Primary amebic meningoencephalitis: a review of Naegleria fowleri and analysis of successfully treated cases.

Primary amebic meningoencephalitis (PAM) is a necrotizing and hemorrhagic inflammation of the brain and meninges caused by Naegleria fowleri, a free-living thermophilic ameba of freshwater systems. PAM remains a neglected disease that disproportionately affects children in tropical and subtropical climates, with an estimated mortality rate of 95-98%. Due to anthropogenic climate change, the average temperature in the USA has increased by 0.72 to 1.06 °C in the last century, promoting the poleward spread of N. fowleri. PAM is often misdiagnosed as bacterial meningitis or viral encephalitis, which shortens the window for potentially life-saving treatment. Diagnosis relies on the patient's history of freshwater exposure and the physician's high index of suspicion, supported by cerebrospinal fluid studies. While no experimental trials have been conducted to assess the relative efficacy of treatment regimens, anti-amebic therapy with adjunctive neuroprotection is standard treatment in the USA. We performed a literature review and identified five patients from North America between 1962 and 2022 who survived PAM with various degrees of sequelae.

Overactive Bladder in Late Pregnancy to 1 Year After First Vaginal Delivery.

IMPORTANCE: Understanding overactive bladder (OAB) during pregnancy and postpartum may increase our knowledge of pathophysiology. OBJECTIVES: The purpose of this study was to understand the prevalence and severity of OAB during pregnancy through 1 year postpartum as well as the associated factors. STUDY DESIGN: This is a secondary analysis of a prospective cohort study evaluating primiparous women with a singleton term vaginal delivery assessed at the third trimester, 8 weeks postpartum, and 1 year postpartum. Overactive bladder was defined as urinary urgency plus nocturia or frequency, or urgency urinary incontinence (UUI). Overactive bladder severity was defined using average visual analog scores (0-100) from OAB symptoms on the Epidemiology of Prolapse and Incontinence Questionnaire. We evaluated associations with OAB at each time point using logistic regression. RESULTS: Among 579 participants, mean age was 29 years. Overactive bladder prevalence was higher at 8 weeks postpartum (23%) than at the third trimester (18%, P = 0.03) and 1 year postpartum (19%, P = 0.03). Overactive bladder severity was higher at the third trimester (42.2) than at 8 weeks postpartum (23.3, P = 0.008), but not at 1 year postpartum (29.1, P = 0.1). In those with OAB, UUI severity was higher at 1 year postpartum compared with that at the third trimester ( P = 0.02). Younger age was associated with third trimester OAB. At 8 weeks postpartum, OAB was associated with older age, urinary tract infection after delivery, birth weight ≥3,500 g, and third trimester OAB. At 1 year postpartum, OAB was associated with birth weight ≥3,500 g and third trimester OAB. CONCLUSIONS: Overactive bladder affects 1 in 5 primiparous women during pregnancy or after vaginal delivery. The increased severity of UUI postpartum and the association between higher birth weight and OAB postpartum suggest an effect of delivery.

Longitudinal Fluctuations in Treatment Response After OnabotulinumToxinA and Sacral Neuromodulation for Refractory Urgency Incontinence.

PURPOSE: We compared fluctuations in treatment response after onabotulinumtoxinA and sacral neuromodulation for urgency incontinence using Markov models. MATERIALS AND METHODS: We fit data from a randomized trial to Markov models to compare transitions of success/failure over 6 months between 200 U onabotulinumtoxinA and sacral neuromodulation. Objective failure was <50% reduction in urgency incontinence episodes from baseline; subjective failure "strongly disagree" to "neutral" to the Patient Global Symptom Control questionnaire. RESULTS: Of the 357 participants (median baseline daily urgency incontinence episodes 4.7 [IQR 3.7-6.0]) 61% vs 51% and 3.2% vs 6.1% reported persistent states of objective success and failure over 6 months after onabotulinumtoxinA vs sacral neuromodulation. Participants receiving onabotulinumtoxinA vs sacral neuromodulation had lower 30-day transition probabilities from objective and subjective success to failure (10% vs 14%, ratio 0.75 [95% CI 0.55-0.95]; 14% vs 21%, ratio 0.70 [95% CI 0.51-0.89]). The 30-day transition probability from objective and subjective failure to success did not differ between onabotulinumtoxinA and sacral neuromodulation (40% vs 36%, ratio 1.11 [95% CI 0.73-1.50]; 18% vs 17%, ratio 1.14 [95% CI 0.65-1.64]). CONCLUSIONS: Over 6 months after treatment, 2 in 5 women's symptoms fluctuate. Within these initial 6 months, women receiving onabotulinumtoxinA transitioned from success to failure over 30 days less often than sacral neuromodulation. For both treatments, there was an almost 20%-40% probability over 30 days that women returned to subjective and objective success after failure. Markov models add important information to longitudinal models on how symptoms fluctuate after urgency incontinence treatment.

Dr. Allen Oldfather Whipple (1881-1963): Namesake of the pancreaticoduodenectomy.

Allen O. Whipple was an American surgeon who popularized the pancreaticoduodenectomy (Whipple procedure) for periampullary cancer, which remains the gold standard for pancreatic tumor resections. Whipple was educated at Princeton University (B.S., 1904) and Columbia University College of Physicians and Surgeons (M.D., 1908). He swiftly ascended the academic ranks, culminating in his appointment as Professor of Surgery at Columbia and Director of Surgical Services at Presbyterian Hospital in 1921. Whipple published three criteria (Whipple's triad) for evaluating hyperinsulinism secondary to pancreatic insulinoma. He also revived interest in portocaval anastomosis to reduce portal hypertension, determining it to be a consequence of liver disease. During his 40-year career, Whipple introduced the concept of multidisciplinary teams and prospective data collection. He also shaped the structure of surgical training as President of the American Surgical Association and Chairman of the American Board of Surgery. Beyond the walls of the operating room, Whipple was a Renaissance Man whose childhood in Persia (Iran) engendered a lifelong interest in the region's art, culture, history, and medicine. Dr. Allen Oldfather Whipple is remembered as a pioneering physician and surgeon beloved by those who trained under him.

Revisiting the policy ecology framework for implementation of evidence-based practices in mental health settings.

BACKGROUND: Over the past three decades, policy actors and actions have been highly influential in supporting the implementation of evidence-based practices (EBPs) in mental health settings. An early examination of these actions resulted in the Policy Ecology Framework (PEF), which was originally developed as a tactical primer for state and local mental health regulators in the field of child mental health. However, the policy landscape for implementation has evolved significantly since the original PEF was published. An interrogation of the strategies originally proposed in the PEF is necessary to provide an updated menu of strategies to improve our understanding of the mechanisms of policy action and promote system improvement. OBJECTIVES: This paper builds upon the original PEF to address changes in the policy landscape for the implementation of mental health EBPs between 2009 and 2022. We review the current state of policy strategies that support the implementation of EBPs in mental health care and outline key areas for policy-oriented implementation research. Our review identifies policy strategies at federal, state, agency, and organizational levels, and highlights developments in the social context in which EBPs are implemented. Furthermore, our review is organized around some key changes that occurred across each PEF domain that span organizational, agency, political, and social contexts along with subdomains within each area. DISCUSSION: We present an updated menu of policy strategies to support the implementation of EBPs in mental health settings. This updated menu of strategies considers the broad range of conceptual developments and changes in the policy landscape. These developments have occurred across the organizational, agency, political, and social contexts and are important for policymakers to consider in the context of supporting the implementation of EBPs. The updated PEF expands and enhances the specification of policy levers currently available, and identifies policy targets that are underdeveloped (e.g., de-implementation and sustainment) but are becoming visible opportunities for policy to support system improvement. The updated PEF clarifies current policy efforts within the field of implementation science in health to conceptualize and better operationalize the role of policy in the implementation of EBPs.

Base Editor Scanning Reveals Activating Mutations of DNMT3A.

DNA methyltransferase 3A (DNMT3A) is a de novo cytosine methyltransferase responsible for establishing proper DNA methylation during mammalian development. Loss-of-function (LOF) mutations to DNMT3A, including the hotspot mutation R882H, frequently occur in developmental growth disorders and hematological diseases, including clonal hematopoiesis and acute myeloid leukemia. Accordingly, identifying mechanisms that activate DNMT3A is of both fundamental and therapeutic interest. Here, we applied a base editor mutational scanning strategy with an improved DNA methylation reporter to systematically identify DNMT3A activating mutations in cells. By integrating an optimized cellular recruitment strategy with paired isogenic cell lines with or without the LOF hotspot R882H mutation, we identify and validate three distinct hyperactivating mutations within or interacting with the regulatory ADD domain of DNMT3A, nominating these regions as potential functional target sites for pharmacological intervention. Notably, these mutations are still activating in the context of a heterozygous R882H mutation. Altogether, we showcase the utility of base editor scanning for discovering functional regions of target proteins.

Chemoproteomics Yields a Selective Molecular Host for Acetyl-CoA.

Chemoproteomic profiling is a powerful approach to define the selectivity of small molecules and endogenous metabolites with the human proteome. In addition to mechanistic studies, proteome specificity profiling also has the potential to identify new scaffolds for biomolecular sensing. Here, we report a chemoproteomics-inspired strategy for selective sensing of acetyl-CoA. First, we use chemoproteomic capture experiments to validate the N-terminal acetyltransferase NAA50 as a protein capable of differentiating acetyl-CoA and CoA. A Nanoluc-NAA50 fusion protein retains this specificity and can be used to generate a bioluminescence resonance energy transfer (BRET) signal in the presence of a CoA-linked fluorophore. This enables the development of a ligand displacement assay in which CoA metabolites are detected via their ability to bind the Nanoluc-NAA50 protein "host" and compete binding of the CoA-linked fluorophore "guest". We demonstrate that the specificity of ligand displacement reflects the molecular recognition of the NAA50 host, while the window of dynamic sensing can be controlled by tuning the binding affinity of the CoA-linked fluorophore guest. Finally, we show that the method's specificity for acetyl-CoA can be harnessed for gain-of-signal optical detection of enzyme activity and quantification of acetyl-CoA from cellular samples. Overall, our studies demonstrate the potential of harnessing insights from chemoproteomics for molecular sensing and provide a foundation for future applications in target engagement and selective metabolite detection.

Biochemical Analysis Leads to Improved Orthogonal Bioluminescent Tools.

Engineered luciferase-luciferin pairs have expanded the number of cellular targets that can be visualized in tandem. While light production relies on selective processing of synthetic luciferins by mutant luciferases, little is known about the origin of selectivity. The development of new and improved pairs requires a better understanding of the structure-function relationship of bioluminescent probes. In this work, we report a biochemical approach to assessing and optimizing two popular bioluminescent pairs: Cashew/d-luc and Pecan/4'-BrLuc. Single mutants derived from Cashew and Pecan revealed key residues for selectivity and thermal stability. Stability was further improved through a rational addition of beneficial residues. In addition to providing increased stability, the known stabilizing mutations surprisingly also improved selectivity. The resultant improved pair of luciferases are >100-fold selective for their respective substrates and highly thermally stable. Collectively, this work highlights the importance of mechanistic insight for improving bioluminescent pairs and provides significantly improved Cashew and Pecan enzymes which should be immediately suitable for multicomponent imaging applications.

Mindfulness and Implementation Planning: Promoting Self-Reported and Behavioral Forgiveness.

The current research examined mindfulness and implementation planning as practices that promote interpersonal forgiveness. A unique contribution of this work includes the investigation of motives and techniques that might promote both self-reported and behavioral forgiveness. Young adults (N = 80; M = 19.2 years) completed a task in which a standardized, interpersonal transgression occurred without the participants' knowledge. Results indicate that individuals who received training in either a mindfulness practice (i.e., mindful breathing) or implementation planning practice (i.e., developing "if-then" plan statements) reported better overall mood following the standardized transgression. Interestingly, mindful breathing appeared to be the most beneficial practice to enhance positive attitudes toward the forgiveness process and promote self-reported and behavioral forgiveness. Findings are consistent with prior research investigating the effectiveness of mindful breathing and implementation planning following an actual interpersonal transgression. Implications as well as future research directions within the context of forgiveness and relationships are discussed.

Phenotyping of Urinary Urgency Patients Without Urgency Incontinence, and Their Comparison to Urgency Incontinence Patients: Findings From the LURN Study.

PURPOSE: We characterize patients with urinary urgency with vs without urgency urinary incontinence who presented to clinics actively seeking treatment for their symptoms. MATERIALS AND METHODS: Participants who enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network were categorized into urinary urgency with vs without urgency urinary incontinence. Participants were followed for 1 year; their urinary symptoms, urological pain, psychosocial factors, bowel function, sleep disturbance, physical activity levels, physical function, and quality of life were compared. Mixed effects linear regression models were used to examine the relationships between urgency urinary incontinence and these factors. RESULTS: Among 683 participants with urinary urgency at baseline, two-thirds (n=453) also had urgency urinary incontinence; one-third (n=230) had urinary urgency-only without urgency urinary incontinence. No differences were detected in urological pain between urinary urgency-only and urgency urinary incontinence. Those with urgency urinary incontinence had more severe urgency and frequency symptoms, higher depression, anxiety, perceived stress scores, more severe bowel dysfunction and sleep disturbance, lower physical activity levels, lower physical function, and worse quality of life than those with urinary urgency-only. Among those with urinary urgency-only at baseline, 40% continued to have urinary urgency-only, 15% progressed to urgency urinary incontinence, and 45% had no urgency at 12 months. Fifty-eight percent with urgency urinary incontinence at baseline continued to report urgency urinary incontinence at 12 months, while 15% improved to urinary urgency-only, and 27% had no urgency. CONCLUSIONS: Patients with urgency urinary incontinence have severe storage symptoms, more psychosocial symptoms, poorer physical functioning, and worse quality of life. Our data suggested urgency urinary incontinence may be a more severe manifestation of urinary urgency, rather than urinary urgency and urgency urinary incontinence being distinct entities.

Natural history of lower urinary tract symptoms in treatment-seeking women with pelvic organ prolapse; the Symptoms of Lower Urinary Tract Dysfunction Research Network (LURN).

BACKGROUND: The association of pelvic organ prolapse with overactive bladder and other lower urinary tract symptoms, and the natural history of those symptoms are not well characterized. Previous cross-sectional studies demonstrated conflicting relationships between prolapse and lower urinary tract symptoms. OBJECTIVE: This study primarily aimed to determine the baseline association between lower urinary tract symptoms and prolapse and to assess longitudinal differences in symptoms over 12 months in women with and without prolapse. Secondary aims were to explore associations between lower urinary tract symptoms and prolapse treatment. We hypothesized that: (1) prolapse is associated with the presence of lower urinary tract symptoms, (2) lower urinary tract symptoms are stable over time in patients with and without prolapse, and (3) prolapse treatment is associated with lower urinary tract symptom improvement. STUDY DESIGN: Women enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network Observational Cohort Study with adequate 12-month follow-up data were included. Prolapse and lower urinary tract symptom treatment during follow-up was guided by standard of care. Outcome measures included the Lower Urinary Tract Symptoms Tool total severity score (in addition to overactive bladder, obstructive, and stress urinary incontinence subscales) and Urogenital Distress Inventory-6 Short Form. Prolapse (yes or no) was defined primarily when Pelvic Organ Prolapse Quantification System points Ba, C or Bp were >0 (beyond the hymen). Mixed-effects models with random effects for patient slopes and intercepts were fitted for each lower urinary tract symptom outcome and prolapse predictor, adjusted for other covariates. The study had >90% power to detect differences as small as 0.4 standard deviation for less prevalent group comparisons (eg, prolapse vs not). RESULTS: A total of 371 women were analyzed, including 313 (84%) with no prolapse and 58 (16%) with prolapse. Women with prolapse were older (64.6±8.8 vs 55.3±14.1 years; P<.001) and more likely to have prolapse surgery (28% vs 1%; P<.001) and pessary treatment (26% vs 4%; P<.001) during the study. Average baseline Lower Urinary Tract Symptoms Tool total severity scores were lower (fewer symptoms) for participants with prolapse compared with those without (38.9±14.0 vs 43.2±14.0; P=.036), but there were no differences in average scores between prolapse groups for other scales. For all urinary outcomes, average scores were significantly lower (improved) at 3 and 12 months compared with baseline (all P<.05). In mixed-effects models, there were no statistically significant interactions between pelvic organ prolapse measurement and visit and time-dependent prolapse treatment groups (P>.05 for all regression interaction coefficients). The Lower Urinary Tract Symptoms Tool obstructive severity score had a statistically significant positive association with Pelvic Organ Prolapse Quantification System Ba, Bp, and point of maximum vaginal descent. The Lower Urinary Tract Symptoms Tool total severity scale had a statistically significant negative association with Pelvic Organ Prolapse Quantification System Ba and point of maximum vaginal descent. No other associations between prolapse and lower urinary tract symptoms were significant (P>.05 for all regression coefficients). Symptom differences between prolapse groups were small: all regression coefficients (interpretable as additive percentage change in each score) were between -5 and 5 (standard deviation of outcomes ranged from 14.0-32.4). CONCLUSION: Among treatment-seeking women with urinary symptoms, obstructive symptoms were positively associated with prolapse, and overall lower urinary tract symptom severity was negatively associated with prolapse. Lower Urinary Tract Symptoms Tool scores improved over 12 months regardless of prolapse status, including in those with treated prolapse, untreated prolapse, and without prolapse.

'You're setting a lot of people up for failure': what formerly incarcerated women would tell healthcare decision makers.

BACKGROUND: Incarcerated women have a higher prevalence of health problems than the general population; however, little is known about their perspectives on the healthcare they receive. Here, we conducted semi-structured interviews with women who had been incarcerated (n = 63) which asked what they would tell healthcare decision-makers about their experiences of healthcare in prisons and the community post-incarceration if provided the opportunity. All participants had a history of sexual violence victimization and had at least one period of incarceration in a community corrections center in Arkansas due to the goals of the larger study from which data were drawn. RESULTS: Four themes arose when participants were asked what they would tell people who make decisions about community healthcare: 1) the healthcare system is not working (52%; n = 33), 2) have compassion for us (27%; n = 17), 3) recognize that we have specific and unique needs (17%; n = 11), and 4) the transition from incarceration is challenging and requires more support (22%; n = 14). Three themes arose when we asked participants what they would tell people who make decisions about healthcare in prisons: 1) we had experiences of poor physical healthcare in prison (44%; n = 28), 2) more specialty care is needed in prison (49%; n = 31), and 3) healthcare providers treat women in prison poorly (37%; n = 23). CONCLUSIONS: Our findings underscore the need for systemic changes including greater oversight of prison-based healthcare services, enhanced access to medical subspecialties in prisons, and healthcare provider training on the unique needs of incarcerated and previously incarcerated women. Polices that expand healthcare access are also likely to benefit formerly incarcerated women given the challenges they experience seeking community-based care.

Loneliness Among College Students: The Influence of Targeted Messages on Befriending.

The objective of the current research was to examine the influence of targeted messages in increasing helping behaviors towards lonely individuals. Previous research on loneliness interventions typically focuses on the lonely individual and working to reduce feelings of loneliness. The current study expands on this research by targeting individuals around lonely others to notice and consider helping those who might be lonely. Five targeted messages, based on Latané and Darley's (1970) bystander intervention model, were utilized. These messages included a "notice" condition (increasing awareness of lonely others), an "assume responsibility" condition (awareness and responsibility towards helping lonely others), a "decide" condition (awareness, responsibility, and steps to reach out to lonely others), and two control conditions. Participants in the "decide" condition were significantly more likely to report feeling prepared to help lonely others in the future. Those in the "assume responsibility" and "decide" conditions also reported more awareness of lonely individuals during a one-week follow-up. Overall, findings indicate that it might be advantageous to approach reducing loneliness from the perspective of those around lonely individuals. Future research and implications of these findings are discussed.

Predicting outcomes after intradetrusor onabotulinumtoxina for non-neurogenic urgency incontinence in women.

AIMS: Develop models to predict outcomes after intradetrusor injection of 100 or 200 units of onabotulinumtoxinA in women with non-neurogenic urgency urinary incontinence (UUI). METHODS: Models were developed using 307 women from two randomized trials assessing efficacy of onabotulinumtoxinA for non-neurogenic UUI. Cox, linear and logistic regression models were fit using: (1) time to recurrence over 12 months, (2) change from baseline daily UUI episodes (UUIE) at 6 months, and (3) need for self-catheterization over 6 months. Model discrimination of Cox and logistic regression models was calculated using c-index. Mean absolute error determined accuracy of the linear model. Calibration was demonstrated using calibration curves. All models were internally validated using bootstrapping. RESULTS: Median time to recurrence was 6 (interquartile range [IQR]: 2-12) months. Increasing age, 200 units of onabotulinumtoxinA, higher body mass index (BMI) and baseline UUIE were associated with decreased time to recurrence. The c-index was 0.63 (95% confidence interval [CI]: 0.59, 0.67). Median change in daily UUIE from baseline at 6 months was -3.5 (IQR: -5.0, -2.3). Increasing age, lower baseline UUIE, 200 units of onabotulinumtoxinA, higher BMI and IIQ-SF were associated with less improvement in UUIE. The mean absolute error predicting change in UUIE was accurate to 1.6 (95% CI: 1.5, 1.7) UUI episodes. The overall rate of self-catheterization was 17.6% (95% CI: 13.6%-22.4%). Lower BMI, 200 units of onabotulinumtoxinA, increased baseline postvoid residual and maximum capacity were associated with higher risk of self-catheterization. The c-index was 0.66 (95% CI: 0.61, 0.76). The three calculators are available at http://riskcalc.duke.edu. CONCLUSIONS: After external validation, these models will assist clinicians in providing more accurate estimates of expected treatment outcomes after onabotulinumtoxinA for non-neurogenic UUI in women.

Reducing Loneliness: The Impact of Mindfulness, Social Cognitions, and Coping.

While many facets of loneliness have been explored, research examining the efficacy of loneliness interventions has been overlooked among young adults. The study of loneliness among young adults has become increasingly important considering the current state of isolation and stay-at-home orders issued to prevent the spread of COVID-19. Preliminary reports suggest an increase in loneliness as a result of the current health pandemic, especially among young adults, who have reported feeling lonelier than any other age group. Such findings warrant the study of ways to help reduce loneliness among young adults. The current study examined the efficacy of strategies that might be used to help young adults manage feelings of loneliness. Two hundred and seventy-eight young adults completed the study. Participants read one of four messages: mindfulness, social cognitions, coping behaviors, or a control. Participants in the mindfulness condition felt better equipped to manage future instances of loneliness and held better attitudes toward this intervention. The current research helps to advance understanding of effective ways of helping young adults cope with loneliness.

Cost-effectiveness of bacteriuria screening before urogynecologic surgery.

BACKGROUND: Currently, there is controversy over who requires preoperative screening for bacteriuria in the urogynecologic population and whether treating asymptomatic bacteriuria reduces postoperative urinary tract infection rates. OBJECTIVE: To evaluate the cost-effectiveness of selective, universal, and no preoperative bacteriuria screening protocols in women undergoing surgery for prolapse or stress urinary incontinence. STUDY DESIGN: A simple decision tree model was created from a societal perspective to evaluate cost and effectiveness of 3 strategies to prevent postoperative urinary tract infection: (1) a universal protocol where all women undergoing urogynecologic surgery are screened for bacteriuria and receive preemptive treatment if bacteriuria is identified; (2) a selective protocol, where only women with a history of recurrent urinary tract infection are screened and treated for bacteriuria; and (3) a no-screening protocol, where no women are screened for bacteriuria. Our primary outcome was the incremental cost-effectiveness ratio, calculated in cost per quality-adjusted life-years. Secondary outcomes were the number of urine cultures, postoperative urinary tract infections, and pyelonephritis associated with each strategy. Costs were derived from the Centers for Medicare & Medicaid Services, Healthcare Cost and Utilization Project, and Medical Expenditure Panel Survey. Clinical estimates were derived from published literature and data from a historic surgical cohort. Quality-of-life-associated utilities for urinary tract infection (0.73), pyelonephritis (0.66), and antibiotic use (0.964) were derived from the published literature using the HALex scale, reported directly by affected patients. One-way sensitivity analyses were performed over the range of reported values. RESULTS: In the base case scenario, selective screening is more costly (no screen: $101.69, selective: $101.98) and more effective (no screen: 0.096459 quality-adjusted-life-year, selective: 0.096464 quality-adjusted-life-year) than no screening, and is cost-effective, with an incremental cost-effectiveness ratio of $49,349 per quality-adjusted-life-year. Both selective screening and no screening dominate universal screening in being less costly (universal: $111.92) and more effective (universal: 0.096446 quality-adjusted-life-year), with a slightly higher rate of postoperative urinary tract infection (no screen: 17.1%, selective: 16.9%, universal: 16.6%). In 1-way sensitivity analyses, selective screening is no longer cost-effective compared with no screening when the cost of a urine culture exceeds $12, cost of a preoperative urinary tract infection exceeds $93, the cost of a postoperative urinary tract infection is below $339, the specificity of a urine culture is less than 96%, or preoperative bacteriuria rates in those without symptoms but a history of recurrent urinary tract infection is <23%. Universal screening only becomes cost-effective when the postoperative urinary tract infection rate increases to >50% in those without risk factors and untreated preoperative bacteriuria. When compared with no screening, selective screening costs an additional $104 per urinary tract infection avoided and $2607 per pyelonephritis avoided. Compared with selective screening, universal screening costs $4609 per urinary tract infection avoided and $115,223 per pyelonephritis avoided. CONCLUSION: Implementation of a selective preoperative bacteriuria protocol is cost-effective in most scenarios and associated with only a <1% increase in the 30-day postoperative urinary tract infection rate. No screening is cost-effective when cost of a preoperative urinary tract infection is high and the rate of preoperative bacteriuria in those without risk factors is low.

Cost-effectiveness of behavioral and pelvic floor muscle therapy combined with midurethral sling surgery vs surgery alone among women with mixed urinary incontinence: results of the Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence randomized trial.

BACKGROUND: Urinary incontinence is prevalent among women, and it has a substantial economic impact. Mixed urinary incontinence, with both stress and urgency urinary incontinence symptoms, has a greater adverse impact on quality of life and is more complex to treat than either stress or urgency urinary incontinence alone. Studies evaluating the cost-effectiveness of treating both the stress and urgency urinary incontinence components simultaneously are lacking. OBJECTIVE: Cost-effectiveness was assessed between perioperative behavioral and pelvic floor muscle therapies combined with midurethral sling surgery and midurethral sling surgery alone for the treatment of women with mixed urinary incontinence. The impact of baseline severe urgency urinary incontinence symptoms on cost-effectiveness was assessed. STUDY DESIGN: This prospective economic evaluation was performed concurrently with the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence randomized trial that was conducted from October 2013 to April 2016. Participants included 480 women with moderate-to-severe stress and urgency urinary incontinence symptoms and at least 1 stress urinary incontinence episode and 1 urgency urinary incontinence episode on a 3-day bladder diary. The primary within-trial analysis was from the healthcare sector and societal perspectives, with a 1-year time horizon. Costs were in 2019 US dollars. Effectiveness was measured in quality-adjusted life-years and reductions in urinary incontinence episodes per day. Incremental cost-effectiveness ratios of combined treatment vs midurethral sling surgery alone were calculated, and cost-effectiveness acceptability curves were generated. Analysis was performed for the overall study population and subgroup of women with Urogenital Distress Inventory irritative scores of ≥50th percentile. RESULTS: The costs for combined treatment were higher than the cost for midurethral sling surgery alone from both the healthcare sector perspective ($5100 [95% confidence interval, $5000-$5190] vs $4470 [95% confidence interval, $4330-$4620]; P<.01) and the societal perspective ($9260 [95% confidence interval, $8590-$9940] vs $8090 [95% confidence interval, $7630-$8560]; P<.01). There was no difference between combined treatment and midurethral sling surgery alone in quality-adjusted life-years (0.87 [95% confidence interval, 0.86-0.89] vs 0.87 [95% confidence interval, 0.86-0.89]; P=.90) or mean reduction in urinary incontinence episodes per day (-4.76 [95% confidence interval, -4.51 to 5.00] vs -4.50 [95% confidence interval, -4.25 to 4.75]; P=.13). When evaluating the overall study population, from both the healthcare sector and societal perspectives, midurethral sling surgery alone was superior to combined treatment. The probability that combined treatment is cost-effective compared with midurethral sling surgery alone is ≤28% from the healthcare sector and ≤19% from the societal perspectives for a willingness-to-pay value of ≤$150,000 per quality-adjusted life-years. For women with baseline Urogenital Distress Inventory irritative scores of ≥50th percentile, combined treatment was cost-effective compared with midurethral sling surgery alone from both the healthcare sector and societal perspectives. The probability that combined treatment is cost-effective compared with midurethral sling surgery alone for this subgroup is ≥90% from both the healthcare sector and societal perspectives, at a willingness-to-pay value of ≥$150,000 per quality-adjusted life-years. CONCLUSION: Overall, perioperative behavioral and pelvic floor muscle therapies combined with midurethral sling surgery was not cost-effective compared with midurethral sling surgery alone for the treatment of women with mixed urinary incontinence. However, combined treatment was of good value compared with midurethral sling surgery alone for women with baseline severe urgency urinary incontinence symptoms.