Adjudication of Self-reported Symptomatic Stone Recurrence in the Prevention of Urinary Stones With Hydration Trial.

OBJECTIVE: To assess accuracy of self-reported stone events in a large clinical trial by adjudication against the weight of documentation for spontaneous stone passage or surgical intervention. METHODS: Participants in the Prevention of Urinary Stones with Hydration (PUSH) trial were randomized to a multi-component behavioral intervention or control arm to increase and maintain high fluid intake. The primary endpoint was urinary stone events including symptomatic stone passage or procedural intervention. An independent adjudication committee blinded to randomization assignments reviewed all events. Confirmed clinical stone events required typical stone symptoms and documentation of stone passage (eg, via photograph, clinical record) and/or surgical intervention. Events with typical symptoms and self-described stone passage but without objective documentation of passage were also considered as meeting the primary endpoint and classified separately as patient-reported passage. Non-events did not meet either criteria. RESULTS: At time of this blinded analysis, a total of 1658 participants were randomized and had a median follow-up of 19 months. Self-reported stone events (n = 217) were adjudicated by the committee as either confirmed clinical events (134; 61.8%), patient-reported passage (71; 32.7%), or non-events (12; 5.5%). Confirmed clinical events consisted of stone passage in 66/134 and procedural interventions in 68/134 (53 for symptoms and 15 without symptoms). CONCLUSION: Rigorous adjudication revealed that self-reported stone events in the PUSH trial overwhelmingly represented clinically documented passage, surgical intervention, and patient-reported passage outside healthcare settings, with only 5.5% failing to satisfy adjudication criteria. Similar adjudication and classification processes warrant consideration for implementation in future stone trials. CLINICAL TRIALS REGISTRATION: NCT03244189.

Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN): An introduction to the Urinary Urgency Phenotyping Protocol LURN II.

AIMS: The Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN) is undertaking a new cohort study in LURN II including cases and controls. METHODS: This new cohort was enrolled to specifically study urinary urgency and urgency urinary incontinence, lower urinary tract symptoms (LUTSs) that are often difficult to treat due to a lack of understanding of their phenotypes and pathophysiologies. RESULTS: This paper will focus on the motivation for the second iteration of LURN and highlight the new research techniques and plans for more thorough phenotyping of this population. CONCLUSIONS: This paper will outline the gaps in understanding in treating LUTSs, specifically urinary urgency.

Using structured problem solving to promote fluid consumption in the prevention of urinary stones with hydration (PUSH) trial.

BACKGROUND: Structured Problem Solving (SPS) is a patient-centered approach to promoting behavior change that relies on productive collaboration between coaches and participants and reinforces participant autonomy. We aimed to describe the design, implementation, and assessment of SPS in the multicenter Prevention of Urinary Stones with Hydration (PUSH) randomized trial. METHODS: In the PUSH trial, individuals with a history of urinary stone disease and low urine output were randomized to control versus a multicomponent intervention including SPS that was designed to promote fluid consumption and thereby prevent recurrent stones. We provide details specifically about training and fidelity assessment of the SPS coaches. We report on implementation experiences related to SPS during the initial conduct of the trial. RESULTS: With training and fidelity assessment, coaches in the PUSH trial applied SPS to help participants overcome barriers to fluid consumption. In some cases, coaches faced implementation barriers such as variable participant engagement that required tailoring their work with specific participants. The coaches also faced challenges including balancing rapport with problem solving, and role clarity for the coaches. CONCLUSIONS: We adapted SPS to the setting of kidney stone prevention and overcame challenges in implementation, such as variable patient engagement. Tools from the PUSH trial may be useful to apply to other health behavior change settings in nephrology and other areas of clinical care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03244189.

Structural Changes in Brain White Matter Tracts Associated With Overactive Bladder Revealed by Diffusion Tensor Magnetic Resonance Imaging: Findings From a Symptoms of Lower Urinary Tract Dysfunction Research Network Cross-Sectional Case-Control Study.

PURPOSE: Our objective was to investigate structural changes in brain white matter tracts using diffusion tensor imaging (DTI) in patients with overactive bladder (OAB). MATERIALS AND METHODS: Treatment-seeking OAB patients and matched controls enrolled in the cross-sectional case-control LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) Neuroimaging Study received a brain DTI scan. Microstructural integrity of brain white matter was assessed using fractional anisotropy (FA) and mean diffusivity. OAB and urgency urinary incontinence (UUI) symptoms were assessed using the OAB Questionnaire Short-Form and International Consultation on Incontinence Questionnaire-Urinary Incontinence. The Lower Urinary Tract Symptoms Tool UUI questions and responses were correlated with FA values. RESULTS: Among 221 participants with evaluable DTI data, 146 had OAB (66 urinary urgency-only without UUI, 80 with UUI); 75 were controls. Compared with controls, participants with OAB showed decreased FA and increased mean diffusivity, representing greater microstructural abnormalities of brain white matter tracts among OAB participants. These abnormalities occurred in the corpus callosum, bilateral anterior thalamic radiation and superior longitudinal fasciculus tracts, and bilateral insula and parahippocampal region. Among participants with OAB, higher OAB Questionnaire Short-Form scores were associated with decreased FA in the left inferior fronto-occipital fasciculus, P < .0001. DTI differences between OAB and controls were driven by the urinary urgency-only (OAB-dry) but not the UUI (OAB-wet) subgroup. CONCLUSIONS: Abnormalities in microstructural integrity in specific brain white matter tracts were more frequent in OAB patients. More severe OAB symptoms were correlated with greater degree of microstructural abnormalities in brain white matter tracts in patients with OAB. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02485808.

A Treatment Algorithm for High-Tone Pelvic Floor Dysfunction.

OBJECTIVE: To develop evidence- and consensus-based clinical practice guidelines for management of high-tone pelvic floor dysfunction (HTPFD). High-tone pelvic floor dysfunction is a neuromuscular disorder of the pelvic floor characterized by non-relaxing pelvic floor muscles, resulting in lower urinary tract and defecatory symptoms, sexual dysfunction, and pelvic pain. Despite affecting 80% of women with chronic pelvic pain, there are no uniformly accepted guidelines to direct the management of these patients. METHODS: A Delphi method of consensus development was used, comprising three survey rounds administered anonymously via web-based platform (Qualtrics XM) to national experts in the field of HTPFD recruited through targeted invitation between September and December 2021. Eleven experts participated with backgrounds in urology, urogynecology, minimally invasive gynecology, and pelvic floor physical therapy (PFPT) participated. Panelists were asked to rate their agreement with rated evidence-based statements regarding HTPFD treatment. Statements reaching consensus were used to generate a consensus treatment algorithm. RESULTS: A total of 31 statements were reviewed by group members at the first Delphi round with 10 statements reaching consensus. 28 statements were reposed in the second round with 17 reaching consensus. The putative algorithm met clinical consensus in the third round. There was universal agreement for PFPT as first-line treatment for HTPFD. If satisfactory symptom improvement is reached with PFPT, the patient can be discharged with a home exercise program. If no improvement after PFPT, second-line options include trigger or tender point injections, vaginal muscle relaxants, and cognitive behavioral therapy, all of which can also be used in conjunction with PFPT. Onabotulinumtoxin A injections should be used as third line with symptom assessment after 2-4 weeks. There was universal agreement that sacral neuromodulation is fourth-line intervention. The largest identified barrier to care for these patients is access to PFPT. For patients who cannot access PFPT, experts recommend at-home, guided pelvic floor relaxation, self-massage with vaginal wands, and virtual PFPT visits. CONCLUSION: A stepwise approach to the treatment of HTPFD is recommended, with patients often necessitating multiple lines of treatment either sequentially or in conjunction. However, PFPT should be offered first line.

Validation of a simple body map to measure widespread pain in urologic chronic pelvic pain syndrome: A MAPP Research Network study.

PURPOSE: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only. MATERIALS AND METHODS: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site. RESULTS: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations. CONCLUSIONS: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes.

Relationships Between Urinary and Nonurinary Symptoms in Treatment-Seeking Women in LURN.

IMPORTANCE: Physical health and psychological health represent modifiable factors in the causal pathway of lower urinary tract symptoms (LUTS). OBJECTIVES: Understand the relationship between physical and psychological factors and LUTS over time. STUDY DESIGN: Adult women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network observational cohort study completed the LUTS Tool and Pelvic Floor Distress Inventory, including urinary (Urinary Distress Inventory), prolapse (Pelvic Organ Prolapse Distress Inventory), and colorectal anal (Colorectal-Anal Distress Inventory) subscales at baseline, 3 months, and 12 months. Physical functioning, depression, and sleep disturbance were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires; relationships were assessed using multivariable linear mixed models. RESULTS: Of 545 women enrolled, 472 had follow-up. Median age was 57 years; 61% and 78% reported stress urinary incontinence and overactive bladder, respectively; and 81% reported obstructive symptoms. The PROMIS depression scores were positively associated with all urinary outcomes (range, 2.5- to 4.8-unit increase per 10-unit increase in depression score; P < 0.01 for all). Higher sleep disturbance scores were associated with higher urgency, obstruction, LUTS Total Severity, Urinary Distress Inventory, and Pelvic Floor Distress Inventory (1.9- to 3.4-point increase per 10-unit increase, all P < 0.02). Better physical functioning was associated with less severe urinary symptoms except stress urinary incontinence (2.3- to 5.2-point decrease per 10-unit increase, all P < 0.01). All symptoms decreased over time; however, no association was detected between baseline PROMIS scores and trajectories of LUTS over time. CONCLUSIONS: Nonurologic factors demonstrated small to medium cross-sectional associations with urinary symptom domains, but no significant association was detected with changes in LUTS. Further work is needed to determine whether interventions targeting nonurologic factors reduce LUTS in women.

Believing women: a qualitative exploration of provider disbelief and pain dismissal among women with interstitial cystitis/bladder pain syndrome from the MAPP research network.

INTRODUCTION AND HYPOTHESIS: Although allusions to the importance of a good physician-patient relationship are present throughout the interstitial cystitis/bladder pain syndrome (IC/BPS) literature, qualitative analysis of patients' perspectives on the clinical encounter is lacking, particularly among women who are most commonly affected by IC/BPS. Therefore, we adopted a patient-centered experiential approach to understanding female patients' perception of clinical encounters. METHODS: We re-analyzed previously collected data from a qualitative study on patient flare experiences including eight focus groups of female IC/BPS patients (n = 57, mean = 7/group). Qualitative analysis applied grounded theory to index all physician-patient interactions, then thematically coded these interactions to elucidate common experiences of clinical encounters. RESULTS: Women with IC/BPS shared common experiences of provider disbelief and pain dismissal. Discussions with participants demonstrated the extent to which these negative encounters shape patients' health care-seeking behavior, outlook, and psychosocial well-being. Appearing in more than one guise, provider disbelief and dismissal occurred as tacit insinuations, explicit statements, silence, oversimplification, and an unwillingness to listen and discuss alternative treatment. As a result, women adopted several strategies including: rotating specialists; "testing" physicians; self-advocacy; self-management; avoiding the stigma of chronic pain; crying; and opting for alternative medicine over biomedicine. CONCLUSIONS: The prevalence of provider disbelief and pain dismissal among women with IC/BPS indicates a need to improve physician-patient communication, informed by the struggles, anxieties, and gendered inequities that female patients with chronic pain experience in their diagnostic journey. Results suggest that further investigation into the power dynamics of clinical encounters might be required.

Naturalistic Bladder Filling Reveals Subtypes in Overactive Bladder Syndrome That Differentially Engages Urinary Urgency-Related Brain Circuits: Results From the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

PURPOSE: Overactive bladder (OAB) may be attributed to dysfunction in supraspinal brain circuits. Overactive bladder participants enrolled in the LURN (Symptoms of Lower Urinary Tract Dysfunction Research Network) study reported sensations of urinary urgency during a bladder-filling paradigm while undergoing brain functional MRI to map supraspinal dysfunction. MATERIALS AND METHODS: OAB participants and controls (CONs) completed 2 resting-state functional MRI scans following consumption of 350 mL water. Scans were conducted at fuller and emptier bladder states, interleaved with voiding. Urgency ratings (0-10) were assessed. Patterns of urgency during bladder filling were investigated using latent class trajectory models. Clusters of participants encompassing each pattern (ie, subtype) were derived from aggregated groups of OAB and CON independent of diagnosis. RESULTS: Two distinct patterns of urgency trajectories were revealed: first subtype with OAB and CON who were unresponsive to bladder filling (OAB-1 and CON-1) and second highly responsive subtype predominantly containing OAB (OAB-2). OAB-2 participants scored significantly higher on urinary symptoms but not pain or psychosocial measures. Neuroimaging analyses showed change in urgency due to both bladder filling and voided volume related to multiple loci of brain network connectivity in OAB-2, and in some cases, different than OAB-1 and/or CON-1. Sensorimotor to dorsomedial/dorsolateral prefrontal connectivity mediated the relationship between stimulus (voided volume) and percept (urgency) in OAB-2. CONCLUSIONS: Our results reveal different OAB subtypes with latent class trajectory models of urgency ratings during natural bladder filling. Functional MRI revealed differences in pathophysiology between subtypes, namely sensorimotor-prefrontal connectivity is a key locus in OAB patients with higher urinary symptoms.

Urologic Chronic Pelvic Pain Syndrome Flares: A Comprehensive, Systematic Review and Meta-Analysis of the Peer-Reviewed Flare Literature.

PURPOSE: We sought to systematically review and summarize the peer-reviewed literature on urologic chronic pelvic pain syndrome flares, including their terminology, manifestation, perceived triggers, management and prevention strategies, impact on quality of life, and insights into pathophysiologic mechanisms, as a foundation for future empirical research. MATERIALS AND METHODS: We searched 6 medical databases for articles related to any aspect of symptom exacerbations for interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome. A total of 1486 abstracts and 398 full-text articles were reviewed, and data were extracted by at least 2 individuals. RESULTS: Overall, we identified 59 articles, including 36 qualitative, cross-sectional, or case-control; 15 cohort-based; and 8 experimental articles. The majority of studies described North American patients with confirmed diagnoses. "Flare" was a commonly used term, but additional terminology (eg, exacerbation) was also used. Most flares involved significant increases in pain intensity, but less data were available on flare frequency and duration. Painful, frequent, long-lasting, and unpredictable flares were highly impactful, even over and above participants' nonflare symptoms. A large number of perceived triggers (eg, diet, stress) and management/prevention strategies (eg, analgesics, thermal therapy, rest) were proposed by participants, but few had empirical support. In addition, few studies explored underlying biologic mechanisms. CONCLUSIONS: Overall, we found that flares are painful and impactful, but otherwise poorly understood in terms of manifestation (frequency and duration), triggers, treatment, prevention, and pathophysiology. These summary findings provide a foundation for future flare-related research and highlight gaps that warrant additional empirical studies.

Image Segmentation for High-Density Surface Electromyography Mappings of Pelvic Floor Muscle Activity of Women with Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) can result in pelvic floor muscle (PFM) overactivity. Current clinical assessment protocols include basic electromyographic assessment of PFM activation; however, they do not provide a comprehensive assessment localized to each region of the PFM. We examined the ability of high-definition features from intravaginal high-density surface electromyography (HD-sEMG) to assess the severity of PFM overactivity in female IC/BPS patients. HD-sEMG was collected from fifteen female IC/BPS patients and fifteen urologically healthy female controls. The 2D mappings of root mean squared amplitude (RMS) at rest normalized by maximal voluntary contraction (resting RMS ratios) were segmented via k-means to identify areas of peak activity and surrounding activity. Female IC/BPS patients exhibited significantly greater resting RMS ratios for peak activity (p=0.0096), surrounding activity (p=0.0003), and average activity (p=0.0016) compared to healthy female controls. Furthermore, the area of peak activity was significantly larger for female IC/BPS patients than for healthy female controls (p=0.0063). Image segmentation of intravaginal HD-sEMG provides a more robust biomarker of PFM as compared to current methods.

Gamma-band Intermuscular Connectivity Is Associated With Increased Neural Drive to Pelvic Floor Muscles in Women With Interstitial Cystitis/Bladder Pain Syndrome.

PURPOSE: Interstitial cystitis/bladder pain syndrome patients can experience overactive pelvic floor muscle activity at rest. While the frequency power spectrum of pelvic floor muscle has briefly been explored, intermuscular connectivity of the pelvic floor muscle has yet to be studied, which may provide useful insight into the neurological component, ie, neural drive to muscles, in interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: High-density surface electromyography was collected from 15 female interstitial cystitis/bladder pain syndrome patients with pelvic floor tenderness and 15 urologically healthy female controls. Intermuscular connectivity was calculated across the maximally active locations of the left and right sides of the pelvic floor muscle as identified from the root mean squared amplitude at rest and compared with Student t tests for common sensorimotor rhythms involved in motor control: alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-70 Hz) frequency bands. The root mean squared amplitudes at rest were also compared across groups. RESULTS: The resting root mean squared amplitude of the pelvic floor muscle was significantly greater in female interstitial cystitis/bladder pain syndrome patients compared to healthy female controls (P = .0046). The gamma-band intermuscular connectivity was significantly different between rest and pelvic floor muscle contraction (P = .0001) for healthy female controls, but not for female patients with interstitial cystitis/bladder pain syndrome (P = .1214). Both results indicate an elevated neural drive to pelvic floor muscle at rest in female interstitial cystitis/bladder pain syndrome patients. CONCLUSIONS: Gamma-band pelvic floor muscle connectivity in female interstitial cystitis/bladder pain syndrome patients is increased at rest. The results of this study may provide insight into the impaired neural drive to pelvic floor muscle implicated with interstitial cystitis/bladder pain syndrome.

Patients' Experiences With the Removal of a Ureteral Stent: Insights From In-depth Interviews With Participants in the USDRN STENTS Qualitative Cohort Study.

OBJECTIVE: To describe the experiences of patients undergoing stent removal in the USDRN Study to Enhance Understanding of Stent-Associated Symptoms (STENTS), a prospective, observational cohort study of patients with short-term ureteral stent placement post-ureteroscopy. METHODS: We conducted a qualitative descriptive study using in-depth interviews. Participants reflected on (1) painful or bothersome aspects of stent removal, (2) symptoms immediately after removal, and (3) symptoms in the days following removal. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. RESULTS: The 38 participants interviewed were aged 13-77 years, 55% female, and 95% White. Interviews were conducted 7-30 days after stent removal. Almost all participants (n = 31) described that they experienced either pain or discomfort during stent removal, but for most (n = 25) pain was of short duration. Many participants (n = 21) described anticipatory anxiety related to the procedure, and several (n = 11) discussed discomfort arising from lack of privacy or feeling exposed. Interactions with medical providers often helped put participants at ease, but also increased discomfort for some. Following stent removal, several participants described lingering pain and/or urinary symptoms, but these largely resolved within 24 hours. A few participants described symptoms persisting for more than a day post stent removal. CONCLUSION: These findings on patients' experiences during and shortly after ureteral stent removal, particularly the psychological distress they experienced, identify opportunities for improvement in patient care. Clear communication from providers about what to expect with the removal procedure, and the possibility of delayed pain, may help patients adapt to discomfort.

The Patient Voice: Stent Experiences After Ureteroscopy-Insights from In-Depth Interviews with Participants in the USDRN STENTS Nested Qualitative Cohort Study.

Purpose: Ureteral stents are commonly used after ureteroscopy and cause significant discomfort, yet qualitative perspectives on patients' stent experiences remain unknown. We describe psychological, functional, and interpersonal effects of post-ureteroscopy stents and whether additional patient-reported assessments may be needed. Materials and Methods: Using a qualitative descriptive study design, we conducted in-depth interviews with a nested cohort of participants in the STudy to Enhance uNderstanding of sTent-associated Symptoms (STENTS). Participants shared their symptoms with a post-ureteroscopy stent and described symptom bother and impact on daily activities. All interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis. During analysis, participants' experiences with interference in daily activities were categorized into three groups based on their impact: minimal, moderate, and substantial. Results: All 39 participants experienced pain, although descriptions varied and differentiated between feelings of pain vs discomfort. Almost all experienced urinary symptoms. Only a few reported other physical symptoms, although several psychological aspects were identified. In the areas of sleep, mood, life enjoyment, work, exercise, activities of daily living, driving, childcare, and leisure/social activities, the stent had little impact on daily living among participants placed in the minimal group (n = 12) and far greater impact for participants in the substantial group (n = 8). For patients in the moderate group (n = 19), some daily activities were moderately or substantially affected, whereas other activities were minimally affected. Conclusions: Counseling to better prepare patients for the impact of stent-associated symptoms may help mitigate symptom burden. While existing instruments adequately cover most symptoms, additional assessments for other domains, particularly psychological factors, may be needed.

Assessment of bladder pressure and discomfort symptoms: How do overactive bladder differ from interstitial cystitis/bladder pain syndrome patients?

BACKGROUND: To better understand the sensation of bladder "pressure" and "discomfort", and how they are similar or distinct from the "pain" and "urgency" symptoms in IC/BPS and OAB. METHODS: IC/BPS and OAB patients rated their bladder pain, pressure, discomfort, and urinary urgency on separate 0-10 numeric rating scales (NRS). Their NRS ratings were compared between IC/BPS and OAB, and Pearson correlations were performed. RESULTS: Among IC/BPS patients (n = 27), their mean numeric ratings of pain, pressure, discomfort, and urinary urgency were almost identical (6.6 ± 2.1, 6.0 ± 2.5, 6.5 ± 2.2, and 6.0 ± 2.8 respectively). The three-way correlations between pain, pressure, or discomfort were very strong (all > 0.77). Among OAB patients (n = 51), their mean numeric ratings of pain, pressure, and discomfort (2.0 ± 2.6, 3.4 ± 2.9, 3.4 ± 2.9) were significantly lower than urgency (6.1 ± 2.6, p < 0.001). The correlations between urgency and pain, and between urgency and pressure were weak in OAB (0.21 and 0.26). The correlation between urgency and discomfort was moderate in OAB (0.45). The most bothersome symptom of IC/BPS was bladder/pubic pain, while the most bothersome symptom of OAB was urinary urgency and daytime frequency. CONCLUSIONS: IC/BPS patients interpreted bladder pain, pressure, or discomfort as the similar concepts and rated their intensity similarly. It is unclear whether pressure or discomfort provide additional information beyond pain in IC/BPS. Discomfort may also be confused with urgency in OAB. We should re-examine the descriptors pressure or discomfort in the IC/BPS case definition.

Widespread Pain Phenotypes Impact Treatment Efficacy Results in Randomized Clinical Trials for Interstitial Cystitis/Bladder Pain Syndrome: A MAPP Network Study.

Clinical trials of pain are notoriously difficult and inefficient in demonstrating efficacy even for known efficacious treatments. Determining the appropriate pain phenotype to study can be problematic. Recent work has identified the extend of widespread pain as an important factor in the likelihood of response to therapy, but has not been tested in clinical trials. Using data from three previously published negative studies of the treatment of interstitial cystitis/ bladder pain with data on the extent of widespread pain, we examined the response of patients to different therapies base on the amount of pain beyond the pelvis. Participants with predominately local but not widespread pain responded to therapy targeting local symptoms. Participants with widespread and local pain responded to therapy targeting widespread pain. Differentiating patients with and without widespread pain phenotypes may be a key feature of designing future pain clinical trials to demonstrate treatments that are effective versus not.

Clinically Important Differences for Pain and Urinary Symptoms in Urological Chronic Pelvic Pain Syndrome: A MAPP Network Study.

PURPOSE: Symptom heterogeneity in interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively termed urological chronic pelvic pain syndrome, has resulted in difficulty in defining appropriate clinical trial endpoints. We determine clinically important differences for 2 primary symptom measures, pelvic pain severity and urinary symptom severity, and evaluate subgroup differences. MATERIALS AND METHODS: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study enrolled individuals with urological chronic pelvic pain syndrome. We defined clinically important differences by associating changes in pelvic pain severity and urinary symptom severity over 3 to 6 months with marked improvement on a global response assessment using regression and receiver operating characteristic curves. We evaluated clinically important differences for absolute and percent change and examined differences in clinically important differences by sex-diagnosis, presence of Hunner lesions, pain type, pain widespreadness, and baseline symptom severity. RESULTS: An absolute change of -4 was clinically important in pelvic pain severity among all patients, but clinically important difference estimates differed by pain type, presence of Hunner lesions, and baseline severity. Pelvic pain severity clinically important difference estimates for percent change were more consistent across subgroups and ranged from 30% to 57%. The absolute change urinary symptom severity clinically important difference was -3 for female participants and -2 for male participants with chronic prostatitis/chronic pelvic pain syndrome only. Patients with greater baseline severity required larger decreases in symptoms to feel improved. Estimated clinically important differences had lower accuracy among participants with low baseline symptoms. CONCLUSIONS: A reduction of 30%-50% in pelvic pain severity is a clinically meaningful endpoint for future therapeutic trials in urological chronic pelvic pain syndrome. Urinary symptom severity clinically important differences are more appropriately defined separately for male and female participants.

Risk Factors for Increased Stent-associated Symptoms Following Ureteroscopy for Urinary Stones: Results From STENTS.

PURPOSE: The STudy to Enhance uNderstanding of sTent-associated Symptoms sought to identify risk factors for pain and urinary symptoms, as well as how these symptoms interfere with daily activities after ureteroscopy for stone treatment. MATERIALS AND METHODS: This prospective observational cohort study enrolled patients aged ≥12 years undergoing ureteroscopy with ureteral stent for stone treatment at 4 clinical centers. Participants reported symptoms at baseline; on postoperative days 1, 3, 5; at stent removal; and day 30 post-stent removal. Outcomes of pain intensity, pain interference, urinary symptoms, and bother were captured with multiple instruments. Multivariable analyses using mixed-effects linear regression models were identified characteristics associated with increased stent-associated symptoms. RESULTS: A total of 424 participants were enrolled. Mean age was 49 years (SD 17); 47% were female. Participants experienced a marked increase in stent-associated symptoms on postoperative day 1. While pain intensity decreased ∼50% from postoperative day 1 to postoperative day 5, interference due to pain remained persistently elevated. In multivariable analysis, older age was associated with lower pain intensity (P = .004). Having chronic pain conditions (P < .001), prior severe stent pain (P = .021), and depressive symptoms at baseline (P < .001) were each associated with higher pain intensity. Neither sex, stone location, ureteral access sheath use, nor stent characteristics were drivers of stent-associated symptoms. CONCLUSIONS: In this multicenter cohort, interference persisted even as pain intensity decreased. Patient factors (eg, age, depression) rather than surgical factors were associated with symptom intensity. These findings provide a foundation for patient-centered care and highlight potential targets for efforts to mitigate the burden of stent-associated symptoms.

Associations Between Urological Chronic Pelvic Pain Syndrome Symptom Flares, Illness Impact, and Health Care Seeking Activity: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study.

PURPOSE: Most studies on interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome use typical or average levels of pelvic pain or urological symptom intensity as their outcome, as both are associated with reduced quality of life. Symptom exacerbations or "flares" have also been found to be associated with reduced quality of life, but no studies, to our knowledge, have investigated whether these associations are independent of typical pelvic pain levels and thus might be useful additional outcome measures (or stated differently, whether reducing flare frequency even without reducing mean pain intensity may be important to patients). MATERIALS AND METHODS: We used screening visit and weekly run-in period data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Symptom Patterns Study to investigate associations between flare frequency and multiple measures of illness impact and health care seeking activity, independent of typical nonflare and overall pelvic pain levels. RESULTS: Among the 613 eligible participants, greater flare frequency was associated with worse condition-specific illness impact (standardized ß coefficients=0.11-0.68, P trends < .0001) and health care seeking activity (odds ratios=1.52-3.94, P trends .0039 to < .0001) in analyses adjusted for typical nonflare and overall pelvic pain levels. Experiencing ≥1/d was also independently associated with worse general illness impact (standardized ß coefficients=0.11-0.25). CONCLUSIONS: Our findings suggest that flare frequency and possibly other flare characteristics may be worth considering as additional outcome measures in urological chronic pelvic pain syndrome research to support the development of new preventive and therapeutic flare strategies.