Spontaneous erectile function recovery among young men with erectile dysfunction taking tadalafil 5 mg once a day.

BACKGROUND: Daily (once a day [OaD]) tadalafil intake is a valuable option for men favoring spontaneous over scheduled sexual intercourse. AIM: The study sought to assess the rate of and the clinical factors associated with spontaneous, medication-free erectile function (EF) recovery after discontinuation of tadalafil 5 mg OaD in a cohort of young men seeking first medical help for psychogenic erectile dysfunction (ED) as their primary complaint. METHODS: Data from 96 consecutive patients <50 years of age seeking first medical help for ED and prescribed tadalafil 5 mg OaD were analyzed. Patients completed the International Index of Erectile Function (IIEF) and underwent baseline penile color Doppler ultrasound. Follow-up involved clinical assessments or phone interviews. Spontaneous medication-free EF recovery was defined as IIEF EF domain score >22 after tadalafil discontinuation, prompting cessation of follow-up. Descriptive statistics compared tadalafil OaD responders and nonresponders. Cox regression hazard models explored the association between baseline characteristics and EF recovery risk post-drug discontinuation. Kaplan-Meier analyses estimated EF recovery probability over time. OUTCOMES: The primary outcome was EF recovery after discontinuation of tadalafil 5 mg OaD. RESULTS: Overall, median age was 39 (interquartile range [IQR], 32-45) years. Of all, 82 (85.4%) patients achieved EF recovery after tadalafil OaD discontinuation, while 14 (14.6%) patients were identified as nonresponders. Median tadalafil usage time (from beginning to discontinuation) was 3 (IQR, 2-11) months. The most common treatment-emergent adverse event was headache in 9 (9.4%) patients. Nonresponders were older (43 [IQR, 42-45] years vs 38 [IQR, 31-44] years; P = .03), had higher body mass index (25.5 [IQR, 23.4-29.9] kg/m2 vs 23.6 [IQR, 21.8-25.9] kg/m2; P = .04), and reported lower baseline IIEF EF domain scores (12 [IQR, 7-15] vs 15 [IQR, 10-22]; P = .02) than responders. Nonresponders and responders did not differ in terms of baseline ED severity, Charlson comorbidity index, smoking, alcohol consumption, regular physical exercise, and color Doppler ultrasound parameters. Upon Cox regression analysis, younger age (hazard ratio, 0.95; 95% confidence interval, 0.92-0.99; P = .01) was associated to EF recovery, after adjusting for baseline ED severity, body mass index, smoking, and Charlson comorbidity index ≥1. The Kaplan-Meier analysis displays the probability of EF recovery over time, indicating rates of 43%, 60%, and 72% at 3-, 6-, and 12-month follow-up intervals, respectively. CLINICAL IMPLICATIONS: Tadalafil 5 mg OaD is an effective short-term treatment for psychogenic ED, allowing its discontinuation after achieving a normal medication-free EF. STRENGTHS AND LIMITATIONS: The main limitations are the limited number of participants and the potential neglect of confounding factors. CONCLUSION: Almost 1 out of 2 young men with primary psychogenic ED who were prescribed with tadalafil 5 mg OaD recovered spontaneous medication-free EF after 3 months of treatment. Overall, the younger the patient was, the higher the chance there was of spontaneous EF recovery after drug discontinuation.

Maternal tadalafil treatment does not increase uterine artery blood flow or oxygen delivery in the pregnant ewe.

Increasing placental perfusion (PP) could improve outcomes of growth-restricted fetuses. One way of increasing PP may be by using phosphodiesterase (PDE)-5 inhibitors, which induce vasodilatation of vascular beds. We used a combination of clinically relevant magnetic resonance imaging (MRI) techniques to characterize the impact that tadalafil infusion has on maternal, placental and fetal circulations. At 116-117 days' gestational age (dGA; term, 150 days), pregnant ewes (n = 6) underwent fetal catheterization surgery. At 120-123 dGA ewes were anaesthetized and MRI scans were performed during three acquisition windows: a basal state and then ∼15-75 min (TAD 1) and ∼75-135 min (TAD 2) post maternal administration (24 mg; intravenous bolus) of tadalafil. Phase contrast MRI and T2 oximetry were used to measure blood flow and oxygen delivery. Placental diffusion and PP were assessed using the Diffusion-Relaxation Combined Imaging for Detailed Placental Evaluation-'DECIDE' technique. Uterine artery (UtA) blood flow when normalized to maternal left ventricular cardiac output (LVCO) was reduced in both TAD periods. DECIDE imaging found no impact of tadalafil on placental diffusivity or fetoplacental blood volume fraction. Maternal-placental blood volume fraction was increased in the TAD 2 period. Fetal D O 2 ${D_{{{\mathrm{O}}_2}}}$ and V ̇ O 2 ${\dot V_{{{\mathrm{O}}_2}}}$ were not affected by maternal tadalafil administration. Maternal tadalafil administration did not increase UtA blood flow and thus may not be an effective vasodilator at the level of the UtAs. The increased maternal-placental blood volume fraction may indicate local vasodilatation of the maternal intervillous space, which may have compensated for the reduced proportion of UtA D O 2 ${D_{{{\mathrm{O}}_2}}}$ .

Effects of sildenafil and tadalafil on skin flap viability.

Vascular complication is one of the causes of skin flap healing failure. Sildenafil and tadalafil, a type-5 phosphodiesterase inhibitor, can improve flap viability, however, the action mechanisms involved in this process are still unclear. To assess the effects of orally administered sildenafil and tadalafil on the healing kinetics and skin flap viability, sixty-two Wistar rats were divided into three groups: control (n = 22), sildenafil (n = 20), and tadalafil (n = 20). The solutions were administered orally (dose: 10 mg/kg) immediately after the surgical procedure and then every 24 h. At postoperative days 7 and 14, the skin flap samples were collected, submitted to histological processing and evaluated under optical microscopy. In experimental groups (sildenafil and tadalafil), we found an increased vascularization (p < 0.05) on the 7th and 14th day associated with the ulcer size decrease on the 14th day, although it was not significant. There was a higher influx of neutrophils and a decrease of mononuclear population on the 7th day (p < 0.05). On the 14th day, these differences were observed only in the tadalafil group (p < 0.05). This study suggested positive results with the use of sildenafil and tadalafil as adjuvant drugs in skin flap viability.

Effects of phosphodiesterase V inhibition alone and in combination with BNP on cardiovascular and renal response to volume load in human preclinical diastolic dysfunction.

Preclinical diastolic dysfunction (PDD) results in impaired cardiorenal response to volume load (VL) which may contribute to the progression to clinical heart failure with preserved ejection fraction (HFpEF). The objective was to evaluate if phosphodiesterase V inhibition (PDEVI) alone or combination PDEVI plus B-type natriuretic peptide (BNP) administration will correct the impaired cardiorenal response to VL in PDD. A randomized double-blinded placebo-controlled cross-over study was conducted in 20 subjects with PDD, defined as left ventricular ejection fraction (LVEF) >50% with moderate or severe diastolic dysfunction by Doppler echocardiography and without HF diagnosis or symptoms. Effects of PDEVI with oral tadalafil alone and tadalafil plus subcutaneous (SC) BNP, administered prior to acute volume loading, were assessed. Tadalafil alone did not result in improvement in cardiac response to VL, as measured by LVEF, LV end diastolic volume, left atrial volume (LAV), or right ventricular systolic pressure (RVSP). Tadalafil plus SC BNP resulted in improved cardiac response to VL, with increased LVEF (4.1 vs. 1.8%, p = 0.08) and heart rate (4.3 vs. 1.6 bpm, p = 0.08), and reductions in both LAV (-4.3 ± 10.4 vs. 2.8 ± 6.6 ml, p = 0.03) and RVSP (-4.0 ± 3.0 vs. 2.1 ± 6.0 mmHg, p < 0.01) versus tadalafil alone. Plasma and urinary cyclic guanosine monophosphate (cGMP) excretion levels were higher (11.3 ± 12.3 vs. 1.7 ± 3.8 pmol/ml, 1851.0 ± 1386.4 vs. 173.4 ± 517.9 pmol/min, p < 0.01) with tadalafil plus SC BNP versus tadalafil alone. There was no improvement in renal response as measured by GFR, renal plasma flow, sodium excretion, and urine flow with tadalafil plus SC BNP compared to tadalafil alone. In subjects with PDD, tadalafil alone resulted in no improvement in cardiac adaptation, while tadalafil and SC BNP resulted in enhanced cardiac adaptation to VL. TRIAL REGISTRATION: ClinicalTrials.gov NCT01544998.

Roflumilast and tadalafil improve learning and memory deficits in intracerebroventricular Aß1-42 rat model of Alzheimer's disease through modulations of hippocampal cAMP/cGMP/BDNF signaling pathway.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent age-dependent neurodegenerative disease characterized by progressive impairment of memory and cognitive functions. Cyclic nucleotides like cAMP and cGMP are well-known to play an important role in learning and memory functions. Enhancement of cAMP and cGMP levels in the hippocampus by phosphodiesterase (PDE) inhibitors might be a novel therapeutic approach for AD. Thus, the present study was planned to explore the therapeutic potential of roflumilast (RFM) and tadalafil (TDF) phosphodiesterase inhibitors in intracerebroventricular (ICV) Aß1-42 induced AD in rats. METHODS: ICV Aß1-42 was administered in rats followed by treatment with RFM (0.05 mg/kg) and TDF (0.51 mg/kg) for 15 days. Novel object recognition (NOR), and Morris water maze (MWM) test were performed during the drug treatment schedule. On the day, 22 rats were sacrificed, and hippocampus was separated for biochemical, neuroinflammation, and histopathological analysis. RESULTS: Aß1-42 infused rats were induce behavioral impairment and increased AChE, BACE-1, Aß1-42, GSK-3ß, phosphorylated tau (p-Tau), pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) levels, oxidative stress (increased MDA, Nitrite and decreased GSH), histopathological changes, and reduced cAMP, cGMP, and BDNF levels. RFM and TDF significantly attenuated Aß1-42 induced memory deficits and neuropathological alterations in the hippocampus. CONCLUSION: The outcomes of the current study indicate that RFM and TDF lead to memory enhancement through upregulation of cAMP/cGMP/BDNF pathway, thus they may have a therapeutic potential in cognitive deficits associated with AD.

The effect of selected drugs on the mitigation of myocardial injury caused by gamma radiation.

Radiation damage of healthy tissues represents one of the complications of radiotherapy effectiveness. This study is focused on the screening of potentially effective drugs routinely used in medical practice and involved in the mechanism of radiation injury, namely for radiation-induced production of free radicals in the body. Experiments in rats revealed significant reduction of oxidative stress (malondialdehyde) and inflammatory marker (tumor necrosis factor α) in 10 Gy irradiated groups after administration of atorvastatin and a slight decrease after tadalafil administration, which indicates that one of the possible mechanisms for mitigation of radiation-induced cardiac damage could be the modulation of nitric oxide (NO) in endothelium and phosphodiesterase 5. In addition, miRNAs were analyzed as potential markers and therapeutically effective molecules. Expression of miRNA-21 and miRNA-15b showed the most significant changes after irradiation. Atorvastatin and tadalafil normalized changes of miRNA (miRNA-1, miRNA-15b, miRNA-21) expression levels in irradiated hearts. This screening study concludes that administration of specific drugs could mitigate the negative impact of radiation on the heart, but more detailed experiments oriented to other aspects of drug effectiveness and their exact mechanisms are still needed.

Oral drugs used to treat persistent pulmonary hypertension of the newborn.

Introduction:Persistent Pulmonary Hypertension of the Newborn (PPHN) is a life-threatening neonatal condition, mostly treated with inhaled nitric oxide (iNO), intravenous prostaglandins, oral bosentan, sildenafil and tadalafil. However, the utility of non-oral agents is limited in PPHN for their side effects and inconvenient deliveries. Therefore, oral agents such as bosentan, sildenafil and tadalafil are becoming appealing for their satisfactory efficacy, easy mode of administration and acceptable side effects. Areas covered: We conducted a comprehensive search on Pubmed, Scopus, Web of Sciences concerning the use of bosentan, sildenafil and tadalafil to treat PPHN and summarized their efficacy, safety and pharmacokinetics. Expert opinion: Current randomized controlled trials (RCTs) have demonstrated the favorable responses and tolerable side effects of bosentan and sildenafil. Nevertheless, those RCTs are small and only one study has described the pharmacokinetics of sildenafil in neonates. Accordingly, bosentan, sildenafil and tadalafil remain off-label in clinical use. More well-designed RCTs with large samples and long-term follow-up and pharmacometrics studies are needed to demonstrate the efficacy, safety and pharmacokinetics of bosentan, sildenafil and tadalafil in PPHN.

The Association Between Phosphodiesterase-5 Inhibitors and Colorectal Cancer in a National Cohort of Patients.

INTRODUCTION: To examine the association between phosphodiesterase-5 (PDE-5) inhibitor use and incidence of colorectal cancer among patients with erectile dysfunction treated in the Veterans Affairs (VA) Healthcare System. METHODS: A retrospective cohort study using the Veterans Affairs Informatics and Computing Infrastructure was conducted, with data spanning January 2001-December 2016. Patients were followed up from index until (i) the first diagnosis of colorectal cancer, (ii) death, or (iii) the end of study period. Statistical analyses evaluated demographics and baseline characteristics between cohorts (PDE-5 exposed or not) and the effect of additional dosages of each specific PDE-5 inhibitor using adjusted multivariate Cox proportional hazards models. RESULTS: A total of 221,538 patients met the study inclusion criteria, 192,691 patients in the PDE-5 cohort and 29,227 patients in the never use PDE-5 cohort. The multivariate Cox proportional hazards model results revealed that the those who had any exposure to a PDE-5 inhibitor have an 18% lower hazard of colorectal cancer (adjusted hazard ratio [HR] = 0.816, 95% confidence interval [CI] = 0.754-0.882). For each additional 100-mg dosage of sildenafil and 10-mg dosage of tadalafil, the hazard of colorectal cancer is reduced by 2.4% (adjusted HR = 0.976, 95% CI = 0.973-0.979) and 1.7% (adjusted HR = 0.983, 95% CI = 0.972-0.996), respectively. DISCUSSION: PDE-5 inhibitor usage in patients with erectile dysfunction is associated with a lower hazard of colorectal cancer compared with patients not exposed to PDE-5 inhibitors.

Treatment persistence with a fixed-dose combination of tadalafil (5 mg) and tamsulosin (0.4 mg) and reasons for early discontinuation in patients with benign prostatic hyperplasia and erectile dysfunction.

Purpose: The primary aim of this study was to assess treatment persistence with a fixed-dose combination (FDC) of tadalafil (5 mg) and tamsulosin (0.4 mg). This study also evaluated the reasons for early treatment discontinuation. Materials and Methods: This retrospective observational study included patients with benign prostatic hyperplasia and erectile dysfunction who started an FDC treatment of tadalafil (5 mg) and tamsulosin (0.4 mg) between July 2017 and February 2018. Treatment persistence and reasons for early discontinuation were evaluated during the first 6 months. The cumulative discontinuation rate and differences in various parameters were assessed using Kaplan-Meier analysis and the log-rank test, respectively. Factors related to persistence were analyzed using a Cox proportional hazard model. Results: Overall, 97 patients were included in the study. The cumulative persistence rate at 30, 90, and 180 days was 88.7%, 66.0%, and 54.6%, respectively. The cumulative persistence over 6 months differed significantly according to the administration of FDC therapy (log-rank p=0.005) and age (log-rank p=0.024). Younger patients (odds ratio, 2.049; p=0.021) and treatment-naive patients (odds ratio, 2.461; p=0.006) were more likely to discontinue therapy within 6 months. The common reasons for discontinuing therapy were side effects (63.6%) and perceived poor efficacy (22.7%). Conclusions: Side effects were reported to be the main reason for treatment discontinuation. Thus, to improve compliance for a once-daily FDC of tadalafil (5 mg) and tamsulosin (0.4 mg), it is recommended to select patients who show adaptation to a combination of α-blockers and phosphodiesterase type 5 inhibitors prior to FDC treatment.

A successful treatment of tadalafil in incontinentia pigmenti with pulmonary hypertension.

We describe a female infant with incontinentia pigmenti complicated by severe pulmonary arterial hypertension that was markedly improved by tadalafil administration. The infant was referred to our institution because of neonatal seizures and generalized skin rash at the age of 1 day. She was diagnosed with incontinentia pigmenti on skin biopsy findings. In addition to incontinentia pigmenti, she had pulmonary arterial hypertension without structural heart disease. The pulmonary hypertension rapidly worsened at the age of 2 months and was confirmed by cardiac catheterization. The pulmonary artery pressure was equal to systemic pressure but it decreased in response to nitric oxide inhalation. We, therefore, initiated treatment with tadalafil of 1 mg/kg/day. The follow-up cardiac catheterization performed at 9 months revealed dramatic improvement in the pulmonary artery pressure. An IKBKG mutation with deletion of exons 4-10 was detected in the blood of both the patient and her mother. Our experience indicates that tadalafil may be beneficial in treating pulmonary arterial hypertension associated with incontinentia pigmenti.

[EVALUATING THE RELATIONSHIP BETWEEN LOWER URINARY TRACT SYMPTOMS AND ENDOTHELIAL FUNCTION USING FLOW-MEDIATED DILATION, AND THE EFFECTS OF TADALAFIL].

(Objective) Recently, lower urinary tract symptoms (LUTS) were reported to be associated with endothelial dysfunction. Endothelial function is non-invasively measured by flow-mediated dilation (FMD). As tadalafil has the potential to improve atherosclerosis, we evaluated the relationship between LUTS and endothelial function using FMD, and the effects of tadalafil. (Patients and methods) We conducted FMD examinations for a total of 122 males, and analyzed its association with IPSS, OABSS, and cardiovascular risks. Furthermore, 21 BPH patients received 5 mg of tadalafil per day for one year. We defined the Low FMD group as FMD < 3.9% and the Control group as other values, and compared the effects of tadalafil between groups. (Results) In the 122 male patients, FMD was negatively correlated with nocturia and OABSS. Patients with hypertension or coronary artery disease had a lower FMD than those without.In the tadalafil administration study, the Low FMD group achieved greater improvement of IPSS, OABSS and FMD than the Control group. (Conclusion) FMD examination revealed that endothelial dysfunction is closely associated with LUTS in males, and that tadalafil is effective for patients with endothelial dysfunction.

The Reversal of Immune Exclusion Mediated by Tadalafil and an Anti-tumor Vaccine Also Induces PDL1 Upregulation in Recurrent Head and Neck Squamous Cell Carcinoma: Interim Analysis of a Phase I Clinical Trial.

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibition. Here we report for the first time interim results of our ongoing phase I clinical trial (NCT02544880) in patients with recurrent HNSCC to evaluate the safety of and immunological effects of combining Tadalafil with the antitumor vaccine composed of Mucin1 (MUC1) and polyICLC. The combined treatment of Tadalafil and MUC1/polyICLC vaccine was well-tolerated with no serious adverse events or treatment limiting toxicities. Immunologically, this trial also confirms the positive immunomodulation of Tadalafil in patients with recurrent HNSCC and suggests an adjuvant effect of the anti-tumor vaccine MUC1/polyICLC. Additionally, image cytometry analysis of scanned tumors indicates that the PDE5 inhibitor Tadalafil in conjunction with the MUC1/polyICLC vaccine effectively reduces the number of PDL1+macrophages present at the tumor edge, and increases the number of activated tumor infiltrating T cells, suggesting reversion of immune exclusion. However, this analysis shows also that CD163 negative cells within the tumor upregulate PDL1 after treatment, suggesting the instauration of additional mechanisms of immune evasion. In summary, our data confirm the safety and immunologic potential of PDE5 inhibition in HNSCC but also point to PDL1 as additional mechanism of tumor evasion. This supports the rationale for combining checkpoint and PDE5 inhibitors for the treatment of human malignancies.

Intranasal Tadalafil nanoemulsions: formulation, characterization and pharmacodynamic evaluation.

This study aims at improving the bioavailability of a poorly soluble phosphodiesterase-5 inhibitor; tadalafil (TD) via developing intranasal (IN) nanoemulsions (NEs). Optimum NE ingredients were selected based on solubility studies, emulsification tests, and phase diagram construction. Both o/w and w/o NEs were selected based on their drug loading capacity. Optimum formulations were subjected to physicochemical characterization and were assessed for nasal toxicity through biochemical analysis of tumor necrosis factor-α (TNF-α) and caspase-3 in rat nasal tissues. Pharmacodynamic study was performed via biochemical analysis of cyclic guanosine monophosphate (cGMP) in rat penis 2-h post-treatment and compared with oral suspension of Cialis® tablets. Optimum o/w and w/o NEs were successfully prepared using different ratios of Capmul-MCM-EP, Labrasol:Transcutol-HP (1:1) and water. Optimized formulations exhibited more than 4000-fold increase in TD solubility compared with its aqueous solubility. Both formulations were optically isotropic with the majority of globules in the nanometric-size range. Nasal toxicity study revealed no significant difference in values of TNF-α and caspase-3 between the NE-treated groups and the control group. Both TD-NEs succeeded to achieve a significant enhancement in cGMP levels. Our findings suggested that IN administration of the developed TD-NEs could provide a safe and effective alternative to TD oral delivery.

A 34-Year-Old Woman With Hoarseness of Voice and an Abnormal Echocardiogram.

CASE PRESENTATION: A 34-year-old woman presented for evaluation of several months of a hoarse voice and dyspnea on exertion that progressed over the last 3 years. She had a clinical diagnosis of asthma that had been treated with bronchodilators and inhaled corticosteroids for a few years. She continued to use her inhalers but with minimal symptomatic improvement. The patient was a lifelong nonsmoker with no history of drug abuse. She worked as a college professor and denied any significant environmental exposures or recent travel.

Effect of co-administration of BRL-37344 and tadalafil on reduction of overactive bladder symptoms after induction of detrusor overactivity in mice1.

PURPOSE: To evaluate the impact of the combination of BRL 37344 and tadalafil (TDF) on the reduction of overactive bladder (OB) symptoms. METHODS: Thirty mice were randomized into 5 groups (G) of 6 animals each. L-NAME was used to induce DO. G1: Control; G2: L-NAME; G3: L-NAME + TDF; G4: L-NAME + BRL 37344; G5: L-NAME + TDF + BRL 37344. After 30 days of treatment, the animals were submitted to cystometry to evaluate non-voiding contractions (NVC), threshold pressure (TP), baseline pressure (BP), frequency of micturition (FM) and threshold volume (TV). Differences between the groups were analyzed with ANOVA followed by the Tukey test. RESULTS: NVC increased in G2 (4.33±2.58) in relation to G1 (1.50±0.55). NVC decreased in G3 (2.00±1.10), G4 (1.50±1.52) and G5 (2.00±1.26) compared to G2 (p<0.05). FM decreased in G3 (0.97±0.71), G4 (0.92±0.38) and G5 (1.05±0.44) compared to G2 (p<0.05). However, the combination of TDF and BRL37344 was not more effective at increasing NVC and improving FM than either drug alone. The five groups did not differ significantly with regard to TV. CONCLUSION: The combination of BRL 37344 and TDF produced no measurable additive effect on reduction of OB symptoms.

[Tadalafil 5 mg once daily is a rationale option for simultaneous treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction].

The lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and erectile dysfunction (ED) are an important medical and social problem. Combination of LUTS and ED is usually underdiagnosed. Selective phosphodiesterase 5 inhibitors (PDE5I) are recommended for treatment of both conditions. The aim of this review is to identify the best PDE5I for simultaneous treatment LUTS and ED.

Sildenafil Use in Children with Pulmonary Hypertension.

OBJECTIVE: To assess the demographics, treatment algorithm, and outcomes in a large cohort of children treated with sildenafil. STUDY DESIGN: A retrospective cohort study of children with pulmonary hypertension (PH) treated with sildenafil at a single institution between 2004 and 2015. Baseline and follow-up data collected by chart review. RESULTS: There were 269 children included in this study: 47 with idiopathic pulmonary arterial hypertension, 53 with congenital heart disease, 135 with bronchopulmonary dysplasia, 24 with congenital diaphragmatic hernia, and 7 with other causes. Sildenafil was initial monotherapy in 84.8% and add-on therapy in 15.2%. Median follow-up time was 3.1 years (2 weeks-12.4 years). On follow-up, 99 (37%) remained on sildenafil or transitioned to tadalafil, 93 (35%) stopped sildenafil for improvement in PH, 54 (20%) died, and 20 (7%) were lost to follow-up. PH was most likely to improve in those with bronchopulmonary dysplasia, allowing for the discontinuation of sildenafil in 45%. Eighteen deaths were related to PH and 36 from other systemic causes. Two patients stopped sildenafil owing to airway spasm with desaturation. Overall survival was significantly lower in World Health Organization group 3 PH (bronchopulmonary dysplasia and congenital diaphragmatic hernia) vs group 1 (idiopathic pulmonary arterial hypertension and congenital heart disease), P = .02. CONCLUSIONS: In this retrospective experience in children with mainly World Health Organization groups 1 and 3 PH, low-dose sildenafil was well-tolerated, safe, and had an acceptable side effect profile. Although patients with group 3 PH have high mortality, survivors have a high likelihood of PH improving.

Efficacy and safety of tadalafil 5 mg once-daily in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction: A phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of tadalafil in Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction. METHODS: The present phase 3, randomized, double-blind, parallel, placebo- and tamsulosin-controlled study was carried out at 40 study centers in the Asia-Pacific region (mainland China, Taiwan and Korea; NCT01937871). Participants were randomized to receive a placebo (n = 361), tadalafil 5 mg (n = 362) or tamsulosin 0.2 mg (n = 185) in a 2:2:1 ratio for 12 weeks. RESULTS: A total of 909 Asian men were randomized into three groups. After 12 weeks of treatment, a statistically significant improvement in least squares mean change from baseline in total International Prostate Symptom Score was observed in the tadalafil versus the placebo group (-5.49 vs -4.08, respectively; P < 0.001). A statistically significant improvement in the change from baseline for the International Index of Erectile Function-Erectile Function domain score, was observed in tadalafil compared with the placebo at 12 weeks (5.24 vs 1.88, respectively; P < 0.001). A significant improvement was observed in the change from baseline in the percentage of "Yes" responses to Sexual Encounter Profile questions 2 and 3 in the tadalafil versus placebo group at 12 weeks (23.87% vs 10.90%; P < 0.001 and 36.62% vs 15.96%; P < 0.001, respectively). Safety results were consistent with the known tadalafil safety profile. CONCLUSIONS: Tadalafil is efficacious and well tolerated in the treatment of Asian men with both lower urinary tract symptoms associated with benign prostatic hyperplasia and erectile dysfunction.