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In this trial, patients with secondary hyperparathyroidism who were undergoing dialysis were assigned to receive either the calcimimetic agent cinacalcet or placebo. Cinacalcet did not significantly reduce the risk of death or major cardiovascular events. Cardiovascular disease is very common among patients with chronic kidney disease, including those treated with hemodialysis, among whom the risk of death from cardiovascular disease is increased by a factor of 10 or more as compared with the risk in the general population. 1 , 2 Cardiovascular risk factors that have been linked to chronic kidney disease include heightened states of inflammation, 3 oxidative stress, 4 activation of the renin–angiotensin–aldosterone system 5 and the sympathetic nervous system, 6 endothelial dysfunction, 7 retention of uremic toxins promoting atherosclerosis and arteriosclerosis, 8 abnormalities in platelet aggregation, 9 anemia, 10 and disorders of bone and mineral metabolism, including hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism. . . .

Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke or other cardiovascular events. We compared the selective thromboxane-prostaglandin receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event. This randomised, double-blind, parallel-group trial was undertaken in 802 centres in 46 countries. Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were randomly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin. Patients and investigators were masked to treatment allocation. The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke, fatal or non-fatal myocardial infarction, or other vascular death (excluding haemorrhagic death). We planned a sequential statistical analysis of non-inferiority (margin 1·05) followed by analysis of superiority. Analysis was by intention to treat. The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee. This study is registered, number ISRCTN66157730. 9562 patients were assigned to terutroban (9556 analysed) and 9558 to aspirin (9544 analysed); mean follow-up was 28·3 months (SD 7·7). The primary endpoint occurred in 1091 (11%) patients receiving terutroban and 1062 (11%) receiving aspirin (hazard ratio [HR] 1·02, 95% CI 0·94–1·12). There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints. We recorded some increase in minor bleedings with terutroban compared with aspirin (1147 [12%] vs 1045 [11%]; HR 1·11, 95% CI 1·02–1·21), but no significant differences in other safety endpoints. The trial did not meet the predefined criteria for non-inferiority, but showed similar rates of the primary endpoint with terutroban and aspirin, without safety advantages for terutroban. In a worldwide perspective, aspirin remains the gold standard antiplatelet drug for secondary stroke prevention in view of its efficacy, tolerance, and cost. Servier, France.

To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS. The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14). No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found. No evidence of differences between the two compared interventions was found. Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4.

Background Premature ejaculation (PE) is a prevalent male sexual dysfunction with limited comparative data on pharmacological treatments. This randomized clinical trial aimed to evaluate the efficacy and safety of four active pharmacological interventions for lifelong PE. Methods A prospective randomized trial was conducted from June 2024 to March 2025 at Beni-Suef University Hospital. Four hundred eligible patients diagnosed with lifelong PE were randomly allocated to one of four active treatment groups ( n  = 100 per group): (1) citalopram 20 mg/day, (2) silodosin 4 mg/day, (3) dapoxetine 30 mg on-demand (1–3 h before intercourse), or (4) dapoxetine 30 mg daily. The primary outcome was the change in intravaginal ejaculatory latency time (IELT) measured by stopwatch. Secondary outcomes included changes in the Premature Ejaculation Profile Questionnaire (PEPQ) scores and the incidence of treatment-emergent adverse events. Statistical analysis was performed using ANOVA with post-hoc tests for continuous variables and chi-square tests for categorical data. Results All four treatment groups demonstrated significant within-group improvements in IELT from baseline ( p  < 0.001 for all). The citalopram group exhibited the greatest mean IELT increase (from 110.4 ± 31.5s to 391.2 ± 45.9s; 260% median gain), outperforming the daily dapoxetine (220%), on-demand dapoxetine (197%), and silodosin (149.5%) groups. Improvements in PEPQ scores mirrored the IELT findings, with citalopram showing a 300% improvement compared to 225%, 166.7%, and 175% in the daily dapoxetine, on-demand dapoxetine, and silodosin groups, respectively. In inter-group comparisons, citalopram was superior to silodosin in all PEPQ domains ( p  < 0.001) and to both dapoxetine regimens in the domain of interpersonal difficulty ( p  < 0.01). Adverse event profiles differed: silodosin was associated with a higher incidence of ejaculatory dysfunction (23% retrograde ejaculation), while daily dapoxetine led to more systemic effects (18% dizziness). Conclusion In this direct head-to-head comparison of active treatments for lifelong PE, daily citalopram (20 mg) demonstrated superior efficacy in prolonging IELT and improving psychosocial outcomes compared to daily or on-demand dapoxetine and silodosin. The findings suggest that citalopram is a highly effective first-line option, while the dose-dependent efficacy of dapoxetine and the distinct side-effect profile of silodosin provide alternative considerations for personalized treatment strategies. Trial registration This clinical trial was registered at ClinicalTrials.gov (Identifier NCT07113145) on 7 August 2025 after the enrollment of the first participant and is therefore retrospectively registered.”

Abstract Background Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. Methods Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days − 7, − 2, 21, and 28, and tick counts were performed on day − 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. Results On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P  = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) ( P  = 0.002, P  < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) ( P  < 0.001) and afoxolaner (6.3%) ( P  < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different ( P  < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) ( P  = 0.020) and afoxolaner (9.0%) ( P  = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% ( P  < 0.001) and afoxolaner (0.0%) ( P  < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24–48 h earlier for lotilaner compared with sarolaner or afoxolaner. Conclusions Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner’s speed of tick kill is sustained throughout the dosing period. Graphical Abstract

The risk of cardiovascular disease (CVD) is approximately doubled in subjects with hypercholesterolemia compared to those with normal blood cholesterol levels. Monacolin K (MK), the main active substance in rice fermented by the Monascus purpureus, acts on cholesterol metabolism. Rice also contains other bioactive compounds such as γ-oryzanol (OZ) and γ-aminobutyric acid (GABA). In a randomized, placebo-controlled, double-blind trial, the efficacy and tolerability of a food supplement (FS) based on an ingredient standardized to contain monacolins (4.5%), OZ, and GABA were evaluated in subjects with mild dyslipidemia. For the duration of the trial, enrolled subjects (n = 44, each group) received the FS or placebo and were instructed to use an isocaloric diet. Compared to the placebo group, after a 3 months of the FS, the mean low-density lipoprotein cholesterol and mean TC values were reduced by 19.3 and 8.3%, respectively, while the mean high-density lipoprotein cholesterol value increased by 29.3%. On average, the subjects shifted from very high to moderate CVD risk. Glucose metabolism and hepatic and renal parameters did not change after the treatment and no adverse events were reported. Guidelines to handle hypercholesterolemia with food supplements in specific clinical settings are needed to better manage mild dyslipidemia.

This ad hoc analysis of a previously conducted phase 3 head-to-head comparison study of evocalcet and cinacalcet in secondary hyperparathyroidism patients undergoing maintenance hemodialysis evaluated the efficacy and safety of combined once-daily oral evocalcet and intravenous vitamin D receptor activator treatment stratified by weekly vitamin D receptor activator dose (117, 45, and 91 patients in no, low [< 1.5 μg], and high [≥ 1.5 μg] dose groups, respectively). Effects of vitamin D receptor activator were assessed on the basis of intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels; percent changes from baseline; proportions of patients who achieved target intact parathyroid hormone, corrected calcium, and phosphorus at Weeks 28–30; and adverse drug reactions. Intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels decreased in all groups; phosphorus and fibroblast growth factor-23 levels remained high in the high dose group. In the low and high dose groups, greater proportions of patients achieved the corrected calcium target compared with the no dose group ( p = 0.043). Ratios of intact-to-C-terminal fibroblast growth factor-23 decreased in all groups. In low and high dose groups, hypocalcemia was less common than in the no dose group ( p = 0.014). Evocalcet with concomitant vitamin D receptor activator demonstrated benefits such that more patients achieved the corrected calcium target and exhibited decreased fibroblast growth factor-23 synthesis; the incidence of hypocalcemia also decreased. Clinical trial registration : ClinicalTrials.gov ( NCT02549391 ) and JAPIC (JapicCTI-153013).

Hypercalcemia and hyperphosphatemia often complicate secondary hyperparathyroidism therapy in patients who are receiving dialysis. Unlike vitamin D and calcium, calcimimetic agents target the calcium-sensing receptor. This study reports the safety and effectiveness of the calcimimetic agent cinacalcet in patients receiving dialysis who had uncontrolled hyperparathyroidism. The mean parathyroid hormone values decreased 43 percent with cinacalcet therapy but increased 9 percent with placebo, and the calcium–phosphorus product declined with cinacalcet but not placebo. The safety and effectiveness of a calcimimetic agent in patients receiving dialysis. Secondary hyperparathyroidism is common in patients with chronic kidney disease, affecting most of those who are receiving hemodialysis. 1 , 2 The disorder is characterized by persistently elevated levels of parathyroid hormone and complicated by important disturbances in mineral metabolism. 3 Bone disease is the most widely recognized consequence of secondary hyperparathyroidism. 4 Several reports indicate, however, that alterations in calcium and phosphorus metabolism, as a result of either secondary hyperparathyroidism or the therapeutic measures used to manage it, contribute to soft-tissue and vascular calcification, cardiovascular disease, and the risk of death. 5 – 10 Episodes of hypercalcemia and hyperphosphatemia are often aggravated by the use . . .

Achieving NKF-K/DOQI™ bone metabolism and disease treatment goals with cinacalcet HCl. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI™) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipar™) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca × P) was investigated in subjects on dialysis with secondary HPT. Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca × P levels. Cinacalcet-treated subjects were more likely to achieve a mean iPTH ≤300 pg/mL (31.8 pmol/L) than were control subjects on traditional therapy (56% vs. 10%, P < 0.001). Cinacalcet-treated subjects were more likely to achieve concentrations of serum calcium within 8.4 to 9.5mg/dL (2.10–2.37mmol/L) and serum phosphorus within 3.5 to 5.5mg/dL (1.13–1.78mmol/L) than were control subjects (49% vs. 24% and 46% vs. 33%, P < 0.001 for each). Cinacalcet also improved achievement of Ca × P < 55mg2/dL2 (4.44mmol2/L2) and concurrent achievement of Ca × P < 55mg2/dL2 (4.44mmol2/L2) and iPTH ≤300 pg/mL (31.8 pmol/L) (65% vs. 36% and 41% vs. 6%, P < 0.001 for each). In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca × P.

Aim: The aim of our study was to investigate whether treatment with red yeast rice added with Coenzyme Q10 is associated with changes in endothelial function and arterial stiffness. Methods: This double blind, placebo-controlled, randomized clinical trial was carried out on 40 non-smoker moderately hypercholesterolemic subjects (ClinicalTrial.gov ID NCT02492464). After 4 weeks of diet and physical activity, patients were allocated to treatment with placebo or with an active product containing 10 mg monacolins and 30 mg Coenzyme Q10, to be assumed for 6 months. Endothelial reactivity and arterial stiffness have been measured through the validated Vicorder® device. Results: During monacolin treatment, patients experienced a more favorable percentage change in low density lipoprotein (LDL)-cholesterol (after monacolin treatment: -26.3%; after placebo treatment: +3.4%, p < 0.05). Endothelial reactivity (pulse volume displacement after monacolin treatment: +6.0%; after placebo treatment: -0.3%, p < 0.05), and arterial stiffness (pulse wave velocity (PWV) after monacolin treatment: -4.7%; after placebo: +1.1%, p < 0.05) also significantly improved only after monacolin treatment. Conclusion: The long-term assumption of the tested dietary supplement is associated with an improvement in LDL-cholesterolemia, endothelial reactivity and PWV in moderately hypercholesterolemic subjects.