Major adverse cardiovascular events related to phosphodiesterase 5 inhibitors: analysis of real-life data from Eudra-Vigilance database.

BACKGROUND: Phosphodiesterase 5 inhibitors (PDE5i) are the standard medical treatment for erectile dysfunction. Aim of our study was to evaluate the rate of major adverse cardiovascular events (MACE) reported during PDE5i treatment based on Eudra-Vigilance (EV) reports. METHODS: EV database is the system for managing and analyzing data on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area. MACE are defined as non-fatal stroke, non-fatal myocardial infarction, non-fatal congestive heart failure, revascularization after aorto-coronary graft bypass and cardiovascular death. We recorded the number of MACE for sildenafil, tadalafil, vardenafil, avanafil per category and severity until 1st July 2023. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall, 951 MACE events were reported. Most of them were observed in younger patients <65 years old (452/951 events, 48%). Overall, 377/8939 (4%) MACE events were observed for sildenafil, 221/5213 (4%) for tadalafil, 50/1029 (4%) for vardenafil and no events for avanafil. No significative differences were reported comparing sildenafil and tadalafil (PRR 0.71-0.99, IQR 0.61-1.35, P>0.05), neither sildenafil vs. vardenafil (PRR 0.68-0.79, IQR 0.43-1.55, P>0.05), neither tadalafil vs. vardenafil (PRR 0.77-0.95, IQR 0.64-1.30. P>0.05) even when compared for age. Comparison between different classes of age showed MACE were more frequent in patients younger than 65 years old taking sildenafil and tadalafil when compared to patients older than 85 years old (PRR 0.02-0.11. IQR 0.01-0.40. P<0.01) and when compared to patients in 65-85 class of age (PRR 0.02-0.12, IQR 0.01-0.95, P<0.01). CONCLUSIONS: Real life data is consistent with MACE related to PDE5i. PDE5is are infrequently (<5%) associated with MACE. However, risk seems higher in younger patients, particularly for sildenafil (452/951 events, 48%). Clinicians should consider these data when prescribing PDE5i especially in young patients.

Medications mostly associated with hematuria: assessment of the EudraVigilance and Food and Drug Administration pharmacovigilance databases entries.

BACKGROUND: Drugs may have a direct causative role in triggering hematuria. The range of medications which may be responsible for hematuria is wide, but little is known on those which are most frequently involved. The aim of our study was to identify and compare drugs mostly related with hematuria. METHODS: The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and the EudraVigilance (EV) database were queried to identify the drugs which were associated the most with hematuria individual reports till 30 September 2021. Rivaroxaban, aspirin, warfarin sodium, clopidogrel bisulfate, dabigatran etexilate mesylate, apixaban, warfarin, cyclophosphamide, lansoprazole, enoxaparin sodium, and ibuprofen were analyzed. Analysis per gender, age and severity was performed. Disproportional analysis was performed to compare drugs. RESULTS: Overall, 15,687 reports of hematuria were recorded in the FDA database and 15 007 in the EV database. Rivaroxaban and Warfarin appear to be the most dangerous medications in terms of hematuria when compared to the other medications (PRR>1, P<0.05) while apixaban is the safest one (PRR<1, P<0.05) when compared to the other medications. In terms of severity only 162/15 007 (1.08%) were fatal. Between the drugs analyzed cyclophosphamide 7.2%, enoxaparin (3%) and dabigatran (2.5%) presented a higher number of fatal hematuria episodes when compared to the other drugs (<1%). CONCLUSIONS: Anticoagulants and antiplatelets are more frequently related to hematuria episodes however some differences exist between them. Particularly warfarin and rivaroxaban should be prescribed with caution in patients at increased risk of hematuria. Prescribers should inform those treated with these medications about the risk of hematuria and its sequelae.

Role of Perilesional Sampling of Patients Undergoing Fusion Prostate Biopsies.

Recently, researchers have proposed perilesional sampling during prostate biopsies to avoid systematic biopsies of patients at risk of prostate cancer. The aim of our study is to evaluate the role of perilesional sampling to avoid systematic biopsies of patients undergoing fusion biopsies. A prospective cohort of patients undergoing transrectal MRI transrectal fusion biopsies were consecutively enrolled. All the patients underwent systematic biopsies (SB), targeted biopsies (TB) and perilesional biopsies within 10 mm from the lesion (PB). The detection rates of different strategies were determined. A total of 262 patients were enrolled. The median age of those enrolled was 70 years. The mean BMI was 27 kg/m2, and the mean and prostate volume was 52 mL. A PIRADS score ≥ 4 was recorded in 163/262 (40%) patients. Overall, the detection rates of cancer were 43.5% (114/262) and 35% (92/262) for csPCa. The use of the target + peri-target strategy resulted in a detection of 32.8% (86/262) of cancer cases and of 29% (76/262) of csPCa cases (Grade Group > 2). Using the target plus peri-target approach resulted in us missing 18/262 (7%) of the csPCa cases, avoiding the diagnosis of 8/262 (3%) of nsPCa cases. A biopsy strategy including lesional and perilesional sampling could avoid unnecessary prostate biopsies. However, the risk of missing significant cancers is present. Future studies should assess the cost-benefit relationship of different strategies.

Adverse events related to alpha-blockers: analysis of real-life data from Eudra-Vigilance.

BACKGROUND: Patients on alpha-blockers (ABs) treatment may have an increased risk of adverse events (AEs). Aim of our study was to compare real-life data on neuro-vascular and sexual AEs associated with ABs based on Eudra-Vigilance reported AEs. METHODS: Eudra-Vigilance (EV) database is the system for managing and analyzing information on suspected adverse reactions to medicines which have been authorized or being studied in clinical trials in the European Economic Area (EEA). We recorded the number of sexual and neuro-vascular AEs for tamsulosin, alfuzosin, silodosin, prazosin and doxazosin per category and severity until July 30th, 2022. Pooled Relative Risk (PRR) was used to compare data between drugs. RESULTS: Overall the number of AEs were 2842 for Alfuzosin, 11,086 for tamsulosin, 792 for terazosin, 572 for prazosin and 4641 for doxazosin. Different percentages of AEs were obtained for each drug and in different age groups according to EV sub-groups (≤65, 65-85, ≥85). On PRR analysis, the risk of ejaculatory disorders for Silodosin (11%) is 18.5 times higher (PRR 18.5 95%CI; 10.7-31.8; P<0.05) when compared to alfuzosin and the risk of orthostatic hypotension is 2 times lower (PRR=1,84 95%CI 1.32-2.57; P<0.05). CONCLUSIONS: Real life data is consistent with registry studies regarding side effects related to alpha-blockers. Alfuzosin is safer in terms of ejaculatory disorders while silodosin and tamsulosin in terms of orthostatic hypotension. Clinicians should consider these data when prescribing ABs especially in younger and older patients.

Patients' Preferences and Expectations in Overactive Bladder: A Systematic Review.

The aim of our study is to review the current available knowledge regarding preferences and expectations of patients with overactive bladder (OAB). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines were followed for this manuscript's preparation. Three online databases were searched: PubMed/Medline, Embase, and Scopus, while a combination of the following keywords was used: detrusor overactivity, overactive bladder, urinary incontinence, perspectives, expectations, and preferences. Overall, 1349 studies were retrieved and screened while only 10 studies appeared to be relevant for the scope of this review. Most of the studies were related to preferences about OAB medications (i.e., antimuscarinics); four of them reported patients' inclinations to alternative treatments in the case of medication therapy failure (i.e., neuromodulation, Botox). No data were found about diagnosis or other aspects of disease management (i.e., surgery, follow-up). Based on these findings, from the patient's point of view, the ideal medication should be cheap, without risk of cognitive function impairment, and able to reduce daytime urinary frequency and incontinence episodes.

Post-voided residual urine ratio as a predictor of bladder outlet obstruction in men with lower urinary tract symptoms: development of a clinical nomogram.

PURPOSE: To confirm the correlation between post-void residual urine ratio (PVR-R) and BOO diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS) and to develop a clinical nomogram. METHODS: A consecutive series of patients aged 45 years or older with non-neurogenic LUTS were prospectively enrolled. Patients underwent standard diagnostic assessment for BOO including International Prostatic Symptoms Score, uroflowmetry, urodynamic studies, suprapubic ultrasound of the prostate, and ultrasound measurements of the bladder wall thickness (BTW). PVR-R was defined as follows: PVR-R = (PVR/total Bladder Volume [BV]) × 100). Logistic regression analysis was used to investigate predictors of pathological bladder emptying (BOO) defined as Schafer > II. A nomogram to predict BOO based on the multivariable logistic regression model was then developed. RESULTS: Overall 335 patients were enrolled. Overall, 131/335 (40%) presented BOO on PFS. In a multivariable logistic age-adjusted regression model BWT (odds ratio [OR]: 2.21 per mm; 95% confidence interval [CI], 1.57-3.09; p = 0.001), PVR-R (OR: 1.02 per %; 95% CI, 1.01-1.03; p = 0.034) and prostate volume (OR: 0.97 per mL; 95% CI, 0.95-0.98; p = 0.001) were significant predictors for BOO. The model presented an accuracy of 0.82 and a clinical net benefit in the range of 10-90%. CONCLUSIONS: The present study confirms the important role of PVR-ratio in the prediction of BOO. For the first time, we present a clinical nomogram including PVR-ratio for the prediction of BOO.

Night shift workers refer higher urinary symptoms with an impairment quality of life: a single cohort study.

BACKGROUND: The aim of the present study is to assess the impact of night shift work (NSW) on urinary symptoms. METHODS: Between March 2018 to October 2018, we evaluated a group of National Health care system workers. Urinary symptoms and quality of life were measured by Overactive Bladder Questionnaire Short Form (OABq-sf). Clinical variables (i.e. age, smoking status, medical history) were collected and analyzed according to be NS workers (NSWs) from subjects working at least one time from 8 pm to 8 am or from traditional workers (TWs). Univariate and multivariate analysis was performed to identify predictive variables of worse OAB outcomes (OABq-sf>30, OABq-SB≥12, OABq HRQL≥18). RESULTS: A total of 136 participants (68 males and 68 females) were included in the study. On OABq-sf, total score, symptoms bother (OABq-SB) and health related quality of life (OABq-HRQL) domains were significantly (P<0.05) higher in NSWs group, respectively: 31 (IQR 26-35) vs. 19 (IQR 19-20); 11 (IQR 10-13) vs. 6 (IQR 6-7); 19 (IQR 16-22) vs. 13 (13-14). Finally, seven NSWs (10.6%) referred nocturia respect to only one (1%) TWs, (P=0.02). On multivariate analysis NSW was an independent predictor of OABq-sf>30 units (OR:30; CI: 9-111, P=0.001), OABq-SB ≥12 units (OR:16, CI: 6-43, P=0.001) and OABq HRQL≥18 units (OR:20, CI: 6-70, P=0.001). CONCLUSIONS: Night shift workers presented worst OAB Score and poor QL when compared to similar traditional workers. Long-term data on NSWs patients are also needed to further clarify this relationship.