Nocturia

Over 90% of adult males develop lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction by age 80, rendering benign prostatic hyperplasia (BPH) the most common proliferative abnormality in humans. LUTS secondary to BPH negatively impact the quality of life of 210 million men globally, accounting for significant life years lost, in addition to costing the US healthcare system over $4 billion per year. Medical therapy for the management of BPH, which includes α-adrenergic blockers (e.g., doxazosin, terazosin, tamsulosin or alfuzosin) and 5α reductase inhibitors (5ARI, i.e., finasteride or dutasteride) targets both stromal and epithelial cells in the prostate gland. Utilization of 5ARI remains ineffective in many patients, leading to invasive therapies in many patients. 5ARI's are the only class of BPH-related drugs that reduce prostate size for the alleviation of LUTS. However, the Medical Therapy of Prostatic Symptoms (MTOPS) trial, which randomized 3047 men, showed that 34% of BPH patients did not respond to individualized treatment with finasteride or doxazosin, while combining the 5ARI and α-blocker relieved LUTS in 66% of BPH patients. Resistance to 5ARI therapy is a major factor limiting the effectiveness of these agents in the management of BPH. Therefore, understanding the molecular pathogenesis of 5ARI resistance is a High-Priority Recommendation of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Prostate Research Strategic Plan. However, it is not yet possible to predict responders vs. non-responders to 5ARI therapy, which creates a significant gap in our ability to effectively manage patients with BPH. 5α reductase (5-AR) plays a critical role in the normal development of the human prostate and in the pathogenesis and progression of prostatic diseases. There are three types of 5-AR isozymes, Steroid 5 Alpha-Reductase 1, 2 3 (SRD5A1, SRD5A2 and SRD5A3), which are encoded by three distinct corresponding genes, SRD5A1, SRD5A2 and SRD5A3. Many studies suggest that all three 5-AR enzymes are expressed in prostate tissues; however, SRD5A2 is the predominant enzyme responsible for prostate development and growth. In addition, since the most commonly prescribed 5ARI, finasteride, is an inhibitor of SRD5A2, regulation of SRD5A2 will remain the focus of this study. It was previously shown that the mechanism of somatic suppression of SRD5A2 during adulthood is dependent on epigenetic changes in the promoter region of the SRD5A2 gene. DNA methylation is one of the most common epigenetic mechanisms affecting gene expression. Methylation of Cytosine-Phosphate-Guanine (CpG) islands has been associated with the regulation of genes during development, cancer initiation, and metastasis. Since the prostate is the only solid organ that grows during adulthood as a result of androgen exposure, it can be considered a benign tumor growth throughout adulthood. Therefore, similar to the neoplastic initiation and progression of many cancers, including prostate cancer, epigenetic changes and variable expression of SRD5A2 in benign prostate tissue is a plausible molecular mechanism. Finasteride, the most commonly prescribed 5ARI, is an inhibitor of SRD5A2. Finasteride has been shown in several large clinical trials to reduce prostate size by 20%, improve urinary flow rate, and improve urinary bothersome symptom scores in men suffering from bladder outlet obstruction caused by BPH. Despite their widespread use and clinical effectiveness, 25% to 30% of patients are resistant to the therapeutic effects of 5ARIs and another 5% to 7% of patients develop worsening symptoms and ultimately may require surgery. Given their age and comorbidities, these patients are often not ideal candidates for surgery. Therefore, understanding the mechanisms of 5ARI treatment failure may pave the way for the development of new medical therapies appropriately targeted to these specific patient groups and is a desirable way to move forward with precision medicine. This proposed work is based on the premise that epigenetic changes to SRD5A2 account for the significant number of patients who are unresponsive to 5ARI therapy. The goal is to assess SRD5A2 methylation and expression as a gene signature to predict which patients will respond to 5ARI therapy. The information gained from this proposal will pave the way toward the development of predictive biomarker assays that can be used to evaluate resistance to BPH-related therapies and allow clinicians to select alternate therapies for managing the most common proliferative disorder affecting men worldwide.

In this trial, we will employ a randomized controlled trial design to determine if women with overactive bladder (OAB) treated with the RiSolve prescription digital therapeutic (PDTx) demonstrate greater improvement in OAB-related health as compared to standard behavioral education with informational handouts. RiSolve is a digital therapeutic device intended to provide behavioral therapy and cognitive behavioral therapy (CBT) for adult women who have been diagnosed with OAB, which includes urinary urgency with or without urge urinary incontinence (UUI), urinary frequency, nocturia, and mixed incontinence with predominant OAB symptoms. RiSolve is indicated as an 8-week treatment to reduce the symptoms of OAB. For the purposes of this trial, the primary outcome to determine improvement in OAB-related health will be defined as achieving the MID (defined as an improvement of 10 points or more) on the OAB-q SF Symptom Severity subscale after 8 weeks of treatment. Secondary outcomes will include achieving the MID on the OAB-q SF Health-Related Quality of Life subscale, meeting the patient's acceptable symptoms state (PASS) on the Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Improvement (PGI-I), and improvements in frequency, nocturia and urge urinary incontinence (UUI) on a 3-day bladder diary and on the ICIQ-FLUTS. Participants will be randomized to either PDTx therapy (active) or standard treatment of behavioral education (control). Participants randomized to control will have the option to crossover to PDTx after the initial 8 weeks of the trial if desired. Participants will continue to be followed and asked about their symptoms at 6 and 12 months. The impact of this trial has enormous potential to improve treatment of OAB. The ability to offer behavioral therapy via PDTx will reduce patient burden while simultaneously increasing quality of life for women suffering from OAB and decreasing provider burden. The high-quality data from this study will be used to support a marketing application with the FDA through the De Novo pathway for an accessible, low-burden, efficient intervention to help millions of women currently suffering from this burdensome condition.

A- Background: Lower urinary symptoms (LUTS) affect many older men and their frequency and severity increase with age. In the age group between 65 and 79 years the rate of men with moderate and severe LUTS is 20 - 25%. This rate increases to 90% in men over 80 years old. The complaints are potentially associated with a considerable impairment of the quality of life. LUTS in older men are commonly caused by a bladder outlet obstruction (BOO) secondary to benign prostatic enlargement (BPE). The histological term "benign prostatic hyperplasia" (BPH) is frequently used in literature and clinical practice as a synonym for this diagnosis. Surgical therapy of BPH has continuously evolved in recent years. Transurethral resection of the prostate (TUR-P) is the current gold standard for the endoscopic management of small to medium prostate volumes. The development of laser-assisted transurethral and other innovative techniques (e.g. REZUM, UROLIFT) have supplemented the surgical spectrum. For large prostate volumes above 80 mL, transurethral laser enucleation (holmium, thulium) is widely established in clinics as an alternative to conventional open surgical simple prostatectomy. One of the latest technologies for transurethral prostate desobstruction is the Aquablation therapy, first described in 2015 (AQUABEAM®, PROCEPT BioRobotics, Redwood Shores, CA, USA). The device applies an ultrasound-guided water jet that precisely ablates the prostate tissue. The second generation of this robot-assisted system is CE-certified and gained market access in Australia, New Zealand, Canada, and the United States. This device for this study is the third generation of the AQUABEAM Robotic System, which is currently only commercialized in the US. In recent years, the technology has been evaluated in a total of three monocentric and three multicentric prospective studies. So far, one randomized controlled trial (RCT) has been conducted - the WATER study. The multi-center study, designed as a double-blind, randomized controlled trial, compares the Aquablation therapy with the gold standard TUR-P in small and medium prostate sizes (30-80 mL). The primary endpoint was defined as IPSS change 6 months postoperatively. The primary safety endpoint was stated as the rate of adverse events three months after surgery with a Clavien-Dindo grade ≥ 2 or a Clavien-Dindo grade 1 with persistent dysfunctions such as incontinence, erectile dysfunction or ejaculation disorders. The WATER study confirmed the non-inferiority of the Aquablation therapy regarding the two primary endpoints. The results for the secondary endpoints erectile function (IIEF) and ejaculatory function (MSHQ-EjD) were significantly better in the Aquablation-arm. Interestingly, a subgroup analysis of the WATER patient collective revealed significantly better results regarding IPSS reduction, the primary safety endpoint and the rate of postoperative anejaculation for patients with medium prostate volumes (50-80 mL). To date, the only prospective study focusing on large prostate volumes is the WATER II trial. In the multi-center and single-arm study design, the safety and efficacy of the procedure was investigated for prostate sizes between 80 and 150 mL. The 1-year follow-up data were published in July 2019. The functional outcome in terms of IPSS reduction, quality of life improvement and Qmax improvement was comparable to previously published data of laser enucleation. The incontinence rate was lower com-pared to the published data for holmium laser enucleation and comparable to the data for open surgical prostate adenoma enucleation. Bleeding complications with necessary blood transfusion were less frequent compared to the data for open surgery but more frequent compared to the data for holmium laser enucleation. In 81% of the sexually active men in this collective, antegrade ejaculation was maintained, which significantly exceeds the published data of the alternative techniques. The main advantage of the method is the short operation time. Since the time of the resection itself is only margin-ally extended as the prostate volume increases, the time advantage is particularly pronounced in the treatment of large prostates. In the WATER II study, the mean procedure time was 37 min (mean resection time: 7.8 min) and was thus significantly shorter than the published data for open surgery (95 min) and laser enucleation (91 min). The safety and effectiveness of the device has been established in the previous generation of the device: AQUABEAM Robotic System P1G2. The P1G3 system is considered substantially equivalent to the P1G2 system. The indications for use, intended patient population, intended user, safety and efficacy profile of the device remains unchanged for P1G3 compared to P1G2. B- Clinical experience: The safety and effectiveness of the AQUABEAM Robotic System P1G3 is equivalent to System P1G2, which has been evaluated in two pivotal US FDA IDE trials, the WATER study (ClinicalTrials.gov ID: NCT02505919), and the WATER II study (ClinicalTrials.gov ID: NCT03123250). * The WATER study was a prospective multi-center randomized double-blind clinical trial comparing Aquablation of the prostate with the AQUABEAM Robotic System with standard transurethral resection of the prostate (TURP) for the treatment of Lower Urinary Tract Symptoms (LUTS) in prostate size 30-80 cc. One hundred and eighty-four (184) study subjects were randomized at the ratio of 2:1 (Aquablation: TURP). The primary endpoint was defined as IPSS change 6 months postoperatively. The primary safety endpoint was stated as the rate of adverse events three months after surgery with a Clavien-Dindo grade ≥ 2 or a Clavien-Dindo grade 1 with persistent dysfunctions such as incontinence, erectile dysfunction or ejaculation disorders. The WATER study confirmed the non-inferiority of the AQUABEAM Robotic System regarding the two primary endpoints. The results for the secondary endpoints erectile function (IIEF) and ejaculatory function (MSHQ-EjD) were significantly better in the Aquablation-arm. Interestingly, a subgroup analysis of the WATER patient collective revealed significantly better results regarding IPSS reduction, the primary safety endpoint and the rate of postoperative anejaculation for patients with medium prostate volumes (50-80 cc). Three-year study data from the study provided high-quality evidence of the Aquablation therapy for LUTS due to BPH in men with prostate sized between 30 and 80 cc with clinical efficacy and durability similar to TURP. * To date, the only prospective study focusing on large prostate volumes is the WATER II study. In the multicenter and single-arm study design, the safety and efficacy of the procedure was investigated for prostate sizes between 80 and 150 cc. The 1-year follow-up data were published in July 2019. The functional outcome in terms of IPSS reduction, quality of life improvement and Qmax improvement was comparable to previously published data of laser enucleation. The incontinence rate was lower compared to the published data for holmium laser enucleation and comparable to the data for open surgical prostate adenoma enucleation. Bleeding complications with necessary blood transfusion were less frequent compared to the data for open surgery but more frequent compared to the data for holmium laser enucleation. In 81% of the sexually active men in this collective, antegrade ejaculation was maintained, which significantly exceeds the published data of the alternative techniques. The main advantage of the method is the short operation time. Since the time of the resection itself is only marginally extended as the prostate volume increases, the time advantage is particularly pronounced in the treatment of large prostates. In the WATER II study, the mean procedure time was 37 min (mean resection time: 7.8 min) and was thus significantly shorter than the published data for open surgery (95 min) and laser enucleation (91 min). The Aquablation procedure is a safe and effective, robotically executed and globally reproducible surgical option for the treatment of BPH-related LUTS in men with large prostate glands with continued durable outcomes at 3 years coupled with short operative times, limited hospitalization and low retreatment rates. C- Clinical investigation design 1. Objectives: Determine the safety and effectiveness of the surgical treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) when using the AQUABEAM Robotic System P1G3 and Apogee 2300 Ultrasound System. 2. Sample size: Minimum fifty (50) subjects will be enrolled and treated in the study. Up to an additional 10 subjects may be enrolled and treated as roll-in subjects to familiarize the surgeon with the AQUABEAM Robotic System P1G3 prior to treating the study subject. 3. Study duration: Enrollment is expected to take 12 months. Each subject is followed post-operatively through 3 months. Note the investigation for the Apogee 2300 ultrasound system and accessories is considered completed after the enrollment goal is achieved and all subjects are discharged. Total study duration from the first subject enrolled to the last subject completing the last study follow-up visit is expected to take less than two years. 4. Number of sites: At minimum 1 clinical site in Canada will participate in the study. 5. Point of enrollment: Each patient will be assigned a study ID after signing the informed consent form. * Investigators will be responsible for obtaining consent using the current study-specific, REB-approved consent documents prior to any baseline testing for eligibility that goes beyond standard care. * Reasons for screen fail will be recorded in study specific form (e.g., did not meet study selection criteria; decline further participating in the study prior to treatment, etc.). * Participants will be consented in a manner understandable by the intended patient population and providing adequate time to address any questions or concerns. * Documentation of the consenting process and the signed/dated consent documents will be filed in the study Trial Master File. An informed consent form must be signed by each patient prior to study enrollment. Informed consent will be obtained according to the Declaration of Helsinki ("Ethical Principles for Medical Research Involving Human Subjects", The World Medical Association Declaration of Helsinki (64th WMA General Assembly, Fortaleza, Brazil, October 2013), requirements of the standard ISO 14155:2020 ("Clinical investigation of medical devices for human subjects-Good clinical practice"), and individual institution guidelines. Re-consent will be required where changes are implemented, new information becomes available, or as required by regulations, and re-consent is needed. 6. Study visits and exams: 6.1. Study visits: Screening and Baseline visit: Potential study participants will undergo screening at the study center. Patients must avoid taking non-steroidal anti-inflammatory agents (NSAIDs) or antiplatelet agents (e.g., aspirin, clopidogrel) prior to surgery per standard of care. Surgical procedure visit: Aquablation therapy will be performed under general or spinal anesthesia at the operating surgeon's discretion. The study surgical procedures will be performed within 90 days of baseline tests.To minimize bleeding, focal cauterization and resection of ablated tissue should be performed for all subjects following the AQUABEAM Handpiece removal. At the end of the procedure, a foley catheter should be placed, continuous bladder irrigation (CBI) should be initiated immediately following the catheter placement and shall continue in the PACU for up to 4 hours. If the degree of hematuria is not clinically significant (grade I-III) after clamping irrigation, subjects will be discharged home. A decision algorithm will be used to discharge subjects. If a patient was discharged home with a catheter, the catheter will be removed at the investigational site. Follow-up visit: All subjects in this study are intended to be discharged the same day of the Aquablation procedure. The subject will return at 3 months for a final follow up visit, which concludes the subject's participation in the study. 6.2. Study assessments (standard of care): All are considered standard examinations prior to transurethral prostate tissue resection surgery. Uroflow (Qmax) and PVR: at baseline and the 3-month follow-up visit, the subject will undergo measurement of urinary flow rate (Qmax), urinary mean flow rate (Qmean), total voided volume (TVV), and post-void residual volume (PVR). For a uroflow test to be valid, the voided volume must be ≥ 125 ml. If the total voided volume is less than 150mL, the voided volume must be equal to or greater than 50% of the bladder capacity (defined as voided volume + PVR). The patient can repeat the test if necessary. International Prostate Symptom Score (IPSS): IPSS is a validated measure of urinary symptoms due to BPH. Subjects will complete an IPSS form at baseline and at the 3-month follow-up visit. Transrectal ultrasound (TRUS): TRUS is performed to measure patient's prostate size at baseline.TRUS should be performed using the site's standard ultrasound equipment D- Risk/benefit analysis Potential benefits: The primary potential benefit of participation is the potential occurrence of successful treatment of lower urinary tract symptoms using the AQUABEAM Robotic System. Additional benefits may be decreased need for urinary catheter postoperatively, faster overall recovery, improved urinary flow and lower residual volumes, low rate of postoperative incontinence and maintenance of ejaculatory function In a patient with urinary retention, the need for catheter use (indwelling or intermittent) may be reduced. Potential risks: As with any surgical urologic procedure, potential risks of the Aquablation procedure include: * Anesthesia risk * Bladder or prostate capsule perforation * Bladder neck contracture * Bleeding * Bruising * Dysuria * Electric shock/burn * Embolism * Incontinence or overactive bladder * Infection * Penile or pelvic pain * Rectal incontinence / perforation * Sexual dysfunction, including ejaculatory and erectile dysfunction * TUR syndrome * Urethral damage causing false passage or stricture * Urinary Retention Risk mitigation: The following steps have or will be taken by the manufacturer and sponsor-site to control or mitigate the risks during the course of this study: * The use of standard medical grade materials that have been thoroughly characterized and tested to assure biocompatibility. * Extensive pre-clinical evaluation including in vitro bench testing and two US FDA IDE studies. * The well-established transurethral prostatic tissue resection procedure and techniques to be used. * The ability to quickly and safely abort the study procedure; the physician may elect to discontinue the use of the device at any time in favor of an alternate device/treatment. E- Ethical oversight: This study shall be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki ("Ethical Principles for Medical Research Involving Human Subjects", 18th World Medical Association General Assembly, Helsinki, Finland, June 1964) and in compliance with the standard ISO 14155:2020 ("Clinical investigation of medical devices for human subjects-Good clinical practice") as well as any regional or national regulations, as appropriate.This study shall not begin until the required approval/favorable opinion from the Ethics Committee or regulatory authority have been obtained, if appropriate. Any additional requirements imposed by the Ethics Committee or regulatory authority shall be followed, if appropriate F- Data collection and storage: Case report forms (CRFs) will be used to collect all subject data during the study. Data will be stored for 10 years as per institution requirements. G- Funding: The present study in funded by PROCEPT. H- Conflict of interest: Although this is an investigator-initiated study, it should be noted that the principal investigator (Dr Naeem Bhojani) is a consultant for PROCEPT.

Parkinson's disease (PD) is the second most common degenerative neurological disease in the elderly. PD is predominantly a movement disorder. In addition, PD is associated with non-motor and autonomic symptoms. Over 75% of PD patients, experience lower urinary tract symptoms (LUTS), one of the most common autonomic symptoms. LUTS consists of urgency, frequency and nocturia with or without urinary incontinence (UI). More than 60% of PD patients experience nocturia. LUTS have a negative impact on Quality of Life(QoL), increases the risk of falls are a barrier to exercise and may lead to early admission into care. Therefore, this potentially increases healthcare related costs. First treatment options for LUTS in the general population are conservative therapy and medication. Conservative therapy consists of e.g., behavioral advice, bladder training, pelvic floor muscle exercises provided by a pelvic physical therapist(PPT) and, electrical stimulation(ES). Knowledge of the effectiveness of conservative treatment options for LUTS in PD is limited. Although ES is used effectively in patients with LUTS, it has not yet been studied in PD patients. ES has hardly any side effects, but there is uncertainty about optimal ES parameters. Objective: to study the effectiveness of pelvic physical therapy and ES in patients with PD suffering from LUTS. Study design: Randomized Controlled Trial (RCT). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Questionnaires are online, allowing participants to complete the questionnaires at home at a convenient time. Participants may have direct benefits of participating in this study. Participants included in the study will have two additional visits to a research PPT that will last one hour each, at baseline and after treatment. During this visit, a digital pelvic floor muscle (PFM) assessment and an EMG measurement of the PFM will be performed. EMG measurement will be done with a small anal- or vaginal probe. No risks are associated with the use of this probe. Participants will be referred to local PPT's close to the subjects home address for the treatment sessions. Intervention: eight treatment sessions of 30 minutes pelvic physical therapy over a 10-week period. The intervention consists of bladder- and behavioral advice, pelvic floor muscle exercises (PFME), urge suppression techniques, biofeedback and ES with an intra anal or intra vaginal probe. The group is divided into three groups. Group 1: ES with small pulse duration, group 2: ES with broad pulse duration, group 3: (control group) receiving sham ES. No adverse events are expected since pelvic physical therapy and ES in LUTS is usual care in the general population in the Netherlands. Expected burden for the participants is very low.

Due to a growing and aging population, cases of benign prostatic hyperplasia (BPH) have been on a steady rise. Studies show that by age 80, 90% of men experience BPH. (Garraway, Lee, Collins, 1991) Thus, treatment of BPH is one of the most performed surgical procedures in urology. Over the past few decades there have been an increasing development of newer surgical treatment options. Additionally, the outcome parameters for BPH treatments have been somewhat standardized. The purpose of this study is to create an ongoing prospective registry to record demographic data and clinical outcomes after medical therapy or different surgical interventions for BPH. The specific aims of the registry are to analyze demographic patterns and baseline characteristics of men undergoing surgical and medical treatments for BPH, to assess global practice patterns for various surgical and medical treatments of BPH, and to assess key outcomes for uni- and multi-modal treatments of BPH. The ongoing global registry will provide important baseline data, functional outcomes, and complications following medical and/or surgical intervention for men with symptomatic BPH. The intention of the registry is to provide real world usage data that may be used for future investigations. It will allow providers to identify areas of interest, areas of unusually low usage or areas of unusual preference on a global scale. It will also shed light on global preferences for unimodal or multimodal approaches to treatments. The registry has been developed using novel database technology, providing an easy-to-use user interface, which enables future creation of patient portals and Electronic Medical Record (EMR) integration. As this is not an experimental setting, there will be no interventions made on behalf of the registry. This is a prospective longitudinal ongoing registry. The study will include medical records of all men ≥18 years old who have a primary diagnosis of BPH with Lower Urinary Tract Symptoms (LUTS) that are prescribed BPH medications, or a surgical intervention. Data extraction includes baseline data, peri-operative data, and follow-up data. Baseline data includes validated patient reported outcome tools, including International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM), Male Sexual Health Questionnaire - Ejaculatory Dysfunction (MSHQ-EjD), as well as Quality of Life (QoL), maximum flow rate (Qmax), Post-void residual (PVR), Prostate Specific Antigen (PSA), and Testosterone. Complications such as Bleeding, Urinary Tract Infection (UTI), Incontinence, Stricture, Retrograde ejaculation, and Erectile Dysfunction (ED) are also tracked from Baseline through Follow-up. The registry will run for 3 years with no end point for follow-up. For three years, various research studies will be formulated, and the results will be published. The possibility of extending the study for continued follow-up will be evaluated. A built-in quality control using data validation during the input process decreases the chance that invalid data will be entered or that datapoints will be omitted. Periodic audits will be performed to verify accuracy of source data by our audit committee based on our audit committee guidelines. Records and cases of all men with a primary diagnosis of BPH with LUTS that are prescribed BPH medications, or a surgical intervention will be identified and included in the registry. All data is hashed (i.e., protected from decryption) except for a medical record number (MRN), which will be used to add follow-up data to the patient's record. This number is encrypted and linked to the hashed and randomly generated institution code. For security purposes, biographical information is not saved on the registry. The registry provides secure access to registered users using a web browser. Registrations are site-specific, which means that users can only access the data that is specific to their own site. The registry application and databases are hosted on secure, encrypted servers behind a firewall. They can only be accessed by registered users via a specific port.

Overactive bladder (OAB) is a common and often debilitating condition in both men and women. OAB symptoms including urinary frequency, urgency, and/or urge incontinence (UI), have been found to negatively impact quality of life. Due to side effects and the lack of patient compliance to pharmacologic treatments for OAB, non-pharmacologic treatments are in high demand for this condition. Neuromodulation therapies have become increasingly popular for the treatment of overactive bladder in men and women. These neuromodulation therapies work in treating OAB by stimulating the pudendal nerve. The BTL EmsellaTM (Emsella Chair) is a conservative neuromodulation therapy that may have a role for patients who are not surgical candidates or who desire a noninvasive treatment option. The ideal treatment for OAB is still lacking. Many patients are interested in pursuing conservative treatment options. The Emsella chair may have a role for patient who do not desire surgery found with SNM or desire a noninvasive treatment option. The Emsella chair is approved as a treatment for stress urinary incontinence (SUI). Overactive bladder patients may benefit from treatment. The Emsella chair generates electromagnetic stimulation which is able to penetrate deep into the pelvic floor muscles inducing stimulation and providing rehabilitation for weak pelvic floor muscles. The Emsella chair is a novel high-intensity focused electromagnetic (HIFEM) technology for the treatment of SUI, in addition to other pelvic floor related disorders. HIFEM technology induces deep pelvic floor muscle contractions designed to deliver the equivalent of 11,200 Kegel exercises over 28 minutes.

One fourth of men older than 70 years have moderate to severe lower urinary tract symptoms (LUTS) that impair their quality of life (QOL). This is most frequently caused by benign prostatic hyperplasia (BPH). Transurethral resection of the prostate (TURP) is still regarded as the gold standard for surgical treatment of BPH. However, TURP is only an option for patients fit for general anesthesia and can result in complications. Consequently, several less invasive procedures have been developed, as prostatic artery embolization (PAE) and transurethral microwave thermotherapy (TUMT). The objective of this clinical trial is to assess if transurethral microwave thermotherapy (TUMT) is non-inferior to prostatic artery embolization (PAE) in reducing lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). The primary aim is to compare LUTS 6 months after the TUMT and PAE procedures, measured by the International Prostate Symptom Score (IPSS). Both treatments have previously been shown to reduce LUTS with a similar post-procedure outcome in mean IPSS. However, the previous studies differed in baseline characteristics thus it is currently unknown if they perform equally well. Secondary objectives include comparison of patient reported and functional outcomes at short- and long-term follow-up. The trial importantly includes analysis of patient-reported outcome measures of satisfaction with treatment, quality of life, incontinence, erectile and ejaculatory function, as well as evaluation of uroflowmetry, prostate volume, prostate specific antigen, catheter dependency, side effects, hospital admissions and re-treatment rate. This study is designed as a multi-centre, non-inferiority, open label randomised clinical trial. Patients will be randomised with a 1:1 allocation ratio between treatments using the randomisation module in REDCap. The primary outcome is expected to be evaluated by a 95% confidence interval against the predefined threshold of +3 points in IPSS for inferiority. Secondary outcomes will be presented descriptively and assessed by students T-test, Chi-squared test and linear mixed models. The patient reported outcomes will be obtained by standardized validated surveys and functional outcomes, side effects and re-treatment rates will be measured at 1 month, 3 months, 6 months, 1 year, 2 years and 5 years post procedure. Assuming a difference in mean IPSS after treatment of 1 point with an standard deviation (SD) of 5 and a non-inferiority margin set at the border for a clinically non-meaningful difference of 3 points, the calculated sample size was 100 patients per arm. To compensate for 10% drop-out the study will include 220 patients. An interim analysis will be performed for every 50 cases. TUMT and PAE are minimally invasive procedures performed in an outpatient setting that have been shown to reduce LUTS in a similar magnitude. To date there are no randomised clinical trials comparing PAE to TUMT, which is problematic as the most prominent problem with minimally invasive BPH treatment is the lack of proper selection of candidates for a specific procedure. Non-inferiority of TUMT to PAE is expected, with analysis of the secondary outcomes, the investigators aspire to contribute to a better understanding of patient selection for either treatment.

For some time now, patient compliance with paper bladder diaries is being questioned. Paper bladder diaries are often incomplete, unreliable and/or of low quality. Multiple electronic bladder diaries have been developed to overcome some of the limitations associated with paper bladder diaries. However, based on several comparison studies between paper and electronic bladder diaries, it is not clear whether an electronic format alone is truly superior to the paper format. The investigators want to introduce and evaluate the feasibility of a new type of bladder diary: an automated bladder diary. In contrast to an electronic diary, an automated diary automatically registers voiding data using a connected measuring device. An electronic diary simply eliminates the use of paper, but the patient still needs to measure the voided volumes with a urinary container and manually enter them in the electronic diary. The investigators believe an automated diary may lead to improved patient compliance by reducing the required efforts from the patient and instead provide guidance and prompts.

This registry study aims to collect data on efficacy and safety of different treatments of benign prostatic enlargement (BPE) and lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH-LUTS). Clinical, patient reported and imaging data that are assessed in clinical routine will be prospectively collected. All patients that are treated for BPE / BPH-LUTS at our institution will be included if they provide written informed consent. This registry enables us to compare novel treatment option (e.g. prostatic artery embolization; PAE) to established interventions (e.g., TURP, HoLEP, open prostatectomy, ThuLEP, Thulium laser vaporization, TUIP) regarding safety and efficacy.

Nocturnal Enuresis (NE) is defined as the involuntary passage of urine during sleep past the age of usual control, which is considered a developmental age of 5 to 7 years. NE is a common problem that causes distress to both children and their families. It has an adverse impact on behavior and social life, affects self-esteem, and can result in poor emotional well-being. In Egypt, the prevalence of NE in primary school children is about 15.4%. The family history was seen to have had a markedly significant impact on the occurrence of NE in the studied children. The mainstay of treatment is urotherapy with information and psychoeducation about normal lower urinary tract function, the underlying cause of MNE, disturbed bladder dysfunction in the child with NMNE, and instructions about therapeutic strategies. Alarm therapy and desmopressin are effective in randomized trials. Children with NMNE first need treatment of the underlying daytime functional bladder problem before treatment of nocturnal enuresis.