Prospective follow-up of overactive bladder symptoms in patients with prior SARS-CoV-2 infection.

PURPOSE: SARS-CoV-2 infection can result in genitourinary symptoms, such as frequency, urgency, nocturia, and pain/pressure. In this study, we followed the progression of overactive bladder (OAB) symptoms in patients that reported new or worsening OAB symptoms after coronavirus disease-19 (COVID-19) diagnosis. MATERIALS AND METHODS: Individuals from a COVID-19 serology study were invited to participate in a follow-up study. Respondents were divided into three groups based on prior COVID-19 testing. Patients scored symptoms retrospectively before the pandemic, at study onset, and prospectively during 12-month follow-up. Genitourinary symptoms were assessed using international consultation on incontinence questionaire for OAB (ICIQ-OAB). Change in ICIQ-OAB scores from baseline were calculated. The minimal important difference of one on ICIQ-OAB is considered a significant change. RESULTS: 26.0% of participants previously had positive COVID polymerase chain reaction (PCR) test (PCR+), 5.6% a positive serology test only (Ser+), and 65.5% were COVID naïve (COVID-). 23.8% of participants reported a significant increase in ICIQ-OAB score at study onset compared to prepandemic. ICIQ-OAB scores were similar at prepandemic but significantly higher at study start (p < 0.001) in PCR+ group. During follow-up, change in ICIQ-OAB scores from baseline remained unchanged for COVID- group, but gradually reduced for PCR+, reaching similar levels as COVID- group by 12 months. By 12 months, 71.4% of PCR+, 42.9% of Ser+, and 68.8% of COVID- participants still reported significant increase in ICIQ-OAB scores. CONCLUSIONS: Most COVID-19 patients experienced return of symptoms to baseline, indicative of the potential resolution of COVID-associated cystitis. A subset of cases did not, raising questions about the underlying factors contributing to this outcome. Additional research is needed to assess long COVID on urological health.

Evaluating symptom severity and urinary cytokine levels in interstitial cystitis/bladder pain syndrome patients, with and without Hunner's lesions.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a condition characterized in part by urinary urgency, frequency, and pain. There is a strong interest in gathering more data to compare and assess the differences in characteristics based on the presence of Hunner's lesions in patients with IC/BPS. MATERIALS AND METHODS: Using a nationwide crowdsource effort, we collected surveys and urine samples from patients with a history of IC/BPS. Participants completed the Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), Overactive Bladder questionnaire (OABq SF), and pain scores. In addition, participants reported any co-morbidities and lifestyle modifications. Urinary cytokine levels were measured and compared to symptom severity. RESULTS: 491 participants enrolled: 119 with history of ulcerative Hunner's lesions (UIC), 372 reported no lesions (NHIC), and 2 unknowns. 96.3% were female, and prevalence of UIC was equal for both genders. Average age was higher for UIC vs. NHIC group (P = 0.011), as was the duration since diagnosis (P < 0.001). Symptom scores were elevated in UIC patients (P < 0.001). Both groups widely implemented lifestyle modifications, with dietary changes being most prevalent (70.1%), followed by prescription medication usage (63.1%). More UIC compared to NHIC participants experienced co-morbidities (P = 0.010). Urine samples were analyzed for GRO, IL-6, IL-8, and MCP-1. MCP-1 levels were significantly higher in UIC patients (P = 0.044). Weak positive correlation was found between cytokines and symptom scores. CONCLUSIONS: Patients with UIC and NHIC from across the United States displayed distinct phenotypic and urine biological characteristics. These findings contribute to increased understanding of IC/BPS and may aid in improving our knowledge of the condition.

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.

Fibrin microthrombi in bladder urothelium after SARS-CoV-2 infection: Case report.

A 45-year-old male with diabetes, hypertension and hyperlipidemia was referred to urology due to persistent symptoms of urinary frequency, urgency, nocturia, erectile dysfunction, and constant pain localized to the bladder, pelvis, and perineal area, 3-4 months after SARS-CoV-2 infection. A bladder biopsy showed urothelial mucosa and submucosa with hemorrhage and fibrin microthrombi in blood vessels. Hydrodistention of the bladder and pelvic floor physical therapy resolved symptoms, though bladder and pain symptoms returned upon reinfection with SARS-CoV-2. Urinalysis revealed elevated urinary interleukin-8, which may indicate localized bladder inflammation.

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.

Pudendal Neuromodulation is Feasible and Effective After Pudendal Nerve Entrapment Surgery.

BACKGROUND: Patients with intractable pain in the pudendal nerve distribution may benefit from pudendal neuromodulation; however, some may have previously undergone pudendal nerve entrapment surgery (PNES), potentially altering nerve anatomy and function. AIM: We examined pudendal neuromodulation outcomes in patients with prior PNES. METHODS: Patients with a history of PNES and quadripolar, tined pudendal lead placement for urogenital pain were reviewed. Symptoms and outcomes were collected from existing medical records. OUTCOMES: Patients with pudendal neuromodulation and prior PNES were compared to patients with no prior PNES who had pudendal lead placement. RESULTS: Fifteen patients with a history of 1, 2, or 3 prior PNES (n = 13, 1, and 1, respectively) were evaluated. Most (10; 67%) were female, with bilateral pain (9; 60%), and symptoms of 5-26 years. After trialing the lead, bladder symptoms and pain were improved in 8 of 12 and 9 of 14 patients, respectively, and 80% of patients (12/15) underwent permanent generator implantation. When prior PNES patients were compared to those with no prior PNES (n = 43), gender (67% vs 77% female; P = .50) and age (median 63 vs 58 years; P = .80), were similar; however, BMI differed (mean 24 vs 29; P = .008) and a lower proportion (12/15; 80% vs 42/43; 98%; P = .049) had generator implantation. Importantly, median lead implant time (48 vs 50 minutes; P = .65) did not differ between the 2 groups. CLINICAL IMPLICATIONS: Pudendal neuromodulation has the potential to provide pain relief for a very difficult-to-treat population; furthermore, it does not appear that prior PNES surgery made lead placement significantly more challenging. STRENGTHS & LIMITATIONS: Study strengths include being a tertiary referral center for urogenital pain and having a single surgeon perform all procedures in a regimented way. Limitations include the retrospective study design, small sample size and various approaches to PN CONCLUSION: Chronic pudendal neuromodulation can be a viable option even after prior PNES. Kristen M. Meier, Patrick M. Vecellio, Kim A. Killinger, Judith A. Boura, Kenneth M. Peters. Pudendal Neuromodulation is Feasible and Effective After Pudendal Nerve Entrapment Surgery. J Sex Med 2022;19:995-1001.

Safety, tolerability, and efficacy of LiRIS 400 mg in women with interstitial cystitis/bladder pain syndrome with or without Hunner lesions.

AIMS: Two phase 2 studies were conducted to assess the efficacy and safety of lidocaine-releasing intravesical system (LiRIS) in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) with (Study 001; NCT02395042) or without, (Study 002; NCT02411110) Hunner lesions (HL). METHODS: Both were multicenter, randomized, double-blind, placebo-controlled, and enrolled women aged ≥18 years. In Study 001, patients were randomized 2:1:1 to LiRIS 400 mg/LiRIS 400 mg, placebo/LiRIS 400 mg, or placebo/placebo for a continuous 28 (2 × 14)-day period. In Study 002, patients were randomized 1:1 to LiRIS 400 mg or placebo for a continuous (single treatment) 14-day period. RESULTS: In total, 59 and 131 patients received treatment in Studies 001 and 002, respectively. There was no statistically significant difference in the primary endpoint, the change from baseline to Week 4 of follow-up post-removal in mean daily average bladder numeric rating scale (NRS) pain score in either study (Study 001: placebo/placebo, -1.6; LiRIS/LiRIS, -2.7, p = 0.142; placebo/LiRIS, -2.5, p = 0.319; Study 002: LiRIS -1.2; placebo, -1.5, p = 0.505). There was no statistically significant difference between groups in daily worst NRS pain score, number of micturitions/day or urgency episodes/day. There was no clear trend for reduction in number of HL for LiRIS vs placebo. The frequency of treatment-emergent adverse events was similar between treatment groups in both studies; most were mild or moderate intensity. CONCLUSION: These studies did not demonstrate a treatment effect of LiRIS 400 mg compared with placebo, either in patients with IC/BPS with HL, or in those without HL.

International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD).

BACKGROUND: Persistent genital arousal disorder (PGAD), a condition of unwanted, unremitting sensations of genital arousal, is associated with a significant, negative psychosocial impact that may include emotional lability, catastrophization, and suicidal ideation. Despite being first reported in 2001, PGAD remains poorly understood. AIM: To characterize this complex condition more accurately, review the epidemiology and pathophysiology, and provide new nomenclature and guidance for evidence-based management. METHODS: A panel of experts reviewed pertinent literature, discussed research and clinical experience, and used a modified Delphi method to reach consensus concerning nomenclature, etiology, and associated factors. Levels of evidence and grades of recommendation were assigned for diagnosis and treatment. OUTCOMES: The nomenclature of PGAD was broadened to include genito-pelvic dysesthesia (GPD), and a new biopsychosocial diagnostic and treatment algorithm for PGAD/GPD was developed. RESULTS: The panel recognized that the term PGAD does not fully characterize the constellation of GPD symptoms experienced by patients. Therefore, the more inclusive term PGAD/GPD was adopted, which maintains the primacy of the distressing arousal symptoms and acknowledges associated bothersome GPD. While there are diverse biopsychosocial contributors, there is a common underlying neurologic basis attributable to spontaneous intense activity of the genito-pelvic region represented in the somatosensory cortex and its projections. A process of care diagnostic and treatment strategy was developed to guide the clinician, whenever possible, by localizing the symptoms as originating in any of five regions: (i) end organ, (ii) pelvis/perineum, (iii) cauda equina, (iv) spinal cord, and (v) brain. Psychological treatment strategies were considered critical and should be performed in conjunction with medical strategies. Pharmaceutical interventions may be used based on their site and mechanism of action to reduce patients' symptoms and the associated bother and distress. CLINICAL IMPLICATIONS: The process of care for PGAD/GPD uses a personalized, biopsychosocial approach for diagnosis and treatment. STRENGTHS AND LIMITATIONS: Strengths and Limitations: Strengths include characterization of the condition by consensus, analysis, and recommendation of a new nomenclature and a rational basis for diagnosis and treatment. Future investigations into etiology and treatment outcomes are recommended. The main limitations are the dearth of knowledge concerning this condition and that the current literature consists primarily of case reports and expert opinion. CONCLUSION: We provide, for the first time, an expert consensus review of the epidemiology and pathophysiology and the development of a new nomenclature and rational algorithm for management of this extremely distressing sexual health condition that may be more prevalent than previously recognized. Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med 2021;18:665-697.

Current advances in neuromodulation techniques in urology practices: A review of literature.

Neuromodulation has become a valid therapeutic option for patients with various lower urinary tract disorders. In clinical practice, the most used and recommended neuromodulation techniques are sacral neuromodulation (SNM), pudendal neuromodulation (PN), and percutaneous tibial nerve stimulation (PTNS). There are many theories concerning the mechanism of action of neuromodulation. Although SNM, PN, and PTNS show their activities through different nerve roots, all provide central and peripheral nervous system modulations. SNM has been approved for the treatment of overactive bladder (OAB), nonobstructive urinary retention, and fecal incontinence, while PTNS has been approved for OAB treatment. However, they are also used off-label in other urinary and nonurinary pelvic floor disorders, such as neurogenic lower urinary system disorder, interstitial cystitis, chronic pelvic pain, and sexual dysfunction. Minor and nonsurgical reversible complications are usually seen after neuromodulation techniques. In addition, in the last few years, there have been various developments in neuromodulation technology. Some of the examples of these developments are rechargeable batteries with wireless charging, improvements in programing, less invasive single-stage implantation in outpatient settings, and lower-cost new devices. We performed a literature search using Medline (PubMed), Cochrane Library, EMBASE, and Google scholar databases in the English language from January 2010 to February 2021. We included reviews, meta-analyses, randomized controlled trials, and prospective and retrospective studies to evaluate the activities and reliability of SNM, PN, and PTNS and the developments in this area in the last decade based on the current literature.

Symptom and Quality of Life Improvements After Pelvic Floor Physical Therapy in a Clinical Population of Women With Pelvic Pain and Other Symptoms.

OBJECTIVES: This study aimed to evaluate changes in validated symptom scores at intake and discharge in women undergoing pelvic floor physical therapy (PFPT) for pain and other pelvic floor symptoms. METHODS: Consecutive women starting PFPT during 1 year were reviewed. History, demographics, and Pelvic Floor Distress Inventory Questionnaire - Short Form 20 (PFDI) total and domain scores (Pelvic Organ Prolapse Distress Inventory-6, Urogenital Distress Inventory-6, Colorectal-Anal Distress Inventory-8), Pelvic Floor Impact Questionnaire (PFIQ-7), and pain levels on a numeric rating scale (NRS) were collected at intake and discharge. Data were analyzed with descriptive statistics and sign tests. RESULTS: Of 474 women, mean age was 50.3 ± 16.7 years (range, 18-87 years) and the most common indication for PFPT was pelvic pain (208/474; 43.9%). In women with complete data, pretreatment to posttreatment median scores improved on the PFDI (77.3 vs 41.8; P < 0.0001), Urogenital Distress Inventory (37.5 vs 16.0; P < 0.0001), and PFIQ (58.0 vs 19.0; P < 0.0001), and the minimal clinically important difference was met for the PFDI, PFIQ, and Colorectal-Anal Distress Inventory. Women with primarily pelvic pain (n = 208) achieved significant improvements in PFDI, PFIQ, and NRS scores (P < 0.0001 for all) as well as the minimal clinically important difference for these measures. Pain patients with a history of pelvic surgery (n = 50) also had significant improvements in PFIQ and NRS but not PFDI scores. CONCLUSIONS: Most women referred to PFPT demonstrated symptom improvements as measured by validated instruments.

Small Fiber Polyneuropathy in Hunner Lesion and Non-Hunner Lesion Interstitial Cystitis/Bladder Pain Syndrome.

OBJECTIVE: This study aimed to determine whether small fiber polyneuropathy (SFPN) diagnosis differs between Hunner lesion interstitial cystitis/bladder pain syndrome (HL IC/BPS) and non-Hunner lesion IC/BPS (NHL IC/BPS). METHODS: This was a pilot study of 20 women with IC/BPS. Results from baseline questionnaires, such as Genitourinary Pain Index, Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index (ICSI/ICPI), Patient Health Questionnaire-2, were collected.Two punch biopsies were performed on each patient: distal leg and thigh. The samples were evaluated for intraepidermal nerve fiber density. One intraepidermal nerve fiber density less than the fifth percentile, regardless of site, indicated a positive SPFN diagnosis. RESULTS: Twenty patients were enrolled; 10 HL IC/BPS and 10 NHL IC/BPS. The HL IC/BPS group was found to be significantly older than the NHL IC/BPS group (63 vs 48 years, P = 0.007). No significant differences were found in employment or relationship statuses, or in levels of education or comorbidities between the 2 groups.Sixty percent (6/10) of patients had SFPN in the NHL IC/BPS group compared with 40% (4/10) in the HL IC/BPS group. No significant differences were seen in SFPN positivity (P = 0.3) or Genitourinary Pain Index, Patient Health Questionnaire-2, or Interstitial Cystitis Symptom Index/Interstitial Cystitis Problem Index scores between the NHL and HL IC/BPS groups. CONCLUSIONS: Similar to previously published studies, 60% of NHL IC/BPS patients in this cohort were positive for SFPN compared with only 40% of the HL IC/BPS patients. Larger studies may be needed to realize the full impact of SFPN in IC/BPS.

Proteomic analysis of bladder biopsies from interstitial cystitis/bladder pain syndrome patients with and without Hunner's lesions reveals differences in expression of inflammatory and structural proteins.

BACKGROUND: Interstitial cystitis/bladder pain syndrome is a bladder disease usually characterized by pain, urgency, and frequency. Interstitial cystitis is currently classified into two subtypes, with and without Hunner's lesions. However, the underlying etiology of interstitial cystitis and its subtypes are largely unknown. METHODS: To better understand the biological changes in the bladder of interstitial cystitis/bladder pain syndrome patients, we directly analyzed bladder tissue of interstitial cystitis patients, both those with Hunner's lesions and those without. Proteins in the bladder biopsies were analyzed using nanoscale high-performance liquid chromatography-tandem mass spectrometry. Disease subgroups were compared and significantly expressed proteins were mapped using STRING to determine protein associations and functions. RESULTS: We found that patients with Hunner's lesions had significant increases in inflammatory and endoplasmic reticulum stress proteins, with a decrease in cellular adhesive proteins, compared to patients without Hunner's lesions. These patients also exhibited a decrease in proteins associated with the Rap1 signaling pathway, which regulates cell proliferation and wound healing. When comparing diseased and non-disease-apparent tissue in patients with Hunner's lesions, diseased tissue exhibited a decrease in ubiquitination proteins. CONCLUSIONS: In summary, there are significant differences in protein expression found in the bladders of interstitial cystitis patients with and without Hunner's lesions, indicating a disturbance in proteins associated with cellular adhesion, proliferation, protein processing, and wound healing.

Targeting the SHIP1 Pathway Fails to Show Treatment Benefit in Interstitial Cystitis/Bladder Pain Syndrome: Lessons Learned from Evaluating Potentially Effective Therapies in This Enigmatic Syndrome.

PURPOSE: In this 12-week, randomized, double-blind, placebo controlled, multicenter, 3-arm, parallel group, phase 3 trial we assessed the effects of a novel SHIP1 activator on bladder pain and urinary symptoms in patients with interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: Subjects with interstitial cystitis/bladder pain syndrome and a mean pain score of 5 or greater on an 11-point scale despite treatment were randomized to 100 or 200 mg of an oral SHIP1 activator or placebo once daily for 12 weeks. Maximum pain scores and urinary frequency were recorded in an e-diary. The ICSI (O'Leary-Sant Interstitial Cystitis Symptom Index) and BPIC-SS (Bladder Pain Interstitial Cystitis Symptom Score) questionnaires were administered. Safety was monitored through 12 weeks of treatment. RESULTS: A total of 298 female subjects with moderate to severe symptoms of interstitial cystitis/bladder pain syndrome were treated with 100 or 200 mg SHIP1 activator orally once daily for 12 weeks. Treatment demonstrated no difference in maximum daily bladder pain compared to placebo. There was no treatment benefit over that of placebo in the secondary end points of urinary voiding frequency, the BPIC-SS, the ICSI and a global response assessment. Exploratory analysis in 87 male subjects yielded a similar result, that is no difference from placebo. Treatment was generally well tolerated at both doses. CONCLUSIONS: SHIP1 activation is a safe but ineffective therapeutic approach to interstitial cystitis/bladder pain syndrome. Although this was a negative trial, the important lessons learned from this study in respect to inflammatory phenotype differentiation, including the potential importance of cystoscopy based classification, will improve current treatment in patients with interstitial cystitis/bladder pain syndrome and allow for better future trial design in those with this difficult urological chronic pain syndrome.

Transvaginal Trigger Point Injections Improve Pain Scores in Women with Pelvic Floor Hypertonicity and Pelvic Pain Conditions.

OBJECTIVES: Chronic pelvic pain in women often requires multimodal treatment regimens. We describe our method of transvaginal trigger point injections (TPIs) and report outcomes using change in pain scores. METHODS: This was a retrospective review of women treated with in-office pelvic floor muscle injections from January 2012 to August 2015. Lidocaine 1% and 2%, bupivacaine 0.5%, or ropivacaine 0.5% with or without the addition of triamcinolone 40 mg was used for the injections. Pain was reported on a 0- to 10-point numerical rating scale before and after injection. Differences in pretreatment and posttreatment pain scores were analyzed after the first injection and after subsequent injections. Repeated-measures analysis was used to determine if any variable affected treatment response. RESULTS: One hundred one women with a mean age of 44 years had a total of 257 separate visits for pelvic floor muscle injections. Triamcinolone was used at 90.2% (230/255) of the TPI visits. After the initial TPI visit, there was significant decrease in total levator numerical rating scale score (maximum score, 20; mean, -6.21 ± 4.7; P < 0.0001), and 77% (70/91) of patients had improved. These significant improvements were noted at all visits 1 through 4 and whether bilateral or unilateral injections were done. Only the total amount of local anesthestic used had a significant effect on the change in total levator pain scores (P = 0.002). Minor adverse effects including leg numbness, dizziness, nausea, bleeding, and headache occurred at 10% of visits. CONCLUSIONS: Pelvic floor muscle injections decrease pain levels in women with pelvic floor dysfunction.

Additional treatments, satisfaction, symptoms and quality of life in women 1 year after vaginal and abdominal pelvic organ prolapse repair.

OBJECTIVES: To evaluate additional treatments, symptoms, satisfaction and quality of life 1 year after vaginal and abdominal pelvic organ prolapse (POP) repair. METHODS: Adult women enrolled in a prospective POP database were reviewed. Baseline and outcomes data 1 year after surgery were collected including the Pelvic Floor Distress Inventory (PFDI) and mailed surveys. Data were analyzed with descriptive statistics, Fisher's exact tests and t tests. RESULTS: Of 222 women, 147 (66%) had vaginal and 75 (34%) had abdominal repair. Vaginal group patients were older (64.1 vs. 59.7 years; p = 0.003), but other demographic characteristics did not differ. Vaginal group patients had lower baseline anterior and apical prolapse grades (anterior 2.7 vs. 3.1, p = 0.003; apical 2.1 vs. 3.1, p < 0.001). Baseline PFDI scores were similar. Scores improved significantly for both groups after 1 year, but 1-year PFDI scores were significantly higher in the vaginal group (45.6 vs. 32.6, p = 0.032). Scores were not different when adjusted for age and prolapse grade (p = 0.24). At 1 year, most patients in the vaginal and abdominal groups reported moderately/markedly improved overall symptoms (72/108 vs. 50/60, p = 0.030) and quality of life (89/101 vs. 54/59, p = 0.601). Most were satisfied with surgery (68/101 vs. 48/59, p = 0.067). Retreatment rates (pelvic floor physical therapy, medications, coping strategies, surgical procedures) were similar (34/109 vs. 15/62, p = 0.381). Vaginal mesh use did not affect additional treatments, patient satisfaction or symptoms. CONCLUSIONS: Although symptoms improve and most women are satisfied with surgery, about one in four women have additional therapy in the first year after POP repair.

Does sex matter? A matched pairs analysis of neuromodulation outcomes in women and men.

AIMS: To evaluate whether baseline symptoms and outcomes are influenced by gender in a matched cohort undergoing neuromodulation. METHODS: Patients in our prospective neuromodulation database that had a tined lead placed were reviewed. Those that had implantable pulse generator (IPG) placed were matched on age and urologic diagnosis. History, voiding diaries, satisfaction, Interstitial Cystitis Symptom/Problem Index (ICSIPI), and overactive bladder symptom severity (OABq ss)/health-related quality of life (HRQOL) preimplant and over 3 years were evaluated using descriptive statistics, repeated measures, and matched pair GEE or mixed analyses. RESULTS: Of 590 patients in the database, more women than men received an IPG (450/488; 92.2 vs. 84/102; 82.4%; p = 0.0011). Eighty matched pairs (n = 160; 81% ≥ 50 years old; 56.25% had urgency/frequency with urge incontinence-UI) were identified and evaluated. On voiding diaries, volume/void was greater in women only at baseline (p = 0.040); both groups improved over time (p < 0.0001). Urinary frequency improved in both women and men (p = 0.0010; p = 0.0025). Over 3 years, UI episodes/day improved only in men (p = 0.017) and UI severity improved only in women (p < 0.0001). ICSIPI, OABq ss, and HRQOL scores improved similarly in both groups (p < 0.0001 for all measures in both groups), and although more women were satisfied at 3 months (p = 0.027), groups did not differ at other time points. CONCLUSIONS: More women undergo neuromodulation and have initial success and subsequent IPG implantation. UI episodes improved only in men, and UI severity improved only in women. Both women and men experienced similar levels of symptom improvement on other measures.

Efficacy and Safety of Sacral and Percutaneous Tibial Neuromodulation in Non-neurogenic Lower Urinary Tract Dysfunction and Chronic Pelvic Pain: A Systematic Review of the Literature.

CONTEXT: Neuromodulation is considered in patients with non-neurogenic lower urinary tract dysfunction (LUTD) not responsive to conservative treatment. OBJECTIVE: To systematically review the available studies on efficacy and safety of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) in non-neurogenic LUTDs not responsive to conservative treatments. EVIDENCE ACQUISITION: A literature research was conducted in PubMed/Medline and Scopus, restricted to articles in English, published between January 1998 and June 2017, with at least 20 patients and 6 mo of follow-up. EVIDENCE SYNTHESIS: Twenty-one reports were identified. Concerning SNM, the improvement of ≥50% in leakage episodes ranged widely between 29% and 76%. Overall dry rate ranged between 43% and 56%. Overall success/improvement rate in PTNS varied between 54% and 59%. Symptom improvement or efficacy in interstitial cystitis/bladder pain syndrome patients appeared to be lower compared with other indications in both techniques. Safety data showed fewer side effects in patients submitted to PTNS. CONCLUSIONS: Neuromodulation gives good results and is a safe therapy for patients with overactive bladder or chronic nonobstructive urinary retention with long-lasting efficacy. Moreover, PTNS has been shown to have good success rates and fewer side effects compared with SNM. These data have to be confirmed with long-term follow-up. PATIENT SUMMARY: Sacral neuromodulation can improve low urinary tract symptoms in selected patients; it appears to be a safe therapy for nonresponders to standard medical therapies. Percutaneous tibial nerve stimulation (PTNS) is a less invasive technique that gives good results in short time with fewer side effects. However, we must consider that PTNS has not been tested in the long term and results are lower if compared with SNM.

Coexisting depressive symptoms do not limit the benefits of chronic neuromodulation: A study of over 200 patients.

AIMS: To examine the relationship between coexisting depressive symptoms and outcomes after staged neuromodulation procedures for refractory urological symptoms. METHODS: Adults who enrolled in a prospective database and completed a Personal Health Questionnaire Depression Scale (PHQ-8) at baseline were reviewed. The PHQ-8 and Generalized Anxiety Disorder (GAD-7) assessed depressive/anxiety symptoms pre and 6 months post device implant. Urological symptoms were assessed with The Interstitial Cystitis Symptom Index/Problem Index (ICSI-PI) and Overactive Bladder Questionnaire (OAB-q) at baseline, 3 and 6 months, and Global Response Assessments (GRA) post implant. Subjects, grouped by PHQ <10 and PHQ ≥10, were compared with Pearson's Chi-square, Fisher's Exact or Wilcoxon rank test, and Spearman's correlations. RESULTS: In 117 PHQ <10 and 84 PHQ ≥10 patients, age differed (mean 59 vs 52 years; P = 0.001), and PHQ <10 had lower GAD-7, ICSI-PI, and OAB-q scores at baseline (P < 0.0001, P = 0.0003, and P < 0.0008, respectively). Implantation rates were similar between groups. Reoperation and complication rates within the first 6 months did not differ, similar proportions (majority) were improved on the GRA at each time point, and ICSI-PI and OAB-q scores improved significantly. PHQ scores only improved significantly for those with baseline PHQ ≥10. Baseline PHQ strongly correlated with GAD-7 at baseline and 6 months, and baseline ICSI-PI. Change in PHQ positively correlated with the change in GAD-7, 6 month ICSI-PI, and change in ICSI-PI from baseline to 6 months. CONCLUSIONS: Coexisting depressive symptoms do not limit the efficacy of neuromodulation and PHQ improvements correlate with improved anxiety and bladder symptoms.