Medications mostly associated with priapism events: assessment of the 2015-2020 Food and Drug Administration (FDA) pharmacovigilance database entries.

A range of drugs have a direct role in triggering ischaemic priapism. We aimed at identifying: a) which medications are associated with most priapism-reports; and, b) within these medications, comparing their potential to elicit priapism through a disproportionality analysis. The FDA Adverse Event Reporting System (FAERS) database was queried to identify those drugs associated the most with priapism reports over the last 5 years. Only those drugs being associated with a minimum of 30 priapism reports were considered. The Proportional Reporting Ratios (PRRs), and their 95% confidence intervals were computed. Out of the whole 2015-2020 database, 1233 priapism reports were identified, 933 of which (75.7%) were associated with 11 medications with a minimum of 30 priapism-reports each. Trazodone, olanzapine and tadalafil showed levels of disproportionate reporting, with a PRR of 9.04 (CI95%: 7.73-10.58), 1.55 (CI95%: 1.27-1.89), and 1.42 (CI95%: 1.10-1.43), respectively. Most (57.5%) of the reports associated with the phosphodiesterase type 5 inhibitors (PDE5Is) were related with concomitant priapism-eliciting drugs taken at the same time and/or inappropriate intake/excessive dosage. Patients taking trazodone and/or antipsychotics need to be aware of the priapism-risk; awareness among prescribers would help in reducing priapism-related detrimental sequelae; PDE5I-intake is not responsible for priapism by itself, when appropriate medical supervision is provided.

Is medicinal ketamine associated with urinary dysfunction issues? Assessment of both the European Medicines Agency (EMA) and the UK Yellow Card Scheme pharmacovigilance database-related reports.

OBJECTIVE: A range of ketamine-induced uropathy (KIU) issues have been typically described in ketamine misusers. Conversely, more knowledge is needed in terms of medicinal ketamine-related urological disturbances, since ketamine prescribing is being increasingly considered for a range of medical and psychopathological conditions. METHODS: To assess medicinal KIU issues, we aimed at analyzing both the 2005-2017 European Medicines Agency (EMA) and the 2006-2018 UK Yellow Card Scheme (YCS) pharmacovigilance databases. RESULTS: A total number (eg, all categories) of 11 632 EMA ketamine-related adverse drug reaction (ADR) reports were here identified. Out of these, some 9971 ADRs (eg, 85.7% of the total) were judged as "suspect" and were here analyzed. Some 1758 ADRs (17.7% of 9971, corresponding to 194 individual patients) referred to urological issues, relating to either kidney/ureter (922 ADRs) or bladder/urethra (837 ADRs). Ketamine was the sole drug administered in 156/194 (80.4%) cases/patients. Although most cases occurred in the 1 month-1 year time frame following the start of ketamine prescribing, in 30 cases the ADR occurred within 48 hours. Most ADR-related cases resolved, although both sequelae (18 cases) and fatalities (79/1758; 4.5%) were recorded. Overall, YCS data were consistent with EMA findings, with some 50/217 (23%) ADRs referring to renal/urinary disorders. CONCLUSIONS: Current data may only represent a gross underestimate of the KIU real prevalence issues. It is here suggested that chronic treatment involving higher doses/repeated exposure to ketamine be restricted to the context of controlled trials or clinical audits.

When to perform lymph node dissection in patients with renal cell carcinoma: a novel approach to the preoperative assessment of risk of lymph node invasion at surgery and of lymph node progression during follow-up.

OBJECTIVE: To identify preoperatively patients who might benefit from lymph node dissection (LND). PATIENTS AND METHODS: We assessed lymph node invasion (LNI) at final pathology and lymph node (LN) progression during the follow-up for 1983 patients with RCC, treated with either partial or radical nephrectomy. LN progression was defined as the onset of a new clinically detected lymphadenopathy (>10 mm) in the retroperitoneal lymphatic area. Logistic regression analyses were used to assess the effect of each potential clinical predictor (age, body mass index, tumour side, symptoms, performance status, clinical tumour size, clinical tumour-node-metastasis stage, and albumin, calcium, creatinine, haemoglobin and platelet levels) on the outcome of interest. The most parsimonious multivariable predictive model was developed, and discrimination, calibration and net benefit were calculated. RESULTS: The prevalence of LNI was 6.1% (120/1983 patients) and during the follow-up period, 82 patients (4.1%) experienced LN progression. On multivariable analyses, the most informative independent predictors were tumour stage (cT3-4 vs cT1-2, odds ratio [OR] 1.52, P = 0.05), clinical nodal status [cN1 vs cN0, OR 7.09, P < 0.001], metastases at diagnosis (OR 3.04, P < 0.001) and clinical tumour size (OR 1.14, P < 0.001). The accuracy of the multivariable model was found to be 86.9%, with excellent calibration and net benefit at decision-curve analyses. CONCLUSIONS: By relying on a unique approach, combining the risk of harbouring LNI and/or LN progression during the follow-up period, we have provided the first clinical presurgery model predicting the need for LND.