Burnout in Urological Education: An In-Depth Study of Residents and Fellows in the 2021 AUA Census.

PURPOSE: Our goal was to explore the current trends in burnout, career choice regret, and well-being needs among urology residents and fellows, with specific emphasis on identifying key factors associated with burnout. MATERIALS AND METHODS: The AUA Workforce Workgroup collaborated with the AUA Data Team to analyze data from the 2021 AUA Census, comprising a total of 243 residents and fellows. Key demographics, benefits and resources, career choice and debt, and burnout levels were analyzed, focusing on variables like gender, PGY (postgraduate year) level, debt burden, and personal health appointments. RESULTS: Overall, 48% of residents and 33% of fellows met criteria for professional burnout, with a higher incidence among PGY-2 residents (70%). Depersonalization was particularly notable, with 74% of residents reporting medium to high levels. Burnout was significantly associated with difficulty attending personal health appointments (52% vs 34%) and lack of access to on-call rooms (54% vs 36%). In contrast, having children during residency was associated with lower burnout levels (30.8% vs 49.1%). Meal plans were ranked as the most desired benefit (32%), followed by ability to attend health appointments during work hours (17%) and paid family leave (16%). Educational debt over $150,000 was carried by 53% of residents and 48% of fellows. Interestingly, burnout rates showed no statistically significant difference in response rates across genders, relationship status, amount of educational debt, presence of paid maternity or paternity leave, and type of childcare arrangements. CONCLUSIONS: Burnout remains a significant issue among urology trainees, with a complex interplay of factors like lack of personal time and provision of call rooms. The alarming rates of depersonalization and exhaustion highlight the urgency of implementing targeted interventions. Enhanced support systems, improved access to health care appointments, provision of call rooms, and debt management programs are recommended to alleviate the growing problem of professional burnout in the field of urology.

Effects of Advanced Practice Providers on Single-specialty Surgical Practice.

OBJECTIVE: To assess the effects of adding advanced practice providers to surgical practices on surgical complications, readmissions, mortality, episode spending, length of stay, and access to care. SUMMARY BACKGROUND DATA: There has been substantial growth in the number of nurse practitioners and physician assistants (ie, advanced practice providers) in the United States. The extent to which advanced practice providers have been integrated into surgical practice, and their impact on surgical outcomes and access is unclear. METHODS: Using a 20% sample of national Medicare claims, we performed a retrospective cohort study of fee-for-service beneficiaries undergoing one of 4 major procedures (coronary artery bypass graft, colectomy, major joint replacement, and cystectomy) between 2010 and 2016. We limited our study population for each procedure to patients treated by single-specialty surgical groups to ensure that the advanced practice providers have direct interactions with its surgeons and patients. All outcomes were measured at the practice level for the year before and the year after the addition of the first advanced practice provider. Outcomes included: complications, readmission, mortality, episode payments, length of stay. Models were adjusted for age, race, sex, comorbidity, socioeconomic class and procedure type. Secondary outcome: practice-level office visits by surgical group type. RESULTS: The number of advanced practice providers increased by 13%, from 6713 to 7596 between 2010 and 2016. The largest relative increases occurred in general (46.9%) and urologic (27.6%) surgical practices. The year after an advanced practice provider was added to a surgical practice, the odds of complications were 17% and 16% lower at 30- and 90-days postprocedure, respectively. Additionally, 90-day readmissions were 18% less likely and length of stay was 0.33 days shorter (a 7.1% reduction). Average 30-day and90-day episode spending was $1294.73 and $1427.76 lower, respectively ( P < 0.001). General surgical, orthopedic, and urology practices realized increases of 49.0 (95% CI 13.5-84.5), 112.0 (95% CI 83.0-140.5), and 205.0 (95% CI 117.5-292.0) in-office visits per surgeon, respectively. CONCLUSIONS: The addition of advanced practice providers to single-specialty surgical groups is associated with improvements in surgical outcomes and access. Future work should clarify the mechanisms by which advanced practice providers within surgical practices contribute to health outcomes to identify best practices for deployment.

Impact of Advanced Practice Provider Integration into Multispecialty Group Practices on Outcomes Following Major Surgery.

Background. While advanced practice providers (APPs) are increasingly integrated into care delivery models, little is known about their impact in surgical settings. Given that many patients undergo surgery in multispecialty group practice settings, we examined the impact of APP integration into such practices on outcomes after major surgery. Methods. We used a 20% sample of national Medicare claims to identify 190 101 patients who underwent 1 of 4 major surgeries (coronary artery bypass graft [CABG], colectomy, major joint replacement, and cystectomy) at multispecialty group practices from 2010 through 2016. The level of APP integration was measured as the ratio of APPs to physicians within each practice. Rates of mortality, major complications, and readmission within 30 days of discharge after the index surgery were compared between patients treated in practices with low, medium, and high levels of APP integration using multivariable regression analysis. Results. Relative to patients treated in practices with low APP integration, those treated in practices with medium or high APP integration had significantly lower rates of mortality (2.4% [low integration] vs 1.9% [medium integration] vs 2.0% [high integration]; P < .01), major complications (34.1% [low] vs 31.2% [medium] vs 30.2% [high]; P < .01), and readmission (11.7% [low] vs 10.6% [medium] vs 10.1% [high]; P < .01). This relationship was consistent for virtually all outcomes when considering each surgery type individually. Conclusions. Integration of APPs into multispecialty group practices was associated with improved postoperative outcomes after major surgery. Future research should identify the mechanisms by which APPs improve outcomes to inform optimal utilization.

Testing-Related Health Impact of Transrectal and Transperineal Prostate Biopsy as Assessed by Health Utilities.

PURPOSE: We sought to assess the temporary health-related quality of life (health utility) of nonmagnetic resonance imaging-guided transrectal and transperineal prostate biopsy. MATERIALS AND METHODS: This is a 2-arm, prospectively enrolled, observational, patient-reported outcomes study, performed between June 2019 and November 2020 at a single academic medical center. Inclusion criteria were men undergoing an outpatient ultrasound-guided prostate biopsy (transrectal or transperineal approach, without magnetic resonance imaging guidance). Patients with a history of Gleason 7+ prostate cancer were excluded. Validated survey instruments were utilized to assess baseline (Short Form 12) and testing-related (Testing Morbidities Index [TMI]) health utility states. The primary outcome was the TMI summary testing-related quality-of-life score (summary utility score; scale: 0=death and 1=perfect health). The TMI is comprised of 7 domains, spanning before, during and after testing experiences. Each domain is scored from 1 (no health impact) to 5 (extreme health impact). Testing-related quality-of-life measures were compared with Mann-Whitney U test. RESULTS: Enrollment rates were 80% (60/75; transrectal) and 86% (60/70; transperineal). All patients (120/120) completed the questionnaire. The TMI summary score for transrectal biopsy was not significantly different from transperineal biopsy (0.86, 95% CI 0.84-0.88 vs 0.83, 95% CI 0.81-0.85; p=0.0774). The largest difference in the testing experiences was related to intraprocedural pain (transrectal biopsy: 2.3, 95% CI 2.1-2.4; transperineal biopsy: 2.9, 95% CI 2.6-3.1; p <0.001). CONCLUSIONS: Transperineal and transrectal prostate biopsies have similar effect on temporary health-related quality-of-life. Transient differences relate to intraprocedural pain. These data can inform clinical decision making and future cost-utility models.

Abrogation of survival disparity between Black and White individuals after the USPSTF's 2012 prostate-specific antigen-based prostate cancer screening recommendation.

BACKGROUND: In May 2012, the US Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA)-based screening for prostate cancer (PCa), assigning it a grade D. This decision then was modified in 2018 to a grade C for men aged 55 to 69 years. The authors hypothesized that changes in screening practices would reduce survival outcomes for both Black and White men but maintain racial discrepancies in outcomes. METHODS: Using the Surveillance, Epidemiology, and End Results database, the authors examined PCa-specific survival based on race and year of diagnosis. The period between January 2010 and December 2012 was categorized as the pre-USPSTF era, whereas the period between January 2014 and December 2016 was classified as the post-USPSTF era. The year 2013 was considered the transition year and was excluded from the analysis. RESULTS: A total of 49,388 men were identified in the pre-USPSTF era who were diagnosed with PCa, approximately 83.7% of whom were White and 16.3% of whom were Black. In the post-USPSTF era, a total of 41,829 men were diagnosed with PCa, approximately 82.7% of whom were White and 17.3% of whom were Black. When compared with the pre-USPSTF era, men diagnosed in the post-USPSTF era were found to have more adverse clinical features. In the pre-USPSTF era, White men were less likely to die of PCa than Black men. This survival disparity between White and Black men was no longer observed in the post-USPSTF era. CONCLUSIONS: In men diagnosed with PCa between 2014 and 2016, a survival disparity between White and Black men was not observed due to a decrease in survival among White men while the survival of Black men remained steady.

Adherence and out-of-pocket costs among Medicare beneficiaries who are prescribed oral targeted therapies for advanced prostate cancer.

BACKGROUND: Abiraterone and enzalutamide are high-cost oral therapies that increasingly are used to treat patients with advanced prostate cancer; these agents carry the potential for significant financial consequences to patients. In the current study, the authors investigated coping and material measures of the financial hardship of these therapies among patients with Medicare Part D coverage. METHODS: The authors performed a retrospective cohort study on a 20% sample of Medicare Part D enrollees who underwent treatment with abiraterone or enzalutamide between July 2013 and June 2015. The authors described the variability in adherence rates and out-of-pocket payments among hospital referral regions in the first 6 months of therapy and determined whether adherence and out-of-pocket payments were associated with patient factors and the socioeconomic characteristics of where a patient was treated. RESULTS: There were 4153 patients who filled abiraterone or enzalutamide prescriptions through Medicare Part D in 228 hospital referral regions. The mean adherence rate was 75%. The median monthly out-of-pocket payment for abiraterone and enzalutamide was $706 (range, $0-$3505). After multilevel, multivariable adjustment for patient and regional factors, adherence was found to be lower in patients who were older (69% for patients aged ≥85 years vs 76% for patients aged <70 years; P < .01) and in those with low-income subsidies (69% in those with a subsidy vs 76% in those without a subsidy; P < .01). Both Hispanic ethnicity and living in a hospital referral region with a higher percentage of Hispanic beneficiaries were found to be independently associated with higher out-of-pocket payments for abiraterone and enzalutamide. CONCLUSIONS: There were substantial variations in the adherence rate and out-of-pocket payments among Medicare Part D beneficiaries who were prescribed abiraterone and enzalutamide. Sociodemographic patient and regional factors were found to be associated with both adherence and out-of-pocket payments.

Impact of pathologic lymph node-positive renal cell carcinoma on survival in patients without metastasis: Evidence in support of expanding the definition of stage IV kidney cancer.

BACKGROUND: Stage III renal cell carcinoma (RCC) encompasses both lymph node-positive (pT1-3N1M0) and lymph node-negative (pT3N0M0) disease. However, prior institutional studies have indicated that among patients with stage III disease, those with lymph node disease have worse oncologic outcomes and experience survival that is similar to that of patients with American Joint Committee on Cancer (AJCC) stage IV disease. The objective of the current study was to validate these findings using a large, nationally representative sample of patients with kidney cancer. METHODS: Patients with AJCC stage III or stage IV RCC were identified using the National Cancer Data Base (NCDB). Patients were categorized as having lymph node-positive stage III (pT1-3N1M0), lymph node-negative stage III (pT3N0M0), or stage IV metastatic (pT1-3 N0M1) disease. Cox proportional hazards models compared outcomes while adjusting for comorbidities. Kaplan-Meier estimates illustrated relative survival when comparing staging groups. RESULTS: A total of 8988 patients met the inclusion criteria, with 6587 patients classified as having lymph node-negative stage III disease, 2218 as having lymph node-positive stage III disease, and 183 as having stage IV disease. Superior survival was noted among patients with lymph node-negative stage III disease, but similar survival was noted between patients with lymph node-positive stage III and stage IV RCC, with 5-year survival rates of 61.9% (95% confidence interval [95% CI], 60.3%-63.4%), 22.7% (95% CI, 20.6%-24.9%), and 15.6% (95% CI, 11.1%-23.8%), respectively. CONCLUSIONS: Current RCC staging systems group pT1-3N1M0 and pT3N0M0 disease as stage III disease. However, the results of the current validation study suggest the need for further stratification and even placement of patients with pT1-3N1M0 disease into the stage IV category. Staging that accurately reflects oncologic prognosis may help clinicians better counsel and select patients who might derive the most benefit from lymphadenectomy, adjuvant systemic therapy, more rigorous imaging surveillance, and clinical trial participation.

Urologists' estimations of the cost of commonly used disposable devices.

INTRODUCTION: To assess whether urologists are able to accurately estimate the cost of commonly used endourologic disposable devices. MATERIALS AND METHODS: An anonymous questionnaire was presented to resident and attending urologists in one academic healthcare system. Respondents estimated the cost of 15 disposable devices commonly used in ureteroscopy. Twenty-five surgeons (9 resident and 16 attending urologists) participated for a response rate of 96.2%. Respondents' cost estimates were compared to actual institutional costs and considered accurate if the absolute percentage error was within 20%. Additional information obtained included: years in practice, participation in purchasing activities, practice setting, number of ureteroscopy procedures performed monthly, degree of confidence in ability to estimate cost, and the importance of cost in device selection for each respondent. RESULTS: Of 375 total responses, 62 (16.5%) were accurate, 308 (82.1%) were inaccurate, and 5 (1.3%) were unanswered. The mean percentage error (MPE) for all responses was 178.8% (IQR 35.1%-211.4%). Overall, 73% of responses were overestimations and 27% were underestimations. Residents had an MPE of 128.4%, while attending urologists had an MPE of 207.8%. The most inaccurately estimated cost was for an endoscopic y-adapter, while the most accurate estimations were for a 1.5Fr nitinol ureteroscopic stone basket. CONCLUSIONS: Neither attending nor resident urologists are able to accurately estimate the cost of commonly used disposable devices. Improving urologists' understanding of device costs is necessary for improved cost control and a reduction in healthcare expenditures.

Medicare Accountable Care Organizations and Use of Potentially Low-Value Procedures.

OBJECTIVE: To evaluate the effect of Accountable Care Organizations (ACOs) on the use of vertebroplasty and arthroscopic partial meniscectomy, 2 procedures for which randomized controlled trials suggest similar outcomes to sham surgery and therefore may provide low value. Medicare Shared Savings Program ACOs aim to improve quality and decrease health care spending. Reducing the use of potentially low-value procedures can accomplish both of these goals. METHODS: We performed a retrospective cohort study of patients who underwent potentially low-value orthopedic procedures (vertebroplasty and partial meniscectomy) and a control (hip fracture) from 2010 to 2015 using a 20% sample of national Medicare claims. We performed an interrupted time-series analysis using linear spline models to evaluate the count of each procedure per 1000 patients, stratified by ACO participation. RESULTS: We identified 76 256 patients who underwent arthroscopic partial meniscectomy, 44 539 patients who underwent vertebroplasty, and 50 760 patients who underwent hip fracture admission. Arthroscopic partial meniscectomy rates decreased, vertebroplasty rates remained stable, and hip fracture rates increased for both groups during the study period, with similar trends among ACO and non-ACO patients. After January 1, 2013, ACO and non-ACO populations had similar trends for vertebroplasty (ACO incidence rate ratio [IRR] = 1.15 [1.08-1.23] vs non-ACO IRR = 1.11 [1.05-1.16]), meniscectomy (ACO IRR = 1.06 [1.01-1.12] vs non-ACO IRR = 1.03 [0.99-1.07]), and hip fracture (ACO IRR = 1.08 [1.01-1.14] vs non-ACO IRR = 1.08 [1.03-1.13]). CONCLUSIONS: ACOs were not associated with a reduction in the frequency of vertebroplasty and arthroscopic partial meniscectomy.

Variation in prostate cancer treatment and spending among Medicare shared savings program accountable care organizations.

BACKGROUND: Accountable care organizations (ACOs) have been shown to reduce prostate cancer treatment among men unlikely to benefit because of competing risks (ie, potential overtreatment). This study assessed whether the level of engagement in ACOs by urologists affected rates of treatment, overtreatment, and spending. METHODS: A 20% sample of national Medicare data was used to identify men diagnosed with prostate cancer between 2012 and 2014. The extent of urologist engagement in an ACO, as measured by the proportion of patients in an ACO managed by an ACO-participating urologist, served as the exposure. The use of treatment, potential overtreatment (ie, treatment in men with a ≥75% risk of 10-year noncancer mortality), and average payments in the year after diagnosis for each ACO were modeled. RESULTS: Among 2822 men with newly diagnosed prostate cancer, the median rates of treatment and potential overtreatment by an ACO were 71.3% (range, 23.6%-79.5%) and 53.6% (range, 12.4%-76.9%), respectively. Average Medicare payments among ACOs in the year after diagnosis ranged from $16,523.52 to $34,766.33. Stronger urologist-ACO engagement was not associated with treatment (odds ratio, 0.87; 95% confidence interval, 0.6-1.2; P = .4) or spending (9.7% decrease in spending; P = .08). However, urologist engagement was associated with a lower likelihood of potential overtreatment (odds ratio, 0.29; 95% confidence interval, 0.1-0.86; P = .03). CONCLUSIONS: ACOs vary widely in treatment, potential overtreatment, and spending for prostate cancer. ACOs with stronger urologist engagement are less likely to treat men with a high risk of noncancer mortality, and this suggests that organizations that better engage specialists may be able to improve the value of specialty care. Cancer 2018. © 2018 American Cancer Society.

Engaging telehealth to drive value-based urology.

PURPOSE OF REVIEW: Telehealth, or the remote delivery of healthcare services using telecommunications technology, has the potential to revolutionize the delivery of healthcare and contribute to ongoing efforts to provide high-value care. RECENT FINDINGS: We discuss several categories of telehealth that have been applied to healthcare. Several of these approaches, in particular video visits and teleconsultations, have promising early data demonstrating the significant benefits of telehealth technology with respect to the quality of care, access, cost savings, and patient experience. Nonetheless, considerable knowledge gaps still exist regarding how and for which patients and diseases telehealth modalities should be applied. Finally, we discuss the barriers to widespread adoption at the institutional, state, and federal levels. SUMMARY: Maximizing the value of healthcare is an important goal for hospitals, physicians, and policymakers. Telehealth leverages advances in technology and the widespread availability of telecommunications devices to make healthcare communication more available, more convenient, and more efficient for patients and providers. With appropriate policies and incentives, telehealth initiatives can improve the value of urologic care and smooth the transition to a value-based healthcare system.

Intracrine androgen biosynthesis in renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) is one of the most lethal genitourinary cancers. The presence of androgen receptor (AR) in RCC has recently been shown to be associated with higher tumour stage irrespective of gender. Because the clinical context of androgens in female RCC patients is similar to that of prostate cancer patients undergoing androgen-deprivation therapy, mechanisms underlying the emergence of castration-resistant prostate cancer (CRPC) may be at play in AR-positive RCC cells. Therefore, we hypothesized that AR-positive RCC has intratumoral steroidogenesis and that anti-androgen therapy may result in tumour suppression. METHODS: Mice were injected with an AR-positive RCC cell line. When tumours became palpable, surgical castration was performed and tumour volume was measured. Using ELISA, the levels of intracellular testosterone and dihydrotesterone were measured in AR-positive human RCC cell lines. Lastly, male mice containing xenografts were treated with enzalutamide or abiraterone acetate (AA) for 3 weeks to measure tumour volume. RESULTS: We first observed in vivo that castration retards the growth of AR-positive RCC tumour xenograft in mice. Next, AR-positive human RCC cell lines and tissues were found to have elevated levels of testosterone and dihydrotestosterone and express key enzymes required for intracellular androgen biosynthesis. A mouse xenograft study with AR-positive RCC cell line using the commonly used anti-androgen therapies showed significant tumour suppression (P<0.01). CONCLUSIONS: Intracrine androgen biosynthesis is a potential source of androgen in AR-positive RCC and that the androgen signaling axis is a potential target of intervention in RCC.

Adrenalectomy for benign and malignant disease: utilization and outcomes by surgeon specialty and surgical approach from 2003-2013.

INTRODUCTION: Data on the utilization of open, laparoscopic and robotic adrenalectomy on a national level is limited. MATERIALS AND METHODS: Data on patients who underwent open, laparoscopic, or robotic adrenalectomy for benign or malignant disease in the US from 2003-2013 were extracted using ICD-9 codes from the Premier Hospital Database. Surgeon specialty, patient demographics, hospital characteristics, and complications were compared. Data were analyzed using univariate and multivariable logistic regression analyses. RESULTS: A total of 8,831 adrenalectomies were performed for benign and malignant tumors. There was no significant difference in rate of adrenalectomy with regards to comorbidities, insurance status, or hospital characteristics. Non-urologists performed adrenalectomy more often for both benign (57% versus 43%; p = 0.011) and malignant disease (66% versus 34%; p = 0.011). Across all indications, non-urologists performed open surgery most often followed by laparoscopic and robotic approaches (56.3% versus 37.4% versus 6.4%, respectively), compared to urologists (48.8% versus 38.4% versus 12.9%, respectively). Overall, urologists were more likely to use laparoscopic or robotic approaches (p = 0.001). There was no difference in complication rates or operative times between surgical specialties or by surgeon/hospital case volume. On multivariable regression analysis, the best predictor of major complication was a Charlson Comorbidity Index (CCI) ≥ 2 (OR 3.9, 95%CI 2.1-7.1; p = < 0.001). Compared to open surgery, laparoscopy had significantly reduced odds of major complication (OR 0.6, 95%CI 0.3-0.9; p = 0.03). Patients undergoing robotic procedures had the shortest length of stay. CONCLUSION: In this retrospective study, adrenalectomy was more commonly performed by non-urologists via an open approach. Patients with CCI ≥ 2 were more likely to have postoperative complications while surgeon volume, hospital volume, and surgical approach did not influence complication rates.

Elevated osmolytes in rainbow smelt: the effects of urea, glycerol and trimethylamine oxide on muscle contractile properties.

Rainbow smelt, Osmerus mordax, experience a wide range of temperatures in their native habitat. In response to cold, smelt express anti-freeze proteins and the osmolytes glycerol, trimethylamine N-oxide (TMAO) and urea to avoid freezing. The physiological influences of these osmolytes are not well understood. Urea destabilizes proteins, while TMAO counteracts the protein-destabilizing forces of urea. The influence of glycerol on muscle function has not been explored. We examined the effects of urea, glycerol and TMAO through muscle mechanics experiments with treatments of the three osmolytes at physiological concentrations. Experiments were carried out at 10°C. The contractile properties of fast-twitch muscle bundles were determined in physiological saline and in the presence of 50 mmol l(-1)urea, 50 mmol l(-1)TMAO and/or 200 mmol l(-1)glycerol in saline. Muscle exposed to urea and glycerol produced less force and displayed slower contractile properties. However, treatment with TMAO led to higher force and faster relaxation by muscle bundles. TMAO increased power production during cyclical activity, while urea and glycerol led to reduced oscillatory power output. When muscle bundles were exposed to a combination of the three osmolytes, they displayed little change in contraction kinetics relative to control, although power output under lower oscillatory conditions was enhanced while maximum power output was reduced. The results suggest that maintenance of muscle function in winter smelt requires a balanced combination of urea, glycerol and TMAO.

Off-Target Effect of Sildenafil on Postsurgical Erectile Dysfunction: Alternate Pathways and Localized Delivery System.

INTRODUCTION: There is no consensus on the best oral phosphodiesterase type 5 inhibitor (PDE5I) for patients undergoing penile rehabilitation after surgical nerve injury. AIM: To determine the mechanism of PDE5I on cultured neuronal cells and the effectiveness of local drug delivery using nanospheres (NSPs) to sites of nerve injury in a rat model of bilateral cavernous nerve injury (BCNI). METHODS: The effects of sildenafil, tadalafil, and vardenafil on cyclic adenosine monophosphate, cyclic guanosine monophosphate, and cell survival after exposure to hypoxia and H2O2 were measured in PC12, SH-SY5Y, and NTERA-2 (NT2) cell cultures. The effects of phosphodiesterase type 4 inhibitor (PDE4I) and PDE5I on neuronal cell survival were evaluated. Male rats underwent BCNI and were untreated (BCNI), immediately treated with application of empty NSPs (BCNI + NSP), NSPs containing sildenafil (Sild + NSP), or NSPs containing rolipram (Rol + NSP). MAIN OUTCOME MEASURES: Viability of neuronal cells was measured. Intracavernous pressure changes after cavernous nerve electrostimulation and expression of neurofilament, nitric oxide synthase, and actin in mid-shaft of penis were analyzed 14 days after injury. RESULTS: Sildenafil and rolipram significantly decreased cell death after exposure to H2O2 and hypoxia in PC12, SH-SY5Y, and NT2 cells. PC12 cells did not express PDE5 and knockdown of PDE4 significantly increased cell viability in PC12, SH-SY5Y, and NT2 cells exposed to hypoxia. The ratio of intracavernous pressure to mean arterial pressure and expression of penile neurofilament, nitric oxide synthase, and actin were significantly higher in the Sild + NSP and Rol + NSP groups than in the BCNI and BCNI + NSP groups. Limitations included analysis in only two PDE families using only a single dose. CONCLUSION: Sildenafil showed the most profound neuroprotective effect compared with tadalafil and vardenafil. Sildenafil- or rolipram-loaded NSP delivery to the site of nerve injury prevented erectile dysfunction and led to increased neurofilament, nitric oxide synthase, smooth muscle content in rat penile tissue after BCNI.