Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Quality of Web-Based Patient Information on Robotic Radical Cystectomy Remains Poor: A Standardized Assessment.

INTRODUCTION: Patients frequently use the Web to obtain health information. This trend increased during the COVID19 pandemic. We aimed to assess the quality of Web-based information on robot-assisted radical cystectomy. METHODS: A Web search was conducted in November 2021 using the 3 most common engines (Google/Bing/Yahoo). Search terms were "robotic cystectomy," "robot-assisted cystectomy," and "robotic radical cystectomy." The top 25 results generated for each term by each search engine were included. Duplicate pages, pages advertised, and pages with paywall access were excluded. Selected websites were classified as academic, physician, commercial, and unspecified. The quality of site contents was evaluated using the DISCERN and Journal of the American Medical Association (JAMA) assessment instruments, and HONcode (Health on the Net Foundation) seal and reference presence. Flesch Reading Ease Score was used for readability assessment. RESULTS: Of the 225 sites examined only 34 were eligible for analysis, including 35.3% classified as "academic," 44.1% "physician," 11.8% "commercial," and 8.8% "unspecified." Average±SD DISCERN and JAMA scores were 45.5±15.7 and 1.9±1.1, respectively. Commercial websites had the highest DISCERN and JAMA scores with a mean±SD of 64.7±8.7 and 3.6±0.5, respectively. Physician websites had a significantly lower JAMA mean score than commercial ones (p <0.001). Six websites had HONcode seals and 10 reported references. Readability was difficult as it was at the level of college graduate. CONCLUSIONS: As the role of robot-assisted radical cystectomy continues to grow worldwide, the overall quality of Web-based information related to this procedure remains poor. An effort should be made by health care providers to assure patients can have better access to reliable and readable informational material.

Sacral neuromodulation remote programming in patients with refractory lower urinary tract dysfunction: China's experience during the COVID-19 pandemic.

Objectives: Sacral neuromodulation is an effective, minimally invasive treatment for refractory lower urinary tract dysfunction. However, regular postoperative programming is crucial for the maintenance of the curative effects of electronic sacral stimulator devices. The outbreak of coronavirus disease 2019 (COVID-19) limited the ability of practitioners to perform traditional face-to-face programming of these stimulators. Therefore, this study aimed to evaluate the application of remote programming technology for sacral neuromodulation during the COVID-19 pandemic in China. Materials and methods: We retrospectively collected data including baseline and programming information of all patients with lower urinary tract dysfunction who underwent sacral neuromodulation remote programming in China after the outbreak of COVID-19 (i.e., December 2019). The patients also completed a self-designed telephone questionnaire on the subject. Results: A total of 51 patients from 16 centers were included. They underwent 180 total remote programming visits, and 118, 2, 25, and 54 voltage, current, pulse width, and frequency adjustments, respectively, were performed. Additionally, remote switching on and off was performed 8 times; impedance test, 54 times; and stimulation contact replacement, 25 times. The demand for remote programming was the highest during the first 6 months of sacral neuromodulation (average, 2.39 times per person). In total, 36 out of the 51 patients completed the questionnaire survey. Of these, all indicated that they chose remote programming to minimize unnecessary travel because they had been affected by COVID-19. The questionnaire also showed that remote programming could reduce the number of patient visits to the hospital, save time, reduce financial costs, and would be easy for patients to master. All surveyed patients indicated that they were satisfied with remote programming and were willing to recommend it to other patients. Conclusion: Remote programming for sacral neuromodulation is feasible, effective, safe, and highly recommended by patients with refractory lower urinary tract dysfunction. Remote programming technology has great development and application potential in the post-pandemic era.

Incidence of New or Worsening Overactive Bladder Among Patients with a Prior SARS-CoV-2 Infection: A Cohort Study.

Background: Literature is sparse on COVID-19-associated cystitis (CAC), a novel condition comprising frequency, urgency, and nocturia after COVID-19 infection. Objective: To determine the incidence of CAC and correlation with SARS-CoV-2 antibody levels. Design setting and participants: This was a retrospective study in which urinary symptoms were scored using the International Consultation on Incontinence Questionnaire-overactive bladder (ICIQ-OAB) at three time points: before the pandemic (January 2020), 2 mo after COVID-19 infection (if applicable), and at the time of the study (May 2021). The setting was a regional health care system. The 18 785 healthcare employees who took part in the BLAST COVID study group were invited to participate, of whom 1895 responded. Outcome measurements and statistical analysis: The outcome measured was the percentage of COVID-positive patients with a significant change on ICIQ-OAB over time. Pearson's χ2 test was used for comparison of categorical data, and one-way analysis of variance for continuous data and multivariate analysis. A sample size of 618 was calculated for power of 80% and α = 0.05. Results and limitations: Of the 1895 participants, 31.9% (n = 605) were positive for COVID-19 according to positive serology or a polymerase chain reaction (PCR) test. Of these, 492 were PCR-positive and had 2-mo postinfection data, with 36.4% (179/492) reporting an increase of ≥1 point on the ICIQ-OAB compared to baseline (before the pandemic), with de novo OAB in 22% of these cases (40/179). Comparison of symptoms between baseline and the study time revealed that 27.4% (31/113) of those with positive serology only (asymptomatic COVID) and 37.8% (186/492) of those with PCR positivity (symptomatic COVID) had an increase of ≥1 point on the ICIQ-OAB, compared to 15.8% (n = 204) of uninfected patients, with odds ratios of 2.013 (95% confidence interval [CI] 1.294-3.138; p = 0.0015) and 3.236 (95% CI 2.548-4.080; p < 0.0001), respectively. The retrospective nature of the study and the volunteer sample are limitations. Conclusions: COVID-19 infection increases the risk of developing new or worsening OAB symptoms. Patient summary: We compared overactive bladder symptoms in a large group of participants between individuals with and without a previous COVID-19 infection. We found that symptomatic infection was associated with a three times greater risk of developing new or worsening overactive bladder symptoms among COVID-19 patients.

Impact of COVID-19 on male urogenital health: Success of vaccines.

Throughout 2021, the scientific and medical communities were concentrated on dealing with the acute morbidity and mortality induced by the COVID-19 pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We reviewed the present data for adverse effects of COVID-19 on the different parts of the male urogenital system during the dynamic situation of the COVID-19 pandemic. With the approval of COVID-19 vaccinations, there is a ray of hope at the end of this dark tunnel and a chance to look ahead for the management of long-term consequences in males with urogenital illness. A multidisciplinary investigation of these cases could provide information for establishing and optimizing treatment protocols.

Biomarkers in the Light of the Etiopathology of IC/BPS.

In this review, we focused on putatively interesting biomarkers of interstitial cystitis/bladder pain syndrome (IC/BPS) in relation to the etiopathology of this disease. Since its etiopathology is still under discussion, the development of novel biomarkers is critical for the correct classification of the patients in order to open personalized treatment options, on the one hand, and to separate true IC/BPS from the numerous confusable diseases with comparable symptom spectra on the other hand. There is growing evidence supporting the notion that the classical or Hunner-type IC (HIC) and the non-Hunner-type IC (NHIC) are different diseases with different etiopathologies and different pathophysiology at the full-blown state. While genetic alterations indicate close relationship to allergic and autoimmune diseases, at present, the genetic origin of IC/BPS could be identified. Disturbed angiogenesis and impairment of the microvessels could be linked to altered humoral signaling cascades leading to enhanced VEGF levels which in turn could enhance leucocyte and mast cell invasion. Recurrent or chronic urinary tract infection has been speculated to promote IC/BPS. New findings show that occult virus infections occurred in most IC/BPS patients and that the urinary microbiome was altered, supporting the hypothesis of infections as major players in IC/BPS. Environmental and nutritional factors may also influence IC/BPS, at least at a late state (e.g., cigarette smoking can enhance IC/BPS symptoms). The damage of the urothelial barrier could possibly be the result of many different causality chains and mark the final state of IC/BPS, the causes of this development having been introduced years ago. We conclude that the etiopathology of IC/BPS is complex, involving regulatory mechanisms at various levels. However, using novel molecular biologic techniques promise more sophisticated analysis of this pathophysiological network, resulting in a constantly improvement of our understanding of IC/BPS and related diseases.

[Practice of urological departments during the COVID-19 pandemic]

INTRODUCTION: The pandemic of novel coronavirus infection has had a strong impact on the whole medical system, including urological departments. MATERIAL AND METHODS: We assessed the impact of restrictions due to the pandemic on the work of urological departments of private (Medical Center "Avicenna", Novosibirsk) and community (KGBUZ "City Clinical Hospital No. 11, Barnaul") hospitals;GBUZ of the Novosibirsk region "City Clinical Emergency Hospital" (GBUZ CCEH) No. 2, Novosibirsk) clinics, as well as the urogenital department of the TB Research Institute of Ministry of Health of Russia during the period from 2019 to 2020. The changes in the spectrum of surgical procedures, as well as the structure of patients' visits to a urologist were evaluated. RESULTS: In March 2020, the urogenital department of the TB Research Institute of Ministry of Health of Russia was redesigned into an observational one. Community departments worked with small restrictions or without any limitations. In KGBUZ "City Clinical Hospital No. 11, Barnaul", an increase in the number patients with bladder cancer, ureteral stones, concomitant kidney and ureteral stones by 3-27% was noted (p<0.05), as well as those with acute epididymo-orchitis, including testicular abscess. At the same time, a significant decrease in the number of patients with varicocele, pyelonephritis, chronic cystitis, chronic prostatitis, and phimosis was found. A surgical department of GBUZ CCEH from October to December 2020 was restructured to an infectious hospital;this led to a decrease in the volume of urological care and the number of procedures. The Avicenna Medical Center also established anti-epidemic measures, which made it possible not only not to reduce, but in a number of procedures to increase the volume of surgical care. CONCLUSION: Owing to anti-epidemic measures, including the patient flow distribution, an introduction of mandatory testing, an early detection of patients and carriers among employees, mask regime, the opening of an observational department, single rooms, the lack of contact between patients, short length of stay, it was possible to prevent an outbreak of coronavirus infection among patients and personnel. Both in the municipal and private urological clinics, well-organized work precluded the negative impact of the pandemic.

A gold standard bladder and bowel service

Bladder and bowel difficulties affect 20% and 10% of the UK population, respectively (Percival et al, 2021). This is most likely not an accurate reflection of the true scale of this often under-reported health issue. Pelvic floor dysfunction can cause symptoms relating to many different systems and its management involves numerous modalities. The management of bladder, bowel and pelvic floor dysfunction should be delivered in the community via general practitioners, pelvic health physiotherapists and bladder and bowel services. An effective multidisciplinary approach using pathways to reduce secondary care involvement unless required should be adopted. Post Covid, community bladder and bowel services are recovering from prolonged redeployment, a backlog of cancelled patients and a rising waiting list. Acute services are the same, with even bigger backlogs for benign lower urinary tract dysfunction and prolapse assessment. Scrutiny of current bladder and bowel services across new clinical commissioning group (CCG) collaborations will undoubtedly uncover the disparity in quality of service provision.

A possible protective role for Bacillus Calmette-Guérin therapy in urinary bladder cancer in the era of COVID-19: a brief report.

Given the systemic immunogenic effects of Bacillus Calmette-Guérin (BCG) therapy in patients with bladder cancer and its non-specific immunogenic effects in viral respiratory diseases, we aimed to study severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in bladder cancer patients with a history of BCG therapy. In the present study, all bladder cancer survivors with a history of BCG therapy were identified and included in the study according to the data recovered from the UORC (Uro-Oncology Research Center) registry database. These patients were followed up in terms of acquiring coronavirus disease 2019 (COVID-19). Among the studied patients, 102 eligible bladder cancer patients with a history of BCG therapy entered the study. The males constituted the majority of the patients (86.3%), and more than half of the study population (55.9%) were above 65 years old. Among the understudy patients, 12.7% were confirmed for COVID-19. The study results did not show a statistically significant association between the time and number of BCG therapy courses and SARS-CoV-2 infection. Although no statistically significant association was observed between receiving BCG therapy and developing COVID-19, the infection rate in patients who had recently received BCG therapy was lower than those who had received therapy more than a year ago.

Prominence of urinary biomarkers for bladder cancer in the COVID-19 era: From the commercially available to new prospective candidates.

Molecular markers detected in urine may improve our understanding of the evolution of bladder cancer (BCa) and its micro- and macroenvironment. Detection of such markers will identify disease earlier, allow stratification of patients according to risk, and improve prognostication and prediction of outcomes, thereby facilitating targeted therapy. However, current guidelines have yet to embrace such markers for routine management of BCa, and most research studies have focused on urine-based tumor markers. In this review, we summarize known urinary biomarkers for BCa and highlight newly identified molecules. We then discuss the challenges that must be overcome to incorporate these markers into clinical care.

Is coronavirus disease 2019 associated with indicators of long-term bladder dysfunction?

OBJECTIVE: Early reports have suggested that coronavirus disease 2019 (COVID-19) can present with significant urinary frequency and nocturia, and that these symptoms correlate with markers of inflammation in the urine. We evaluated surrogate markers of chronic urinary symptoms to determine if they were more frequent after COVID-19 infection. METHODS: Routinely collected data from the province of Ontario was used to conduct a matched, retrospective cohort study. We identified patients 66 years of age or older who had a positive COVID-19 test between February and May 2020 and survived at least 2 months after their diagnosis. We matched them to two similar patients who did not have a positive COVID-19 test during the same time period. We measured the frequency of urology consultation, cystoscopy, and new prescriptions for overactive bladder medications during a subsequent 3-month period. Proportional hazard models were adjusted for any baseline differences between the groups. RESULTS: We matched 5617 patients with COVID-19 to 11,225 people who did not have COVID-19. The groups were similar, aside from a higher proportion of patients having hypertension and diabetes in the CoVID-19 cohort. There was no significantly increased hazard of new receipt of overactive bladder medication (hazards ratio [HR]: 1.04, p = 0.88), urology consultation (HR: 1.40, p = 0.10), or cystoscopy (HR: 1.14, p = 0.50) among patients who had COVID-19, compared to the matched cohort. CONCLUSION: Surrogate markers of potential bladder dysfunction were not significantly increased in the 2-5 months after COVID-19 infection.

BCG vaccine and COVID-19: implications for infection prophylaxis and cancer immunotherapy.

The COVID-19 pandemic has killed over 400 000 people globally. Ecological evidence indicates that countries with national universal BCG vaccination programs for tuberculosis (TB) prevention have a much lower incidence of severe COVID-19 and mortality compared with those that do not have such programs. BCG is a century old vaccine used for TB prevention via infant/childhood vaccination in lowto middle-income countries with high infection prevalence rate and is known to reduce all-cause neonatal mortality. BCG remains the standard immunotherapy treatment for patients with high-risk non-muscle invasive bladder cancer globally for more than 44 years. Several trials are, therefore, investigating BCG as a prophylactic against COVID-19 in healthcare workers and the elderly. In this commentary, we discuss the potential mechanisms that may underlie BCG associated heterologous protection with a focus on tertiary lymphoid structure (TLS) organogenesis. Given the significance of TLSs in mucosal immunity, their association with positive prognosis and response to immune checkpoint blockade with a critical role of Type I interferon (IFN-1) in inducing these, we also discuss potentiating TLS formation as a promising approach to enhance anti-tumor immunity. We propose that lessons learned from BCG immunotherapy success could be applied to not only augment such microbe-based therapeutics but also lead to similar adjunctive IFN-1 activating approaches to improve response to immune checkpoint blockade therapy in cancer.

Bladder Cancer at the time of COVID-19 Outbreak.

The COVID-19 outbreak has led to the deferral of a great number of surgeries in an attempt to reduce transmission of infection, free up hospital beds, intensive care and anaesthetists, and limit aerosol-generating procedures. Guidelines and suggestions have been provided to categorize Urological diseases into risk groups and recommendations are available on procedures that can be or cannot be deferred. We aim to summarise updates on diagnosis, treatment and follow up of bladder cancer during the COVID-19 outbreaks.