Risk Classification for Interstitial Cystitis/Bladder Pain Syndrome Using Machine Learning Based Predictions.

OBJECTIVE: To improve diagnosis of interstitial cystitis (IC)/bladder pain syndrome(IC) we hereby developed an improved IC risk classification using machine learning algorithms. METHODS: A national crowdsourcing resulted in 1264 urine samples consisting of 536 IC (513 female, 21 male, 2 unspecified), and 728 age-matched controls (318 female, 402 male, 8 unspecified) with corresponding patient-reported outcome (PRO) pain and symptom scores. In addition, 296 urine samples were collected at three academic centers: 78 IC (71 female, 7 male) and 218 controls (148 female, 68 male, 2 unspecified). Urinary cytokine biomarker levels were determined using Luminex assay. A machine learning predictive classification model, termed the Interstitial Cystitis Personalized Inflammation Symptom (IC-PIS) Score, that utilizes PRO and cytokine levels, was generated and compared to a challenger model. RESULTS: The top-performing model using biomarker measurements and PROs (area under the curve [AUC]=0.87) was a support vector classifier, which scored better at predicting IC than PROs alone (AUC=0.83). While biomarkers alone (AUC=0.58) did not exhibit strong predictive performance, their combination with PROs produced an improved predictive effect. CONCLUSION: IC-PIS represents a novel classification model designed to enhance the diagnostic accuracy of IC/bladder pain syndrome by integrating PROs and urine biomarkers. The innovative approach to sample collection logistics, coupled with one of the largest crowdsourced biomarker development studies utilizing ambient shipping methods across the US, underscores the robustness and scalability of our findings.

Comparing online crowdsourcing with clinic patient enrollment: Findings from the IP4IC Study on interstitial cystitis/bladder pain syndrome.

Introduction: Interstitial cystitis/bladder pain syndrome (IC/BPS) manifests as urinary symptoms including urgency, frequency, and pain. The IP4IC Study aimed to establish a urine-based biomarker score for diagnosing IC/BPS. To accomplish this objective, we investigated the parallels and variances between patients enrolled via physician/hospital clinics and those recruited through online crowdsourcing. Methods: Through a nationwide crowdsource effort, we collected surveys from patients with history of IC/BPS. Study participants were asked to complete the validated instruments of Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), as well as provide demographic information. We then compared the survey responses of patients recruited through crowdsourcing with those recruited from three specialized tertiary care urology clinics engaged in clinical research. Results: Survey responses of 1300 participants were collected from all 50 states of the USA via crowdsourcing and 319 from a clinical setting. ICSI and ICPI were similar for IC/BPS patients diagnosed by the physicians in clinic and self-reported by subjects via crowdsourcing stating they have a history of previous physician diagnosis of IC/BPS. Surprisingly, ICSI and ICPI were significantly lower in crowdsourced control than in-clinic control subjects. Conclusion: The IP4IC Study provides valuable insights into the similarities and differences between patients recruited through clinics and those recruited through online crowdsourcing. There were no significant differences in disease symptoms among these groups. Individuals who express an interest in digital health research and self-identify as having been previously diagnosed by physicians with IC/BPS can be regarded as reliable candidates for crowdsourcing research.

Improvement in International Prostate Symptom Score after prostatic urethral lifts is dependent on prostatic volume.

INTRODUCTION: Prostatic urethral lifts (PUL) provide improvement in urinary symptoms for men with benign prostatic hyperplasia (BPH). The aim of this study is to determine operative factors associated with improvement in urinary symptoms after PUL in men with bothersome BPH. MATERIALS AND METHODS: Men with BPH undergoing PUL at a single, tertiary center were identified from 2019 to 2022. Inclusion criteria included documented prostate volume as well as preoperative and postoperative cystoscopic images of the prostatic urethra. Multivariate regression modeling was performed to determine the predictive factors-including prostate volume, number of implants, and degree of unobstructed prostatic urethral channel-for improvement in International Prostate Symptom Score (IPSS) after PUL. RESULTS: Of the 47 men, the distribution of prostate volume was 1 patient with < 30 grams, 33 patients with 30-79 grams, five patients with 80-100 grams, and six patients with > 100 grams. The mean number of implants used was six implants. The mean preoperative and postoperative IPSS were 23 and 14, respectively. The mean (standard error (SE)) change and percent change in IPSS score following PUL was 14 and 60%, respectively. The mean percent improvement in prostatic urethral channel after anterior clip placements was 67%. On multivariate analysis, larger prostate volume was associated with greater change in IPPS follow surgery (p = 0.0091) while number of implants and percent of prostatic urethral opening were not associated with change in IPSS (p = 0.3094 and p = 0.2249, respectively). CONCLUSION: Men with larger prostates are associated with greater improvement in urinary symptom after PUL regardless of number of implants utilized and degree of prostatic urethral channel opening after prostatic implants.

A Mesozoic fossil lagerstätte from 250.8 million years ago shows a modern-type marine ecosystem.

Finely preserved fossil assemblages (lagerstätten) provide crucial insights into evolutionary innovations in deep time. We report an exceptionally preserved Early Triassic fossil assemblage, the Guiyang Biota, from the Daye Formation near Guiyang, South China. High-precision uranium-lead dating shows that the age of the Guiyang Biota is 250.83 +0.07/-0.06 million years ago. This is only 1.08 ± 0.08 million years after the severe Permian-Triassic mass extinction, and this assemblage therefore represents the oldest known Mesozoic lagerstätte found so far. The Guiyang Biota comprises at least 12 classes and 19 orders, including diverse fish fauna and malacostracans, revealing a trophically complex marine ecosystem. Therefore, this assemblage demonstrates the rapid rise of modern-type marine ecosystems after the Permian-Triassic mass extinction.

A Cost, Time, and Demographic Analysis of Participant Recruitment and Urine Sample Collection Through Social Media Optimization.

INTRODUCTION: Clinical research can be expensive and time consuming due to high associated costs and/or duration of the study. We hypothesized that urine sample collection using online recruitment and engagement of research participants via social medial has the potential to reach a large population in a small timeframe, at a reasonable cost. METHODS: We performed a retrospective cost analysis of a cohort study comparing cost per sample and time per sample for both online and clinically recruited participants for urine sample collection. During this time, cost data were collected based on study associated costs from invoices and budget spreadsheets. The data were subsequently analyzed using descriptive statistics. RESULTS: Each sample collection kit contained 3 urine cups, 1 for the disease sample and 2 for control samples. Out of the 3,576 (1,192 disease + 2,384 control) total sample cups mailed, 1,254 (695 control) samples were returned. Comparatively, the 2 clinical sites collected 305 samples. Although the initial startup cost of online recruitment was higher, cost per sample for online recruited was found to be $81.45 compared to $398.14 for clinic sample. CONCLUSIONS: We conducted a nationwide, contactless, urine sample collection through online recruitment in the midst of the COVID-19 pandemic. Results were compared with the samples collected in the clinical setting. Online recruitment can be utilized to collect urine samples rapidly, efficiently, and at a cost per sample that was 20% of an in-person clinic, and without risk of COVID-19 exposure.

Exceptional fossil assemblages confirm the existence of complex Early Triassic ecosystems during the early Spathian.

The mass extinction characterizing the Permian/Triassic boundary (PTB; ~ 252 Ma) corresponds to a major faunal shift between the Palaeozoic and the Modern evolutionary fauna. The temporal, spatial, environmental, and ecological dynamics of the associated biotic recovery remain highly debated, partly due to the scarce, or poorly-known, Early Triassic fossil record. Recently, an exceptionally complex ecosystem dated from immediately after the Smithian/Spathian boundary (~ 3 myr after the PTB) was reported: the Paris Biota (Idaho, USA). However, the spatiotemporal representativeness of this unique assemblage remained questionable as it was hitherto only reported from a single site. Here we describe three new exceptionally diverse assemblages of the same age as the Paris Biota, and a fourth younger one. They are located in Idaho and Nevada, and are taxonomic subsets of the Paris Biota. We show that the latter covered a region-wide area and persisted at least partially throughout the Spathian. The presence of a well-established marine fauna such as the Paris Biota, as soon as the early Spathian, indicates that the post-PTB biotic recovery and the installation of complex ecosystems probably took place earlier than often assumed, at least at a regional scale.

Use of Botulinum Toxin in the Genitourinary System.

Botulinum toxin injection has been widely accepted by the urology and urogynecology medical communities as a safe and effective treatment for refractory urinary incontinence. There are two approved genitourinary indications for botulinum toxin. OnabotulinumtoxinA (onaBoNTA) 200 U for the treatment of urinary incontinence due to detrusor overactivity associated with a neurologic condition (e.g., spinal cord injury, multiple sclerosis) in adults who have an inadequate response to or are intolerant of an anticholinergic medication. In addition, onaBoNTA 100 U is used for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and frequency, in adult patients who have an inadequate response to or are intolerant of an anticholinergic medication. We will discuss the application of botulinum toxin for genitourinary indications with a focus on bladder injection and on potential use of BoNT use in the prostate and pelvic floor.

High-density surface electromyographic assessment of pelvic floor hypertonicity in IC/BPS patients: a pilot study.

INTRODUCTION AND HYPOTHESIS: To assess the feasibility of objectively assessing pelvic floor hypertonicity (PFH) in women with interstitial cystitis/bladder pain syndrome (IC/BPS) using an intra-vaginal high-density surface electromyography (HD-sEMG) probe. METHODS: Seven female subjects (mean age 44 ± 13 years) with a prior diagnosis of IC/BPS were recruited. A full digital pelvic examination was administered to identify hypertonic muscles. Intra-vaginal HD-sEMG was acquired during rest. Root-mean-squared (RMS) amplitude during rest was calculated for each channel to define a hypertonicity index and hypertonic zone. Innervation zones (IZs) were identified from the bipolar mapping of decomposed HD-sEMG signals and summarized into an IZ distribution mapping. RESULTS: Of the seven subjects recruited, five had normal pelvic floor muscle tone and two exhibited hypertonicity upon muscle palpation. Subjects with PFH demonstrated a higher hypertonicity index (12.6 ± 3.5 vs. 4.5 ± 1.2) in sessions 1 and 2. The hypertonic zone defined by the 64-channel RMS mapping coincided with the digital pelvic examination findings. The corresponding IZs were localized for each motor unit. The hypertonicity indices between two consecutive sessions were well correlated (CC = 0.95). CONCLUSIONS: This study represents the first effort to employ intra-vaginal HD-sEMG to assess PFH in women with IC/BPS. Our results demonstrate the feasibility of HD-sEMG to provide a quantitative diagnosis of PFH and the precise localization of hypertonic muscles and IZs. The proposed HD-sEMG-based techniques provide promising tools for clinical diagnosis and treatment of PFH, such as the personalized guidance of BoNT injections.

Safety, Feasibility, and Efficacy of Transcutaneous Tibial Nerve Stimulation in Acute Spinal Cord Injury Neurogenic Bladder: A Randomized Control Pilot Trial.

OBJECTIVES: We investigated whether transcutaneous tibial nerve stimulation (TTNS) in acute spinal cord injury was safe and feasible, and could achieve neuromodulation and improve cystometrogram parameters during acute inpatient rehabilitation. MATERIALS AND METHODS: Participants were consecutive acute traumatic spinal cord injury patients admitted for acute inpatient rehabilitation, randomized to a 2-week trial of TTNS v sham stimulation. Primary outcomes were safety and feasibility of TTNS and secondary outcomes were bladder measures based on pre- and post-TTNS cystometrogram by group and within groups, including bladder capacity, detrusor hyperreflexia, pressures, and detrusor-sphincter dyssynergia, as well as filling sensations and desire to void. The principle investigator and subjects were blinded to treatment allocation. RESULTS: A total of 19 subjects consented to the study and completed the stimulation protocol. Morbidity was similar between groups and compliance was 100% to the TTNS protocol. Based on a lack of rehabilitation interruptions and comments from staff, TTNS was feasible. Post-cystometrogram parameters were significant for lower volumes until sensation in the control group and prolonged volumes until sensation in the TTNS group. The control group had significant changes of increased detrusor-sphincter dyssynergia and decreased bladder capacity. This was not significantly changed in the TTNS group. CONCLUSIONS: TTNS is a safe and feasible modality that can be performed during inpatient rehabilitation of acute traumatic spinal cord injury. Bladder capacity and episodes of detrusor-sphincter dyssynergia significantly worsened in the control group and did not significantly change in the TTNS group, suggesting that TTNS can alter the course of neurogenic bladder via neuromodulation.

Non-surgical urologic management of neurogenic bladder after spinal cord injury.

PURPOSE: To review the available data on non-surgical management for neurogenic bladder in patients with spinal cord injury (SCI). Before the introduction of urinary catheters and antibiotics, neurogenic bladder was one of the main culprits for death in those patients with SCI. Currently, the management of neurogenic bladder is focused in improving quality of life and preserving renal function. METHODS: A literature review was performed and therapeutic management for neurogenic bladder was divided in six sections: (1) intermittent bladder catheterization; (2) indwelling catheters; (3) condom catheter drainage; (4) reflex voiding and bladder expression with Valsalva or Credé; (5) oral drug therapy of the spinal cord injured bladder; and (6) botulinum neurotoxin (BoNT). RESULTS: Intermittent catheterization is recommended as the preferable method for management of neurogenic bladder in patients with SCI based on limited high-quality data. However, this may not be feasible or available to all and other alternative options include condom catheter drainage or indwelling catheters such as urethral catheters or suprapubic tube, reflex voiding, and bladder expression with Valsalva or Credé. Non-invasive medical therapies are the key to improve incontinence, urodynamic parameters, and quality of life in this population. Botulinum neurotoxin has revolutionized the management of neurogenic bladder in the last two decades decreasing the need for reconstruction or diversion. CONCLUSION: The Joint SIU-ICUD (Société Internationale d'Urologie) (International Consultation on Urological Diseases) International Consultation reviewed the available presented data and provided specific conclusions and recommendations for each non-surgical urologic method to address neurogenic bladder after SCI.

Rapid Detection of Zika Virus in Urine Samples and Infected Mosquitos by Reverse Transcription-Loop-Mediated Isothermal Amplification.

Infection with Zika virus (ZIKV) is of growing concern since infection is associated with the development of congenital neurological disease. Quantitative reverse transcription PCR (qRT-PCR) has been the standard for ZIKV detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper testing. Studies have suggested that ZIKV detection in urine is more sensitive and has a longer window of detection compared to serum and saliva. The objective of this study was to develop a urine diagnostic test that could be completed in under 30 minutes. Urine samples spiked with ZIKV or dengue virus were tested using RT-LAMP as well as by conventional quantitative qRT-PCR. These techniques were then validated using crude lysates made from ZIKV infected mosquitoes in addition to urine and serum samples from ZIKV infected patients. RT-LAMP specifically detected ZIKV in urine and serum for ZIKV infected patients and crude mosquito lysates. This test was performed in under 30 minutes and did not require RNA extraction from urine nor mosquitos. This approach could be used for monitoring of exposed individuals, especially pregnant women, couples wanting to conceive, or individuals with suspicious symptoms as well as surveillance of mosquito populations.

Botulinum toxin to treat pelvic pain.

Botulinum toxin's (BoNT) success in treating several pain disorders has triggered interest in its application for pelvic pain disorders. This article summarizes results presented at the recent Neurotoxins Meeting in Madrid, Spain, in January 2017. It does not include BoNT use for Interstitial Cystitis/Bladder Pain Syndrome, which was the topic of a separate lecture. It includes studies documenting the beneficial effects of OnaBoNTA for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men using both transrectal and transurethral injection techniques. It also focuses on research using OnaBoNTA to treat levator spasms in women with chronic pelvic pain. Finally, it presents a novel approach using high density quantitative surface EMG to map out innervation zones and allow for more precise targeting of hypertonic pelvic floor muscles.

Chylous Ascites Complicating Modified Radical Hysterectomy for Placenta Percreta.

BACKGROUND: Chylous ascites is defined as the pathologic accumulation of lymphatic fluid within the peritoneal cavity and has been reported to complicate gynecologic surgeries, with an incidence of 0.17-2%. We report a case of chylous ascites after complex surgery for placenta percreta. CASE: A 26-year-old woman underwent cesarean delivery followed by bilateral uterine artery embolization and modified radical hysterectomy at 26 5/7 weeks of gestation for placenta percreta invading the urinary bladder. No surgical dissection was performed above the pelvic brim or deep into the pelvic sidewalls. On postoperative day 4, milky fluid consistent with chylous ascites was noted coming from a percutaneous drain. This completely resolved after 12 days of conservative management with intravenous nutritional support. CONCLUSION: Chylous ascites is a potential complication of modified radical hysterectomy for placenta percreta that responds to conservative management.

Male chronic pelvic pain: An update.

INTRODUCTION: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and interstitial cystitis/bladder pain syndrome collectively referred to as urologic CPPS (UCPPS) is defined by the absence of identifiable bacterial infection as a cause for the chronic pain and urinary symptoms. METHODS: A PubMed search of all recent relevant articles using the keywords/phrases: CPPS, CPPS, and male pelvic pain, was conducted. RESULTS: CPPS has a high worldwide prevalence and its negative impact on quality of life compares with or exceeds common chronic morbidities. Triggers include certain comestibles as well as psychosocial factors that promote catastrophizing and illness focused behavior. Several validated tools are currently available to help diagnose and direct targeted therapy. Treatment should begin with the most simple and least invasive based on the presenting clinical phenotype. CONCLUSIONS: Although no gold-standard treatment exists, a multidisciplinary approach with multimodal therapy gives the UCPPS patient the best chance of symptom relief.

Botulinum Toxin to Treat Neurogenic Bladder.

Alteration in neural control from suprapontine areas to the nerves innervating the bladder can lead to bladder dysfunction and the development of a neurogenic bladder (NGB). Patients with NGB often suffer from urinary incontinence, which can lead to adverse events such as urinary tract infections and decubiti, in addition to creating a large care burden for family members or healthcare providers and significantly impairing patient quality of life. The common failure of anticholinergic medications has spurned the development of second-line treatments, including the use of botulinum toxin. OnabotulinumtoxinA (onaBoNT-A; BOTOX, Allergan, Inc.) was approved by the U.S. Food and Drug Administration (FDA) in 2011 to treat neurogenic detrusor overactivity in patients with urinary incontinence resulting from a NGB. In this review the authors summarize pertinent results from key trials leading to FDA approval of onaBoNT-A as well as more recent long-term data.

Transurethral use of a nephroscope significantly AIDS in the surgical management of an intrauterine device eroding into the bladder.

BACKGROUND: Intravesical migration of an intrauterine device (IUD) is a rare occurrence. The IUD becomes the nidus for calcification. Three approaches to remove the device include the use of open cystolithotomy, transurethral grasping forceps, or minimally invasive laparoscopy. CASE: A 50-year-old woman presented with vague abdominal pain and recurrent urinary tract infections. She was found to have an intravesical migration or malplacement of an IUD which was unretrievable 20 years ago and was encrusted with a calculus formation. We removed the foreign body through a transurethral approach aided by the use of a nephroscope which allowed for easy access of laparoscopic scissors and grasping forceps. CONCLUSIONS: The transurethral approach with the use of a nephroscope significantly aids in the removal of an IUD embedded into the bladder wall.

Diabetic plasticity of non-adrenergic non-cholinergic and P2X-mediated rat bladder contractions.

We investigated the plasticity effects of diabetes mellitus and diuresis on the non-adrenergic non-cholinergic (NANC) and purinergic (P2X-type) contractile responses in longitudinal rat bladder strips. Female Sprague-Dawley rats received streptozotocin to induce diabetes, or sucrose in water to induce diuresis as a control condition for polyuria. Experiments were carried out at four weeks after treatments, using bladders from non-treated rats as control. Urinary bladder strips were electrically stimulated throughout the experiments to generate neurally evoked contractions (NEC). In all cases, P2X-mediated purinergic contractions were evaluated at the beginning and end of the stimulations with α,ß-methylene-adenosine triphosphate (α,ßMeATP). The NANC responses were assessed by using two independent protocols. First, cholinergic receptors were activated with carbachol (CCh), followed by inhibition of the muscarinic component with atropine. In the second protocol, the application order for CCh and atropine was reversed. The NANC response, unmasked with the application of atropine, and the P2X purinergic contractions were analyzed. NANC contractions in diabetic bladder strips are more resistant to the desensitizing effects caused by activation of cholinergic receptors. In early stages of experimental diabetes, NANC responses in diabetic strips are less sensitive to functional inhibition mediated by the cholinergic activation. However, P2X-mediated purinergic contractions are more sensitive to desensitization in diabetic or diuretic bladders. For instance preventing muscarinic receptor activation with atropine does not counteract the desensitization of purinergic contractions in either diabetic or diuretic strips. We suggest that diabetes may induce a plasticity of the NANC and P2X-mediated bladder contractile responses. The first one may be associated with diabetic neuropathic damage to bladder nerves, while impaired P2X purinergic contractions might be associated with detrusor hypertrophy observed in diabetic and diuretic strips.

Evidence-based review and assessment of botulinum neurotoxin for the treatment of urologic conditions.

Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of certain urologic conditions, including detrusor sphincter dyssynergia (DSD), lower urinary tract symptoms due to benign prostatic hyperplasia (BPH), and detrusor overactivity (both neurogenic [NDO] and idiopathic [IDO]), an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, for the serotypes BoNT-A and BoNT-B, as well as for the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations on the use of BoNT for the management of these urologic conditions based upon the strength of clinical evidence and following the AAN classification scale. For the treatment of DSD, the evidence supported a Level B recommendation for the use of A/Ona; A/Abo, A/Inco, and B/Rima received a Level U recommendation. For the treatment of NDO, there was sufficient clinical evidence to support a Level A recommendation for BoNT-A as well as for both A/Ona and A/Abo; no published data were identified for either A/Inco or B/Rima (Level U). For the treatment of IDO, the evidence supported a Level A recommendation for A/Ona; A/Inco, A/Abo, and B/Rima received a Level U recommendation. For the management of BPH, the evidence supported a Level B recommendation for BoNT and A/Ona; no published studies were identified for A/Abo, A/Inco, or B/Rima, warranting a Level U recommendation for these three formulations. Further studies are needed to evaluate the efficacy and safety of BoNT for the management of urologic conditions.

Evidence-based review and assessment of botulinum neurotoxin for the treatment of adult spasticity in the upper motor neuron syndrome.

Botulinum neurotoxin (BoNT) can be injected to achieve therapeutic benefit across a large range of clinical conditions. To assess the efficacy and safety of BoNT injections for the treatment of spasticity associated with the upper motor neuron syndrome (UMNS), an expert panel reviewed evidence from the published literature. Data sources included English-language studies identified via MEDLINE, EMBASE, CINAHL, Current Contents, and the Cochrane Central Register of Controlled Trials. Evidence tables generated in the 2008 Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (AAN) review of the use of BoNT for autonomic disorders were also reviewed and updated. The panel evaluated evidence at several levels, supporting BoNT as a class, the serotypes BoNT-A and BoNT-B, as well as the four individual commercially available formulations: abobotulinumtoxinA (A/Abo), onabotulinumtoxinA (A/Ona), incobotulinumtoxinA (A/Inco), and rimabotulinumtoxinB (B/Rima). The panel ultimately made recommendations on the effectiveness of BoNT for the management of spasticity, based upon the strength of clinical evidence and following the AAN classification scale. While the prior report by the AAN provided recommendations for the use of BoNT as a class of drug, this report provides more detail and includes recommendations for the individual formulations. For the treatment of upper limb spasticity, the evidence supported a Level A recommendation for BoNT-A, A/Abo, and A/Ona, with a Level B recommendation for A/Inco; there was insufficient evidence to support a recommendation for B/Rima. For lower limb spasticity, there was sufficient clinical evidence to support a Level A recommendation for A/Ona individually and BoNT-A in aggregate; the clinical evidence for A/Abo supported a Level C recommendation; and there was insufficient information to recommend A/Inco and B/Rima (Level U). There is a need for further comparative effectiveness studies of the available BoNT formulations for the management of spasticity.

Modulation of bladder afferent signals in normal and spinal cord-injured rats by purinergic P2X3 and P2X2/3 receptors.

OBJECTIVE: To evaluate the role of bladder sensory purinergic P2X3 and P2X2/3 receptors on modulating the activity of lumbosacral neurones and urinary bladder contractions in vivo in normal or spinal cord-injured (SCI) rats with neurogenic bladder overactivity. MATERIALS AND METHODS: SCI was induced in female rats by complete transection at T8-T9 and experiments were performed 4 weeks later, when bladder overactivity developed. Non-transected rats were used as controls (normal rats). Neural activity was recorded in the dorsal horn of the spinal cord and field potentials were acquired in response to intravesical pressure steps via a suprapubic catheter. Field potentials were recorded under control conditions, after stimulation of bladder mucosal purinergic receptors with intravesical ATP (1 mm), and after intravenous injection of the P2X3/P2X2/3 antagonist AF-353 (10 mg/kg and 20 mg/kg). Cystometry was performed in urethane-anaesthetised rats intravesically infused with saline. AF-353 (10 mg/kg) was systemically applied after baseline recordings; the rats also received a second dose of AF-353 (20 mg/kg). Changes in the frequency of voiding (VC) and non-voiding (NVC) contractions were evaluated. RESULTS: SCI rats had significantly higher frequencies for field potentials and NVC than NL rats. Intravesical ATP increased field potential frequency in control but not SCI rats, while systemic AF-353 significantly reduced this parameter in both groups. AF-353 also reduced the inter-contractile interval in control but not in SCI rats; however, the frequency of NVC in SCI rats was significantly reduced. CONCLUSION: The P2X3/P2X2/3 receptors on bladder afferent nerves positively regulate sensory activity and NVCs in overactive bladders.