of IDC design features are lacking, which is partly due to reliance on proxy measures and the challenges of undertaking trials. CONCLUSIONS AND CLINICAL IMPLICATIONS: Design changes are legitimate lines of development, but are only indirect for UTI prevention. Modifications may be advantageous, but might potentially bring problems in other ways. Education of health care professionals can improve UTIs and should be prioritised. PATIENT SUMMARY: Catheters used to help bladder drainage can cause urinary infections, and improvements in design might reduce the risk. Several approaches are described in this review. However, proving that these approaches work is a challenge. Training professionals in the key aspects of catheter care is important.

Towards a Reference Standard Definition of Urinary Tract Infection for Research.

Urinary tract infection (UTI) is among the most common human bacterial infections. In the context of increasing antibiotic resistance, there are many research efforts to improve the pathophysiological understanding, diagnosis, and treatment of UTI. Despite the high clinical relevance of UTI, there is high variability in definitions in the literature, making interpretation and comparison of research studies difficult, and even impossible in some cases. A recent Delphi consensus study generated a new reference standard definition for UTI that incorporates symptoms, pyuria, and urine culture results. This definition allows for designation of systemic involvement, and no longer categorizes UTIs as complicated or uncomplicated. The definition aligns with guidance from regulatory bodies for approval of UTI drugs. Implementation of a reference standard definition in the design and reporting of future investigations will allow better research design and interpretability within and outside the urology field. The new reference standard resolves some issues and offers a suitable way to unify methodology, and hence increase the potential strength of research in this area. There are some limitations and challenges for implementation, such as difficulties in establishing sensitivity and specificity values for the various settings in which the definition will be used. The inclusion of "probable" and "possible" UTI categories could be a problem in studies that require dichotomous outcomes. Nonetheless, the reference standard should be recommended until new developments become available, notably a more specific UTI biomarker than pyuria. Approaches to standardized diagnosis of catheter-associated UTIs remain unresolved. PATIENT SUMMARY: A new research definition for urinary tract infection (UTI) has been developed. Use of a single standardized definition in research will help in better design of research studies and comparison of results. Although the new definition will help in reducing the variability in UTI research reports, it has some limitations and there may be challenges to overcome before it is widely used.

The Urinary Microbiome Is a Potential Driver of Urinary Tract Pathology Through Multiple Mechanisms Including Deglucuronidation and DNA Damage.

Chronic urinary infection may have implications for disease because of reactivation of toxins in the urine or damage to bladder defences. Exploration of these possibilities requires a scrupulous scientific approach.

High-Performance Dopamine-Based Supramolecular Bio-Adhesives.

The need for wound closure or surgical procedures has been commonly met by the application of sutures. Unfortunately, these are often invasive or subject to contamination. Alternative solutions are offered by surgical adhesives that can be applied and set without major disruption; a new class of supramolecular-based adhesives provides potential solutions to some of these challenges. In this study, a series of polymers utilizing dopamine as a self-assembling unit are synthesized. It is found that these motifs act as extremely effective adhesives, with control over the mechanical strength of the adhesion and materials' tensile properties enabled by changing monomer feed ratios and levels of cross-linking. These materials significantly outperform commercially available bio-adhesives, showing yield strengths after adhesion at least two times higher than that of BioGlue and Tisseel, as well as the ability to re-adhere with significant recovery of adhesion strength. Promisingly, the materials are shown to be non-cytotoxic, with cell viability > 90%, and able to perform in aqueous environments without significant loss in strength. Finally, the removal of the materials, is possible using benign organic solvents such as ethanol. These properties all demonstrate the effectiveness of the materials as potential bio-adhesives, with potential advantages for use in surgery.

Bladder Outlet Obstruction Relief and Symptom Improvement Following Medical and Surgical Therapies for Lower Urinary Tract Symptoms Suggestive of Benign Prostatic Hyperplasia: A Systematic Review.

BACKGROUND AND OBJECTIVE: Symptomatic benefit and urodynamic obstruction relief represent relevant outcomes of therapies for lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). We summarized evidence from studies concurrently assessing variations in terms of symptoms severity and invasive urodynamic measures of obstruction following medical and surgical therapies for LUTS/BPH. METHODS: We performed a systematic review of PubMed, Scopus, and Web of Science in June 2023. KEY FINDINGS AND LIMITATIONS: We identified 29 publications: 14 (872 patients) and 15 (851 patients) studies addressing medical and surgical therapies, respectively. The mean percentage total International Prostate Symptom Score (IPSS) improvements ranged from -2.5% to 56.3% and from 35.1% to 82.1% following medical and surgical therapies, respectively. The corresponding mean percentage Bladder Outlet Obstruction Index (BOOI) improvements ranged from 7.8% to 53.5% and from 22.4% to 138.6%, respectively. Holmium laser enucleation of the prostate (HoLEP) provided IPSS improvements in the higher range and the greatest BOOI reduction. CONCLUSIONS AND CLINICAL IMPLICATIONS: Globally, based on available evidence, more pronounced symptomatic benefits are observed following treatments providing greater deobstructive effect. In detail, patients undergoing surgery exhibit greater IPSS and BOOI improvements than those receiving medical therapy.

Lower urinary tract symptoms in men: the TRIUMPH cluster RCT.

Background: Conservative therapies are recommended as initial treatment for male lower urinary tract symptoms. However, there is a lack of evidence on effectiveness and uncertainty regarding approaches to delivery. Objective: The objective was to determine whether or not a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for lower urinary tract symptoms to usual care. Design: This was a two-arm cluster randomised controlled trial. Setting: The trial was set in 30 NHS general practice sites in England. Participants: Participants were adult men (aged ≥ 18 years) with bothersome lower urinary tract symptoms. Interventions: Sites were randomised 1 : 1 to deliver the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions trial intervention or usual care to all participants. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions intervention comprised a standardised advice booklet developed for the trial from the British Association of Urological Surgeons' patient information sheets, with patient and expert input. Patients were directed to relevant sections by general practice or research nurses/healthcare assistants following urinary symptom assessment, providing the manualised element. The healthcare professional provided follow-up contacts over 12 weeks to support adherence to the intervention. Main outcome measures: The primary outcome was the validated patient-reported International Prostate Symptom Score 12 months post consent. Rather than the minimal clinically important difference of 3.0 points for overall International Prostate Symptom Score, the sample size aimed to detect a difference of 2.0 points, owing to the recognised clinical impact of individual symptoms. Results: A total of 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A difference in mean International Prostate Symptom Score at 12 months was found (adjusted mean difference of -1.81 points, 95% confidence interval -2.66 to -0.95 points), with a lower score in the intervention arm, indicating less severe symptoms. Secondary outcomes of patient-reported urinary symptoms, quality of life specific to lower urinary tract symptoms and perception of lower urinary tract symptoms all showed evidence of a difference between the arms favouring the intervention. No difference was seen between the arms in the proportion of urology referrals or adverse events. In qualitative interviews, participants welcomed the intervention, describing positive effects on their symptoms, as well as on their understanding of conservative care and their attitude towards the experience of lower urinary tract symptoms. The interviews highlighted that structured, in-depth self-management is insufficiently embedded within general practitioner consultations. From an NHS perspective, mean costs and quality-adjusted life-years were similar between trial arms. The intervention arm had slightly lower mean costs (adjusted mean difference of -£29.99, 95% confidence interval -£109.84 to £22.63) than the usual-care arm, and a small gain in quality-adjusted life-years (adjusted mean difference of 0.001, 95% confidence interval -0.011 to 0.014). Conclusions: The intervention showed a small, sustained benefit for men's lower urinary tract symptoms and quality of life across a range of outcome measures in a UK primary care setting. Qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. Limitations of the study included that trial participants were unmasked, with limited diversity in ethnicity and deprivation level. Additional research is needed to assess the applicability of the intervention for a more ethnically diverse population.. Trial registration: This trial is registered as ISRCTN11669964. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information.

Urinary problems among men become more common with age. Nearly one-third of all men aged > 65 years experience some urinary symptoms, which can have a substantial effect on their daily lives. Symptoms include needing to pass urine more often, urgently or during the night, and difficulties in passing urine. Men are usually diagnosed and treated by their general practitioner, and should be offered advice on controlling their symptoms themselves (e.g. lifestyle changes and exercises) before trying tablets or surgery. However, it is not known how helpful such advice is, and how general practices can effectively provide it. Thirty general practices in the West of England and Wessex took part in the study. Practices were split into two groups, with each practice providing either the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions care package or the practice's usual care to all of its patients in the trial. The TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package included a booklet of advice to help control urinary symptoms, with a nurse or healthcare assistant directing men to relevant sections according to their symptoms, and providing follow-up contacts. We mainly assessed the benefits of the TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package, compared with usual care, by using a questionnaire on urinary symptoms completed by participants. A total of 1077 men with urinary symptoms that bothered them joined the study. The main result was that men reported greater improvement in urinary symptoms with the TRIUMPH care package than with usual care, 12 months after joining the study. We also found that men receiving the TRIUMPH care package had a slight improvement in quality of life and outlook on their urinary symptoms. There was no difference between the two groups in the number of patients referred to hospital for treatment, the type, number and severity of side effects or cost to the NHS. Overall, the TRIUMPH care package was more effective in treating men with urinary symptoms than usual care by their general practice.

Cost-effectiveness of a primary healthcare intervention to treat male lower urinary tract symptoms: the TRIUMPH cluster randomised controlled trial.

OBJECTIVES: To estimate the cost-effectiveness of a primary care intervention for male lower urinary tract symptoms (LUTS) compared with usual care. DESIGN: Economic evaluation alongside a cluster randomised controlled trial from a UK National Health Service (NHS) perspective with a 12-month time horizon. SETTING: Thirty NHS general practice sites in England. PARTICIPANTS: 1077 men aged 18 or older identified in primary care with bothersome LUTS. INTERVENTIONS: A standardised and manualised intervention for the treatment of bothersome LUTS was compared with usual care. The intervention group (n=524) received a standardised information booklet with guidance on conservative treatment for LUTS, urinary symptom assessment and follow-up contacts for 12 weeks. The usual care group (n=553) followed local guidelines between general practice sites. MEASURES: Resource use was obtained from electronic health records, trial staff and participants, and valued using UK reference costs. Quality-adjusted life-years (QALYs) were calculated from the EQ-5D-5L questionnaire. Adjusted mean differences in costs and QALYs and incremental net monetary benefit were estimated. RESULTS: 866 of 1077 (80.4%) participants had complete data and were included in the base-case analysis. Over the 12-month follow-up period, intervention and usual care arms had similar mean adjusted costs and QALYs. Mean differences were lower in the intervention arm for adjusted costs -£29.99 (95% CI -£109.84 to £22.63) while higher in the intervention arm for adjusted QALYs 0.001 (95% CI -0.011 to 0.014). The incremental net monetary benefit statistic was £48.01 (95% CI -£225.83 to £321.85) at the National Institute for Health and Care Excellence UK threshold of £20 000 per QALY. The cost-effectiveness acceptability curve showed a 63% probability of the intervention arm being cost-effective at this threshold. CONCLUSIONS: Costs and QALYs were similar between the two arms at 12 months follow-up. This indicates that the intervention can be implemented in general practice at neutral cost. TRIAL REGISTRATION NUMBER: ISRCTN11669964.

Predicting Prostate Surgery Outcomes from Standard Clinical Assessments of Lower Urinary Tract Symptoms To Derive Prognostic Symptom and Flowmetry Criteria.

BACKGROUND: Assessment of male lower urinary tract symptoms (LUTS) needs to identify predictors of symptom outcomes when interventional treatment is planned. OBJECTIVE: To develop a novel prediction model for prostate surgery outcomes and validate it using a separate patient cohort and derive thresholds for key clinical parameters. DESIGN, SETTING, AND PARTICIPANTS: From the UPSTREAM trial of 820 men seeking treatment for LUTS, analysis of bladder diary (BD), International Prostate Symptom Score (IPSS), IPSS-quality of life, and uroflowmetry data was performed for 176 participants who underwent prostate surgery and provided complete data. For external validation, data from a retrospective database of surgery outcomes in a Japanese urology department (n = 227) were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Symptom improvement was defined as a reduction in total IPSS of ≥3 points. Multiple logistic regression, classification tree analysis, and random forest models were generated, including versions with and without BD data. RESULTS AND LIMITATIONS: Multiple logistic regression without BD data identified age (p = 0.029), total IPSS (p = 0.0016), and maximum flow rate (Qmax; p = 0.066) as predictors of outcomes, with area under the receiver operating characteristic curve (AUC) of 77.1%. Classification tree analysis without BD data gave thresholds of IPSS <16 and Qmax ≥13 ml/s (AUC 75.0%). The random forest model, which included all clinical parameters except BD data, had an AUC of 94.7%. Internal validation using the bootstrap method showed reasonable AUCs (69.6-85.8%). Analyses using BD data marginally improved the model fits. External validation gave comparable AUCs for logistic regression, classification tree analysis, and random forest models (all without BD; 70.9%, 67.3%, and 68.5%, respectively). Limitations include the significant number of men with incomplete baseline data and limited assessments in the external validation cohort. CONCLUSIONS: Outcomes of prostate surgery can be predicted preoperatively using age, total IPSS, and uroflowmetry data, with prognostic thresholds of 16 for IPSS and 13 ml/s for Qmax. PATIENT SUMMARY: This study identified key preoperative factors that can predict outcomes of prostate surgery for bothersome urinary symptoms, including which patients are at risk of a poor outcome.

The association of lower urinary tract symptoms with schizophrenia and its treatments: A narrative review.

BACKGROUND: A higher incidence of lower urinary tract symptoms (LUTS) in people with schizophrenia compared to the general population is often suggested. However, it is not clear whether this is a genuine association, and whether it is a direct result of schizophrenia itself, or a side-effect of certain antipsychotics. METHODS: We undertook a narrative review evaluating how the published literature reports the relationship between LUTS and schizophrenia and its treatments. We searched Embase, Ovid Emcare, and Ovid MEDLINE(R) ALL to August 2022, limited to the English language. We selected the following search terms: schizophrenia, schizophrenic, LUTS, overactive bladder, urinary urgency, urinary incontinence, overactive bladder, enuresis, nocturnal enuresis, and voiding dysregulation. We identified seven domains for assessment in advance of commencing the review. These were the categorization, description, and treatment status of schizophrenia; evaluation of LUTS; categorization of LUTS confounders; recapturing of the disease states of both schizophrenia and LUTS after therapies; assessment of the association between LUTS and schizophrenia and/or antipsychotics. RESULTS: The association between LUTS and schizophrenia was poorly described. The evidence was low quality and focused predominantly on urinary incontinence as an antipsychotic side effect, neglecting other LUTS. The status of schizophrenia was often incompletely characterized, and no papers made use of a bladder diary or LUTS-specific questionnaires to assess symptoms. No papers collected information about LUTS in patients not on antipsychotics, nor did any thoroughly evaluate the influence of confounding variables. Despite the tendency of symptoms and severity of both conditions to fluctuate over time, no studies fully assessed the status of both schizophrenia and LUTS at baseline, therapy initiation, and follow-up. CONCLUSIONS: It is not possible to state whether there is an association between LUTS and schizophrenia or its treatments. This review highlights the need to improve research and clinical management of the urinary tract in schizophrenia, with meticulously designed longitudinal studies.

Developing new ways to assess neural control of pelvic organ function in spinal conditions: ICI-RS 2023.

OBJECTIVES: Several central nervous system (CNS) centers affect muscle groups of the lower urinary tract (LUT) and anorectal tract (ART) via autonomic and somatic pathways, working in different modes (storage or expulsion). Hence spinal cord dysfunction can affect the LUT and ART by several possible mechanisms. METHODS: This review reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities of spinal dysfunction. RESULTS: Discussion focussed on the levator ani nerve, mechanisms underpinning sensory function and sensation, functional imaging, dyssynergia, and experimental models. The following key research questions were identified. (1) Clinically, how can we evaluate the levator ani muscle to support assessment and identify prognosis for effective treatment selection? (2) How can we reliably measure levator ani tone? (3) How can we evaluate sensory information and sensation for the LUT and the ART? (4) What is the role of functional CNS imaging in development of scientific insights and clinical evaluation? (5) What is the relationship of detrusor sphincter dyssynergia to renal failure? CONCLUSIONS: Spinal cord dysfunction can fundamentally disrupt LUT and ART function, with considerable clinical impact. The evaluation needs to reflect the full scope of potential problems, and new clinical and diagnostic approaches are needed, for prognosis and treatment. The preclinical science evaluating spinal cord function in both LUT and ART storage and elimination remains a major priority, even though it is a challenging experimental context. Without this underpinning evidence, development of new clinical evidence may be held back.

Development and first-in-human testing of FLUME urinary catheter with protected tip and relocated drainage holes.

Purpose: Evaluation of a catheter design which protects its tip with the retaining balloon when inflated, and has eyeholes at the base of the balloon to improve drainage. Materials and methods: Preclinical tests included assessment of retaining balloon performance, and microbiological blockage. Clinical testing evaluated short-term use and safety in hospital (stage 1) or the patient's usual residence (stage 2). Results: The retaining balloon supported static loads of 0.7kg, with reduced trauma when modelling forced evulsion. In vitro time to blockage with P. Mirabilis was significantly slower for FLUME compared with latex Foley catheters, but not the silicone Foley. Stage 1 testing (10 patients) confirmed balloon inflation, drainage, retention and removal, with no serious adverse events caused by catheterisation; one balloon failed to inflate, one patient could not be catheterised. Of five patients at stage 2, one had the catheter for 28 days without complication, one experienced spontaneous balloon deflation (14th day) and three needed early removal (blood clot, bypassing, difficulty connecting the drainage bag). Bacterial profiles of two FLUME catheters retained at least 2 weeks matched the Foley catheters. Acquired catheter colouration (two FLUME, one Foley) was not associated with biochemical change in the material. Conclusion: FLUME catheter performed well in preclinical blockage and balloon tests. Tests in 15 patients confirmed basic function and additional training was not needed for staff familiar with Foley catheterisation. Clinical issues commonly seen with catheters included failed catheterisation, clot blockage and bypassing. In addition, an unintended balloon deflation and a failure of bag connection occurred. Plain language summary: This article describes a new catheter design which aims to improve patient comfort and safety, and maximise bladder drainage, by protecting the bladder from the exposed catheter tip and by locating the drainage holes better. Various tests were done to check the catheter retaining balloon was safe and how well the catheter did when exposed to bacteria that could block it. The catheter was also used in people for the first time, to check it could be put in safely and functioned as intended. The results showed the FLUME catheter did well in the balloon and blockage tests. Tests in 15 patients confirmed basic function and showed placement was easy for staff familiar with conventional catheters. There were some clinical issues typical of urinary catheters and some possible improvements were identified.

Functional neuroimaging related to lower urinary tract sensations: Future directions for study designs and selection of patient groups: ICI-RS 2023.

OBJECTIVES: Neuroimaging studies have advanced our understanding of the intricate central nervous system control network governing lower urinary tract (LUT) function, shedding light on mechanisms for urine storage and voiding. However, a lack of consensus in methodological approaches hinders the comparability of results among research groups and limits the translation of this knowledge to clinical applications, emphasizing the need for standardized methodologies and clinical utilization guidelines. METHODS: This paper reports the discussions of a workshop at the 2023 meeting of the International Consultation on Incontinence Research Society, which reviewed uncertainties and research priorities to progress the field of neuroimaging in LUT control and dysfunction. RESULTS: Neuroimaging holds great potential for improving our understanding of LUT control and pathophysiological conditions. To date, functional neuroimaging techniques have not yet achieved sufficient strength to make a direct clinical impact. Potential approaches that can improve the clinical utilization of neuroimaging were discussed and research questions proposed. CONCLUSIONS: Neuroimaging offers a valuable tool for investigating LUT control, but it's essential to acknowledge the potential for oversimplification when interpreting brain activity due to the complex neural processing and filtering of sensory information. Moreover, technical limitations pose challenges in assessing key brain stem and spinal cord centers, particularly in cases of neurological dysfunction, highlighting the need for more reliable imaging of these centers to advance our understanding of LUT function and dysfunction.

Treatment of lower urinary tract symptoms in men in primary care using a conservative intervention: cluster randomised controlled trial.

OBJECTIVE: To determine whether a standardised and manualised care intervention in men in primary care could achieve superior improvement of lower urinary tract symptoms (LUTS) compared with usual care. DESIGN: Cluster randomised controlled trial. SETTING: 30 National Health Service general practice sites in England. PARTICIPANTS: Sites were randomised 1:1 to the intervention and control arms. 1077 men (≥18 years) with bothersome LUTS recruited between June 2018 and August 2019: 524 were assigned to the intervention arm (n=17 sites) and 553 were assigned to the usual care arm (n=13 sites). INTERVENTION: Standardised information booklet developed with patient and expert input, providing guidance on conservative and lifestyle interventions for LUTS in men. After assessment of urinary symptoms (manualised element), general practice nurses and healthcare assistants or research nurses directed participants to relevant sections of the manual and provided contact over 12 weeks to assist with adherence. MAIN OUTCOME MEASURES: The primary outcome was patient reported International Prostate Symptom Score (IPSS) measured 12 months after participants had consented to take part in the study. The target reduction of 2.0 points on which the study was powered reflects the minimal clinically important difference where baseline IPSS is <20. Secondary outcomes were patient reported quality of life, urinary symptoms and perception of LUTS, hospital referrals, and adverse events. The primary intention-to-treat analysis included 887 participants (82% of those recruited) and used a mixed effects multilevel linear regression model adjusted for site level variables used in the randomisation and baseline scores. RESULTS: Participants in the intervention arm had a lower mean IPSS at 12 months (adjusted mean difference -1.81 points, 95% confidence interval -2.66 to -0.95) indicating less severe urinary symptoms than those in the usual care arm. LUTS specific quality of life, incontinence, and perception of LUTS also improved more in the intervention arm than usual care arm at 12 months. The proportion of urology referrals (intervention 7.3%, usual care 7.9%) and adverse events (intervention seven events, usual care eight events) were comparable between the arms. CONCLUSIONS: A standardised and manualised intervention in primary care showed a sustained reduction in LUTS in men at 12 months. The mean difference of -1.81 points (95% confidence interval -0.95 to -2.66) on the IPSS was less than the predefined target reduction of 2.0 points. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11669964.

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.

Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications ("Sleep C.A.L.M.") in the evaluation and management of nocturia: A simple approach to a complex diagnosis.

INTRODUCTION: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. METHODS: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management. RESULTS: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. CONCLUSION: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets.

Stimulation of the Tibial nerve Repetitively to Improve Incontinence in Parkinson's Electronically (STRIPE trial): a randomised control trial of tibial nerve stimulation for bladder symptoms in Parkinson's disease using a self-contained wearable device.

BACKGROUND: Bladder symptoms are common in Parkinson's disease (PD), affecting half of all individuals. These have significant impact on quality of life as well as implications for morbidity, contributing to falls and hospital admission. The treatment of bladder symptoms can be complicated by the tendency to side-effects in people with PD including cognitive impairment and gait instability with anti-muscarinics. The development of new, better treatments is therefore warranted. Tibial nerve stimulation is a form of neuromodulation demonstrated to improve overactive bladder symptoms in non-neurogenic cohorts. Previously requiring hospital attendance, we aim to explore the use of this intervention using a simple device that can be used by patients at home. METHODS: STRIPE is a phase II randomised control trial of tibial nerve stimulation delivered by the Geko™ device, a small, self-adhesive neuromuscular stimulation device currently used for thromboembolism prophylaxis post-surgery. Active tibial nerve stimulation will be compared to sham stimulation, with participants blinded to treatment allocation and undertaking outcome assessment whilst still blinded. Participants will be asked to self-administer stimulation at home twice per week, for 30 min per session, over the course of 3 months. Primary outcome measure will be the International Consultation on Incontinence Overactive Bladder Questionnaire (OAB) at week 12. Secondary outcomes will include pre- and post-intervention bladder diary (frequency, urgency episodes, nocturia), patient perception of global change, bowel function and bladder-related quality of life. Participants will be recruited from the Proactive Integrated Management and Empowerment (PRIME) cross-sectional trial in which participants have been screened for bladder symptoms and invited to take part, as well as clinician referral from around the region. DISCUSSION: This trial will involve a randomised control trial of a novel and easy to use method of delivering tibial nerve stimulation for PD in the patient's own home. This may potentially have huge benefit, avoiding the problems with side effects that can be seen with anti-muscarinics and providing a new potential modality of treatment. TRIAL REGISTRATION: ISRCTN11484954. Registered on 22 June 2021.

Selective reduction of neurotransmitter release by cAMP-dependent pathways in mouse detrusor.

Parasympathetic nerve-mediated contractions of detrusor smooth muscle are generated by ATP and acetylcholine (ACh) release from efferent nerve terminals. In humans, ACh is responsible for detrusor contractions in normal human bladders, whereas ATP has an additional role in overactive bladder pathologies. The ATP metabolite, adenosine, relaxes nerve-mediated contractions, with a potential action via presynaptic adenosine A1 receptor activation and subsequent suppression of neuronal ATP release. We investigated the effect of A1 receptor activation and downstream cAMP-dependent pathways on nerve-mediated ATP and ACh release, and detrusor contraction in mouse detrusor. Bladders from male C57BL/6 mice (12 wk) were used for in vitro experiments. Upon electrical field stimulation of intact preparations (detrusor and mucosal layers), ATP or ACh release was measured simultaneously with tension recordings. Activation of A1 receptors by adenosine or exogenous agonists reduced the lower frequency component of nerve-mediated contractions and neuronal ATP release. The A1 receptor antagonist abolished these effects. A1 receptor activation inhibits adenylyl cyclase (AC) activity and cAMP generation. The effect of A1 receptor activation was mimicked by a PKA antagonist but not by modulators of exchange proteins activated by cAMP, demonstrating that modulation of nerve-mediated ATP release is via PKA. Adenosine had no effect on ACh release or the higher frequency component of nerve-mediated contractions. Differential regulation of neurotransmitter release is possible at the detrusor nerve-muscle junction, as demonstrated by A1 receptor activation, and downstream inhibition of AC, cAMP generation, and PKA. The ability to specifically attenuate ATP release offers a potential to target purinergic motor pathways enhanced in overactive bladder pathologies.