Effects of a 24-week intervention with freeze-dried blueberries on brain health in older adults: A randomized double-blind, placebo-controlled trial.

Safety, Pharmacokinetics, and Pharmacodynamics of SHR6508, a Calcium-Sensing Receptor Agonist, in Maintenance Hemodialysis Patients With Secondary Hyperparathyroidism: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 1 Study.

Triage administration of sucrose for gastroenteritis in children; a randomized controlled trial.

Efficacy and safety of the Chinese herbal medicine Yiaikang capsule in treating AIDS: a randomized, double-blind, controlled trial.

Objective: To evaluate the antiviral effect, clinical efficacy, safety and tolerability of pixavir marboxil in adult patients with acute, uncomplicated influenza. Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging phase Ⅱ clinical trial. Eligible participants were adults aged 18 to 64 years with acute, uncomplicated influenza, presenting within 48 hours of symptom onset with an axillary temperature ≥38.0 ℃ and ≥1 moderate-to-severe influenza symptom, who were neither severely ill nor at high risk for severe disease. Exclusion criteria included known hypersensitivity and recent antiviral use or vaccination. Participants were centrally randomized (1∶1∶1∶1) to oral pixavir marboxil (40 mg, 80 mg, or 40+40 mg) or placebo. Randomization was stratified by body weight (<80 kg vs.≥80 kg) and baseline influenza symptom score (<12 points vs.≥12 points). Rescue medications were permitted as clinically indicated during follow-up. The primary endpoint was the time to influenza virus RNA negativity by RT-PCR (time from first dose to the first RNA measurement below the lower limit of detection). Secondary endpoints included the time to relief of all influenza symptoms (severity scores of 0 or 1 for all 7 symptoms, sustained for ≥21.5 hours), time to cessation of infectious viral shedding by virus titer, time to resolution of fever, time to recovery to pre-influenza health status, changes from baseline in EQ-5D-5L scores, and the incidence of adverse events. Statistical analyses were performed using SAS 9.4. Efficacy was analyzed in the intention-to-treat infected (ITTI) and intention-to-treat (ITT) populations. Time-to-event data, including the primary endpoint, were estimated using the Kaplan-Meier method and compared between groups using the stratified Peto-Prentice generalized Wilcoxon test. Categorical data were analyzed using the Fisher's exact test or the Mantel-Haenszel test. Results: A total of 202 patients with influenza B were enrolled. In the ITTI population (107 cases), the median time to influenza virus RNA negativity was 28.2 h (95%CI: 19.73-43.88) in the 80 mg group, 35.5 h (95%CI: 23.43-45.05) in the 40 mg+40 mg group, and 42.4 h (95%CI: 22.60-57.53) in the 40 mg group, compared with 48.1 h (95%CI: 23.25-83.67) in the placebo group; between-group differences were not statistically significant (all P>0.05). The median times to cessation of infectious viral shedding by virus titer (TCID50) for the pixavir marboxil were [80 mg: 19.5 h (95%CI: 15.17-22.80); 40 mg: 22.6 h (95%CI: 14.72-44.85); 40 mg+40 mg: 23.1 h (95%CI: 18.63-26.98)] were versus the 45.8 h (95%CI: 20.20-68.57) in the placebo group; only the 80 mg group reached a statistically significant difference (P=0.027). In the ITT population (200 cases), pixavir marboxil 40 mg significantly shortened the median time to relief of all influenza symptoms compared to the placebo group [37.7 h (95%CI: 22.23-49.33) vs. 68.2 h (95%CI: 47.70-97.17), P=0.009], whereas the 80 mg group showed only a non-significant trend toward shortening 45.8 h [(95%CI: 34.50-62.67) vs. 68.2 h]. The median time to resolution of fever was significantly reduced in both the 40 mg [24.1 h (95%CI: 19.40-30.97)] and 80 mg [22.9 h (95%CI: 19.48-27.00)] groups compared with placebo [44.0 h (95%CI: 34.67-50.85)], with reductions of 19.9 h and 21.1 h, respectively (both P<0.001). The median time to recovery to pre-influenza health status was significantly shortened in the 80 mg [127.7 h (95%CI: 99.65-168.77)] and 40 mg [152.1 h (95%CI: 105.55-171.83)] groups compared with placebo [198.1 h (95%CI: 167.10-210.52)], with reductions of 70.4 h and 46.0 h, respectively (both P<0.05). The incidence of adverse events was comparable across groups: 13.5% (40 mg), 18.0% (80 mg), 20.4% (40 mg+40 mg), and 20.4% (placebo). No baseline or treatment-emergent resistance mutations were detected. Conclusion: Single-dose pixavir marboxil regimens demonstrated potential benefits in improving infectivity-related virologic measures and alleviating clinical symptoms in adults with uncomplicated influenza, with favorable overall tolerability. These findings provide a basis for subsequent confirmatory clinical trials.

Effects of a 6-week subcutaneous infusion of native GIP alone or as add-on to semaglutide in people with type 2 diabetes: a single-centre, double-blind, parallel-group, randomised, placebo-controlled trial.

This study investigated the efficacy of thiazolidinediones in mitigating diet-induced obesity and associated glucose intolerance in canines in vivo. We used a multitechnique approach and compared the results related to 1) fasting metabolites, hormones, and lipides; 2) oral glucose tolerance test (OGTT), and 3) hyperinsulinemic euglycemic (HIEG) clamps in 24 healthy dogs that were then fed a high-fat diet and assigned to a placebo group (n = 8) or received a daily dose of pioglitazone group (n = 16) for 56 days. The animals were studied before and after treatment, acting as their own controls, and we used a principal component analysis to combine the results obtained for the three different techniques. Both groups experienced weight gain, with 12% and 14% increases in the placebo and pioglitazone groups, respectively. The fasting level of free fatty acids was increased in both placebo (+17.5%) and pioglitazone groups (+7.7%), as were the insulin levels (+27% and 35%, respectively, in placebo and pioglitazone), but fasting glucose levels were reduced slightly in both (-2.7 and -2.9 mg/dL, respectively). Pioglitazone increased fasting adiponectin levels by 54% between day -1 and day 56. OGTTs revealed a significantly better glucose tolerance in the pioglitazone treatment group compared with the placebo group, as the level of insulin secreted during the OGTT was normalized. HIEG clamps demonstrated that, in the placebo group, glucose infusion rate and glucose utilization decreased in response to the diet, but this effect was prevented by pioglitazone. In conclusion, these findings show that pioglitazone is beneficial in preventing the consequences of dietary metabolic stress and overfeeding in canines.NEW & NOTEWORTHY This study validates the efficacy of the thiazolidinediones (TZD) drug pioglitazone in a fat-fed canine model. Using a novel principal component analysis integrating multimodal data (fasting metabolites, OGTT, and clamp results), we demonstrate that pioglitazone effectively reverses diet-induced glucose intolerance and significantly improves insulin sensitivity. Mechanistically, this improvement is driven by adiponectin action. These findings provide strong evidence supporting TZD use as a prophylactic tool for mitigating metabolic syndrome.

Efficacy and safety of enpatoran, a Toll-like receptor 7/8 inhibitor, in patients with skin manifestations of cutaneous lupus erythematosus or systemic lupus erythematosus: findings from Cohort A of a multicentre, international, double-blind, placebo-controlled, dose-finding phase 2 trial.

Augmentation of collateral circulation is an alternative method to improve cerebral hypoperfusion when revascularization is not suitable. DL-3-n-butylphthalide (NBP) has been shown to enhance cerebral collateral circulation and improve cerebral blood flow (CBF) in previous studies. The objective of this study was to explore the effect of NBP on cerebral hemodynamic impairment due to atherosclerotic stenosis in internal carotid system. This was a double-blind, placebo-controlled, randomized clinical trial conducted in 38 Chinese hospitals between 14 January 2022, and 11 April 2024. Eligible participants were aged 35-85 years with ≥70% stenosis in unilateral internal carotid artery or middle cerebral artery, accompanied by cerebral hypoperfusion and no recent cerebral ischemic events. The patients were randomly assigned in a 1:1 ratio to a treatment group receiving 600 mg NBP daily or a placebo group receiving an ineffective dose of NBP daily for 4 weeks. The cerebral perfusion was assessed by computed tomography perfusion. The grades of cerebral perfusion change from baseline to 12 weeks were classified into amelioration, stabilization, and deterioration. The primary efficacy outcome was the percentage of patients achieving CBF amelioration. Of 485 enrolled patients (median age 63 years, 66.6% men), 244 were assigned to the NBP group and 241 to the placebo group. At the end of follow-up, 204 in the NBP group and 212 in the placebo group completed second cerebral perfusion. NBP group had 113 (55.4%) patients with CBF amelioration in stenotic territory and placebo group had 93 (43.9%) comparable patients at 12 weeks (risk ratio 1.32; 95% confidence interval 1.08-1.61; p=0.006). For cerebral hypoperfusion from atherosclerotic stenosis in internal carotid system, NBP treatment resulted in a higher proportion of patients achieving CBF amelioration than placebo. chictr.org.cn: ChiCTR2100053112.

The addition of a glycopeptide antimicrobial to cephalosporin therapy has been reportedly adopted in practice to prevent surgical site infections (SSIs). We conducted an economic evaluation from the healthcare sector perspective to assess the cost-effectiveness of adding vancomycin to cefazolin prophylaxis in patients undergoing arthroplasty. Data were collected over 180 days in a randomised controlled trial conducted at 11 hospitals in Australia, involving 2044 patients assigned to vancomycin and 2069 to placebo, both in addition to cefazolin. Health utilities were measured using EQ-5D-3L at baseline and 30 days, 90 days, and 180 days post-surgery. Healthcare costs (Australian dollars [AU$]; 2022 values) were estimated using Medicare claim data and hospital administrative records. Bootstrap was used to estimate means and 95% confidence intervals (CIs) of healthcare costs and quality-adjusted life years (QALYs). The net monetary benefit framework was used to construct a cost-effectiveness acceptability curve. Over 180 days, 96 SSIs occurred in the vancomycin group, and 79 in the placebo group. Mean QALYs were 0.392 (95% CI 0.389-0.395) in the vancomycin group and 0.394 (95% CI 0.391-0.397) in the placebo group. Mean total healthcare costs were AU$5184 (95% CI 4926-5480) in the vancomycin group and AU$5018 (95% CI 4772-5293) in the placebo group. Using willingness-to-pay and willingness-to-accept thresholds from AU$0 to AU$3,000,000, the probability of vancomycin being not cost-effective ranged from 0.79 to 0.87. Adding vancomycin to cephazolin prophylaxis in arthroplasty is most likely not cost-effective. Omitting vancomycin could lead to substantial annual savings for the healthcare sector without compromising health outcomes.

To investigate if providing additional parenteral amino acids to extremely low birthweight (ELBW) infants improves neurocognitive function, lean mass, and muscle strength at early school age, without adverse effects on blood pressure and general health. Multicenter, 2-arm parallel, double-blinded randomized trial of an additional 1 g/d of parenteral amino acids for 5days after birth or placebo (1:1 ratio), with follow-up at 6 to 7years old' corrected age. The primary outcome was survival free of neurocognitive impairment, defined as a standard score more than 1 SD below the age-corrected mean in 1 or more National Institutes of Health Toolbox cognitive and motor tests. Fifteen secondary outcomes included measures of motion perception, numeracy, body size and composition, blood pressure, and emotional-behavioral and psychosocial health. Of 309 eligible children, 280 (153 [55%] girls) were assessed at school age. The proportion surviving without neurocognitive impairment was similar between the amino acid and placebo groups (21% vs 23%; adjusted risk difference [aRD], -5.0; 95% CI, -12.8 to 2.7; P = .21). Children in the amino acid group had lower muscle strength than placebo group (relative handgrip strength z-score: mean, -0.73 [SD, 1.01] vs mean, -0.33 [SD, 1.17]; adjusted mean difference, -0.39; 95% CI, -0.65 to -0.13) and may have had increased risk of low psychosocial functioning (26% vs 18%; aRD, 10.7; 95% CI, -1.3 to 22.6). Other secondary outcomes were similar between groups. In ELBW infants, providing an additional 1 g/d of parenteral amino acids for 5days after birth has little to no effect on survival without neurocognitive impairment at school age and may have adverse effects on strength and psychosocial functioning.

The impact of timing on bright light therapy: Alleviating anhedonia and circadian rhythm disturbances in depression patients: a randomized controlled trial.

To assess the impact of omega-3 fatty acid (O3FA) supplements on tear inflammatory cytokines in dry eye patients with an omega-3 index below 4%. This randomized controlled study involved 102 dry eye patients with an omega-3 index below 4%. Participants received either four capsules of O3FAs (325 mg eicosapentaenoic acid, 175 mg docosahexaenoic acid) or a placebo containing olive oil twice daily for 6 months. Patients were evaluated at baseline and 1, 3, and 6 months. The primary outcome measured changes in tear cytokines (IL-1β, IL2, IL4, IL5, IL6, IL8, IL10, IF-γ, and TNF-α). Secondary outcomes included improvements in dry eye symptoms, Nelson grade, goblet cell density, Schirmer test values, and tear film breakup time. Group means (pretreatment, 1, 3, and 6 months) were compared using repeated measure analysis of variance. At baseline, impression cytology revealed that mRNA levels of IL-1β, IL-6, IL-8, and TNF-α were elevated by 1.6- to 2.4-fold in the O3FA group and 1.74 to 2.6-fold in the placebo group ( P = 0.123). The O3FA group experienced a statistically significant reduction ( P < 0.05) in tear cytokines. This group showed a 60% increase in the omega-3 index at 6 months, indicating high adherence to treatment. The dry eye symptom score, goblet cell density, and Nelson grade improved significantly in the O3FA group. However, these changes were not significant in the placebo group. This study underscores the potential advantages of O3FA supplementation in decreasing tear inflammatory cytokines in dry eye patients with an omega-3 index below 4%.

Atorvastatin and left ventricular strain during anthracycline-based chemotherapy.

Repurposing leflunomide and hydroxychloroquine to treat Sjögren's disease (RepurpSS-II): a randomised, double-blind, placebo-controlled, phase 2b trial.

Efficacy and safety of branebrutinib (BMS-986195), an irreversible Bruton's tyrosine kinase inhibitor, for the treatment of rheumatoid arthritis: a phase 2a, randomised, double-blind, placebo-controlled study.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors provide cardiovascular and renal protection in type 2 diabetes and chronic kidney disease (CKD). Although both excess and restricted sodium intake are linked to adverse outcomes, the interaction of sodium intake with SGLT2 inhibitors has not been explored. This study aimed to examine how dietary sodium intake affects cardiorenal outcomes and whether canagliflozin modifies these effects. A post hoc analysis of the CREDENCE trial (median follow-up 2.6 years) was conducted in individuals with type 2 diabetes and CKD randomised to canagliflozin 100 mg or placebo. Using a validated formula, we estimated daily sodium intake from urine in 2573 participants, divided into low-normal sodium (LNS; n=1286) and high sodium (HS; n=1287) groups. Outcomes included the following: cardiovascular death or hospitalisation for heart failure; heart failure alone; a composite renal outcome; and all-cause death. Cox models were adjusted for confounders. Sodium intake was additionally analysed as a continuous variable to assess non-linearity. In the placebo group, LNS intake increased the risk of heart failure/cardiovascular death vs HS (adjusted HR [adjHR] 1.56 [95% CI 1.10, 2.23]). Canagliflozin significantly reduced this risk in the LNS group (adjHR 0.48 [95% CI 0.33, 0.70]) but not in the HS group (adjHR 1.05 [95% CI 0.73, 1.53]). Similar patterns were seen for heart failure alone. Sodium intake had no effect on renal outcomes, while canagliflozin reduced renal risk in both the LNS group and the HS group. Neither sodium intake nor canagliflozin influenced all-cause mortality. Continuous modelling revealed a near-linear rise in heart failure/cardiovascular death risk as sodium intake decreased in placebo recipients, while this gradient was flattened with canagliflozin. In individuals with type 2 diabetes and CKD, LNS intake increases the risk of heart failure and cardiovascular death, while renal outcomes are unaffected by sodium intake. Canagliflozin mitigates the increased cardiovascular risk in individuals with LNS intake, while offering renal protection irrespective of dietary sodium. Clinicaltrial.gov NCT02065791.

This study aimed to evaluate the efficacy and safety of mufemilast, a novel small-molecule selective phosphodiesterase 4 (PDE4) inhibitor, in patients with Behçet's syndrome (BS). Patients diagnosed with BS according to the International Diagnostic (Classification) Criteria for Behçet's Disease 2013 and with active oral ulcers were eligible. Patients were randomly assigned to mufemilast (45 mg or 60 mg) or placebo, administered orally twice daily for 12 weeks. The primary endpoint was the area under the curve (AUC) for the number of oral ulcers from baseline to week 12. Safety was measured in all patients who received at least 1 dose of the study drug (ClinicalTrials: NCT04609397). Ninety patients were randomly assigned to the mufemilast 45 mg, 60 mg, or placebo groups (29, 31, and 30, respectively). The least-squares mean difference in AUC0-12 for oral ulcers between the 45 mg and 60 mg groups and the placebo was -104.8 (95% CI, -156.3 to -53.2; P < .001) and -142.5 (95% CI, -192.4 to -92.7; P < .001), respectively. The visual analogue pain scores and time to ulcer-free remission were significantly improved with mufemilast (P < .001). PDE4-related side effects were transient and resolved spontaneously, and discontinuation rates were low (7% for 45 mg, 7% for 60 mg, and 3% for placebo). No serious adverse events were reported related to the drug. Among patients with oral ulcers associated with BS, mufemilast significantly reduced the number of oral ulcers, improved pain scores, and induced significantly more ulcer-free remissions compared with placebo, with an acceptable safety profile.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has emerged as an effective lipid-lowering strategy, particularly for patients with hypercholesterolemia not adequately managed with statins. Ongericimab is a novel monoclonal antibody targeting PCSK9. In this meta-analysis, we aim to evaluate the efficacy and safety of ongericimab in Chinese patients with hypercholesterolemia. A comprehensive literature search was conducted on PubMed, Embase, Scopus, and ClinicalTrials.gov from inception to November 2025, to identify studies assessing the lipid-lowering effects of ongericimab. Effect estimates and 95% confidence intervals (CIs) were calculated using a random-effects model. Five RCTs (n = 1415; mean age 57.65 ± 10.94 years; 55.7% male) were included. Ongericimab significantly reduced LDL-C by approximately 71%, Lp(a) by 48%, ApoB by 60%, total cholesterol by 47%, and non-HDL-C by 65%. Subgroup analysis revealed dose-dependent effects for LDL-C, ApoB, TC, and non-HDL-C (p < 0.05), while Lp(a) reduction remained consistent across doses (p = 0.75). At the 150 mg dose, ongericimab also increased HDL-C by 10% and ApoA1 by 8%, and reduced triglycerides (TGs) by 23%. Adverse events were comparable between ongericimab and placebo groups. Ongericimab reduces LDL-C and other atherogenic lipoproteins in Chinese patients with hypercholesterolemia, with a tolerability profile comparable to placebo. These findings support its potential role as an adjunct therapy for patients who do not meet LDL-C targets with statins. PROSPERO identifier no. CRD420251086724.

Post Hoc Analysis of a Phase 2 Randomized Trial of Pemafibrate in Metabolic Dysfunction-associated Steatotic Liver Disease: Associations With Platelet Count, Liver Stiffness, and Spleen Volume.