Emily S. Lukacz

Importance: Transurethral bulking agent (TBA) injections and single incision slings (SIS) are low risk, minimally invasive options increasingly being used in the treatment of primary stress urinary incontinence (SUI); however, comparative trials are lacking. Objectives: We describe the study design and rationale for the Transurethral Bulking Agent Injection versus Single-Incision Sling for Stress Urinary Incontinence (BASIS) trial. Study Design: The study methods, inclusion criteria, assessments, safety and efficacy outcomes, and follow-up are reported. We also present methods for selection of surgical devices and public private partnerships for product donation. The engagement of anesthesia co-investigators to develop an office-based protocol is also described. Results: The BASIS trial is a multicentered, double-blind, randomized controlled, superiority study of up to 2 injections of TBA (Bulkamid) versus SIS (Solyx) at 12 months, with follow-up through 36 months. Women with primary, stress-predominant urinary incontinence without indication for general or regional anesthesia are eligible. A patient-centered primary outcome of Patient Global Impression of Improvement was used to calculate the sample size of 358. Secondary efficacy and safety outcomes of objective and subjective success, retreatment, and adverse events (including de novo pelvic floor muscle tenderness and dyspareunia), and cost-effectiveness analyses are planned. The feasibility of an office-based anesthesia protocol with sedation and local anesthesia will also be evaluated. Conclusions: Results from the BASIS study will provide level 1 evidence on the comparative-effectiveness of 2 minimally invasive office-based treatments. Important safety data and 3-year outcomes will help clinicians and patients make informed decisions about primary SUI procedure options.

Importance: Population-based research is necessary to understand the relationship between the urobiome and bladder health. Objective: Using advanced contamination controls and ecological metrics, we aimed to evaluate the concordance of microbiota in self-collected urogenital specimens from home versus a clinical research setting. Study Design: A subset of community-dwelling women was enrolled in a longitudinal cohort study, self-collected urogenital samples at 3 time points: 1-day prior, the day of and during an in-person evaluation. Samples were sequenced with V4 16S rRNA and KatharoSeq removed samples indistinguishable from background contamination. Data were matched to Greengenes2-2022.10 and rarefied to 1000 seqs/sample. Intersample concordance pairs above the KatharoSeq threshold were assessed between samples. Unweighted UniFrac distances, Mantel Pearson correlations, Kruskal-Wallis, and chi-square tests were used for comparisons. Results: Detectable sequences were obtained in 261 samples from the 114 participants with 186 (71%) above the KatharoSeq threshold. Escherichia_710834 , Lactobacillus , and Prevotella were most prevalent. Intersample concordance was determined for samples above the threshold from 38 participants with 2 home samples and 47 with home and clinic samples. Correlations between 2 home and between home and clinic were significant (r = 0.43, P = 0.001; r = 0.362, P = 0.001, respectively). There were no significant differences across time points ( X ² = 2.72, P = 0.256). Conclusions: Home-collected urine samples for urogenital microbiome ecological analysis have sufficient short-term similarity and concordance with self-collected urine samples from a research clinic setting for use in population-based research, which may facilitate inclusion of participants with limited access to clinic-based research.

Given the growing impact of antimicrobial resistance, improvements in diagnosis and treatment of the most common outpatient infection, urinary tract infection (UTI), are of great interest to stakeholders. Regulatory authorities have long accepted a microbial threshold of 10⁵ CFU/mL as the standard for diagnosing UTI based on standard urine cultures. However, microbial thresholds considered clinically relevant remain in dispute. The aim of this systematic scoping review is to assess the evidence supporting a threshold of 10⁵ CFU/mL, to review microbial threshold guidelines, and highlight knowledge gaps in the diagnosis of UTI. A total of 36 guidelines containing 144 recommendations were identified with 64% of guidelines (n = 23) and 58% of recommendations (n = 83) published in the last six years (2016– 2023). Recommendations have changed over time and across variables including the geographical location of the guideline, urine specimen collection method, patient sex, and category of UTI. Guidelines uniformly agreed with suprapubic needle specimen collection; however, there was no consensus for midstream collected urine samples. Guideline microbial thresholds for clinical UTI diagnosis were higher for women at average risk (10⁵ CFU/mL) than for men (10² to 10⁵ CFU/mL) and high-risk patients (10² to 10⁴ CFU/mL). Guidelines relied heavily on 48 research articles from 20 author teams published between 1956 and 2019 and recommendations frequently cited 23 research articles by 15 author teams published between 1956 and 2013. Evidence supporting 10⁵ CFU/mL threshold originated in the mid-1950s from 4 research articles, whereas 18 frequently cited peer-reviewed publications focused their research on the clinical relevance of lower thresholds (10¹ to < 10⁵ CFU/mL). This review demonstrates a lack of consensus for urine culture microbial threshold recommendations for the clinical diagnosis of UTI. Guidelines are primarily based upon sparse and dated evidence. Additional research is needed to inform clinically meaningful diagnostic microbial thresholds in the diagnosis of UTI.

Purpose: Develop real-world evidence that rapid identification of uropathogens and susceptibilities improves urologic outcomes for patients with complicated or history of recurrent urinary tract infections (r/cUTIs). Standard urine culture (SUC) is slow, often missing polymicrobial infections and altered antibiotic resistance from their metabolic interactions. Materials and Methods: We compared 1-year UTI-related health care utilization and costs for UTIs diagnosed by outpatient multiplex polymerase chain reaction/pooled antibiotic susceptibility testing (mPCR/P-AST) vs SUC among Medicare beneficiaries with r/cUTIs, using claims from a deidentified random 5% sample of beneficiaries with an index UTI in 2018 followed by 12 months during which all outpatient UTI tests were either mPCR/P-AST or SUC. Outcomes were compared between 69 individuals diagnosed using mPCR/P-AST and 678 propensity-matched individuals using SUC. Regression models modeled cost differences with 95% confidence intervals (CIs). Results: Of 1,654,548 enrollees in 2018, 11.6%, 0.06%, and 9.6% had claims for UTI, mPCR/P-AST, and SUC, respectively. The matched mPCR/P-AST and SUC cohorts were statistically equivalent at baseline. The mPCR/P-AST cohort was nonsignificantly less likely than the SUC cohort to have a postindex UTI (65.2% vs 72.0%, P = .24). Cost per subsequent UTI was significantly lower for mPCR/P-AST ($767 vs $1,303, P = .0013). Average total 1-year UTI-related cost was $501.85 (95% CI: $79.87, $562.08 P = .004) lower per mPCR/P-AST member vs SUC ($629.55 vs $1131.39). Nonoutpatient treatment accounted for 22.5% of mPCR/P-AST vs 53.4% of SUC UTI-related costs. Conclusions: In patients with r/cUTI, rapid identification of pathogens and antibiotic susceptibilities using mPCR/P-AST is associated with lower UTI-related clinical care and utilization costs compared with SUC.

Introduction: The prevalence of healthy bladder storage and emptying function in community‐dwelling women is not well established.Methods: A planned secondary analysis of a US cross‐sectional study designed to validate a bladder health instrument was conducted in women aged ≥18 years. A subset was invited to complete the novel 2‐day bladder health diary capturing bladder storage and emptying experiences. Overall healthy bladder function was defined as ≤8 waking/daytime voids and ≤1 void during sleeping/nighttime; along with the absence of leakage, urgency, emptying difficulties (initiation, flow, efficacy, relief of urge sensation) and pain. Descriptive statistics of healthy bladder functions and regression models of factors associated with healthy function are reported.Results: Of the 383 invited, 237 (62%) eligible women returned complete dairies. Of these, 12% (29/237) met criteria for overall healthy bladder function. Most (96%) denied pain, 74% had healthy daytime and 83% had healthy nighttime voiding frequency, 64% were continent, 36% reported healthy emptying and 30% denied any urgency episodes. Middle income (odds ratio [OR]:95% confidence interval [CI] = 11.4:1.9–67.4 for $75k–$99 999 vs. $25 000–$49 999), Graduate education (4.8:1.4–17) and previously seeking treatment for bladder problems (OR:95%CI = 0.1; 0–0.9) were associated with overall healthy function.Conclusion: The prevalence of overall healthy bladder function was very low based on our strict definition of health as measured on a 2‐day diary. However, most women had healthy voiding frequency and denied pain or urinary leakage. Postvoid dribbling and urgency most commonly contributed to an overall unhealthy bladder. Further investigation is needed to determine whether these diary derived measures are meaningful for patient‐oriented bladder health research.

Introduction and hypothesis: In randomized trials both percutaneous tibial nerve stimulation (PTNS) and sham result in clinically significant improvements in accidental bowel leakage (ABL). We aimed to identify subgroups who may preferentially benefit from PTNS in women enrolled in a multicenter randomized trial. Methods: This planned secondary analysis explored factors associated with success for PTNS vs sham using various definitions: treatment responder using three cutoff points for St. Mark’s score (≥3-, ≥4-, and ≥5-point reduction); Patient Global Impression of Improvement (PGI-I) of ≥ much better; and ≥50% reduction in fecal incontinence episodes (FIEs). Backward logistic regression models were generated using elements with significance of p<0.2 for each definition and interaction terms assessed differential effects of PTNS vs sham. Results: Of 166 women randomized, 160 provided data for at least one success definition. Overall, success rates were 65% (102 out of 158), 57% (90 out of 158), and 46% (73 out of 158) for ≥3-, ≥4-, and ≥5-point St Mark’s reduction respectively; 43% (68 out of 157) for PGI-I; and 48% (70 out of 145) for ≥50% FIEs. Of those providing data for all definitions of success, 77% (109 out of 142) met one success criterion, 43% (61 out of 142) two, and 29% (41 out of 142) all three success criteria. No reliable or consistent factors were associated with improved outcomes with PTNS over sham regardless of definition. Conclusions: Despite exploring diverse success outcomes, no subgroups of women with ABL differentially responded to PTNS over sham. Success results varied widely across subjective and objective definitions. Further investigation of ABL treatment success definitions that consistently and accurately capture patient symptom burden and improvement are needed.

Objectives: To describe the methods for the in‐person assessment of the RISE FOR HEALTH (RISE) study, a population‐based multicenter prospective cohort study designed to identify factors that promote bladder health and/or prevent lower urinary tract symptoms in adult women, conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS).Methods and results: A subset of RISE participants who express interest in the in‐person assessment will be screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete 15 physical assessments in addition to height and weight, to assess pelvic floor muscle function, musculoskeletal (MSK) status, and pain, and to provide urogenital microbiome samples. Pelvic floor muscle assessments include presence of prolapse, strength, levator attachment integrity (tear) and myofascial pain. MSK tests evaluate core stability, lumbar spine, pelvic girdle and hip pain and function. Participants are asked to complete the Short Physical Performance Battery to measure balance, lower extremity strength, and functional capacity. All participants are asked to provide a voided urine sample and a vaginal swab for microbiome analyses; a subset of 100 are asked to contribute additional samples for feasibility and validation of a home collection of urinary, vaginal, and fecal biospecimens.Results: Online and in‐person training sessions were used to certify research staff at each clinical center before the start of RISE in‐person assessments. Standardized protocols and data collection methods are employed uniformly across sites.Conclusions: The RISE in‐person assessment is an integral portion of the overall population‐based RISE study and represents an innovative approach to assessing factors hypothesized to promote bladder health and/or prevent lower urinary tract symptoms. Data collected from this assessment will be used to prioritize future research questions and prevention strategies and interventions. This description of the assessment methods is intended to provide methodologic transparency and inform other researchers who join efforts to understand and improve bladder health.