Aims: OnabotulinumtoxinA (onabotA) is an approved treatment for overactive bladder (OAB). This chart review study aims to determine treatment persistence in patients receiving onabotA (100 U) via a reduced injection-site paradigm distributed across ≤ 3 injection sites.
Methods: This study was a single site, noninterventional, retrospective chart review evaluating adult female OAB patients refractory to behavioral modification and pharmacotherapy before receiving ≥ 1 treatment with onabotA (100 U) via 1-3 injections between July 2017 and June 2021. Patients with neurologic OAB, predominance of stress incontinence, or who expired during the study were excluded. Baseline demographics, treatment patterns, treatment persistence, treatment intervals, lidocaine pretreatment, patient-reported treatment response, and adverse urological events were documented and evaluated. Persistence was defined as the percent of patients receiving ≥ 3 treatments during the study period via three or fewer injections. Continuous variables were summarized with sample size, mean (standard deviation [SD]), and median (1st and 3rd quartiles); categorical variables were calculated as frequencies and percentages.
Results: Of the 90 patients included in this study, 55 (61.1%) were persistent to treatment with onabotA for OAB, completing 3 treatments by the end of the data collection period. Urinary tract infection (UTI) was reported after 18/370 (4.9%) treatments. Of 90 patients,15 (16.7%) reported UTI after any treatment, and none required clean intermittent catheterization.
Conclusion: When onabotA was administered via a reduced injection-site paradigm, 61.1% of patients were persistent to OAB treatment. Given the limited pool of patients included in this study and relatively low sample sizes at later timepoints, results may not be generalizable. No new safety signals were identified using the reduced injection-site paradigm.
Clinical trial registration: Due to the nature of this study, no clinical trial registration was required.
Purpose: While urinary tract infections (UTIs) are thought to be common among women, as many as 65% of UTI diagnoses may be inaccurate. To identify strategies to improve antibiotic stewardship, we sought to determine the clinical and laboratory factors associated with overdiagnosis and overtreatment of UTIs.
Methods: Electronic health records identified patients bearing an isolated diagnostic code for UTI within a single healthcare system during July 2019. Demographic, clinical, and microbial data were collected by manual chart review. Regression analyses were utilized to determine factors associated with guideline non-concordant UTI diagnosis and treatment utilizing R statistical software (version 4.3.1).
Results: In patients diagnosed with UTI, 64% were treated with antibiotics despite only 28% having symptoms consistent with UTI diagnostic criteria. Of patients diagnosed with a UTI who were treated in an emergency room (ER) setting, 95% were given antibiotics compared with only 55% of patients in an outpatient setting. Even without any urinary symptoms, 95% of patients in the ER and 27% of patients in outpatient settings were treated with antibiotics. Patients who presented to the ER for non-localizing symptoms, such as mental status changes (MSC), were more likely to be diagnosed with UTI compared with those in an outpatient setting.
Conclusion: The results of this study demonstrate that patients were frequently diagnosed with and treated for a UTI despite not meeting diagnostic criteria. This pattern of overdiagnosis leads to overtreatment, particularly in acute care settings, contributing to worsening antibiotic resistance in conjunction with incomplete evaluation of patients' primary complaints.
Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating pain condition of unknown etiology. Effective therapies for this condition could not have been developed in the last century. Drug repurposing is a practical strategy for enhancing patient access to successful therapies. It is an approach for discovering novel applications for licensed or investigational pharmaceuticals that extend beyond the initial medical indication. This work aims to identify repurposable medications through bioinformatics to discover potential drugs or compounds that can reverse the IC/BPS disease signature.
Methods and material: The analysis involved examining the differentially expressed genes in IC/BPS patients with two distinct disease phenotypes (Hunner's lesion disease, non-Hunner's lesion disease) and controls using the datasets GSE11783, GSE28242, and GSE57560. The goal was to assess the reversal of the disease signature on the L1000CDS2 and cMAP platforms.
Results: Twenty-one compounds were repurposed, consisting of 11 small molecules, 10 chemical compounds, 3 natural products, and 6 FDA-approved drugs, currently used for clinical indications such as cancer, myelofibrosis, and diabetes.
Discussion: Bioinformatics can be useful for identifying therapeutic agents for IC/BPS by accessing and processing big data on molecular and cellular levels. Prospective in vivo experiments must validate repurposed drugs. The expansion of large-scale genome sequencing, gene expression studies, and clinical data for IC/BPS will improve successful drug selection.
Aims: This study aimed to investigate the role of N-methyl-D-aspartate receptors (NMDARs) in bladder smooth muscle (BSM) function and their potential as therapeutic targets for overactive bladder conditions.
Methods: We employed a multi-faceted approach to assess NMDAR activity in BSM. Myography was used to evaluate the effects of NMDAR antagonists and agonists on BSM contraction. Calcium imaging was conducted to determine changes in intracellular calcium ions. We also analyzed single-cell RNA sequencing data to examine NMDAR subunit expression in bladder cell subpopulations from both human and mouse tissues. Immunofluorescence staining was performed to localize the obligate NMDAR subunit, GluN1, in mouse BSM.
Results: NMDAR agonists did not modulate BSM contractile force. NMDAR antagonists had varied effects: D-AP5 showed no impact, CGS-19755 significantly inhibited contraction at the highest concentration, and MK-801 enhanced contractile force in a concentration-dependent manner at EFS frequencies of 1, 2, and 5 Hz. Neither agonists nor antagonists, including MK-801, induced calcium ion shifts in BSM cells. Single-cell RNA sequencing revealed no NMDAR subunit expression in BSM cells from human or mouse tissues. Immunofluorescence confirmed GluN1 expression in pulmonary artery smooth muscle but not in BSM.
Conclusions: Our findings indicate the absence of functional active NMDARs in BSM, suggesting that the therapeutic benefits of NMDAR inhibition observed in vivo for treating overactive bladder are unlikely to be directly mediated through effects on the BSM itself. This highlights the need to explore alternative mechanisms or targets for therapeutic interventions in overactive bladder conditions.
Background and objective: This study aimed to assess the prevalence of urinary incontinence (UI) and lower urinary tract symptoms (LUTS) in five selected low and middle-income countries to provide appropriate evidence for other related studies.
Materials and methods: In this multinational population-based cross-sectional survey between August 2019 and April 2021, validated questionnaires were used to assess LUTS in adults over 18 years from Iran, Egypt, Bangladesh, Brazil, and Cameroon.
Results: A total of 1477 participants from five countries completed the questionnaires. The mean age of participants was 43.5 ± 15.7 years. 37.1% reported at least one episode of UI per week. UUI prevalence in different countries analysis showed that the commonest prevalence was reported in Cameron (40.0%; n = 30), while the lowest was 15.0% (n = 31) in Brazil. Stress UI was common in Iran (38.7%; n = 338), and Bangladesh had the lowest rate (7.8%; n = 16). Urinary urgency was the common LUTS among participants (59.9%, n = 818 out of 1477 participants). Nocturia was the other prevalent symptom among cases (50.6%; 748 out of 1477 cases), and this symptom had a higher rate in elderly populations. Men reported voiding and postmicturition symptoms more frequently than women. Storage symptoms except for nocturia, including frequency, urgency, and UI were common in women while voiding symptoms, including straining, and intermittency were reported more frequently in men than women.
Conclusion: A high prevalence of urinary symptoms was reported in low to middle-income countries.
Introduction: Detrusor contractions can be classified as either volitional or involuntary. The latter are a hallmark of urge urinary incontinence. Understanding differences in neuroactivation associated with both types of contractions can help elucidate pathophysiology and therapeutic targets. In this study we aim to compare brain activity associated with voluntary and involuntary detrusor contractions.
Methods: Twenty seven stroke survivors with secondary storage lower urinary tract symptoms underwent four filling cycles of simultaneous urodynamics and BOLD-signal fMRI. After each fill, participants were instructed to void. Voids inside the designated 10-s period were considered voluntary contractions. All others were considered involuntary. Each contraction was then segmented into phases: Early (10 s before start of contraction), Rise (start of contraction to peak vesical pressure), Plateau, and Fall (from peak pressure to resolution of the contraction). BOLD-effect was compared between the two contraction types, employing a minimum cluster size of 25 voxels and significance threshold at p < 0.005.
Results: Compared to volitional contractions, involuntary contractions were associated with diminished brain activity in each contraction phase. During the Early phase, this difference was most prominent in areas implicated with sensory and autonomic function, shifting to regions tasked with motor control as the contraction continued and eventually attenuating as the contraction resolved.
Conclusion: This study uniquely contrasts brain activation associated with volitional and involuntary contractions. Relative to involuntary contractions, volitional contractions revealed increased activity in motor, sensory, and executive functioning regions. These findings reflect both the physiological mechanism of volitional contractions and suggest the displacement of this mechanism by a subcortical reflex in involuntary contractions.
Clinical trial registration: NCT05301335.
Aim: To compare the vaginal wall thickness (VWT) measurement by two-dimensional ultrasound (2D-US) and pelvic floor muscle morphometry by four-dimensional translabial ultrasound (4D-TLUS) in women with vaginal laxity (VL) who underwent treatment with radiofrequency (RF) or pelvic floor muscle training (PFMT) after 30 days and 6 months.
Methods: A secondary analysis of a randomized clinical trial that occurred between February 2020 and December 2021 was performed. Women with VL were enrolled and treated with RF or PFMT for 12 weeks. Ultrasound examiners were blinded for the groups. Transabdominal (TAUS) and transvaginal (TVUS) ultrasound were performed with 2D-US analysis. The 4D-TLUS was used for PFM morphometry assessment. We performed per-protocol and intention-to-treat analysis (5% significance).
Results: Women with ballooning presented significantly worse scoring in sexual function (p = 0.037) and vaginal symptoms (p = 0.007) than women without ballooning. Analysis of variance among 2D-US, intervention groups and assessment periods has shown that measurements of the TAUS proximal vagina increased in the PFMT group after 6 months (from 9.90 ± 3.14 mm to 10.53 ± 2.71 mm; p = 0.006). TAUS/TVUS distal vagina measurements were reduced after 6 months of RF (TAUS from 11.79 ± 3.67 mm to 10.51 ± 2.51 mm; p = 0.018/TVUS from 7.94 ± 1.83 mm to 7.32 ± 2.10 mm; p = 0.037). On the other hand, 4D-TLUS measurements did not present differences according to the intervention and/or groups.
Conclusion: Women with ballooning on 4D-TLUS presented significantly worse scoring in sexual function and vaginal symptoms. 2D-US found that RF reduced the VWT of the distal vagina after 6 months and PFMT increased the VWT of the proximal vagina after 6 months.
Clinical trial registration: Registro Brasileiro de Ensaios Clínicos-REBEC-RBR-2zdvfp as a clinical trial.
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