BackgroundEpithelial tubo-ovarian cancer (EOC) has high mortality partly due to late diagnosis. Prevention is available but may be associated with adverse effects. A multifactorial risk model based on known genetic and epidemiological risk factors (RFs) for EOC can help identify women at higher risk who could benefit from targeted screening and prevention.MethodsWe developed a multifactorial EOC risk model for women of European ancestry incorporating the effects of pathogenic variants (PVs) in BRCA1, BRCA2, RAD51C, RAD51D and BRIP1, a Polygenic Risk Score (PRS) of arbitrary size, the effects of RFs and explicit family history (FH) using a synthetic model approach. The PRS, PV and RFs were assumed to act multiplicatively.ResultsBased on a currently available PRS for EOC that explains 5% of the EOC polygenic variance, the estimated lifetime risks under the multifactorial model in the general population vary from 0.5% to 4.6% for the first to 99th percentiles of the EOC risk distribution. The corresponding range for women with an affected first-degree relative is 1.9%–10.3%. Based on the combined risk distribution, 33% of RAD51D PV carriers are expected to have a lifetime EOC risk of less than 10%. RFs provided the widest distribution, followed by the PRS. In an independent partial model validation, absolute and relative 5-year risks were well calibrated in quintiles of predicted risk.ConclusionThis multifactorial risk model can facilitate stratification, in particular among women with FH of cancer and/or moderate-risk and high-risk PVs. The model is available via the CanRisk Tool (www.canrisk.org).

Impairment of erectile function compromises quality of life in millions of men and their partners, many of whom prefer to suffer in silence. It is important to maintain an elevated index of clinical suspicion in patients with erectile dysfunction (ED) risk factors (e.g. hypertension, diabetes, coronary heart disease). There remains a high rate of voluntary discontinuation of therapy associated with most treatment modalities. Since the introduction of sildenafil, a greater awareness and openness regarding the epidemiology and treatment of male erectile dysfunction has emerged. The development of newer and potentially more efficacious phosphodiesterase type 5 (PDE5) inhibitors will serve to treat an even greater number of patients, allowing once daily and more convenient dosing. An increased understanding of the physiological principles of penile erection has allowed the development of novel oral pharmacological therapies. The new agents offer a potential benefit in a broader range of patients and clinical situations. They may provide a more acceptable alternative than other more invasive options (intracavernosal/urethral injection, implant surgery). The dopamine agonist apomorphine acts on the central control of penile erection to allow a sublingual preparation to produce a prompt response. It is not contraindicated in patients on nitrate medication for coronary artery disease, or in patients with depression or on antidepressants. As with any other treatment, the clinician's responsibility in the care of ED patients does not end with the writing of a prescription. Adequate education and follow-up are needed to optimize the efficacy and safety of oral ED therapy. Furthermore, patients and their partners need to be advised that the agents are not effective in the absence of sexual stimulation. Communicating with both the patient and his partner in a discreet, non-judgmental manner that fosters the physician-patient alliance can facilitate the recognition and treatment of ED.

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