Efficacy and safety of dapoxetine in treatment of premature ejaculation: an evidence‐based review

SummaryBackground Premature ejaculation (PE) is a major issue in male sexual health, with a global prevalence estimated to be between 20% and 40%, making it the most common sexual dysfunction in men. PE causes distress and reduced quality of life for patients and has a negative impact on interpersonal relationships. Historically, it has been treated with cognitive therapy, behavioural methods and off-label use of selective serotonin reuptake inhibitors (SSRIs) usually used to treat depression and other psychological disorders. Dapoxetine is the only SSRI specifically designed to treat PE. Mechanism of action Dapoxetine hydrochloride is a potent inhibitor of serotonin reuptake transporters. Dapoxetine is suited for 'on-demand' treatment of PE because of its rapid absorption and short initial half-life. Efficacy Evidence from published studies showed that dapoxetine 30 mg or 60 mg taken 'on-demand' results in a significant increase in intravaginal ejaculatory latency time (IELT) when compared with placebo. Most patient-reported outcomes are clearly improved relative to placebo following dapoxetine therapy, indicating greater control over ejaculation, more satisfaction with intercourse, less ejaculation-related distress and significantly reduced interpersonal difficulties. Safety The most common adverse events with dapoxetine are nausea, dizziness, somnolence, headache, diarrhoea and insomnia. Usually they do not lead to drug discontinuation. Conclusion Dapoxetine is the only effective and safe available on-label oral treatment for PE, and its use can result in better quality of life for the patient and their sexual partner

Attitude towards active surveillance: a cross-sectional survey among patients with uroandrological disorders

OBJECTIVES: We looked at subjective attitude towards active surveillance (AS) as the first option for cancer management in a cohort of patients seeking first medical help for uroandrological disorders prior to a formal discussion with a caregiver. DESIGN: Cross-sectional observational study. SETTING: Uroandrological outpatient clinic of a European academic centre. PARTICIPANTS: Data of 1059 patients at their first access for uroandrological purposes from January 2014 to December 2016 were analysed. INTERVENTION: Patients were invited to complete a survey with closed questions investigating their attitude towards AS, prior to any clinical evaluation. Likewise, patients were invited to score the importance given to different aspects of personal life in the case of a cancer diagnosis, using a 10-point Likert scale. PRIMARY AND SECONDARY OUTCOMES MEASURES: The reported opinion towards AS management for cancer was assessed. Logistic regression analyses tested participants' sociodemographic characteristics associated with a positive opinion on AS. RESULTS: Positive, negative and doubtful attitudes towards AS were observed in 347 (33%), 331 (31%) and 381 (36%) patients, respectively. Female patients were more likely to report a negative attitude towards AS (38.7% vs 29.6%, p=0.04) while patients with previous parenthood more frequently reported a positive opinion on AS (37.2% vs 29.9%, p=0.005). Patient age emerged as the only predictor of a positive attitude towards AS (OR 1.03; 95% CI 1.01 to 1.04, p<0.001), with a 46% and 33% probability of being pro-AS for a patient aged 65 and 45 years, respectively. CONCLUSIONS: One out of three patients would express positive feedbacks on AS in the unfortunate case of tumour diagnosis, only according to his/her baseline personal opinion and prior to any discussion with a cancer caregiver. The older the patient, the higher the probability of being compliant with a conservative management for cancer

Influence of the static magnetic field on cell response in a miniaturized optically accessible bioreactor for 3D cell culture

Hydraulic sealing is a crucial condition for the maintenance of sterility during long term operation of microfluidic bioreactors. We developed a miniaturized optically accessible bioreactor (MOAB) allowing perfused culture of 3D cellularised constructs. In the MOAB, the culture chambers are sealed by magnets that generate a weak static magnetic field (SMF). Here, we predicted computationally the exact level of SMF to which cells are subjected during culture in the MOAB and we assessed its influence on the viability, metabolic activity and gene expression of neuroblastoma-derived cells cultured up to seven days. The predicted SMF ranged from 0.32 to 0.57 T using an axial-symmetric model of a single chamber, whereas it ranged from 0.35 to 0.62 T using a 3D model of the complete device. Cell function was evaluated in SH-SY5Y neuroblastoma cells at 2 and 7 days of culture in the MOAB, compared to 2D monolayer, 3D non-perfused constructs, and 3D perfused constructs cultured in a modified MOAB with magnet-free sealing. We measured the cell metabolic activity normalized by the DNA content and the expression levels of heat-shock protein 70 (Hsp-70), Bcl-2 and Bax. We found that the level of SMF applied to cells in the MOAB did not influence their metabolic activity and exerted a stressful effect in 2D monolayer, not confirmed in 3D conditions, neither static not perfused. Instead, the magnets provided a significantly greater hydraulic sealing in long-term culture, thus the MOAB might be potentially exploitable for the development of reliable in vitro models of neurodegeneration

Effectiveness of Ginseng, Rutin and Moringa for the Treatment of Erectile Dysfunction: A Systematic Review

Introduction, The aim of this systematic review was to evaluate the current evidence for the effectiveness of ginseng, Rutin and Moringa for treating erectile dysfunction. Methods, A broad search of the Scopus, PubMed, Cochrane and Web of Science databases was performed in complicance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The following criteria were required for articles to be included in the review: English language; observational studies (cohort studies, case control/comparative studies, single-arm studies); randomized controlled trials; non-randomized comparative studies; case series; number of participants: ≥5 for case series or ≥5 patients per group for comparative studies. The Cochrane risk of bias (RoB) assessment tool for RCTs was used to assess the risk of bias of included studies. Results, Seven full-text articles were included in this review. All studies were randomized controlled trials. No studies on Rutin and Moringa alone matched the inclusion criteria. The methodological quality of the RCTs was variable. In all studies, the group treated with ginseng reported an improvement of erectile function (EF) compared to the control groups. IIEF and IIEF-5 were used to evaluate erectile function in six studies and in four of them, the improvement of the scores in the group treated with ginseng over the control group reached the statistical significance. Conclusion, This review suggests a positive effect of ginseng on EF in men. The association of ginseng along with other nutritional components with potential beneficial effects on ED appears promising and deserves further investigation in large randomized controlled trials

The Need of Multidisciplinary Approaches and Engineering Tools for the Development and Implementation of the Smart City Paradigm

This paper is motivated by the concept that the successful, effective, and sustainable implementation of the smart city paradigm requires a close cooperation among researchers with different, complementary interests and, in most cases, a multidisciplinary approach. It first briefly discusses how such a multidisciplinary methodology, transversal to various disciplines such as architecture, computer science, civil engineering, electrical, electronic and telecommunication engineering, social science and behavioral science, etc., can be successfully employed for the development of suitable modeling tools and real solutions of such sociotechnical systems. Then, the paper presents some pilot projects accomplished by the authors within the framework of some major European Union (EU) and national research programs, also involving the Bologna municipality and some of the key players of the smart city industry. Each project, characterized by different and complementary approaches/modeling tools, is illustrated along with the relevant contextualization and the advancements with respect to the state of the art

Clinical comparison between conventional and microdissection testicular sperm extraction for non-obstructive azoospermia: Understanding which treatment works for which patient

Objectives: The superiority of microdissection testicular sperm extraction (mTESE) over conventional TESE (cTESE) for men with non-obstructive azoospermia (NOA) is debated. We aimed to compare the sperm retrieval rate (SRR) of mTESE to cTESE and to identify candidates who would most benefit from mTESE in a cohort of Caucasian-European men with primary couple’s infertility. Material and methods: Data from 49 mTESE and 96 cTESE patients were analysed. We collected demographic and clinical data, serum levels of LH, FSH and total testosterone. Patients with abnormal karyotyping were excluded from analysis. Age was categorized according to the median value of 35 years. FSH values were dichotomized according to multiples of the normal range (N) (N and 1.5 N: 1-18 mIU/mL, and > 18 mIU/mL). Testicular histology was recorded for each patient. Descriptive statistics and logistic regression analyses tested the impact of potential predictors on positive SRR in both groups. Results: No differences were found between groups in terms of clinical and hormonal parameters with the exception of FSH values that were higher in mTESE patients (p = 0.004). SRR were comparable between mTESE and cTESE (49.0% vs. 41.7%, p = 0.40). SRRs were significantly higher after mTESE in patients with Sertoli cell-only syndrome (SCOS) (p = 0.038), in those older than 35 years (p = 0.03) and with FSH >1.5N (p 1.5N (p = 0.018). Moreover, increased FSH levels (p = 0.03) and both SCOS (p = 0.01) and MA histology (p = 0.04) were independent predictors of SRR failure. Conclusions: Microdissection and cTESE showed comparable success rates in our cohort of patients with NOA. mTESE seems beneficial for patients older than 35 years, with high FSH values, or when SCOS can be predicted. Given the high costs associated with the mTESE approach, the identification of candidates most likely to benefit from this procedure is a major clinical need

Prevalence of Drug-Resistant HIV-1 Variants in Untreated Individuals in Europe: Implications for Clinical Management

BackgroundInfection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis penta increase-spacing 1>MethodsWe determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002 ResultsIn Europe, 1 of 10 antiretroviral-naive patients carried viruses with ⩾1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P=.006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%; P<.01). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001 ConclusionsDrug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are update

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors

Purpose The primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade &gt;= 2).Methods This study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients.Results 705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naive (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1-2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p &lt; 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG &gt;= 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS &gt;= 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively.Conclusions Exposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions.Trial registration The present study was registered at ClinicalTrials.gov number: NCT05078359

A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

<p>Abstract</p> <p>Background</p> <p>HIV-1 genotypic susceptibility scores (GSSs) were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART) switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed.</p> <p>Methods</p> <p>We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90^thday after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb) and other covariates by means of Cox regression and random survival forests (RSF). Prediction models were validated via the bootstrap and c-index measure.</p> <p>Results</p> <p>The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70), while RSF showed a better performance (c-index≈0.73, p < 0.0001 vs. Cox regression). Variable importance according to RSF was concordant with the Cox hazards.</p> <p>Conclusions</p> <p>GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.</p

Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

<p>Abstract</p> <p>Background</p> <p>The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced.</p> <p>Results</p> <p>In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred.</p> <p>Conclusion</p> <p>Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants.</p