Interstate Telemedicine for Urologic Cancer Care.

PURPOSE: US states eased licensing restrictions on telemedicine during the COVID-19 pandemic, allowing interstate use. As waivers expire, optimal uses of telemedicine must be assessed to inform policy, legislation, and clinical care. We assessed whether telemedicine visits provided the same patient experience as in-person visits, stratified by in- vs out-of-state residence, and examined the financial burden. MATERIALS AND METHODS: Patients seen in person and via telemedicine for urologic cancer care at a major regional cancer center received a survey after their first appointment (August 2019-June 2022) on satisfaction with care, perceptions of communication during their visit, travel time, travel costs, and days of work missed. RESULTS: Surveys were completed for 1058 patient visits (N = 178 in-person, N = 880 telemedicine). Satisfaction rates were high for all visit types, both interstate and in-state care (mean score 60.1-60.8 [maximum 63], P > .05). More patients convening interstate telemedicine would repeat that modality (71%) than interstate in-person care (61%) or in-state telemedicine (57%). Patients receiving interstate care had significantly higher travel costs (median estimated visit costs $200, IQR $0-$800 vs median $0, IQR $0-$20 for in-state care, P < .001); 55% of patients receiving interstate in-person care required plane travel and 60% required a hotel stay. CONCLUSIONS: Telemedicine appointments may increase access for rural-residing patients with cancer. Satisfaction outcomes among patients with urologic cancer receiving interstate care were similar to those of patients cared for in state; costs were markedly lower. Extending interstate exemptions beyond COVID-19 licensing waivers would permit continued delivery of high-quality urologic cancer care to rural-residing patients.

Urgent versus elective surgical disparities among American Indian and Alaska Native patients.

BACKGROUND: American Indian and Alaska Native (AIAN) health issues are understudied despite documentation of lower-than-average life expectancy. Urgent surgery is associated with higher rates of postsurgical complications and postoperative death. We assess whether American Indian and Alaska Native (AIAN) patients in Washington State are at greater risk of requiring urgent rather than elective surgery compared with non-Hispanic Whites (NHW). METHODS: We accessed data for the period 2009-2014 from the Washington State Comprehensive Hospital Abstract Reporting System (CHARS) database, which captures all statewide hospital admissions, to examine three common surgeries that are performed both urgently and electively: hip replacements, aortic valve replacements, and spinal fusions. We extracted patient race, age, insurance status, comorbidity, admission type, and procedures performed. We then constructed multivariable logistic regression models to identify factors associated with use of urgent surgical care. RESULTS: AIAN patients had lower mean age at surgery for all three surgeries compared with NHW patients. AIAN patients were at higher risk for urgent surgery for hip replacements (OR = 1.49, 95% CI 1.19-1.88), spinal fusions (OR = 1.39, 95% CI 1.04-1.87), and aortic valve replacements (OR = 2.06, 95% CI 1.12-3.80). CONCLUSION: AIAN patients were more likely to undergo urgent hip replacement, spinal fusion, and aortic valve replacement than NHW patients. AIAN patients underwent urgent surgery at younger ages. Medicaid insurance conferred higher risks for urgent surgery across all surgeries studied. Further research is warranted to more clearly identify the factors contributing to disparities among AIAN patients undergoing urgent surgery.

Racial inequities in the quality of surgical care among Medicare beneficiaries with localized prostate cancer.

BACKGROUND: US Black men are twice as likely to die from prostate cancer as men of other races. Lower quality care may contribute to this higher death rate. METHODS: Sociodemographic and clinical data were obtained for men in Surveillance, Epidemiology, and End Results-Medicare diagnosed with clinically localized prostate cancer (cT1-4N0/xM0/x) and managed primarily by radical prostatectomy (2005-2015). Surgical volume was determined for facility and surgeon. Relationships between race, surgeon and/or facility volume, and characteristics of treating facility with survival (all-cause and cancer-specific) were assessed using multivariable Cox regression and competing risk analysis. RESULTS: Black men represented 6.7% (n = 2123) of 31,478 cohort. They were younger at diagnosis, had longer time from diagnosis to surgery, lower socioeconomic status, higher prostate-specific antigen (PSA), and higher comorbid status compared with men of other races (p < .001). They were less likely to receive care from a surgeon or facility in the top volume percentile (p < .001); less likely to receive surgical care at a National Cancer Institute-designated cancer center and more likely seen at a minority-serving hospital; and less likely to travel ≥50 miles for surgical care. On multivariable analysis stratified by surgical volume, Black men receiving care from a surgeon or facility with lower volumes demonstrated increased risk of prostate cancer mortality (hazard ratio, 1.61; 95% confidence interval, 1.01-2.69) adjusting for age, clinical stage, PSA, and comorbidity index. CONCLUSIONS: Black Medicare beneficiaries with prostate cancer more commonly receive care from surgeons and facilities with lower volumes, likely affecting surgical quality and outcomes. Access to high-quality prostate cancer care may reduce racial inequities in disease outcomes, even among insured men. PLAIN LANGUAGE SUMMARY: Black men are twice as likely to die of prostate cancer than other US men. Lower quality care may contribute to higher rates of prostate cancer death. We used surgical volume to evaluate the relationship between race and quality of care. Black Medicare beneficiaries with prostate cancer more commonly received care from surgeons and facilities with lower volumes, correlating with a higher risk of prostate cancer death and indicating scarce resources for care. Access to high-quality prostate cancer care eases disparities in disease outcomes. Patient-centered interventions that increase access to high-quality care for Black men with prostate cancer are needed.

Patient-centered outcomes of telehealth for the care of rural-residing patients with urologic cancer.

BACKGROUND: Patients residing in rural areas with urologic cancers confront significant obstacles in obtaining oncologic care. In the Pacific Northwest, a sizeable portion of the population lives in a rural county. Telehealth offers a potential access solution. METHODS: Patients receiving urologic care through telehealth or an in-person appointment at the Fred Hutchinson Cancer Center in Seattle, Washington, were surveyed to assess appointment-related satisfaction and travel costs. Patients' residences were classified as rural or urban based on their self-reported ZIP code. Median patient satisfaction scores and appointment-related travel costs were compared by rural versus urban residence within telehealth and in-person appointment groups using Wilcoxon signed-rank or χ2 testing. RESULTS: A total of 1091 patients seen for urologic cancer care between June 2019 and April 2022 were included, 28.7% of which resided in a rural county. Patients were mostly non-Hispanic White (75%) and covered by Medicare (58%). Among rural-residing patients, telehealth and in-person appointment groups had the same median satisfaction score (61; interquartile ratio, 58, 63). More rural-residing than urban-residing patients in the telehealth appointment groups strongly agreed that "Considering the cost and time commitment of my appointment, I would choose to meet with my provider in this setting in the future" (67% vs. 58%, p = .03). Rural-residing patients with in-person appointments carried a higher financial burden than those with telehealth appointments (medians, $80 vs. $0; p <.001). CONCLUSIONS: Appointment-related costs are high among rural-residing patients traveling for urologic oncologic care. Telehealth provides an affordable solution that does not compromise patient satisfaction.

Urinary symptoms and female sexual dysfunction in women with type 1 diabetes: the role of depression.

BACKGROUND: Some reports suggest that women with type 1 diabetes (T1D) have a greater burden of female sexual dysfunction (FSD) than women without T1D, but the etiology of this elevated risk is poorly understood. AIM: To examine the associations between FSD and urinary incontinence/lower urinary tract symptoms (UI/LUTS) in women with T1D and to evaluate how depression may mediate these relationships. METHODS: LUTS and UI symptoms were assessed in women with T1D who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study. Multivariable logistic regression models estimated associations between FSD and UI/LUTS (overall and specific domains) and the impact of depression on these associations. OUTCOMES: FSD was measured with the Female Sexual Function Index-Reduced. RESULTS: In total, 499 self-reported sexually active women completed validated assessments of sexual and urinary function (mean ± SD age, 47.7 ± 7.6 years; T1D duration, 23.4 ± 5.15 years). FSD was reported in 232 (46%) responders. The frequency of UI and LUTS was 125 (25.1%) and 96 (19.2%), respectively. Neither UI nor its subcategories (urge, stress) were associated with FSD. Although LUTS (odds ratio [OR], 1.75; 95% CI, 1.09-2.77) and its symptoms of urgency (OR, 1.99; 95% CI, 1.09-3.61) and incomplete emptying (OR, 2.44; 95% CI, 1.23-4.85) were associated with FSD, these associations were attenuated following adjustment for depression and antidepressant medication use. Depression indicators were independently associated with FSD overall and across domains. CLINICAL IMPLICATIONS: The complex interplay of voiding dysfunction, mental health, and sexual function warrants further investigation to understand the potential implications for patient assessment, goal setting, treatment, and care planning. STRENGTHS AND LIMITATIONS: Data are from a prospective study of individuals with T1D. These results are unable to explore cause-and-effect relationships among LUTS, UI, depression, and FSD. The sample may not be representative of the general population of women with T1D. Because participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study are mostly White, generalizing the findings to other races and to type 2 diabetes may not be appropriate. While exclusion of sexually inactive women likely biases our findings toward the null, this design element permitted study of LUTS and UI in relation to aspects of FSD, the primary objective of this study. CONCLUSIONS: The significant associations between LUTS/UI and FSD among middle-aged women with T1D were greatly attenuated when depression was considered a mediating factor.

Extensive sequence and structural evolution of Arginase 2 inhibitory antibodies enabled by an unbiased approach to affinity maturation.

Affinity maturation is a powerful technique in antibody engineering for the in vitro evolution of antigen binding interactions. Key to the success of this process is the expansion of sequence and combinatorial diversity to increase the structural repertoire from which superior binding variants may be selected. However, conventional strategies are often restrictive and only focus on small regions of the antibody at a time. In this study, we used a method that combined antibody chain shuffling and a staggered-extension process to produce unbiased libraries, which recombined beneficial mutations from all six complementarity-determining regions (CDRs) in the affinity maturation of an inhibitory antibody to Arginase 2 (ARG2). We made use of the vast display capacity of ribosome display to accommodate the sequence space required for the diverse library builds. Further diversity was introduced through pool maturation to optimize seven leads of interest simultaneously. This resulted in antibodies with substantial improvements in binding properties and inhibition potency. The extensive sequence changes resulting from this approach were translated into striking structural changes for parent and affinity-matured antibodies bound to ARG2, with a large reorientation of the binding paratope facilitating increases in contact surface and shape complementarity to the antigen. The considerable gains in therapeutic properties seen from extensive sequence and structural evolution of the parent ARG2 inhibitory antibody clearly illustrate the advantages of the unbiased approach developed, which was key to the identification of high-affinity antibodies with the desired inhibitory potency and specificity.

Ureteral Strictures Following Ureteroscopy for Kidney Stone Disease: A Population-based Assessment.

PURPOSE: As the prevalence of urolithiasis increases and ureteroscopy is used more frequently, the risks of uncommon complications such as ureteral stricture may become more notable. Our objective is to assess the rate and associated risk factors of ureteral stricture formation in patients undergoing ureteroscopy. MATERIALS AND METHODS: Utilizing the IBM MarketScan research database, we evaluated data from 2008 to 2019 and compared ureteral stricture rates and their management following ureteroscopy to subjects who had shock wave lithotripsy. Shock wave lithotripsy was used as a comparison group to represent the rate of stricture from stone disease alone. A third group of those having both shock wave lithotripsy and ureteroscopy was included. Patients and secondary procedures were identified using Current Procedural Terminology, and International Classification of Diseases-9 and -10 codes. RESULTS: A total of 329,776 patients received ureteroscopy, shock wave lithotripsy, or shock wave lithotripsy+ureteroscopy between 2008 and 2019. Stricture developed in 2.9% of patients after ureteroscopy, 1.5% after shock wave lithotripsy, and 2.6% after shock wave lithotripsy+ureteroscopy. In the multivariable model, rates of stricture were 1.7-fold higher after ureteroscopy vs shock wave lithotripsy (OR:1.71, 95% CI 1.62-1.81). Preoperative hydronephrosis, age, prior stones/intervention, and concurrent kidney and ureteral stones were associated with increased risk of stricture. Of those with strictures incurred after ureteroscopy, 35% required drainage, 21% had endoscopic intervention, 4.8% required reconstructive surgery, and 1.7% underwent nephrectomy. CONCLUSIONS: Ureteral stricture rate after ureteroscopy of nearly 3% was higher than expected and approximately twice the rate attributable to stone disease alone. Factors associated with the stone as well as instrumentation were found to be risk factors. The morbidity of stricture disease following ureteroscopy was significant.

Intravesical BCG and Incidence of Alzheimer Disease in Patients With Bladder Cancer: Results From an Administrative Dataset.

INTRODUCTION: Alzheimer disease (AD) is a common neurodegenerative disease, and immunomodulation offers treatment opportunities. Preclinical data suggest that intravesical Bacillus Calmette-Guerin (BCG) treatment could delay AD development. We investigated this relationship in a population-based cancer database. SAMPLE AND METHODS: We queried the Surveillance, Epidemiology, and End Results-Medicare database for patients with high-risk nonmuscle-invasive bladder cancer (hrNMIBC). BCG dosage and subsequent Alzheimer diagnosis were collected through ICD-9/10 codes. Multivariable Cox regression was performed to assess the association between BCG therapy and subsequent Alzheimer diagnosis. RESULTS: We identified 26,584 hrNMIBC patients; 51% received BCG and 8.3% were diagnosed with Alzheimer. BCG exposure was significantly associated with lower Alzheimer occurrence (hazard ratio: 0.73, P <0.05), which was dose-dependent. Increasing age, female sex, Black race, and increasing comorbidity index were significantly associated with a greater risk of subsequent Alzheimer diagnosis. DISCUSSION: Treatment with intravesical BCG among patients with hrNMIBC was associated with a significantly lower risk for subsequent Alzheimer diagnosis, which seemed dose-dependent.

Longitudinal patterns of urinary incontinence and associated predictors in women with type 1 diabetes.

AIMS: Urinary incontinence (UI) in women is a dynamic condition with numerous risk factors yet most studies have focused on examining its prevalence at a single time. The objective of this study was to describe the long-term time course of UI in women with type 1 diabetes (T1D). METHODS: Longitudinal data in women with T1D were collected from 568 women in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort. Over a 12-year period, participants annually responded to whether they had experienced UI in the past year. RESULTS: We identified four categories of UI in this population over time: 205 (36.1%) women never reported UI (no UI), 70 (12.3%) reported it one or two consecutive years only (isolated UI), 247 (43.5%) periodically changed status between UI and no UI (intermittent UI), and 46 (8.1%) reported UI continuously after the first report (persistent UI). Compared to women reporting no/isolated UI, women displaying the intermittent phenotype were significantly more likely to be obese (OR: 1.86, 95% CI 1.15, 3.00) and report prior hysterectomy (OR: 2.57, 95% CI: 1.39, 4.77); whereas women with persistent UI were significantly more likely to have abnormal autonomic function (OR: 2.36, 95% CI: 1.16-4.80). CONCLUSIONS: UI is a dynamic condition in women with T1D. Varying risk factors observed for the different phenotypes of UI suggest distinctive pathophysiological mechanisms. These findings have the potential to be used to guide individualized interventions for UI in women with diabetes.

Short term reoperation rates after artificial urinary sphincter placement in pediatric patients.

INTRODUCTION: Artificial urinary sphincters (AUS) have demonstrated good functional outcomes in pediatric populations. We sought to examine the nationwide short term reoperation rates in pediatric patients after AUS placement. MATERIALS AND METHODS: An observational cohort study was designed utilizing claims from the Truven MarketScan Commercial Claims and Encounters database from 2007 to 2018. Patients under 18 years of age undergoing an AUS procedure were identified using CPT and ICD9/10 codes. Reoperations included any removal, replacement, or AUS placement codes which occurred after the initially identified placement code. Follow up time was the amount of time between AUS placement and the end of MarketScan enrollment. RESULTS: From 2007-2018, we identified 57 patients under the age of 18 who underwent AUS placement and after excluding 8 for concurrent AUS complication procedure codes and 4 for follow up < 60 days, the final cohort included 45 patients. The median age was 13 years (IQR 9-16 years) at the time of AUS placement, and the median follow up time after AUS placement was 787 days (IQR 442-1562 days), approximately 2.2 years. Total reoperation rate was 22%. Reoperations included 40% device removals (4/10) and 60% replacements (6/10). Neither gender (p = 0.70) nor age (p = 0.23) was associated with need for reoperation. Patients who had a concurrent bladder surgery had a higher rate of undergoing reoperation (50% vs. 12%, p = 0.007). CONCLUSIONS: The rate of reoperation after AUS placement approached 1 in 4 in pediatric patients. These data may be instrumental for providers and parents in counseling and decision-making regarding risks of prosthetic implantation.

Efficacy of Platinum Rechallenge in Metastatic Urothelial Carcinoma After Previous Platinum-Based Chemotherapy for Metastatic Disease.

BACKGROUND: Fit patients with metastatic urothelial carcinoma (mUC) receive first-line platinum-based combination chemotherapy (fPBC) as standard of care and may receive additional later-line chemotherapy after progression. Our study compares outcomes with subsequent platinum-based chemotherapy (sPBC) versus subsequent non-platinum-based chemotherapy (sNPBC). MATERIALS AND METHODS: Patients from 27 international centers in the Retrospective International Study of Cancers of the Urothelium (RISC) who received fPBC for mUC and at least two cycles of subsequent chemotherapy were included in this study. A multivariable Cox proportional hazards model compared overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred thirty-five patients received sPBC and 161 received sNPBC. Baseline characteristics were similar between groups, except patients who received sPBC had higher baseline hemoglobin, higher disease control rate with fPBC, and longer time since fPBC. OS was superior in the sPBC group (median 7.9 vs 5.5 months) in a model adjusting for comorbidity burden, performance status, liver metastases, number of fPBC cycles received, best response to fPBC, and time since fPBC (hazard ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .035). There was no difference in PFS. More patients in the sPBC group achieved disease control than in the sNPBC group (57.4% vs 44.8%; p = .041). Factors associated with achieving disease control in the sPBC group but not the sNPBC group included longer time since fPBC, achieving disease control with fPBC, and absence of liver metastases. CONCLUSION: After receiving fPBC for mUC, patients who received sPBC had better OS and disease control. This may help inform the choice of subsequent chemotherapy in patients with mUC. IMPLICATIONS FOR PRACTICE: Patients with progressive metastatic urothelial carcinoma after first-line platinum-based combination chemotherapy may now receive immuno-oncology agents, erdafitinib, enfortumab vedotin, or sacituzumab govitecan-hziy; however, those ineligible for these later-line therapies or who progress after receiving them may be considered for subsequent chemotherapy. In this retrospective study of 296 patients, survival outcomes and disease control rates were better in those receiving subsequent platinum-based rechallenge compared with non-platinum-based chemotherapy, suggesting that patients should receive platinum rechallenge if clinically able. Disease control with platinum rechallenge was more likely with prior first-line platinum having achieved disease control, longer time since first-line platinum, and absence of liver metastases.

Delays in radical cystectomy for muscle-invasive bladder cancer.

BACKGROUND: Delays from the diagnosis of muscle-invasive bladder cancer (MIBC) to radical cystectomy (RC) longer than 12 weeks result in higher mortality and shorter progression-free survival. This study sought to identify factors associated with RC delays and to determine whether delays in care in the current treatment paradigm, which includes neoadjuvant chemotherapy (NAC), affect survival. METHODS: Subjects with American Joint Committee on Cancer stage II urothelial carcinoma of the bladder who underwent RC from 2004 to 2012 were identified from the linked Surveillance, Epidemiology, and End Results national cancer registry and the Medicare claims database and were stratified into RC groups with or without NAC. Cox multivariable proportional hazard models and multivariable logistic regression models assessed the significance of delays in RC for survival and identified independent characteristics associated with RC delays, respectively. RESULTS: This study identified 1509 patients with MIBC who underwent RC during the study period. In comparison with timely surgery, delays in RC increased overall mortality, regardless of the use of NAC (hazard ratio [HR] without NAC, 1.34; 95% confidence interval [CI], 1.03-1.76; HR after NAC, 1.63; 95% CI, 1.06-2.52). Patients proceeding to RC without NAC had higher odds of delayed care if they lived in a high-poverty neighborhood (odds ratio [OR], 1.37; 95% CI, 1.01-2.08) or nonmetropolitan area (OR, 1.61; 95% CI, 1.01-2.55), were men (OR, 2.22; 95% CI, 1.25-4.00), or required a provider transfer for bladder cancer care (OR, 1.82; 95% CI, 1.10-3.03). CONCLUSIONS: Delays in care from the time of either the initial diagnosis or the completion of NAC to RC are associated with worse overall survival among patients with MIBC. Timely surgery is fundamental in the treatment of MIBC, and this necessitates attention to disparities in access to complex surgical care and care coordination.

Does the Diagnosis of Bladder Cancer Lead to Higher Rates of Smoking Cessation? Findings from the Medicare Health Outcomes Survey.

PURPOSE: Smoking is the most common risk factor for bladder cancer and it is associated with adverse clinical outcomes. The bladder cancer diagnosis represents a teachable moment for smoking cessation. We investigated the likelihood of smoking cessation after bladder cancer diagnosis in a population database. MATERIALS AND METHODS: We evaluated the 1998 to 2013 SEER (Surveillance, Epidemiology and End Results)-MHOS (Medicare Health Outcomes Survey) data on all patients diagnosed with incident bladder cancer on whom survey data were available before and after diagnosis. We compared these patients to propensity matched noncancer controls and to a cohort of patients with incident renal cell carcinoma. Differences in smoking cessation were compared between the groups and multivariate logistic regression was performed to assess the likelihood of smoking cessation. RESULTS: We propensity matched 394 patients with newly diagnosed bladder cancer to 1,970 noncancer controls and compared them with 169 patients with incident renal cell carcinoma. Baseline smoking prevalence was more common in patients diagnosed with bladder cancer compared to renal cell carcinoma (16% vs 11%) but the difference was not significant. The smoking cessation rate in patients with bladder cancer was 27% compared with 21% in noncancer controls and 26% in patients with renal cell carcinoma (p = 0.30 and 0.90, respectively). There was no significant difference in the adjusted OR of quitting smoking in patients with bladder cancer vs those with renal cell carcinoma compared to noncancer controls (OR 1.3, 95% CI 0.7-2.5 vs OR 1.2, 95% CI 0.4-3.6). Independent predictors of smoking cessation in patients with bladder cancer included age (p = 0.03), African American race (p = 0.03) and college education (p = 0.01). CONCLUSIONS: Compared to propensity matched noncancer controls smoking cessation did not significantly differ after a diagnosis of bladder cancer. The proportion of individuals who quit was low overall, suggesting that improved efforts are needed to use this teachable moment in patients with bladder cancer.

Postoperative Imaging Patterns of Pediatric Nephrolithiasis: Opportunities for Improvement.

PURPOSE: Imaging following surgical intervention for nephrolithiasis is important to define operative success and ensure the absence of silent obstruction. We assessed nationwide postoperative imaging patterns in children undergoing ureteroscopy and shock wave lithotripsy. MATERIALS AND METHODS: We reviewed the MarketScan® Commercial Claims and Encounters database from 2007 to 2013 for patients 1 to 18 years old undergoing ureteroscopy or shock wave lithotripsy. We assessed imaging exposure following index procedure within 90 days as a primary analysis and 180 days as a secondary analysis of the index procedure. Univariate and multivariate statistical analyses were performed to assess factors associated with undergoing postoperative imaging. RESULTS: A total of 4,251 children met inclusion criteria, of whom 1,647 had undergone shock wave lithotripsy and 2,604 had undergone ureteroscopy. Postoperative imaging was performed in 57.5% of the cohort, with a higher proportion of children undergong imaging following shock wave lithotripsy compared to ureteroscopy (73% vs 47.8%, p <0.001). Noncomputerized tomographic imaging modalities were most common following ureteroscopy (70.8%) and shock wave lithotripsy (84.6%). Younger children and those with complex medical conditions or complicated postoperative courses were more likely to undergo followup imaging. Computerized tomography was more commonly used in older children and females. At 180-day followup 63% of the cohort had undergone any imaging, again more frequently following shock wave lithotripsy (77.0%) vs ureteroscopy (45.0%). CONCLUSIONS: A large percentage of children with nephrolithiasis do not undergo followup imaging after shock wave lithotripsy, and even fewer undergo imaging after ureteroscopy. Most followup imaging is done within 90 days of surgery. Further work is needed to define appropriate postoperative imaging practices in this population.

Reduction of Pain during Flexible Cystoscopy: A Systematic Review and Meta-Analysis.

PURPOSE: The BCAN (Bladder Cancer Advocacy Network) Patient Survey Network identified pain during intravesical procedures as a research priority for patients. Although intraurethral lidocaine is the standard of care in this setting, evidence of its use is equivocal. We systematically reviewed studies of interventions to reduce discomfort during cystoscopy and intravesical therapy of bladder cancer. We performed a meta-analysis of interventions using available randomized, controlled trials. MATERIALS AND METHODS: Search terms derived from the key questions were incorporated into the literature search constructed by a research librarian and the English medical literature from 1990 to 2017 was accessed. The initial search yielded 626 potential studies and the final review incorporated 62. We combined 12 trials into a meta-analysis with a random effects model of the efficacy of intraurethral lidocaine vs plain lubricant to reduce pain during flexible cystoscopy as measured on a 10-point visual analogue scale. RESULTS: Data from 12 randomized controlled trials in a total of 1,549 patients were included in the final intraurethral lidocaine meta-analysis. The standardized mean difference between visual analogue scale pain scores in patients who underwent flexible cystoscopy with intraurethral lidocaine and plain lubricant was -0.22 (95% CI -0.39--0.05). Evidence was insufficient to evaluate other interventions to mitigate the discomfort of invasive bladder procedures. CONCLUSIONS: Intraurethral lidocaine provides statistically significant pain reduction in men who undergo flexible cystoscopy, particularly with a longer dwell time. The evidence was insufficient for other tested interventions. A prospective study is needed to further clarify interventions to decrease patient discomfort during cystoscopy and other intravesical procedures in a diverse population.

Measurement and modelling of primary sex ratios for species with temperature-dependent sex determination.

For many oviparous animals, incubation temperature influences sex through temperature-dependent sex determination (TSD). Although climate change may skew sex ratios in species with TSD, few available methods predict sex under natural conditions, fewer still are based on mechanistic hypotheses of development, and field tests of existing methods are rare. We propose a new approach that calculates the probability of masculinization (PM) in natural nests. This approach subsumes the mechanistic hypotheses describing the outcome of TSD, by integrating embryonic development with the temperature-dependent reaction norm for sex determination. Further, we modify a commonly used method of sex ratio estimation, the constant temperature equivalent (CTE), to provide quantitative estimates of sex ratios. We test our new approaches using snapping turtles (Chelydra serpentina). We experimentally manipulated nests in the field, and found that the PM method is better supported than the modified CTE, explaining 69% of the variation in sex ratios across 27 semi-natural nests. Next, we used the PM method to predict variation in sex ratios across 14 natural nests over 2 years, explaining 67% of the variation. We suggest that the PM approach is effective and broadly applicable to species with TSD, particularly for forecasting how sex ratios may respond to climate change. Interestingly, we also found that the modified CTE explained up to 64% of variation in sex ratios in a Type II TSD species, suggesting that our modifications will be useful for future research. Finally, our data suggest that the Algonquin Park population of snapping turtles possesses resilience to biased sex ratios under climate change.

Chemotherapy regimen is associated with venous thromboembolism risk in patients with urothelial tract cancer.

OBJECTIVE: To assess the association of venous thromboembolism (VTE) with different chemotherapy regimens in patients with urothelial tract cancer. PATIENTS AND METHODS: We identified patients aged ≥66 years, diagnosed with urothelial tract cancer in the period 1998 to 2011 in the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked database. The chemotherapy regimens analysed were gemcitabine/cisplatin (GC), methotrexate/vinblastine/doxorubicin/cisplatin (MVAC), or gemcitabine/carboplatin (CarboG). Propensity scores for treatment regimen based on comorbidities, tumour characteristics, age, and year of diagnosis were calculated. VTE rates within 120 days of chemotherapy initiation were calculated. VTE risk stratified by chemotherapy regimen was modelled using multivariable logistic regression, adjusting for treatment propensity scores and additional demographic characteristics. Overall survival stratified by VTE and chemotherapy regimen was estimated using Kaplan-Meier methods and the log-rank test. RESULTS: Of 5594 identified patients, a VTE occurred in 13.0%. The VTE rates within 120 days of chemotherapy initiation were 15.3% for GC, 8.7% for MVAC, and 12.0% for CarboG. On multivariable analysis, MVAC (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.39-0.94) and CarboG (OR 0.71, 95% CI: 0.59-0.85) were associated with lower VTE risk compared with GC. VTE was associated with worse overall survival (P < 0.001). CONCLUSIONS: Compared with GC, MVAC and CarboG were associated with a lower rate of VTE. This finding suggests that gemcitabine may add to the increased thrombosis risk from cisplatin. Additionally, patients with a VTE had worse survival outcomes than those without a VTE. Analysis of the risk of blood clots with different chemotherapy regimens in patients with urothelial tract cancer showed that GC was associated with the highest rate. We also found that blood clots were associated with worse patient outcomes.

PSA screening, prostate biopsy, and treatment of prostate cancer in the years surrounding the USPSTF recommendation against prostate cancer screening.

BACKGROUND: The 2012 United States Preventive Services Task Force recommendation against screening for prostate cancer has impacted rates of prostate-specific antigen (PSA) screening and appears to be associated with declining prostate cancer incidence. Our objective was to characterize health care utilization that may explain these observed trends. METHODS: MarketScan claims, which capture >30 million privately insured patients in the United States, were queried for all men aged 40-64 years for the years 2008-2014. PSA testing, prostate biopsy, prostate cancer diagnosis, and definitive local treatment were determined using associated International Classification of Diseases, Ninth Revision and Current Procedural Terminology, Fourth Edition codes. RESULTS: There were approximately 6 million qualifying men with a full year of data. PSA testing, prostate biopsy, and prostate cancer detection declined significantly between 2009 and 2014, most notably after 2011. The prostate biopsy rate per 100 patients with a PSA test decreased over the study period from 1.95 (95% confidence interval [CI], 1.92-1.97) to 1.52 (95% CI, 1.50-1.54). Prostate cancer incidence per prostate biopsy increased over the study period from 0.36 (95% CI, 0.35-0.36) to 0.39 (95% CI, 0.39-0.40). Of new prostate cancer diagnoses, the proportion managed with definitive local treatment decreased from 69% (95% CI, 69%-70%) to 54% (95% CI, 53%-55%). Both PSA testing and prostate cancer incidence decreased significantly after 2011 (P < .001). CONCLUSION: In a large cohort of privately insured men, PSA testing, prostate biopsy, prostate cancer incidence, and local definitive treatment for prostate cancer decreased between 2008 and 2014, most notably after 2011. This decrease may be driven by differential referral patterns from primary care providers to urologists. Cancer 2018;124:2733-2739. © 2018 American Cancer Society.

Activation of apoptosis in NAF-1-deficient human epithelial breast cancer cells.

Maintaining iron (Fe) ion and reactive oxygen species homeostasis is essential for cellular function, mitochondrial integrity and the regulation of cell death pathways, and is recognized as a key process underlying the molecular basis of aging and various diseases, such as diabetes, neurodegenerative diseases and cancer. Nutrient-deprivation autophagy factor 1 (NAF-1; also known as CISD2) belongs to a newly discovered class of Fe-sulfur proteins that are localized to the outer mitochondrial membrane and the endoplasmic reticulum. It has been implicated in regulating homeostasis of Fe ions, as well as the activation of autophagy through interaction with BCL-2. Here we show that small hairpin (sh)RNA-mediated suppression of NAF-1 results in the activation of apoptosis in epithelial breast cancer cells and xenograft tumors. Suppression of NAF-1 resulted in increased uptake of Fe ions into cells, a metabolic shift that rendered cells more susceptible to a glycolysis inhibitor, and the activation of cellular stress pathways that are associated with HIF1α. Our studies suggest that NAF-1 is a major player in the metabolic regulation of breast cancer cells through its effects on cellular Fe ion distribution, mitochondrial metabolism and the induction of apoptosis.

National Imaging Trends after Ureteroscopic or Shock Wave Lithotripsy for Nephrolithiasis.

PURPOSE: The study of diagnostic imaging after procedural intervention for nephrolithiasis is limited. We sought to characterize actual national imaging patterns and longitudinal trends after ureteroscopic or shock wave lithotripsy. MATERIALS AND METHODS: We analyzed the MarketScan® database and identified a nationally representative sample of insured, employed patients, 17 to 64 years old who underwent ureteroscopic or shock wave lithotripsy for nephrolithiasis between 2007 and 2014. Patients were excluded from study if they lacked at least 1 year of postoperative database enrollment or underwent a repeat nephrolithiasis procedure of any type within 90 days after the initial procedure. We identified and tracked postoperative imaging modalities by medical billing codes. RESULTS: We identified 101,554 patients treated with ureteroscopy, of whom 55% and 39% underwent no postoperative imaging within 3 and 12 months, respectively. Of the 101,590 patients treated with shock wave lithotripsy 23% and 16% underwent no postoperative imaging within 3 and 12 months, respectively. Abdominal x-ray was the most common imaging modality after either procedure type. Ultrasound use increased with time while computerized tomography decreased. In about 25% of ureteroscopy and shock wave lithotripsy cases at least 1 postoperative computerized tomography was done within a year. Female gender and older age were associated with higher imaging rates. Ultrasound was more commonly performed in the northeast region and in more densely populated areas. CONCLUSIONS: A notable portion of patients treated with ureteroscopy and a smaller percent treated with shock wave lithotripsy do not undergo any followup imaging within 1 year. In the majority who undergo imaging abdominal x-ray is done, precluding the ability to screen for hydronephrosis or silent obstruction in almost 75% of patients treated with ureteroscopy.