Bladder Syndrome Research Articles

The peptide regulator Vezusten in the management of overactive bladder syndrome: an efficacy evaluation

Introduction. Overactive bladder (OAB) remains one of the most difficult-to-treat conditions in neurourology. The number of patients seeking help for OAB symptoms does not decrease each year, while a pathogenetic treatment has not yet been developed. This motivates the search for new approaches.Objective. To assess the efficacy of the peptide regulator Vezusten for women with idiopathic OAB based on their health condition and urodynamic assessment of bacterial detrusor overactivity (DO).Materials & methods. A prospective cohort study included 20 patients diagnosed with OAB, which was confirmed by a comprehensive urodynamic study of DO. The patients visited the clinic three times a week. Each patient received ten intramuscular injections of the peptide regulator Vezusten. Within one month after the last injection, the women were given a monitoring voiding diary, a validated Continental Society OAB Symptom Questionnaire, the Overactive Bladder Questionnaire (OAB-q), and a follow-up urodynamic study (UDS).Results. We obtained statistically significant differences in the following indicators: the number of daily urinations according to the urination diary decreased from 14.0 [13.0; 16.3] to 11.0 [8.8; 12.0] (p < 0,001), patient’s episodes of urge incontinence began to be noted for the first time (p = 0.004). At the same time, the urodynamic maximum cystometric capacity (MCC) increased from 267 [158; 332] to 320 [267; 433] ml. Subjectively, participants noted an improvement in the scores of the OAB questionnaire (OAB-q) — the score decreased from 28 [22; 30] to 19 [14; 24] (p = 0.001), and the number of episodes of nocturia decreased from 4 to 2 (p < 0.001). No side effects from therapy were observed in any of the patients.Conclusion. This study demonstrated a statistically significant improvement in subjective symptoms of OAB in DO-women treated with the peptide regulator Vezusten, but further large placebo-controlled studies are required for confirmation.

Association between weight-adjusted waist index and overactive bladder syndrome among adult women in the United States: a cross-sectional study

PurposeThe weight-adjusted waist index (WWI) is a recently developed index for measuring obesity. The aim of this study was to investigate the association between WWI levels and overactive bladder (OAB) in a nationally representative population.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2016. OAB was defined as the Overactive Bladder Syndrome Symptom Score (OABSS, score ≥ 3). The WWI index was calculated as the square root of waist circumference (WC, cm) divided by body weight (kg). We used weighted logistic regression models to assess the relationship between the WWI index and OAB in adult women. The reliability of the findings was assessed using restricted cubic spline, subgroup analysis.ResultsA total of 10,563 individuals were included in the study, and the prevalence of OAB was 18.6%. Higher WWI was associated with an increased risk of overactive bladder syndrome. In model 1 with unadjusted variables (OR = 1.148; 95% CI = 1.148–1.149, p < 0.001), model 2 (OR = 1.253; 95% CI = 1.253–1.254, p < 0.001) and model 3 with fully adjusted variables (OR = 1.215; 95% CI = 1.214–1.215, p < 0.001) in which the association was significant. The results of the subgroup analyses showed that age stratification and stroke status could modify this association between WWI and OAB. Restricted cubic spline showed a nonlinear relationship between WWI and OAB (p for nonlinear < 0.05).ConclusionWeight-adjusted waist circumference index (WWI) values are positively associated with the risk of developing OAB in adult women in the United States, but further studies are needed to elucidate the causal relationship between WWI and OAB.

Discrete Mathematics in Dynamic Network Analysis: Long-Term Efficacy Evaluation of Fotona Laser Therapy for Overactive Bladder Syndrome Using Clustering-Based Patient Subgroup Identification.

Dynamic network analysis, a state-of-the-art application of discrete mathematics, offers unprecedented insight into complex, time-evolving clinical data. This technical report demonstrates the value of evaluating the long-term efficacy of Fotona laser therapy (Fotona d.o.o., Ljubljana, Slovenia) in overactive bladder (OAB) syndrome. We analyzed data from 101 female patients aged ≥60 years who underwent Fotona laser treatment, including Vaginal Erbium Laser (VEL) and Urethral Erbium Laser (UEL), between 2020 and 2022. OAB symptom scores (OABSS) were collected at baseline (T0) and at six, 12, 18, and 24 months post treatment. Network graphs were constructed, representing patients as nodes, and symptom similarities as edges. Clustering techniques identify patient subgroups, whereas principal component analysis reduces dimensionality. The dynamic evolution of patient clusters was visualized through changes in average degree centrality over time. This approach revealed three distinct patient clusters with unique treatment response patterns. The results showed a progressive reduction in OABSS, with the total score decreasing by 2.82 ± 3.03 at 24 months. Our method provides novel visualization and analysis of complex longitudinal clinical data, offering insights into personalized treatment strategies for OAB. This report presents one of the first applications of discrete mathematics and dynamic network analysis to evaluate the long-term outcomes of Fotona laser therapy for OAB and introduces an innovative perspective for clinical decision-making in urogynecology.

Management of Complications of Prosthetic Mid-urethral Tape Surgery for Stress Urinary Incontinence in Women

OBJECTIVESto propose guidelines for the management of complications of prosthetic mid-urethral tape surgery for stress urinary incontinence in women. METHODSThese guidelines are based on an exhaustive literature review on retropubic and trans-obturator mid-urethral tape complications. The expert panel rated the level of evidence of each study, summarized literature for the treatment of each complication, and proposed guidelines. RESULTSManagement of these complications is complex and the first treatment is crucial to offer the best functional result to the patient. We propose a standardized approach and guidelines for the management of complications to help physicians to early identify a surgical complication, offer adequate treatment for each complication and provide clear and appropriate information to patients. We detailed management of intraoperative complications: bladder, urethral, vaginal, visceral and vascular injury; short term post-operative complications: bleeding/hematoma, voiding dysfunction, pain, infection; and long-term post-operative complications: chronic voiding dysfunction, de novo overactive bladder syndrome, chronic pain, dyspareunia, vaginal, bladder and urethral tape erosion. CONCLUSIONThese guidelines may help physicians to improve management of prosthetic mid-urethral sling complications that may occur following stress urinary incontinence surgery.

How do oral anticholinergic drugs compare with placebo for adults with overactive bladder syndrome?

How do oral anticholinergic drugs compare with placebo for adults with overactive bladder syndrome?

Mirabegron 50 mg once daily, long-term treatment maximizes benefit in middle-aged and older people with overactive bladder syndrome: a systematic review and meta-analysis of nine phase II/III, randomized, double-blind, parallel-design, placebo-controlled, multicenter, and multinational trials.

The prevalence and severity of overactive bladder increase with age, and mirabegron is an approved treatment for this condition. This meta-analysis systematically evaluated the efficacy and safety of mirabegron compared with placebo for overactive bladder treatment. We searched PubMed and the Cochrane Library (30 October 2023) for relevant articles (source: MEDLINE, EMBASE, ClinicalTrials.gov, ICTRP, CINAHL). We included randomized controlled trials involving adults with overactive bladder syndrome that compared mirabegron with placebo treatment. Data were analyzed according to the Cochrane Handbook for Systematic Reviews of Interventions [Review Manager (computer program) Version 5.4]. Nine parallel-group trials (10 articles) were included. The evaluation included a total of 8,527 adults, including 6,445 women and 2,082 men, of whom 5,726 were White, 2,462 were Asian, and 161 were Black. The mean age of the participants ranged from 53.4 to 60.3 years. This evaluation involved three specifications of mirabegron: 25 mg, 50 mg, and 100 mg. In all trials, patients were enrolled in a 12-week double-blind treatment period, and the dose was once daily. The review of trials found that on average, people taking mirabegron had about 13 ml more volume voided per micturition, five fewer micturitions, and four fewer incontinence episodes every week, with moderate improvements in quality of life. About one in five people taking the drug reported TRAEs. Mirabegron treatment is well tolerated, with the risk of adverse events similar to that of a placebo. For best results, a dose of 50 mg once daily is recommended for long-term use. It is unclear whether any benefits are sustained after treatment discontinuation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42023430737).

Physiological and metabolic functions of the β3-adrenergic receptor and an approach to therapeutic achievements.

A specific type of beta-adrenergic receptor was discovered in the decade of 1980s and subsequently recognized as a new type of beta-adrenergic receptor, called beta3-adrenoceptor (β3-AR). β3-AR expresses in different tissues, including adipose tissue, gall bladder, stomach, small intestine, cardiac myocytes, urinary bladder, and brain. Structurally, β3-AR is very similar to β1- and β2-AR and belongs to a G-protein coupled receptor that uses cAMP as an intracellular second messenger. Alternatively, it also activates the NO-cGMP cascade. Stimulation of the β3-AR increases lipolysis, fatty acid oxidation, energy expenditure, and insulin action, leading to anti-obesity and anti-diabetic activity. Moreover, β3-AR differentially regulates the myocardial contraction and relaxes the urinary bladder to balance the cardiac activity and delay the micturition reflex, respectively. In recent years, this receptor has served as an attractive target for the treatment of obesity, type 2 diabetes, congestive heart failure, and overactive bladder syndrome. Several β3-AR agonists are in the emerging stage that can exert novel pharmacological benefits in different therapeutic areas. The present review focuses on the structure, signaling, physiological, and metabolic activities of β3-AR. Additionally, therapeutic approaches of β3-AR have also been considered.

Pain from Internal Organs and Headache: The Challenge of Comorbidity.

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature. The conditions addressed are as follows: visceral pain from the cardiovascular, gastrointestinal, and urogenital areas and primary headache conditions such as migraine and tension-type headache. The most frequent comorbidities involve the following: cardiac ischemic pain and migraine (possible shared mechanism of endothelial dysfunction, oxidative stress, and genetic and hormonal factors), functional gastrointestinal disorders, particularly IBS and both migraine and tension-type headache, primary or secondary dysmenorrhea and migraine, and painful bladder syndrome and headache (possible shared mechanisms of peripheral and central sensitization processes). The data also show that the various visceral pain-headache associations are characterized by more than a simple sum of symptoms from each condition but often involve complex interactions with the frequent enhancement of symptoms from both, which is crucial for diagnostic and treatment purposes.

Elucidation of the pathophysiology of interstitial cystitis/bladder pain syndrome via experimental autoimmune cystitis rat model.

Although the cause of interstitial cystitis/painful bladder syndrome (IC/PBS) remains unknown, autoimmune involvement has been strongly suggested to be a contributing factor. To elucidate the pathophysiology of IC/PBS, we characterized the experimental autoimmune cystitis (EAC) in rats. Adult female Sprague-Dawley rats were divided into the EAC and control groups. The EAC rats were generated by administrating a homogenate of donor rat bladder tissue as a bladder antigen. The characteristics of the two groups were determined by evaluating pain behavior and conducting cystometry, histopathology, and molecular analyses. The EAC rats showed: 1) a decreased paw withdrawal threshold, 2) a reduced intercontraction interval on cystometry, 3) the irregular surfaces of the umbrella cells of epithelium throughout the bladder wall, 4) accumulation of stress granules in the bladder and vascular endothelium, 5)the increased expression of genes related to inflammation and ischemia at the mRNA and protein levels, 6) a significantly increased paw withdrawal threshold with pain treatment, and 7) the induction of glomerulation of the bladder wall, epithelium denudation, and lymphocyte infiltration in the interstitium by bladder distension. These results suggest that the EAC rats showed pain and frequent urination with the overexpression of inflammatory chemokines, reflecting clinical IC/BPS, and the bladder epithelium and vascular endothelium may be the primary sites of IC/BPS, and bladder injury, such as bladder distension, can cause progression from BPS to IC with Hunner lesions.NEW & NOTEWORTHY The experimental autoimmune cystitis model rats showed pain and frequent urination with the overexpression of inflammatory chemokines, reflecting clinical interstitial cystitis/painful bladder syndrome (IC/PBS), and the bladder epithelium and vascular endothelium may be the primary sites of IC/BPS, and bladder injury, such as bladder distension, can cause progression from BPS to IC with Hunner lesions.

LACTOFERRIN IN THE TREATMENT OF INTERSTITIAL CYSTITIS: A RETROSPECTIVE PILOT STUDY.

Interstitial cystitis (IC), defined as a painful bladder syndrome (PBS), is a chronic condition that manifests itself as a suprapubic pain associated with an enhancing of frequency/urgency of urination, and for which there is no cure. Here, we present a retrospective pilot study on women affected from IC/PBS and treated with bovine lactoferrin (bLf). A total of 31 women, affected (20) or unaffected (11) from hereditary thrombophilia (HT), presented the median of 6 episodes of IC/PBS during the 6 months before the study. Treatment consisted of 17 weeks of orally administered Valpalf® capsules, containing bLf plus sodium bicarbonate and citrate. Out of 31 patients, only 3 women had one episode of IC/PBS during the follow-up period, while no episode was observed in 28 women. In the HT group, a significant decrease in both serum IL-6 and D-dimers was found after Valpalf® treatment. Moreover, in Valpalf®-treated women, cystoscopy revealed a global improvement in the appearance of the bladder, especially in term of inflammation/irritation and presence of Hunner ulcers. Even if our results must be corroborated by randomized double-blinded controlled trials on a larger number of patients, our observations indicate that bLf treatment is efficient in relieving IC/PBS symptoms, without side effects.

Using artificial intelligence to generate medical literature for urology patients: a comparison of three different large language models

PurposeLarge language models (LLMs) are a form of artificial intelligence (AI) that uses deep learning techniques to understand, summarize and generate content. The potential benefits of LLMs in healthcare is predicted to be immense. The objective of this study was to examine the quality of patient information leaflets (PILs) produced by 3 LLMs on urological topics.MethodsPrompts were created to generate PILs from 3 LLMs: ChatGPT-4, PaLM 2 (Google Bard) and Llama 2 (Meta) across four urology topics (circumcision, nephrectomy, overactive bladder syndrome, and transurethral resection of the prostate). PILs were evaluated using a quality assessment checklist. PIL readability was assessed by the Average Reading Level Consensus Calculator.ResultsPILs generated by PaLM 2 had the highest overall average quality score (3.58), followed by Llama 2 (3.34) and ChatGPT-4 (3.08). PaLM 2 generated PILs were of the highest quality in all topics except TURP and was the only LLM to include images. Medical inaccuracies were present in all generated content including instances of significant error. Readability analysis identified PaLM 2 generated PILs as the simplest (age 14–15 average reading level). Llama 2 PILs were the most difficult (age 16–17 average).ConclusionWhile LLMs can generate PILs that may help reduce healthcare professional workload, generated content requires clinician input for accuracy and inclusion of health literacy aids, such as images. LLM-generated PILs were above the average reading level for adults, necessitating improvement in LLM algorithms and/or prompt design. How satisfied patients are to LLM-generated PILs remains to be evaluated.

Intestinal Absorption Site-Guided Development and Evaluation of Oral Disintegrating Controlled Release Tablets of Mirabegron

The aim was to employ site-dependent absorption of mirabegron (MB) as a guide for fabrication of oral disintegrating controlled release tablet (ODCRT) which undergoes instantaneous release of loading fraction followed by delayed release of the rest of MB. The goal was to release MB in a manner consistent with the chronobiology of overactive bladder (OAB) syndrome. In situ rabbit intestinal permeability of MB was adopted to assess absorption sites. MB was subjected to dry co-grinding with citric acid to develop the fast-dissolving fraction in the mouth. Delayed release fraction was formulated by ethanol-assisted co-processing with increasing proportions of Eudragit polymer (S100) as pH responsive polymer. The developed dry mixtures underwent thermal (DSC) and physical (X-ray diffraction) characterization, in addition to in vitro release behavior. Optimized fast dissolving and delayed release formulations were mixed with tablet excipient before compression in ODCRT which was assessed for release profile using continuous pH variation. MB underwent preferential permeation through ileum and colon. Co-grinding with citric acid provided co-amorphous powder with fast dissolution. Co-amorphization of MB with Eudragit S100 (1:5) showed pH-dependent release to release most of the dose at pH 7.4. The developed ODCRT released 43.5% of MB in the buccal environment and retained MB at acidic pH to start release at pH 7.4. The study successfully fabricated ODCRT guided by site-dependent absorption. The ODCRT instantaneously released loading fraction to support the patient after administration with delayed fraction to sustain the effect.Graphical

Serum Profiles of Solifenacin and Interleukin-6 and Their Relationship With Psychiatric Symptoms in a Patient With Overactive Bladder Syndrome and Systemic Inflammation.

Serum Profiles of Solifenacin and Interleukin-6 and Their Relationship With Psychiatric Symptoms in a Patient With Overactive Bladder Syndrome and Systemic Inflammation.

Comparative evaluation of bioavailability of Botulinum toxin A complexed with Tizol (titanium glycerosolvate aquacomplex) versus pure Botulinum toxin A solution for bladder mucosa: an experimental study

Introduction. For the treatment of overactive bladder syndrome (OAB), injection of botulinum toxin A (BoNT-A) has been shown to be effective. However, there is a need for a less invasive method for administering BoNT-A, which could significantly expand the treatment options for OAB.Objective. To assess the impact of tizol on the absorption of BoNT-A by the bladder mucosa and compare it to the individual absorption of BoNT-A.Materials &amp; Methods. Dialysis through the mucous membrane of the сalf bladder was used as an experimental model to study changes in bioavailability of BoNT-A complexed with tisol (BoNT-A + T) and pure BoNT-A solution during in vitro experiment. After dialysis, the BoNT-A concentration in both samples was determined using a spectrophotometer. Dialysis curves were plotted according to the data obtained. Kruvchinsky equilibrium dialysis method was used to determine botulinum toxin A bioavailability. The UV spectrophotometry method was used to determine the concentration of BoNT-A in the acceptor medium by reaction of BoNT-A with Benedict's reagent.Results. It was established that the maximum concentration of BoNT-A diffused into the acceptor medium from the blend of the test substance with tizol after nine hours. The area under the curve for dialysis of BoNT-A + T exceeds the area under the curve of pure BoNT-A by almost 20%, suggesting an improvement in the drug's bioavailability when blended with tizol.Conclusion. Based on our experiment, it was found out that the BoNT-A + T has greater bioavailability than a solution of pure BoNT-A. However, the diffusion rate of the component mixture is sufficiently low.

Screening of overactive bladder syndrome and its relation with insomnia: A public health experience.

Overactive bladder (OAB) syndromes are a vital global issue linked to sleep disturbances and insomnia. This survey explores the relationship between these health burden issues and their risk factors. A survey-based study was conducted among Makkah city citizens' in April 2023. A standardized tool of OAB symptom score and Insomnia Severity Index was used to screen participants. The collected data were statistically analyzed using SPSS. Overall, 529 participants were enrolled in this survey with mean = 37.3 and standard deviation = 13.7. Most participants had mild OAB 74.67%, while insomnia represents no clinically significant subtype among the majority 55.39%. About 25.33% of participants had clinical OAB (moderate and severe), while approximately 44.61% had insomnia. Similarly, participants with the mild subtype of OAB show a significant correlation with no clinically significant subtype of insomnia (P ˃ 0.001). Furthermore, participants with moderate OAB were statistically associated with subthreshold insomnia (P ˃ 0.001). Medical attention and public awareness are mandatory for the early detection of OAB and insomnia.

Update on Overactive Bladder Therapeutic Options.

Millions of Americans are burdened by overactive bladder (OAB) syndrome and the psychogenic and economic hardships that accompany it. Several theories attempt to explain OAB as a neurogenic dysfunction, myogenic dysfunction, urothelial dysfunction, or decreased expression of a channel protein secondary to bladder outlet obstruction. Given that the etiology of OAB is a working theory, the management of OAB is also an evolving subject matter in medicine. There are uncertainties surrounding the pathophysiology of OAB, the strength of a clinical diagnosis, and accurate reporting because of the disease's stigma and decreased use of health care. This is a narrative review that used PubMed, Google Scholar, Medline, and ScienceDirect to review literature on current and future OAB therapies. Currently, first-line treatment for OAB is behavioral therapy that uses lifestyle modifications, bladder-control techniques, and psychotherapy. Second-line therapy includes antimuscarinic agents or beta 3 adrenergic agonists, and studies have shown that combination therapy with antimuscarinics and beta 3 adrenergic agonists provides even greater efficacy than monotherapy. Third-line therapies discussed include onabotulinumtoxinA, posterior tibial nerve stimulation, and sacral neuromodulation. OnabotulinumtoxinA has been FDA-approved as a nonpharmaceutical treatment option for refractory OAB with minimal side effects restricted to the urinary tract. Posterior tibial nerve modulation and sacral neuromodulation are successful in treating refractory OAB, but the costs and complication rates make them high-risk procedures. Therefore, surgical intervention should be a last resort. Estrogen therapy is effective in alleviating urinary incontinence in postmenopausal women, consistent with the association between estrogen deficiency and genitourinary syndrome. Potassium channel activators, voltage-gated calcium channel blockers, and phosphodiesterase inhibitors look to be promising options for the future of OAB management. As new therapies are developed, individuals with OAB can better personalize their treatment to maximize their quality of life and cost-effective care.

Efficacy of Percutaneous vs Transcutaneous Posterior Tibial Nerve Stimulation in Overactive Bladder Syndrome: A Randomized Clinical Trial

Efficacy of Percutaneous vs Transcutaneous Posterior Tibial Nerve Stimulation in Overactive Bladder Syndrome: A Randomized Clinical Trial

Effect of Low Intensity Laser Therapy on Painful Bladder Syndrome

Effect of Low Intensity Laser Therapy on Painful Bladder Syndrome

To assess the effectiveness of Mirabegron in reducing urodynamic detrusor overstimulation in patients with Overactive Bladder Syndrome (OAB).

Objective: To investigate the efficacy of mirabegron in treating overactive bladder by assessing its impact on urodynamic detrusor overactivity (DO). Study Design: Cross-sectional study. Setting: Center for Urology and Transplantation in Sindh. Period: April 6, 2022, to October 4, 2022. Methods: Sixty-four individuals presenting OAB symptoms and without prior OAB medication use were included after obtaining informed consent and conducting relevant medical evaluations. Patients demonstrating signs of detrusor overactivity were evaluated through urodynamic assessments. Collected data, including patient history and study outcomes, were recorded using a standardized Proforma (Annexure I). Patient demographics, age, and gender distribution were documented. Patients with urodynamic detrusor overactivity were administered 50.0 mg mirabegron tablets once daily for a period of 13 weeks. A noteworthy percentage of patients reported substantial success after three months of treatment. Results: The average age of study participants was 50 years. The mean duration of OAB symptoms was 20.22 ± 15.38 months. Of the total 64 patients, 41 were female (64.06%) and 23 were male (34.94%). Notably, successful treatment outcomes were observed in 49 cases (76.56%). Conclusion: Mirabegron emerges as a valuable therapeutic option for individuals dealing with overactive bladder. This study underscores its efficacy in managing OAB sympt0oms, with a notable success rate of 76.6%. These findings contribute to the growing body of evidence supporting mirabegron as an effective treatment for overactive bladder syndrome.

How can we explain the poor medication adherence in patients with overactive bladder syndrome?

How can we explain the poor medication adherence in patients with overactive bladder syndrome?