Oral phosphodiesterase type 5 inhibitors and priapism: A VigiBase analysis.

PURPOSE: To explore the differences of priapism events among a diverse cohort taking erectogenic medicines (i.e., phosphodiesterase type 5 inhibitors [PDE5i] and intracavernousal drugs). METHODS: We queried the World Health Organization global database of individual case safety reports (VigiBase) for records of the adverse drug reactions (ADR) with sildenafil, tadalafil, avanafil, vardenafil, papaverine, and alprostadil. Disproportionality analyses (case/non-case approach) were performed to assess the reporting odds ratio (ROR) of priapism reporting in PDE5i consumers compared to intracavernousal drug recipients. RESULTS: From a total of 133 819 ADR events for erectogenic medications, 632 were priapism (PDE5is: n = 550, 0.41%; intracavernousal drugs: n = 82, 9.92%). Priapism disproportionality signals from intracavernousal drugs were 25 times stronger than PDE5is (ROR = 34.7; confidence interval [CI] 95%: 27.12-43.94 vs. ROR = 1.38; 95% CI: 1.24-1.54). For all PDE5i agents, the 12-17 years age group had the highest ROR (9.49, 95% CI: 3.76-19.93) followed by 2-11 years (4.31, 95% CI: 1.57-9.4). Disproportionality signals for consumers under 18 for both all PDE5is as a whole (ROR = 4.57, 95% CI: 2.48-7.73) and sildenafil (ROR = 4.89, 95% CI: 2.51-8.62) were stronger than individuals 18 or older (ROR = 1.06, 95% CI: 0.93-1.21 and ROR = 1.08, 95% CI: 0.91-1.26, respectively). CONCLUSIONS: PDE5i use shows disproportionate priapism signals which are higher in young patients.

Adverse reactions of PDE5 inhibitors: An analysis of the World Health Organization pharmacovigilance database.

BACKGROUND: Despite their efficacy and general safety, rare but devastating adverse drug reactions have been associated with phosphodiesterase type 5 inhibitors. OBJECTIVES: To determine the safety profile of oral phosphodiesterase type 5 inhibitors with a particular focus on priapism and malignant melanoma. MATERIALS AND METHODS: In this case-non-case study, we queried the individual case safety reports for phosphodiesterase type 5 inhibitors within the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021. We included all individual case safety reports for sildenafil, tadalafil, vardenafil, and avanafil in men. For comparison, we also extracted the safety data from the Food and Drug Administration trials for these drugs. We assessed the safety profile of phosphodiesterase type 5 inhibitors by disproportionality analysis by measuring reporting odds ratio for their most commonly reported adverse drug reactions, once for all phosphodiesterase type 5 inhibitor reports and once for reports of oral phosphodiesterase type 5 inhibitor use in adult men (≥18 years old) with sexual dysfunction. RESULTS: A total of 94,713 individual case safety reports for phosphodiesterase type 5 inhibitors were extracted. A total of 31,827 individual case safety reports were identified relating to adult men taking oral sildenafil, tadalafil, vardenafil, or avanafil for sexual dysfunction. The most common adverse drug reactions included poor drug efficacy (42.5%), headache (10.4% vs. 8.5%-27.6% [Food and Drug Administration]), abnormal vision (8.4% vs. ≤4.6% [Food and Drug Administration]), flushing (5.2% vs. 5.1%-16.5% [Food and Drug Administration]), and dyspepsia (4.2% vs. 3.4%-11.1% [Food and Drug Administration]). Priapism showed significant signals for sildenafil (reporting odds ratio = 13.81, 95% confidence interval: 11.75-16.24), tadalafil (reporting odds ratio = 14.54, 95% confidence interval: 11.56-18.06), and vardenafil (reporting odds ratio = 14.12, 95% confidence interval: 8.36-22.35). Comparing with other medications in VigiBase, sildenafil (reporting odds ratio = 8.73, 95% confidence interval: 7.63-9.99) and tadalafil (reporting odds ratio = 4.25, 95% confidence interval: 3.19-5.55) had significantly higher reporting odds ratios for malignant melanoma. CONCLUSION: Phosphodiesterase type 5 inhibitors show significant signals correlating with priapism among a large international cohort. Further clinical study is needed to elucidate whether this is from proper or inappropriate use or other confounding conditions, as analysis of pharmacovigilance data does not allow for quantifying the clinical risk. Also, there appears to be a relationship between phosphodiesterase type 5 inhibitor use and malignant melanoma, which warrants additional study to better understand causation.

Cushioning the blow: role of perirenal fat in renal trauma injury severity.

OBJECTIVES: To explore the association between perirenal fat thickness (PFT) and renal trauma grade. We hypothesise this association is related to a shock-absorbing effect of adiposity around the kidney. PATIENTS AND METHODS: We identified all patients with renal trauma who arrived at the emergency department of a single trauma centre between 2014 and 2020. Radiology images were reviewed to measure the PFT around the uninjured kidney due to disrupted PFT around the traumatised kidney. Patients with no available images or penetrating trauma mechanism were excluded. Logistic regression was used to assess the relation between PFT and high-grade renal trauma (HGRT; defined as American Association for the Surgery of Trauma Renal Grade IV-V), adjusting for age, sex, and Injury Severity Scale (ISS). RESULTS: A total of 150 patients with renal trauma were included. The median (interquartile range) age was 38.5 (26-52) years and 106 (70.7%) were males. The PFT ranged between 2.1 and 50.1 mm, and 31 (20.7%) had HGRT. Interestingly, PFT only mildly correlated with body mass index (BMI; Pearson correlation coefficient 0.42, P < 0.001). Those with HGRT had significantly lower PFT compared to those without HGRT (median 9.5 vs 11.9 mm, P = 0.047). In the multivariable analysis adjusting for age, sex, and ISS, increasing PFT was associated with decreased odds (odds ratio 0.91, 95% confidence interval 0.84-0.98; P = 0.015) of HGRT. CONCLUSION: Increasing PFT is associated with lower risk of HGRT following blunt injury. These results support a protective cushion role of adiposity in renal trauma. Notably, PFT was not strongly correlated with BMI, underscoring limitations of BMI in measuring adiposity.

Alcohol Intoxication Is Associated With Bladder Injury and Bladder Surgical Repair in Patients Sustaining Motor Vehicle Collisions.

PURPOSE: Alcohol intoxication is a known risk factor for motor vehicle collisions. We hypothesize ethanol intoxication increases the risk of bladder injury and surgical repair, especially at higher blood alcohol content levels. MATERIALS AND METHODS: We identified all patients involved in motor vehicle collisions from the National Trauma Data Bank from 2017-2019. Patients were categorized into an intoxication and intoxication negative group. Variables collected included age, sex, blood alcohol content level, driver status, seat belt restraint use, nonalcoholic intoxication, pelvic fracture, and Injury Severity Scale. Primary outcome measures of bladder injury and bladder surgical repair were assessed and interaction with pelvic fracture and restraint use were measured. RESULTS: We identified 594,484 patients and 97,831 (16.5%) had a positive alcohol screen. Patients in the intoxication group were more likely to be intoxicated with other substances (32.8% vs 14.6%, P < .001), have a bladder injury (1% vs 0.4%, P < .001) and receive bladder surgical repair (0.7% vs 0.15%, P < .001). Injury Severity Scale and pelvic fracture were statistically significant predictors of bladder injury. In adjusted analysis, higher blood alcohol content was associated with both outcomes. Above the legal limit, alcohol intoxication was more predictive of bladder surgical repair than pelvic fracture. The association of alcohol intoxication with both outcomes did not differ by pelvic fracture, but strengthened with seat belt use at higher intoxication levels. CONCLUSIONS: Alcohol intoxication is independently associated with increased risk of bladder injury and subsequent bladder surgical repair following motor vehicle collisions. Trauma providers should have a high index of suspicion for bladder injuries in alcohol intoxicated patients, particularly those using seat belt restraints.

Posterior urethral stenosis: a comparative review of the guidelines.

PURPOSE: We aimed to provide a thorough comparative review of the available guidelines on the diagnosis, management, and follow-up for patients with posterior urethral stenosis by the American Urologic Association (2016), Société Internationale d'Urologie (2010), and European Urologic Association (2022). METHODS: The AUA, SIU, and EAU guidelines were evaluated for recommendations on the diagnosis, evaluation, and treatment of posterior urethral stenosis. We also included the EAU and AUA urologic trauma guidelines for the trauma-related stenosis. The level or strength of recommendations is included in case of disparity between the guidelines. RESULTS: The three guidelines align considerably in recommendations provided for the diagnosis, management, and follow-up of patients with posterior urethral stenosis. SIU and EAU emphasize the role of repeat endoscopic treatment in guidelines compared to AUA. CONCLUSION: The preferred method to repair bulbo-membranous stricture/stenosis following radiation therapy remains an area of active interest, focusing on continence preservation. Additionally, there may be a role for advanced endoscopic treatments with or without adjunct therapies to manage even obliterated stenoses.

Incidence of venous thromboembolism in benign urologic reconstructive cases.

PURPOSE: To evaluate the rate of perioperative venous thromboembolism (VTE) among patients undergoing common benign urologic reconstructive cases. We hypothesize that this rate will be lower than previously described. METHODS: We utilized the American College of Surgeons National Surgical Quality Improvement Project database from 2015 to 2019 to evaluate 30-day perioperative risk of VTE. Patients ≥ 18 years old undergoing benign urologic reconstructive cases were selected using Current Procedural Terminology (CPT) codes. Demographic, comorbidity, and operative variables were captured. The primary outcome was VTE within the 30-day postoperative period. RESULTS: We identified 8467 patients who met inclusion criteria. The majority of patients were male (> 95%) with an average age of 65 and BMI of 29.6. There were 23 VTE events (0.27%) within the 30-day perioperative period. Fourteen (14/59) procedures had a perioperative VTE. Many of the traditional factors for VTE including operative time and obesity significantly increased risk of VTE in univariate analysis. In multivariate analysis, only BMI (OR 1.09; 95% CI 1.01-1.12) and inpatient status (OR 4.42; 95% CI 1.9-10.2) were correlated with increased perioperative VTE. CONCLUSION: The rate of VTE among patients undergoing benign urologic reconstructive cases is low. Providers should continue to have high index of suspicion particularly for inpatients with high BMI in addition to other known risk factors for VTE.

Foley Catheter Balloon Rupture and Risk of Free Fragment Formation.

OBJECTIVES: To assess the volume of foley catheter balloon rupture and the incidence of free fragment formation. MATERIALS AND METHODS: Forty Latex and 30 Silicone catheters of common sizes (14-20 French) were inflated with sterile water in an aqueous environment without positive pressure. Catheters producing fragments, fragment size, and maximum instilled volume prior to rupture ("burst volume") were recorded. A subset of catheters was inflated to recommended balloon volume and the balloon was needle punctured. RESULTS: Of the 40 latex catheters, 32 (80%) produced a free fragment during spontaneous rupture. Fragments ranged from 2.1 to 3.2 cm with an average size of 2.74 ± 0.33 cm. Latex catheters had average burst volume of 83 mL, 90 mL, 112 mL,120 mL, and 422 mL for 14 Fr, 16 Fr, 18 Fr, 16 Fr 3-way, and 20 Fr 30 cc, respectively. Of the 30 silicone catheters, spontaneous rupture produced no fragments. Average burst volume for silicone catheters was 57 mL, 45 mL, and 55 mL for 14 Fr, 16 Fr, and 18 Fr, respectively. No catheter balloons produced fragments when needle punctures at recommended balloon volumes. CONCLUSION: Latex catheter balloons tolerate higher fill volumes but have a high likelihood of releasing fragments. Silicone catheters burst at lower volumes, but do not release fragments. At normal fill volumes, needle puncture is safe, and cystoscopy is likely unnecessary.

Comparative review of the guidelines for anterior urethral stricture.

PURPOSE: We aimed to provide a detailed comparison between the American Urologic Association (AUA), Société Internationale d'Urologie (SIU), and the European Association of Urology (EAU) guidelines on the evaluation, management, and follow-up of the patients with anterior urethral stricture disease (USD). METHODS: The urethral stricture guidelines from SUI, AUA, and EAU were collected and evaluated regarding the recommendations on diagnosis, evaluation, and treatment of anterior USD. The strength of evidence for each statement was included and discussed when guidelines differed. RESULTS: While the guidelines remarkably align in terms of the diagnostic workup and follow-up, there is discordance in the management of anterior urethral strictures, specifically for the use of endoscopic treatment and stenting. Further, the EAU offers more comprehensive recommendations regarding urethroplasty techniques and patient follow-up. The EAU guidelines are the most recent and first to offer guidance for USD in transgender people and women. CONCLUSION: Reconstructive urology is a rapidly adapting field, and best practices change accordingly. Guideline statements have become more inclusive and expansive but will require further research to improve the level of evidence and continue to provide patients and providers with the best treatment plans.