Recurrent and complicated urinary tract infections in women: Utility of advanced testing to enhance care.

BACKGROUND: The United States currently faces a public health crisis with regarding to antibiotic-resistant bacteria, and new urinary tract infection (UTI) diagnostics are needed. Women with recurrent UTI (rUTI) and complicated UTI (cUTI) are at particular risk given their complexity and the paucity of adequate testing modalities. The standard urine culture (SUC) is the cornerstone for diagnosis, but it has many shortcomings. These pitfalls lead to dissatisfaction and frustration among women afflicted with rUTI and cUTI, as well as overuse of antibiotics. One innovation is PCR UTI testing, which has been shown to outperform SUC among symptomatic women. AIMS: This article discusses UTI PCR testing, as well as a possible role in clinical practice. MATERIALS AND METHODS: Published literature was reviewed and summarized. RESULTS: Management of rUTI and cUTI is complex, and providers should have all diagnostics available to facilitate providing optimal care. Urine PCR testing faces reimbursement issues despite fulfilling clinical indication parameters as described by insurance companies. DISCUSSION: The role of UTI PCR testing remains unclear. Reimbursement issues have led to underuse and limited real-world outcomes reinforcing benefit. CONCLUSION: This study proposes an algorithm for PCR testing among women with rUTI and cUTI.

Coping With Interstitial Cystitis/Bladder Pain Syndrome.

AIMS: Compensatory coping, or maladaptive alterations in behavior with the intention of preventing or managing symptoms, is increasingly being explored as a key factor in how people respond to bladder conditions. Preliminary investigations have identified relations between coping behaviors and psychological distress in urologic conditions, including interstitial cystitis/bladder pain syndrome (IC/BPS). However, previous explorations of coping have not accounted for heterogeneity in coping behaviors or addressed the likelihood that some coping behaviors may be more adaptive than others. This study sought to examine how two specific types of coping behaviors, primary control coping and disengaged coping, are related to distress and symptoms in IC/BPS, and to explore the potential role of pain phenotype in this relationship. MATERIALS AND METHODS: A secondary data analysis was conducted with a large community data set (N = 677 women with IC/BPS) and employed descriptive and inferential statistics to characterize coping patterns and explore novel predictors of distress. RESULTS: Results indicated that almost all participants engaged in at least one compensatory coping behavior within the last week. Both types of coping behaviors correlated with psychological symptoms, and when controlling for relevant clinical variables (i.e., age and severity of urinary symptoms), disengaged coping behaviors were significantly associated with psychological distress. Further, the addition of pain phenotype to multiple regression models resulted in a more effective predictive model when considering the relation between coping behaviors and depression. CONCLUSIONS: By investigating more deeply the relationship between coping and distress, understanding of potential risk factors and mechanisms is increased, offering valuable insights for intervention strategies for IC/BPS patients.

A prospective study to assess the effectiveness and safety of the BlueWind System in the treatment of patients diagnosed with urgency urinary incontinence.

BACKGROUND: Overactive bladder (OAB) affects one in six adults in Europe and the United States and impairs the quality of life of millions of individuals worldwide. When conservative management fails, third-line treatments including tibial neuromodulation (TNM) is often pursued. TNM has traditionally been accomplished percutaneously in clinic. OBJECTIVE: A minimally invasive implantable device activated by a battery-operated external wearable unit has been developed for the treatment of urgency urinary incontinence (UUI), mitigating the burden of frequent clinic visits and more invasive therapies that are currently commercially available. METHODS: A prospective, multicenter, single-arm, open-label, pivotal study evaluated the safety and effectiveness of the device in adult females with UUI (i.e., wet OAB) (BlueWind Implantable Tibial Neuromodulation [iTNM] system; IDE number #G200013; NCT03596671). Results with the device were previously published under the name RENOVA iStim, which has been since renamed as the Revi™ System. Approximately 1-month post-implantation of the device, participants delivered therapy at their convenience and completed a 7-day voiding diary before visits 6- and 12-months post-treatment initiation. The primary efficacy and safety endpoints were the proportion of responders to therapy ( ≥ 50% improvement on average number of urgency-related incontinence episodes) and incidence of adverse events from implantation to 12-month post-activation. RESULTS: A total of 151 participants, mean age 58.8 (SD: 12.5), were implanted; 144 and 140 completed the 6- and 12-month visits, respectively. The participants demonstrated mean baseline of 4.8 UUI/day (SD 2.9) and 10 voids/day (SD 3.3). Six and 12-months post-activation, 76.4% and 78.4% of participants, respectively, were responders to therapy in an intent-to-treat analysis. Of the 139 participants with completed 12-month diaries, 82% were responders, 50% were classified as "dry" (on at least 3 consecutive diary days), and 93.5% of participants reported that their symptoms improved. No implanted participant experienced an SAE related to the procedure or device. CONCLUSIONS: iTNM, delivered and powered by a patient-controlled external wearable communicating with an implant, demonstrated clinically meaningful and statistically significant improvement in UUI symptoms and a high safety profile. This therapy highlights the value of patient-centric therapy for the treatment of UUI.

The biopsychosocial impacts of anxiety on overactive bladder in women.

AIMS: Links between emotional state and the bladder have long been recognized, as psychological comorbidity is a common feature of overactive bladder (OAB). However, how psychological factors might contribute to the development and severity of OAB remains unclear. Therefore, we sought to examine the effect of anxiety on OAB with a specific focus on bladder hypersensitivity. METHODS: In a sample of 120 adult women with OAB, we compared those with at least mild anxiety (PROMIS Anxiety score ≥55) to those with lower anxiety. Analyses focused on patient-reported questionnaires assessing urinary symptom severity and quality of life, psychological stress symptoms, general somatic symptoms, and results of quantitative sensory testing (QST), including temporal summation to heat pain (TSP). TSP was used to index elevated C-fiber responsiveness (i.e., central sensitization). RESULTS: Thirty-six (30%) women had at least mild anxiety. While there were no group differences for urinary symptom severity, more anxious women reported worse OAB-specific quality of life, greater psychological stress burden, higher stress reactivity, and greater somatic symptoms. On QST, there were no differences between anxiety groups for pain threshold (43.6 ± 3.1°C vs. 44.0 ± 3.1°C, p = 0.6) and tolerance (47.3 ± 1.5°C vs. 47.4 ± 1.6°C, p = 0.7). However, those with anxiety had significantly higher TSP than those without anxiety (6.0 ± 4.8 vs. 3.7 ± 3.9, p = 0.006), indicating greater central sensitization. CONCLUSIONS: Women with OAB and at least mild anxiety symptoms reported greater psychosocial burdens (i.e., psychological stress, stress reactivity, OAB-specific QOL) and somatic symptom severity and demonstrated greater central sensitization on QST than those without anxiety. These findings support the hypothesis that anxiety and psychological stress impact hypersensitivity mechanisms that may underlie and contribute to OAB, although further research is needed to better understand how and to what extent.

Recurrent urinary tract infection management and prevention techniques among a population-based cohort of women.

INTRODUCTION: Recurrent urinary tract infection (rUTI), defined as three or more UTIs in 12 months, has psychological, physical, and financial burden. Many women with rUTI are not satisfied with care and report only starting preventative measures after several infections. The goal of this study is to elucidate current UTI management trends and the implementation of UTI prevention strategies. METHODS: A web-based study was sent to a national sample of adult women enrolled in ResearchMatch.org. Women were recruited to participate if they had a self-reported UTI in the past 12 months. RESULTS: Of the 755 subjects, nearly 30% reported rUTI. Among women with rUTI, more than 50% reported being peri- or postmenopausal, and two-thirds reported vaginal symptoms. 15.8% of women with rUTI reported dissatisfaction with care versus 7.9% of women without rUTI. Most women see their primary care physician for UTI management and only 26% of women with rUTI follow with a urologist. More than 65% of women increase their fluid intake, wipe from front to back, and urinate after sexual activity to prevent UTIs. Significantly more women with rUTI use transvaginal estrogen, cranberry extract, and low-dose prophylactic antibiotics. These interventions appear to be driven by urologists. CONCLUSION: Most women who have had a UTI in the last 12 months implement lifestyle changes to prevent future infections. Most women see their PCP for UTI management and women with rUTI are twice as likely to report dissatisfaction with care. Despite urologists optimizing medical rUTI prevention, they appear to be underutilized.

Compensatory coping and depression in women with interstitial cystitis/bladder pain syndrome.

INTRODUCTION: Women with genitourinary pain, a hallmark symptom of interstitial cystitis/bladder pain syndrome (IC/BPS), are at a two- to four-fold risk for depression as compared to women without genitourinary pain. Despite the pervasive impact of IC/BPS on psychological health, there is a paucity of empirical research on understanding the relation between IC/BPS and psychological distress. It has been previously reported that women with overactive bladder use increased compensatory coping and these behaviors are associated with heightened anxiety and stress. However, it is unknown whether a similar pattern emerges in IC/BPS populations, as ICBPS and OAB share many similar urinary symptoms. The current study examined the relationship between compensatory coping behaviors and symptoms of psychological distress in a sample of women with IC/BPS to inform understanding of risk and potential mechanisms for intervention. METHOD: This was a secondary analysis of an observational cohort of women with bladder symptoms. Fifty-five adult women with IC/BPS completed validated assessments of genitourinary symptoms, emotional distress, and bladder coping behaviors. Five compensatory coping behaviors were summed to create a total Bladder Coping Score. Linear regression examined associations between individual coping behaviors, total compensatory coping scores, and other risk variables. RESULTS: Most (93%) participants reported use of at least one compensatory coping behavior. Age, education level, history of vaginal birth, and symptom severity were all associated with greater compensatory coping scores, and anxiety was not. Beyond the influence of symptom severity, higher levels of depression were significantly associated with higher compensatory coping scores. DISCUSSION: Greater compensatory coping was associated with increased depression but not anxiety, suggesting different profiles of coping and psychological distress may exist among different types of bladder dysfunction.

Clinical hypnosis can reduce lower urinary tract symptoms in individuals with chronic pain.

STUDY PURPOSE: Lower urinary tract symptoms (LUTS) can occur in chronic pain populations at high rates and drastically affect quality of life. Hypnosis is a nonpharmacological treatment used in chronic pain known to have beneficial implications to health outside of pain reduction. This study evaluated the potential for hypnosis to reduce LUTS in a sample of individuals with chronic pain, if baseline LUTS severity affected outcomes, and specific LUTS that may respond to hypnosis. METHODS: Sixty-four adults with chronic pain and LUTS at a level of detectable symptom change (American Urological Association Symptom Index, AUASI 3) participated in an 8-week group hypnosis protocol. Participants completed validated assessments of LUTS, pain, and overall functioning before, after, 3- and 6-months posttreatment. Linear mixed effects models assessed improvement in LUTS over time while accounting for known factors associated with outcome (e.g., age, gender). The interaction of baseline symptom severity and treatment assessed the potential effect of baseline symptoms on change scores. RESULTS: Participants experienced significant and meaningful improvements in LUTS following group hypnosis (p = 0.006). There was a significant interaction between baseline symptom severity and treatment (p < 0.001), such that those with severe symptoms experienced the most pronounced gains over time (e.g., an 8.8 point reduction). Gains increased over time for those with moderate and severe symptoms. Changes in LUT symptoms occurred independently of pain relief. CONCLUSIONS: This pilot study suggests hypnosis has the potential to drastically improve LUTS in individuals with chronic pain, even when pain reduction does not occur. Results provide initial evidence for the treatment potential of hypnosis in urologic pain (and possibly non-pain/benign) populations, with randomized trials needed for definitive outcomes.

Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications ("Sleep C.A.L.M.") in the evaluation and management of nocturia: A simple approach to a complex diagnosis.

INTRODUCTION: Nocturia arises from a fundamental mismatch between nocturnal urine production, storage capacity, and sleep architecture, which may be driven by abnormalities of the genitourinary tract, but also by sleep disorders, medical diseases, patient actions/lifestyle factors, or medications. This article introduces a novel system for organizing the complex differential diagnosis for nocturia, as proposed by an international collective of practicing urologists, physician specialists, and sleep experts: "Sleep CALM"-Sleep Disorders, Comorbidities, Actions, Lower Urinary Tract Dysfunction, and Medications. METHODS: Narrative review of current evidence regarding the relevance of each "Sleep CALM" factor to nocturia pathogenesis, evaluation, and management. RESULTS: Nocturia and sleep disorders are highly intertwined and often bidirectional, such that nocturnal awakenings for reasons other than a sensation of bladder fullness should not be used as grounds for exclusion from nocturia treatment, but rather leveraged to broaden therapeutic options for nocturia. Nocturia is an important potential harbinger of several serious medical conditions beyond the genitourinary tract. Urologists should have a low threshold for primary care and medical specialty referral for medical optimization, which carries the potential to significantly improve nocturnal voiding frequency in addition to overall health status. Adverse patient actions/lifestyle factors, lower urinary tract dysfunction, and medication use commonly coexist with disordered sleep and comorbid medical conditions, and may be the primary mediators of nocturia severity and treatment response, or further exacerbate nocturia severity and complicate treatment. CONCLUSION: "Sleep CALM" provides a memorable and clinically relevant means by which to structure the initial patient history, physical exam, and clinical testing in accordance with current best-practice guidelines for nocturia. Although not intended as an all-encompassing diagnostic tool, the "Sleep CALM" schema may also be useful in guiding individualized ancillary testing, identifying the need for specialty referral and multidisciplinary care, and uncovering first-line treatment targets.

Study design of a phase 4, real-world study (COMPOSUR) to evaluate vibegron in patients with overactive bladder.

BACKGROUND: Overactive bladder (OAB) is defined as urinary urgency accompanied by frequency and nocturia, with or without urge urinary incontinence (UUI). Vibegron, a selective ß3-adrenergic receptor agonist approved in the US in December 2020, demonstrated efficacy in reducing symptoms of OAB and was safe and well tolerated in the 12-week EMPOWUR trial and its 40-week, double-blind extension trial. The goal of the COMPOSUR study is to evaluate vibegron in a real-world setting to assess patient treatment satisfaction, tolerability, safety, duration of treatment, and persistence. METHODS: This is a 12-month, prospective, observational, real-world study, with an optional 12-month extension to 24 months, in the US assessing adults ≥ 18 years old starting a new course of vibegron. Patients must be previously diagnosed with OAB with or without UUI, symptomatic for ≥ 3 months before enrollment, and receive prior treatment with an anticholinergic, with mirabegron, or with a combination of an anticholinergic and mirabegron. Enrollment is performed by the investigator following exclusion and inclusion criteria guided by US product labeling, reinforcing a real-world approach. Patients complete the OAB Satisfaction with Treatment Questionnaire (OAB-SAT-q) monthly and the OAB Questionnaire short form (OAB-q-SF) and Work Productivity and Activity Impairment Questionnaire (WPAI:US) at baseline and monthly for 12 months. Patients are followed up via phone call, in-person visits, or telehealth (ie, virtual) visits. The primary endpoint is patient treatment satisfaction as determined by the OAB-SAT-q satisfaction domain score. Secondary endpoints include percent positive responses to individual OAB-SAT-q questions, additional OAB-SAT-q domain scores, and safety. Exploratory endpoints include adherence and persistence. DISCUSSION: OAB leads to a significant decrease in quality of life, as well as impairment of work activities and productivity. Persistence with OAB treatments can be challenging, often due to lack of efficacy and adverse effects. COMPOSUR is the first study to provide long-term, prospective, pragmatic treatment data for vibegron in the US and the resultant effect on quality of life among patients with OAB in a real-world clinical setting. Trial registration ClinicalTrials.gov identifier: NCT05067478; registered: October 5, 2021.

Associations Between Unmet Social Needs and Overactive Bladder.

PURPOSE: There is growing interest in how social determinants of health may explain relationships between social conditions and health. Overactive bladder is common in the United States, posing a significant public health burden. It was the goal of the present study to assess whether overactive bladder was associated with unmet social needs in a large, cross-sectional sample of patients. MATERIALS AND METHODS: A community-based sample of adults was recruited electronically to complete questionnaires on clinical and demographic information, urinary symptoms and unmet social needs. Multivariable logistic regression was used to assess for association between overactive bladder and multiple unmet social needs. RESULTS: The sample of 3,617 participants had a mean±SD age of 47.9±17.3 years. The majority of participants identified as White, non-Hispanic (83.5%), and female (77.6%). A total of 1,391 patients (38.5%) were found to have overactive bladder. The presence of overactive bladder was associated with numerous unmet social needs, including housing instability, food insecurity, worry about utilities, lack of transportation, skipping medical appointments, needing legal help, stress in personal relationships, worry about toilet access and plumbing at home, and lack of social supports. On multivariable analysis adjusting for multiple covariates, all associations between overactive bladder and social needs remained significant. CONCLUSIONS: Multiple unmet social needs were associated with overactive bladder, which may have implications for the overall management of overactive bladder patients. It is important for providers to consider these unmet social needs of patients, as highlighting and addressing these factors hopefully can help improve care of individuals with overactive bladder.

Sexual Dysfunction in Women after Traumatic Pelvic Fracture Negatively Affects Quality of Life and Mental Health.

BACKGROUND: While the impact of female sexual dysfunction (FSD) on mental health and overall health-related quality of life (HrQOL) has been previously documented, no prior work has evaluated this relationship in women following traumatic pelvic injuries. AIM: This study aims to understand the relationship of FSD with HrQOL and depression in women with a history of traumatic pelvic fracture. METHODS: Data were collected with an electronic survey that included queries regarding mental and sexual health. Inverse probability weighting and multivariate regression models were utilized to assess the relationships between sexual dysfunction, depression and HrQOL. OUTCOMES: Study outcome measures included the Female Sexual Function Index (FSFI) to evaluate sexual functioning, the 8-item patient health questionnaire (PHQ-8) to assess depression symptoms, and the visual analog scale (VAS) component of the EuroQol 5 Dimensions Questionnaire (EQ-5D) to determine self-reported HrQOL. RESULTS: Women reporting FSD had significantly higher PHQ-8 scores with a median PHQ-8 score of 6 (IQR 2, 11) relative to those without FSD who had a median score of 2 (IQR 0, 2) (P < .001). On multivariate linear regression, presence of FSD was significantly associated with higher PHQ-8 scores (ß = 4.91, 95% CI 2.8-7.0, P < .001). FSFI score, time from injury, and age were all independently associated with improved HrQOL, with FSFI having the largest effect size (ß = 0.62, 95% CI 0.30-0.95, P < .001). CLINICAL IMPLICATIONS: These results underscore importance of addressing not just sexual health, but also mental health in female pelvic fracture survivors in the post-injury setting. STRENGTHS AND LIMITATIONS: This study is one of the first to examine women with traumatic pelvic fractures who did not sustain concomitant urinary tract injuries. Study limitations include low response rate and the inherent limitations of a cross-sectional study design. CONCLUSION: Patients with persistent, unaddressed FSD after pelvic fracture are at unique risk for experiencing depression and reporting worse health-related quality of life due to complex biopsychosocial mechanisms. Gambrah HA, Hagedorn JC, Dmochowski RR, et al. Sexual Dysfunction in Women after Traumatic Pelvic Fracture Negatively Affects Quality of Life and Mental Health. J Sex Med 2022;19:1759-1765.

Understanding sexual health concerns in women after traumatic pelvic fracture.

INTRODUCTION: While there is a well-known association between pelvic fracture and sexual dysfunction, few studies discuss the treatment patterns and utilization of healthcare services following injury. Those that do exist pertain to men. How women experience sexual dysfunction after traumatic injury and how they navigate the healthcare system is currently not well documented in the literature. This study aims to understand the prevalence and spectrum of sexual health issues in women after pelvic fracture, and to highlight barriers associated with accessing care for these concerns. MATERIALS AND METHODS: Women admitted and treated for traumatic pelvic fractures at a single Level 1 trauma center over a 6-year period were invited to participate in an electronic cross-sectional survey. Sexual health issues and care-seeking behaviors around sexual health were assessed. Inverse probability weighting based on available common data points in the registry was utilized to adjust for nonresponse bias. All data presented are of weighted data unless otherwise specified. RESULTS: Of the 780 potential subjects, 98 women responded to the survey (12.6% crude response rate). With weighting, 71% of responders were white and 42% had private insurance, with a mean age at the time of injury of 42.2 years (SD 22.4) and median time since the injury of 45 months (interquartile range: 30.0, 57.4). 49.5% stated that sexual function was important to very important to their quality of life, with an additional 25.3% reporting it was moderately important. Of responders, 59.0% (95% confidence interval: 47.1%-71.0%) reported de novo postinjury sexual dysfunction. Specific complaints included dyspareunia (37.1%), difficulty with sexual satisfaction (34.4%), difficulty with sexual desire (31.3%), difficulty with orgasm (26.0%), and genital pain (17.8%). Of those with postinjury sexual dysfunction, 30.4% of women reported spontaneous resolution without treatment. An additional 15.4% indicated that they have continued concerns and desire treatment. Only 11.6% of women stated they had received treatment, all patients with access to insurance. Of those with postinjury sexual dysfunction, 60.8% had sexual health discussions with providers, 83.3% of which were patient-initiated. Common reasons why patients with sexual dysfunction did not raise the topic of sexual health with providers included embarrassment/fear (23.6%), assuming the issue would resolve with time (23.5%), sexual health not being a health priority (22.4%), and lack of information about the condition or available treatments (19.9%). CONCLUSION: Sexual dysfunction is common in women after traumatic pelvic fracture, with patients experiencing dysfunction in multiple domains. Concerns are inadequately addressed in the healthcare setting due to several modifiable barriers at both the patient and provider levels. Standardization in the postinjury recovery period is needed to better address patients' sexual health concerns.

The cumulative effect of unmet social needs on noncancerous genitourinary conditions and severity of lower urinary tract symptoms.

PURPOSE: There is growing awareness on how social determinants of health may significantly influence health outcomes. The purpose of this study was to investigate the relationship between unmet social needs and the incidence and severity of multiple noncancerous genitourinary conditions. MATERIALS AND METHODS: A community-based sample of United States adults was recruited electronically to complete questionnaires on clinical and demographic information, urinary symptoms, and social needs. Logistic regression was used to assess the effect between the number of unmet social needs and various noncancerous genitourinary conditions and severity of lower urinary tract symptoms. Model was adjusted for age, gender, race, insurance, and type of living community. RESULTS: A total of 4,224 participants were included for final analysis. The incidence of all genitourinary conditions assessed was associated with an increasing number of unmet social needs. Additionally, having three or more unmet social needs, as compared to no needs, was associated with an increased risk of all conditions and worse symptoms-including a 23.7% increased risk of interstitial cystitis (95% confidence interval [CI] 18.8%-28.7%, p < 0.001), 21.9% risk of urge urinary incontinence (95% CI 16.8%-27.0%, p < 0.001), and 20.6% risk of overactive bladder (95% CI 15.6-25.7, p < 0.001). CONCLUSIONS: Unmet social needs are associated with an increased incidence of noncancerous genitourinary conditions as well as worse symptom severity, with multiple unmet social needs displaying a cumulative effect. These findings suggest that there is utility in screening patients for unmet social needs, and that the healthcare system should develop a more integrated approach to manage  patients with urinary conditions.

The burdens of incontinence: Quantifying incontinence product usage and costs in women.

INTRODUCTION: Urinary incontinence is a common condition in women, who often use incontinence containment products to self-manage. Few studies have sought to quantify use and costs of incontinence products associated with subtypes of incontinence and severity, therefore this study aimed to quantify incontinence product use and personal costs to women. METHODS: This is a secondary analysis from a sample of adult women recruited electronically via ResearchMatch for a study on urinary symptoms and social determinants of health. Participants completed validated questionnaires on urinary symptoms, and were asked about daily numbers and types of incontinence products used and weekly costs, along with demographic and baseline clinical information, and information about unmet social needs. Descriptive statistics were performed, in addition to Wilcoxon rank sum and Kruskal-Wallis tests to compare incontinence product usage and cost based on type of incontinence, symptom severity, and other demographics, in addition to multivariable linear regression. RESULTS: A total of 702 women who reported using weekly incontinence products were included in the final analytic sample. Overall, women reported using a mean of 1.8 ± 2.1 incontinence products in 24 h (median: 1, interquartile range [IQR]: 1), with a maximum of 32. Mean weekly cost of was $5.42 ± $8.59 (median: $3, IQR: $4), with cost up to $100. Nonwhite women trended towards having higher product usage and cost, with significant cost increase seen among non-Hispanic Black women and Hispanic women. Usage and cost were higher in women who had less education, had household income below the poverty line, were on disability, were using Medicaid or were uninsured, had more unmet social needs, and in those with mixed incontinence. Additionally, daily product use and weekly costs increased with incontinence symptom severity, with the biggest increase between those with severe and very severe symptoms. CONCLUSIONS: In this study, we were able to quantify the number of incontinence products used daily and the weekly costs in incontinent women across types and severity of incontinence. Costs were even greater and may be prohibitive, in women with more unmet social needs, Medicaid or no insurance, less than a college education, lower income, or on disability.

Compensatory bladder behaviors ("coping") in women with overactive bladder.

AIMS: There is little information on how often or within what contexts individuals with OAB use compensatory behaviors ("coping") to manage symptoms. We sought to examine how frequently women with OAB report using coping behaviors and whether these are associated with psychosocial factors. METHODS: One hundred twenty adult women with OAB completed the OAB questionnaire (OAB-q), ICIQ-FLUTS questionnaire, PROMIS Anxiety and Depression, Perceived Stress Scale, patient perception of bladder condition, and demographic and clinical data. Responses from five items from the OAB-q Quality-of-Life scale asking about coping with OAB symptoms (i.e., "compensatory coping behaviors") were summed to generate a total Coping Score. Linear regression was used to identify associations between individual coping behaviors, total Coping Scores, and exposure variables. RESULTS: Most (88%) subjects reported using at least one compensatory coping behavior at least "a little of the time," with "locating the nearest restroom in a new place" the most frequent. Higher BMI, lower education, using OAB medication, and urgency incontinence as well as urinary symptom severity were all associated with higher coping scores. Beyond the influence of OAB severity, higher anxiety (ß = 0.15, 95% CI [0.05-0.26], p = 0.004) and stress (ß = 0.16 [0.03-0.25], p = 0.02) were significantly associated with higher total coping scores, although depression was not. CONCLUSIONS: Compensatory bladder behaviors (coping) were common in women with OAB and were associated with greater urinary symptom severity and higher anxiety and stress. Further study is needed to understand how coping behaviors and psychosocial factors relate, as these may represent important opportunities for interventions.

Urgency and urgency incontinence following stress urinary incontinence surgery: A review of evaluation and management.

The presence of urgency urinary incontinence (U/UUI) after sling surgery is a common reason for dissatisfaction and imposition on quality of life. We aimed to evaluate and analyze the pathophysiology, evaluation, and treatment of U/UUI after sling surgery. A MEDLINE review was performed for relevant, English-language articles relating to storage and emptying symptoms after sling surgery. U/UUI may persist, be improved, or worsen in women with preoperative mixed urinary incontinence and may appear de novo in those women originally presenting with pure stress urinary incontinence (SUI). While the exact mechanism is not clear, partial bladder outlet obstruction (BOO) should always be suspected, especially in those women with worsened or de novo symptoms soon after sling surgery. Initial workup should elucidate the temporality, quality, and bother associated with symptoms and to evaluate the woman for urinary tract infection (UTI), pelvic organ prolapse (POP), or perforation of the lower urinary tract. The utility of urodynamics in attaining a definitive diagnosis of BOO is inconclusive. Treatment options include reevaluation of the patient after sling incision or after addressing UTI, POP, and perforation of the bladder or urethra. Women also typically undergo a multitiered approach to storage lower urinary tract symptoms outlined in the American Urological Association/Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction Overactive Bladder Guidelines. While improvement is typically seen with multimodality treatment, all women should be counseled regarding need for additional treatment for U/UUI, BOO, and SUI in the future.

A uro-protective agent with restorative actions on urethral and striated muscle morphology.

PURPOSE: Aging increases oxidative stress, which can have delirious effects on smooth and striated muscle resulting in bladder dysfunction. Consequently, in women aged over 60 years, urinary incontinence (UI) is a prevalent health problem. Despite the prevalence and consequences, UI continues to be undertreated simply because there are few therapeutic options. METHODS: Here we investigated whether 8-aminoguanine (8-AG), a purine nucleoside phosphorylase (PNPase inhibitor), would restore urethra and external sphincter (EUS) muscle morphology in the aged rat. Aged (> 25 months) female Fischer 344 rats were randomized to oral treatment with 8-AG (6 weeks) or placebo, and the urethra and EUS were evaluated by electron microscopy and protein expression (western immunoblotting). RESULTS: Aging was associated with mitochondrial degeneration in smooth and striated muscle cells as compared to young rats. We also observed a significant increase in biomarkers such as PARP, a downstream activator of oxidative/nitrosative stress. Treatment of aged rats with 8-AG normalized all abnormalities to that of a younger state. CONCLUSIONS: 8-AG, a potent inhibitor of PNPase, reverses age-related lower urinary tract morphological and biochemical changes. Our observations support the concept that 8-AG will reverse age-induced lower urinary tract disorders such as UI. These initial findings could have therapeutic implications for the prevention and treatment of age-related UI.

A randomized, placebo-controlled clinical development program exploring the use of litoxetine for treating urinary incontinence.

AIMS: To investigate the safety and efficacy of litoxetine, a serotonin reuptake inhibitor, in treating urinary incontinence (UI) and mixed urinary incontinence (MUI). METHODS: Two randomized, double-blind, placebo-controlled clinical trials (RCT1 and RCT2) were conducted. RCT1, which included 196 women aged 18-75 with MUI randomized 1:1:1:1 to receive 10, 20, or 40 mg litoxetine or placebo orally twice daily (BID) for 12 weeks, investigated the efficacy (including changes in patient reported outcomes) and safety of litoxetine compared to placebo. RCT2, which included 82 men and women aged 18-70 with any UI type randomly assigned 2:1 to receive 30 mg litoxetine or placebo orally BID for 8 weeks including a 2 week dose titration period, investigated the safety (including psychiatric safety) and efficacy of litoxetine compared to placebo. Efficacy was measured as the change in number of incontinence episodes per week and assessed using an analysis of covariance with missing data imputed by Predictive Mean Matching. Safety was assessed by adverse events (AEs) and physical examinations and analyzed using descriptive statistics. RESULTS: The 30-mg and placebo groups in RCT2 showed no difference in frequency of AEs, and litoxetine reduced the number of incontinence episodes per week compared to placebo. Although RCT1 suffered an unexpectedly high placebo response, and therefore did not meet the primary efficacy endpoint, 71% of participants receiving 40 mg litoxetine reported a clinically meaningful improvement in the King's Health Questionnaire. CONCLUSIONS: Litoxetine may be a safe, effective and well-tolerated treatment for patients with UI.

Increased risk of incident dementia following use of anticholinergic agents: A systematic literature review and meta-analysis.

BACKGROUND/RATIONALE: Long-term treatment with anticholinergic agents may increase the risk of cognitive impairment or dementia. This systematic literature review and meta-analysis aimed to assess the impact of ≥3 months of exposure to anticholinergics as a class on the risk of dementia, mild cognitive impairment, and change in cognitive function. The impact of anticholinergic agents specifically used to treat overactive bladder was also evaluated. MATERIALS AND METHODS: A systematic literature review was conducted to identify English language articles evaluating the impact of anticholinergic use for ≥3 months on dementia or cognitive function in adult patients. Databases searched included PubMed, Embase, and the Cochrane Library. Meta-analyses were conducted using random-effects models; 95% confidence intervals (CIs) and 95% prediction intervals (PIs) were reported. RESULTS: A total of 2122 records were identified. Out of those, 21 studies underwent qualitative synthesis and 6 reported endpoints relevant for inclusion in a meta-analysis assessing the risk of incident dementia. The overall rate ratio for incident dementia was 1.46 (95% CI: 1.17-1.81; 95% PI: 0.70-3.04; n = 6). The risk of incident dementia increased with increasing exposure (n = 3). In addition, two studies from the meta-analysis reported an increased risk of dementia with ≥3 months of use of bladder antimuscarinics (adjusted odds ratios ranged from 1.21 to 1.65, depending on exposure category). CONCLUSION: Anticholinergic use for ≥3 months increased the risk of dementia on average by an estimated 46% versus nonuse. This relationship was consistent in studies assessing overactive bladder medications. The risk of developing dementia should be carefully considered in the context of potential benefit before prescribing anticholinergics.

First voided volume: A novel approach to characterize nocturia.

AIMS: Nocturnal polyuria syndrome (NPS) denotes nocturnal polyuria (NP) in the absence of identifiable contributory factors. The trajectory of nocturnal urine production (NUP; typically expressed as ml/hour) may be useful in delineating between NP patients with versus without NPS, but changes in absolute urine volume, the directly measured substrate for behavioral and pharmacologic interventions targeting nocturnal urine production, have not been well characterized. This study compares the ratio of the first nocturnal voided volume (FNVV) to the nocturnal average voided volume (NAVV) in patients with versus without NPS. METHODS: Secondary analysis of 24-h voiding diaries from male patients greater than or equal to 18 years of age with two or more nocturnal voids and NP using two different criteria for NP: NUP greater than or equal to 90 ml/h and nocturnal polyuria index (NPi) greater than or equal to 0.33. Patients with diabetes insipidus and CPAP-adherent obstructive sleep apnea (OSA) were excluded. Patients were divided into 2 groups: secondary NP (OSA, congestive heart failure, and chronic kidney disease) and NPS (absence of edema, diuretic use, and the aforementioned comorbidities). FNVV was defined as the volume of urine accompanying the first nocturic episode. NAVV was defined as nocturnal urine volume/(number of nocturnal voids + 1). The nocturnal urine trajectory ratio (NUTR) was defined as FNVV/NAVV. RESULTS: At NUP greater than or equal to 90 ml/h, NUTR was significantly greater in patients with (n = 73) versus without (n = 28) NPS (1.10 [0.89-1.33] vs. 0.91 [0.55-1.15], p = .012). At NPi greater than or equal to 0.33, NUTR was likewise significantly greater in patients with (n = 92) versus without (n = 32) NPS (1.09 [0.90-1.33] vs. 0.91 [0.57-1.17], p = .010). CONCLUSIONS: The volume of urine produced in the early hours of sleep is central to identification of NPS in patients with nocturia.