A Review of Combined Phosphodiesterase-5-Inhibitors and α-Blockers versus Phosphodiesterase-5-Inhibitors Alone for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia.

Guidelines from the American Urological Association (AUA) and the European Association of Urology (EAU) present conflicting recommendations regarding combination therapy of phosphodiesterase 5 inhibitors (PDE5is) with α-blockers to treat benign prostatic hyperplasia (BPH) with lower urinary tract symptoms (LUTS). Use of PDE5is is widespread in the population of patients with LUTS/BPH. In this scoping review, we examine the evidence regarding the safety and efficacy of combined PDE5is and α-blockers compared to PDE5i medications alone. A search was conducted using PubMed, Cochrane, and Web of Science to identify manuscripts discussing the safety of PDE5i and α-blockers in combination or comparing this combination to PDE5is alone in the treatment of LUTS/BPH. Study designs, data, and conclusions were qualitatively analyzed. Combination therapy was found to be safe across all studies; importantly, no evidence documents increased risk of hypotension. Most studies reported added improvement in symptom and quality of life scores compared to PDE5i alone, with additional International Prostate Symptom Score (IPSS) change ranging from -1.30 to -8.50 and IPSS quality of life score change ranging from -0.15 to -1.50. Objective metrics such as postvoid residual volumes and maximum flow rate were inconsistently reported. Taken together, the current body of data suggests that combining PDE5i α-blocker therapy is safe and that there are opportunities for additional symptomatic improvement, though it should be utilized for select patients. Situations with particular utility could include patients with comorbid erectile dysfunction or without sufficient improvement on monotherapy.

KEY POINTS combination therapy with PDE5i and α-blockers is more effective than PDE5i medications alone for lowering IPSScombination therapy with PDE5i and α-blockers is not associated with a significantly greater number of adverse events than PDE5i medications alonethe improvements seen in IPSS with combination therapy compared to PDE5i alone may or may not reach the threshold of clinical significancePDE5i and α-blocker combination therapy should be considered a safe regimen that can be used in appropriate clinical situations, like for patients with comorbid ED and those who do not achieve sufficient control of symptoms with a daily PDE5i alone.

How Female Is the Future of Urology? Projecting Various Trajectories of the United States Urology Workforce.

OBJECTIVE: To project the number and proportion of women in the urology workforce using recent demographic trends and develop an app to explore updated projections using future data. METHODS: Demographic data were obtained from AUA Censuses and ACGME Data Resource Books. The proportion of female graduating urology residents was characterized with a logistic growth model. "Stock and Flow" models were used to project future population numbers and proportions of female practicing urologists, accounting for trainee demographics, retirement trends, and growth in the field. RESULTS: Assuming growth in urology graduate numbers and continued logistic growth in the proportion of women, 10,957 practicing urologists (38%) will be female by 2062. If the rate of women entering urology residency stagnates, 7038 urologists (24%) will be female. If the retirement rates for women in urology change to mirror those of men and the proportion of female residents continues to experience logistic growth, 11,178 urologists (38%) will be female. An interactive app was designed to allow for a range of assumptions and future data: https://stephenrho.shinyapps.io/uro-workforce/. CONCLUSION: Workforce projections should incorporate recent growth in numbers of female residents. If current growth continues, 38% of urologists will be female by 2062. The app allows for exploration of different scenarios and can be updated with new data. The projections demonstrate the need for targeted efforts to recruit women into urology, address disparities within the field, and work toward retaining female urologists. We must continue working toward an equitable future workforce that can address the impending shortage of urologists.

The Omission of Genitourinary Physical Exam in Telehealth Pre-Vasectomy Consults Does not Reduce Rates of Office Procedure Completion.

OBJECTIVE: To determine whether the omission of preprocedure genitourinary exam for vasectomy inherent to a virtual consultation reduces the likelihood of successfully completing in-office vasectomy. Currently, the AUA Vasectomy guidelines encourage in-person examination when possible, though COVID-19 has catalyzed the uptake of virtual consultations at many institutions. We hypothesized that rates of completed in-office vasectomy do not significantly differ between patients examined during consultation in the office and those seen virtually with no exam. METHODS: Virtual vasectomy consults from April to December 2020 were retrospectively reviewed and compared to a size-matched, randomly-selected control group who underwent in-office vasectomy consultation. The primary outcome was completion of in-office bilateral vasectomy. Baseline demographic characteristics were compared. Fisher's exact test and Student's t-test were performed on categorical and continuous variables, respectively. RESULTS: Of 211 patients who underwent virtual vasectomy consultation during the study period, 153 presented for in-office vasectomy. They were compared to 153 vasectomies from the in-person consult cohort. No demographic differences were observed between virtual and in-office consult groups. No statistical difference was observed in completion rates of in-office vasectomy, which was 97.4% (149/153) in the virtual consult cohort and 98.7% (151/153) in the in-office consultation cohort (P = .68). CONCLUSION: Rates of completed in-office vasectomy did not significantly differ based on consult platform, suggesting that a pre-vasectomy physical exam is not required to predict successful completion of the procedure. Telehealth should be utilized as an additional platform to improve access for male contraceptive procedures in a young and busy population.

Isotonic ion replacement can lower the threshold for selective infrared neural inhibition.

Significance: Infrared (IR) inhibition can selectively block peripheral sensory nerve fibers, a potential treatment for autonomic-dysfunction-related diseases (e.g., neuropathic pain and interstitial cystitis). Lowering the IR inhibition threshold can increase its translational potentials. Aim: Infrared induces inhibition by enhancing potassium channel activation. We hypothesized that the IR dose threshold could be reduced by combining it with isotonic ion replacement. Approach: We tested the IR inhibition threshold on the pleural-abdominal connective of Aplysia californica. Using a customized chamber system, the IR inhibition was applied either in normal saline or in isotonic ion-replaced saline, which could be high glucose saline, high choline saline, or high glucose/high choline saline. Each modified saline was at a subthreshold concentration for inhibiting neural conduction. Results: We showed that isotonically replacing ions in saline with glucose and/or choline can reduce the IR threshold and temperature threshold of neural inhibition. Furthermore, the size selectivity of IR inhibition was preserved when combined with high glucose/high choline saline. Conclusions: The present work of IR inhibition combined with isotonic ion replacement will guide further development of a more effective size-selective IR inhibition modality for future research and translational applications.

C-reactive protein and interleukin-6 are decreased in transgenic sickle cell mice fed a high protein diet.

Sickle cell disease is associated with hypermetabolism and a consequent shortage of substrates for normal growth and healthy immune response. The protein:energy ratio is a major determinant of dietary adequacy; the requirement for optimal growth of control mice is 20% of energy from dietary protein. This study investigated the efficacy of increased dietary protein for improving weight gain and reducing inflammation in the Berkeley sickle cell mouse model (S). The study examined the effect of diet on weight gain and circulating levels of 2 inflammatory proteins, C-reactive protein (CRP), and cytokine interleukin-6 (IL-6). Male C57BL/6 (C) control (n = 8) and S mice (n = 8) were randomized at weaning to 40 d of isoenergetic diets containing 20% (normal) and 35% (high) of energy from protein (C20, C35, S20, S35), replacing dextrin. Rate of weight gain was calculated and plasma CRP and IL-6 concentrations determined by ELISA. Liver mRNA expression of these proteins was measured by real-time PCR and L-arginase by colorimetric assay. S35 mice tended to gain weight more rapidly than S20 mice (P = 0.06) and more rapidly than C35 mice (P < 0.01). Circulating CRP and IL-6 levels were also lower in S35 mice than in S20 mice (P < 0.05), as was liver CRP mRNA expression (P < 0.01). These results demonstrate that introducing a high protein diet at weaning attenuates the steady-state inflammation in this S mouse model. Dietary L-arginine availability was investigated as a possible mechanism for increased nitric oxide production and consequent reduced inflammation.

Pregnancy outcome in infertile patients with polycystic ovary syndrome who were treated with metformin.

OBJECTIVE: To analyze pregnancy complications and outcome in patients with polycystic ovary syndrome (PCOS) treated with metformin. DESIGN: Single center retrospective case analysis. SETTING: Private regional nonurban referral subspecialty practice. PATIENT(S): After 7 months of average metformin use, 188 patients with PCOS (average infertility: 27 months) achieved 237 pregnancies. INTERVENTION(S): Of pregnancies established, metformin alone was used before conception in 124/237 (52%), oral fertility agents (CC or letrozole) in 81 (34%), gonadotropin therapy in 7 (3.0%), assisted reproduction in 17 (7.2%), and other fertility-promoting regimens in 8 (3.4%). MAIN OUTCOME MEASURE(S): Analysis of prepregnancy health parameters (weight, blood pressure, glucose tolerance, fasting and stimulated insulin levels) and pregnancy outcomes (miscarriage, pregnancy length, hypertension, gestational diabetes, weight gain, birth weight, sex ratio, congenital malformations, and breastfeeding success). RESULT(S): Metformin appears to decrease the rate of spontaneous abortion. The co-morbidities of PCOS including obesity, insulin resistance, and glucose sensitivity served as indicators of increased risk for pregnancy complications, especially gestational diabetes. No increase in pregnancy-induced hypertension was evident. Prematurity was increased. Neither PCOS nor metformin use appears to increase the rate of congenital anomaly. PCOS did not affect lactation. CONCLUSION(S): PCOS or its co-morbidities are associated with poorer pregnancy outcome. Implications and interventions are discussed.