Efficacy of tadalafil on improvement of men with erectile dysfunction caused by COVID-19:A randomized placebo-controlled trial

Objective: According to the high prevalence of COVID-19 and the subsequent risk of men's sexual health, we decided to investigate the efficacy of tadalafil on improvement of men with erectile dysfunction caused by COVID-19.Methods: In this study, 70 outpatients who were recovered from COVID-19 without acute respiratory distress syndrome with negative polymerase chain reaction test and a complaint of erectile dysfunction were divided into two groups: 35 patients who received tadalafil 5 mg daily and 35 who received placebo. For each patient, basic assessment of sexual function was performed using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Then, treatment was started from 2 months after complete recovery of COVID-19 with negative polymerase chain reaction test for 3 months. At the end of the treatments, the patients were re-evaluated for sexual function using the complete version of IIEF questionnaire. Finally, the results before and after treatment in the intervention group were compared with those of the control group.Results: Treatment with both tadalafil and placebo improved the patients' sexual function criteria compared to the baseline. However, this improvement was significantly higher in the intervention group with tadalafil than the control group with placebo (p<0.05).Conclusion: Daily administration of tadalafil 5 mg seems to be effective and safe for improvement of erectile dysfunction caused by COVID-19.

基于能量算子的声源定位技术在TADS探测车轮故障中的应用

车轮故障是影响铁道车辆运行安全的重要因素。使用TADS技术可以实现对车轮故障等走行部部件的故障检测。由于同转向架车轮噪声信号的叠加干扰会造成车轮故障等噪声信号区分困难,容易造成车轮故障的误报和误判,因此对故障噪声来源进行定位和区分十分重要。在TADS探测车轮故障进行数据分析时,借鉴了医学领域广泛应用的基于近距离麦克风的双耳结构多运动声源定位的经验。利用TADS的短间距声学阵列,结合TADS探测中声源移动速度快、难捕捉的特点,综合使用谱峭度、Gammatone滤波器、能量算子等技术和手段建立了适应铁道车辆动态检测运用场景的运动声源定位模型,能够实现对快速运动声源的追踪和定位。通过对实际案例进行分析验证了运动声源定位模型方法的有效性,可以给出快速运动声源的运动轨迹。通过运动轨迹与理论轨迹相匹配进行声源性质的判定,可用于辅助诊断车轮故障。

国产TAD纸机的研发及应用

本文探讨了TAD(Through—Air Drying)热风穿透纸机的技术特点、国产TAD纸机的研发过程及其在市场中的应用。通过技术分析和市场调研,本文旨在展示TAD技术在提升纸品质量和市场竞争力方面的显著优势,分享国内生活用纸设备企业在TAD纸机方面的最新技术进展。

Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study

A highly sensitive liquid chromatography-tandem mass spectrometry（LC-MS/MS） method was developed for the determination of tadalafil（TAD） in human plasma. TAD and its deuterated internal standard（IS）, tadalafil-d3, were extracted from 200 mL plasma using Phenomenex Strata-X-C 33 m extraction cartridges. Chromatographic analysis was carried out on Synergi Hydro-RP C18（100 mm × 4.6 mm, 4 mm）column with a mobile phase consisting of methanol and 10 m M ammonium formate, p H 4.0（90：10, v/v）,delivered at a flow rate of 0.9 m L/min. Quantitation of the protonated analyte was done on a triple quadrupole mass spectrometer using multiple reaction monitoring via electrospray ionization. The precursor to product ions transitions monitored for TAD and TAD-d3 were m/z 390.3-268.2 and m/z393.1-271.2, respectively. The calibration curve was linear over the concentration range of 0.50–500 ng/m L with correlation coefficient, r2 Z 0.9994. Acceptable intra-batch and inter-batch precision（r3.7%） and accuracy（97.8% to 104.1%） were obtained at five concentration levels. The recovery of TAD from spiked plasma was highly precise and quantitative（98.95% to 100.61%）. Further, the effect of endogenous matrix components was minimal. TAD was found to be stable under different storage conditions in human plasma and also in whole blood samples. The validated method was successfully used to determine TAD plasma concentration in a bioequivalence study with 20 mg TAD tablets in 24 healthy volunteers. Method performance was evaluated by reanalyzing 115 study samples.

Efficacy and safety of on demand tadalafil in the treatment of East and Southeast Asian men with erectile dysfunction:a randomized double-blind,parallel,placebo-controlled clinical study

Aim： To assess the efficacy and safety of tadalafil in comparison to a placebo, when taken on demand for 12 weeks by East/Southeast Asian men with erectile dysfunction （ED）, Methods： This multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted at 17 centers across East and Southeast Asia between August 2002 and February 2003. Men more than 18 years of age with mild to severe ED of various etiologies were randomized to receive a placebo or 20 mg of tadalafil taken as needed （maximum once daily）. Efficacy assessments included the International Index of Erectile Function, the Sexual Encounter Profile diary and Global Assessment Questions. Results： Tadalafil significantly improved erectile function as compared to the placebo （P 〈 0.001）. At the endpoint, the patients receiving 20 mg of tadalafil reported a greater mean per patient percentage of successful intercourse attempts （Sexual Encounter Profile question 3： 70.9% compared to 33.5% in the placebo） and a greater proportion of improved erections （Global Assessment Question： 86.2% compared to 30.1%）. Most （≥3%） treatment emergent adverse events were mild or moderate. The most common treatment emergent adverse events were headache, back pain, dizziness and dyspepsia. Conclusion： Tadalafil was an effective and well-tolerated treatment for ED in East and Southeast Asian men.

Efficacy and safety of tadalafil taken as needed for the treatment of erectile dysfunction in Asian men： results of an integrated analysis

We evaluated the efficacy and safety of as-needed tadalafil in a diverse clinical population （with varying patient demographics, disease severity, and comorbid medical conditions） of Asian men with erectile dysfunction （ED）. An integrated analysis of five double-blind, placebo-controlled trials （N = 1 046） was performed. Patients were randomly assigned to receive 10 mg tadalafil （N = 185）, 20 mg tadalafil （N = 510）, or placebo （N = 351）. Efficacy assessments included the International Index of Erectile Function （IIEF）, Sexual Encounter Profile （SEP） diary and Global Assessment Question （GAQ）. Patients receiving 10 mg or 20 mg tadalafil showed significant improvement from baseline-to-end point on the Erectile Function domain of the International Index of Erectile Function （IIEF-EF） domain score in all clinical sub-populations analyzed, compared with patients receiving placebo （P 〈 0.001）. The 10-mg and 20-mg tadalafil groups showed a mean success rate of 64.1% and 70.5% for sexual intercourse attempts （SEP3, successful intercourse）, respectively, compared with 33.4% in the placebo group （P 〈 0.001）, and 85.5% and 85.4% reported improved erections at end point GAQ, respectively, versus 43.5% in the placebo group （P 〈 0.001）. Tadalafil was well tolerated across all groups studied. Headache and back pain were the most frequently reported adverse events. Overall, tadalafil was effective and well tolerated across a diverse clinical spectrum of Asian men with ED.

Treatment preferences in men with erectile dysfunction： an open label study in Korean men switching from sildenafil citrate to tadalafil

To evaluate patient preferences for sildenafil citrate or tadalafil （PDE-5 inhibitors available for the treatment of erectile dysfunction [ED]） and assess potential reasons for these preferences. Methods： This open-label study was conducted on Korean men taking sildenafil, at least 6 weeks prior to study entry, for ED. Following screening, patients continued sildenafil treatment for 4 weeks, then after a 1-week washout period, switched to tadalafil for 8 weeks. Patients then continued with their treatment of choice during an extension phase. Psychosocial factors （time concern, spontaneity, sexual self-confidence） were evaluated using Psychological and Interpersonal Relation- ship Scales （PAIRS）, while timing of dose to sexual attempt patterns were assessed from patient diaries. Results： The present study enrolled 160 Korean men （mean age 55 years） with prior median sildenafil use of 585 days. During the extension phase, 73.7% of patients elected to take tadalafil, whereas 26.3% chose sildenafil （P 〈 0.001）. After switching from sildenafil to tadalafil, mean PAIRS time concern scores decreased from 2.54 to 2.42 （P = 0.002）, with no statistically significant differences observed between the sildenafil and tadalafil assessment phases in sexual spontaneity and self-confidence scores. Sexual attempts made 〉 4 h to 〈 36 h post-dose occurred in 4.5% of patients during the sildenafil assessment phase compared with 17.5% during the tadalafil assessment phase. Conclusion： After experiencing both sildenafil and tadalafil, the majority of patients exhibited a preference for tadalafil. This preference might be influenced by psychosocial factors, such as decreased time concerns, and a broader window of opportunity available for sexual activity.

Hemodynamic effects of ambrisentan-tadalafil combination therapy on progressive portopulmonary hypertension

Intravenous epoprostenol is recommended for World Health Organization functional class(WHO-FC) Ⅳ patients with pulmonary arterial hypertension(PAH) in the latest guidelines. However, in portopulmonary hypertension(PoP H) patients, advanced liver dysfunction and/or thrombocytopenia often makes the use of intravenous epoprostenol challenging. Here we report the cases of two WHO-FC Ⅳ PoP H patients who were successfully treated with a combination of two oral vasodilators used to treat PAH: ambrisentan and tadalafil. Oral vasodilator therapy using a combination of ambrisentan and tadalafil may be a safe and effective therapeutic option for WHO-FC Ⅳ PoP H patients and should be considered for selected patients with severe and rapidly progressing PoP H.

Evaluation of an alternative dosing regimen with tadalafil, three times per week, for men with erectile dysfunction： SURE study in Italy

Aim： To examine the preference for two dosing regimens of 20 mg of tadalafil, on demand or three times per week, in men affected with erectile dysfunction （ED） in Italy. Methods： Scheduled Use versus on demand Regimen Evaluation （SURE） is a multicenter, crossover and open-label study, involving 94 urology centers in Italy. Patients aged 18 years or older affected with ED for at least 3 months were enrolled and randomized to 20 mg of tadalafil treatment on demand or three times per week for 5-6 weeks. After a 1-week washout, patients were crossed over to the alternate regimen for 5-6 weeks. A treatment preference question was used to determine the preferred treatment regimen. International Index of Erectile Function （IIEF） and Sexual Encounter Profile （SEP） questionnaire were used as efficacy measures. Results： A total of 1 058 men （mean age 54.8 years）, were randomized to treatment. Overall, 59.1% of patients preferred the on-demand regimen and 41.9% preferred the three times per week dosing. Both regimens were efficacious and well tolerated. Although a statistically higher improvement of the IIEF erectile function （IIEF-EF） domain score and the SEP questionnaire was reported for the three times per week compared to the ondemand treatment regimen, this difference was numerically minimal and lacking in clinical significance. Conclusion： Tadalafil is effective and well tolerated whether used on demand or three times per week. Patients should be given the option to choose the best treatment regimen according to personal needs and preferences.

Effect of tamsulosin versus tamsulosin plus tadalafil on renal calculus clearance after shock wave lithotripsy:An open-labelled,randomised,prospective study

Objectives:To compare the efficacy of tamsulosin versus tamsulosin plus tadalafil in achieving clearance of fragments after shock wave lithotripsy(SWL)to treat renal calculi.Methods:Between January 2016 to December 2017,140 patients with solitary,non-branched,non-lower calyceal renal calculus and measuring less than 20 mm and treated with SWL were randomized to tamsulosin(group A)or tamsulosin plus tadalafil(group B).Therapy was given for a period of 4 weeks.Stone clearance rate,analgesic requirement,occurrence of steinstrasse,need for auxiliary procedures(endoscopic treatment),and adverse effects of drugs were recorded.Results:The overall clearance rate was 72.5%(50/69)in the group A and 90.1%(64/71)in the group B(pZ0.007).For stones up to 12 mm,the difference in the clearance rate was significant(pZ0.039)while it was not so for stones larger than 12 mm(pZ0.151).There was no statistically significant difference between the two groups with regards to analgesic requirement(pZ0.94),occurrence of steinstrasse(pZ0.101),need for auxiliary procedures(pZ0.76),and adverse effects of the drugs(pZ0.148).Conclusion:Our study shows that adjunctive medical expulsive therapy with tamsulosin and tadalafil achieves better clearance rate than tadalafil alone in patients receiving SWL for renal stones.

Neuroprotective effects of tadalafil on gerbil dopaminergic neurons following cerebral ischemia

Impairment of dopamine function, which is known to have major effects on behaviors and cognition, is one of the main problems associated with cerebral ischemia. Tadalafil, a long-acting phosphodiesterase type-5 inhibitor, is known to ameliorate neurologic impairment induced by brain injury, but not in dopaminergic regions. We investigated the neuroprotective effects of treatment with tadalafil on cyclic guanosine monophosphate level and dopamine function following cerebral ischemia. Forty adult Mongolian gerbils were randomly and evenly divided into five groups （n = 8 in each group）： Sham-operation group, cerebral ischemia-induced and 0, 0.1, 1, and 10 mg/kg tadalafil-treated groups, respectively. Tadalafil dissolved in distilled water was administered orally for 7 consecutive days, starting 1 day after surgery. Cyclic guanosine monophosphate assay and immunohistochemistry were performed for thyrosine hydroxylase expression and western blot analysis for dopamine D2 receptor expression. A decrease in cyclic guanosine monophosphate level following cerebral ischemia was found with an increase in thyrosine hydroxylase activity and a decrease in dopamine D2 receptor expression in the striatum and substantia nigra region. However, treatment with tadalafil increased cyclic guanosine monophosphate expression, suppressed thyrosine hydroxylase expression and increased dopamine 92 receptor expression in the striatum and substantia nigra region in a dose-dependent manner. Tadalafil might ameliorate cerebral ischemia-induced dopaminergic neuron injury. Therefore, tadalafil has the potential as a new neuroprotective treatment strategy for cerebral ischemic injury.

Efficacy of a combination of dutasteride, tadalafil, and solifenacin in the treatment of previously unsuccessful patients

Objective To evaluate the efficacy and safety of simultaneous administration of dutasteride,tadalafil and solifenacin in the treatment of benign prostatic hyperplasia(BPH)with overactive bladder symptoms and lower urinary tract obstruction in previously unsuccessfully treated men.Methods Patients in Group A(n=97)received dutasteride 0.5 mg/day,tadalafil 2.5 mg/day,and solifenacin 2.5 mg/day;Group B(n=95)received dutasteride 0.5 mg/day,tadalafil 5 mg/day,and solifenacin 5 mg/day;Group C(n=103)received dutasteride 0.5 mg/day,tadalafil 20 mg/day,and solifenacin 10 mg/day.The functional status of the lower urinary tract was assessed using the International Prostate Symptom Score(I-PSS),Overactive Bladder Questionnaire(OABq),International Index of Erectile Function(IIEF),and Male Sexual Health Questionnaire Ejaculatory Dysfunction(MSHQ-EjD)as well as uroflowmetry.Results The total score of the sexual function remained unchanged in Group B of patients 81.3 points vs.80.2 points(p>0.05)according to MSHQ-EjD,61.4 points vs.51.2 points(p>0.05)according to IIEF data.The total assessment of symptoms of hyperactivity significantly decreased in Group C according to OABq data after the 4th week of the study(17.5 points vs.26.1 points,p<0.05)and remained below the baseline until the end of the study(15.2 points).Conclusions The simultaneous administration of standard doses of dutasteride,solifenacin,and tadalafil for 3 months is safe,effective,and can be recommended for patients with BPH to reduce symptoms of obstruction and hyperactivity of the bladder and maintain sexual function.

Haemodynamic and renal effects of tadalafil in patients with cirrhosis

A recent report introduced the phosphodiesterase-5 inhibition by vardenafil as a novel treatment of portal hypertension in patients with cirrhosis.In the herein presented"letter to the editor",the administration of tadalafil did not influence portal haemodynamics but impaired systemic haemodynamics in patients with cirrhosis.Our observations concur with the results of a report in a previous issue of World Journal of Gastroenterology(October 2008).Moreover,tadalafil adversely affected renal function in patients with decompensated liver disease.

Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk

The number of the circulating angiogenic cells （CACs） and colony forming units （CFUs） derived from cultured circulating mononuclear cells （MNCs） represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction （ED） and vascular risk factors （VRFs） showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4weeks of treatment with tadalafil （20 mg every other day） or with a placebo. The tadalafil treatment improved erectile function （P = 0.0028）, but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 （P = 0.011） and tissue type plasminogen activator （P = 0.005） were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.

A Study to Compare the Safety and Efficacy of Solifenacin, Tamsulosin and Tadalafil in Relieving Double-J Stent Related Symptoms

Objective: To evaluate and compare the safety and efficacy of Solifenacin, Tamsulosin, and Tadalafil in treating ureteral stent related symptoms (SRS) in patients with indwelling Double-J ureteral stents. Materials and Methods: A prospective randomized controlled study was conducted on 146 consecutive patients in the department of urology, Government Stanley Medical College & Hospital, Chennai, Tamilnadu, India between Sept 2017-March 2019, with SRS after taking informed consent and confirming DJ Stent position by X-ray KUB post-operatively. Patients were randomized into 4 groups: Group A (Placebo), Group B (Solifenacin 5 mg), and Group B (Tamsulosin 0.4 mg) and group D (Tadalafil 5 mg) at end of 1st week till the removal of DJ stent at end of 3 weeks. All patients were assessed for bothersome lower urinary tract symptoms (LUTS) using the validated Ureteral Stent Symptom Questionnaire (USSQ) at 1st week and 3 weeks after the starting of medications. Appropriate statistical analysis as carried out and the level of significance was set at P Results: LUTS, general health, and work performance improved with Solifenacin, Tamsulosin and Tadalafil and all the three were comparable in relieving urinary symptoms. Tadalafil was better at relieving body pain, additional problems and sexual problems better than Tamsulosin. Tadalafil showed comparable improvement in LUTS, better sexual health and decreased body pain compared to solifenacin, whereas the latter had better general health, additional problems & work performance scores. Conclusion: Solifenacin is more effective than Tamsulosin in alleviating LUTS associated with SRS and both show a distinctive advantage over placebo. PDE inhibitor Tadalafil can also be tried for SRS and is as effective as antimuscarinics and α-blockers in relieving urinary symptoms and is more efficacious in relieving sexual symptoms and body pain.

Tadalafil是治疗ED的首选药

根据美国提交给国际药物经济与产出研究学会第11届国际会议的研究报告，tadalafil（Ⅰ）是治疗男性勃起功能障碍（ED）最划算的口服药物。