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

Substructure and Scatter in the Mass-Temperature Relations of Simulated Clusters

Galaxy clusters exhibit regular scaling relations among their bulk properties. These relations establish vital links between halo mass and cluster observables. Precision cosmology studies that depend on these links benefit from a better understanding of scatter in the mass-observable scaling relations. Here we study the role of merger processes in introducing scatter into the $M$-$T_{\rm X}$ relation, using a sample of 121 galaxy clusters simulated with radiative cooling and supernova feedback, along with three statistics previously proposed to measure X-ray surface brightness substructure. These are the centroid variation ($w$), the axial ratio ($\eta$), and the power ratios ($P_{20}$ and $P_{30}$). We find that in this set of simulated clusters, each substructure measure is correlated with a cluster's departures $\delta \ln T_{\rm X}$ and $\delta \ln M$ from the mean $M$-$T_{\rm X}$ relation, both for emission-weighted temperatures $T_{\rm EW}$ and for spectroscopic-like temperatures $T_{\rm SL}$, in the sense that clusters with more substructure tend to be cooler at a given halo mass. In all cases, a three-parameter fit to the $M$-$T_{\rm X}$ relation that includes substructure information has less scatter than a two-parameter fit to the basic $M$-$T_{\rm X}$ relation.Comment: Accepted by ApJ, 10 pages, 10 figure

Influence of stabilisers on the catalytic activity of supported Au colloidal nanoparticles for the liquid phase oxidation of glucose to glucaric acid: understanding the catalyst performance from NMR relaxation and computational studies

Supported Au colloidal nanoparticles have been prepared in the presence of stabilising polymers, such as, PVA, PVP and PEG (polyvinylalcohol, polyvinylpyrrolidone, polyethylene glycol). The effect of the polymer to Au weight ratio was investigated, for the synthesis of Au nanoparticles with varying particle size and particle size distribution. By varying the polymer/Au wt/wt ratio, Au nanoparticles with mean diameters from 3 to 8 nm were synthesised. The synthesised Au catalysts were studied in the liquid phase oxidation of glucose to glucaric acid under alkaline conditions. We demonstrated that the choice of polymer and polymer to Au weight ratio, have an important influence in terms of catalytic activity and yield to glucaric acid. The highest yield to glucaric acid (22%) was obtained using Au–PVA catalysts. A strong deactivation was observed using Au catalysts. Further evaluation of the possible reasons for deactivation were investigated using experimental, computational and NMR relaxation studies

SHBG levels in primary infertile men : A critical interpretation in clinical practice

Objective: We aimed to test the association between age, BMI and sex-hormone\u2013binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple\u2019s infertility. Design: Retrospective study. Methods: Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (<33, 33-41, >41 years) and BMI as normal weight (18.5\u201324.9 kg/m2), overweight (25.0\u201329.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG. Results: Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P < 0.001). For each year increase in age, SHBG increased 0.32 nmol/L; conversely, for each unit increase in BMI, SHBG decreased by 1.1 nmol/L (all P < 0.001). SHBG levels decline with increasing BMI was greater than SHBG progressive increase with age. Overall, BMI explained 3.0 times more of the variability in SHBG than did ageing. At multivariate linear model, age and BMI were the most significant factors influencing SHBG concentration (all P < 0.001), after accounting for CCI, albumin levels and smoking status. Conclusions: We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG

Multiple PDE5Is use as a marker of decreased overall men's health: A real-life study

Erectile dysfunction (ED) is considered a sentinel marker for poor general men's health status. Severe ED has been associated with poor response to phosphodiesterase type 5 inhibitors (PDE5Is) therapy. We sought to assess the association of multiple PDE5Is prescription with the overall patients' health status. Socio-demographic and clinical variables from 939 consecutive white-European, heterosexual, sexually-active men seeking medical help for ED at same tertiary-referral academic outpatient clinic were analyzed. Health-significant comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients have been stratified into na\uefve and non-na\uefve according to their history of previous prescriptions of any PDE5I. Every patient completed the International Index of Erectile Function (IIEF) questionnaire. Logistic regression models tested the association between patients' baseline characteristics (thus including previous PDE5Is prescriptions) and the overall health status. Overall, 328 (35%) patients were non-na\uefve for PDE5Is. Of them, 172 (52%), 99 (30%), and 57 (17%) had been prescribed with 1, 2 or 3 different PDE5Is, respectively. Na\uefve and nonna\uefve patients did not differ in terms of age, BMI, baseline ED severity; conversely, nonna\uefve patients had a higher CCI score. At logistic MVA, the number of PDE5Is prescriptions emerged as an independent predictor of a higher burden of comorbidities regardless of ED severity; the higher the number of PDE5Is prescriptions, the higher the CCI score (OR 1.69, 2.49, and 2.90 for 1, 2 or 3 previous PDE5Is, respectively), after accounting for age, BMI, baseline ED severity and cigarette smoking. More than a third of patients seeking medical help for ED at a single tertiary-referral center were non-na\uefve for PDE5Is. The increasing number of previous prescriptions of PDE5Is emerged as a worrisome marker of a poorer overall men's health status regardless of ED severity

Social distancing in chronic migraine during the covid-19 outbreak: Results from a multicenter observational study

Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life

Clinically Meaningful Improvements in LUTS/BPH Severity in Men Treated with Silodosin Plus Hexanic Extract of Serenoa Repens or Silodosin Alone

To assess the rate and predictors of clinically meaningful improvements (CMI) in patients with lower urinary tract symptoms (LUTS) treated with either silodosin (SIL) alone or with a combination of SIL+ serenoa repens (Ser) hexanic lipidosterolic extract for 6512 months. Data from 186 patients were collected. Patients completed the International Prostatic Symptoms Score (IPSS) at baseline and at follow-up assessment. Descriptive statistics and logistic regression models tested rates and predictors of CMI. Two CMI were assessed: 1) >3 points improvement in total IPSS from baseline to end (CMI#1); 2) >25% IPSS improvement from baseline to end (CMI#2). Overall, 93 (50%) patients were treated with SIL and SIL+ Ser, respectively. At a mean 13.5-mos follow-up [range: 12-20], mean IPSS scores were significantly lower in patients treated with SIL\u2009+\u2009Ser compared to those after SIL (p\u2009=\u20090.002). SIL\u2009+\u2009Ser patients more frequently achieved CMI#1 (69.9% vs. 30.1%, p\u2009=\u20090.001) and CMI#2 (68.8% vs. 31.2%, p\u2009<\u20090.001) compared SIL men. At multivariable analyses, younger age, IPSS severity and SIL\u2009+\u2009Ser (all p\u2009<\u20090.03) were independent predictors of CMI#1 and CMI#2. In conclusion, SIL\u2009+\u2009Ser therapy was more effective than SIL alone in improving IPSS scores in men with LUTS. SIL\u2009+\u2009Ser treatment led to CMIs in up to seven out of ten men

Azathioprine for prevention of clinical recurrence in Crohn's disease patients with severe endoscopic recurrence: an IG-IBD randomized double-blind trial

The recurrence of Crohn's Disease after ileo-colonic resection is a crucial issue. Severe endoscopic lesions increase the risk of developing early symptoms. Prevention and treatment of post-operative Endoscopic Recurrence (ER) have been studied with conflicting results. We compare effi cacy of azathioprine (AZA) vs. high-dose 5-aminosalicylic acid (5-ASA) in preventing clinical recurrence and treating severe post-operative ER

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

Sequencing the transcriptome of milk production: milk trumps mammary tissue

Background: Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results: We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions: RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation