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    Spironolactone versus placebo in patients undergoing maintenance dialysis - ACHIEVE: an international, parallel-group, randomised controlled trial
    (Elsevier BV, 2025-08)
    Michael Walsh
    ;
    David Collister
    ;
    Martin Gallagher
    ;
    Patrick B Mark
    ;
    Janak R de Zoysa
    Background: Patients undergoing maintenance dialysis for kidney failure are at substantial risk of cardiovascular morbidity and mortality. We aimed to establish if spironolactone reduces heart failure and cardiovascular deaths in these patients. Methods: ACHIEVE was an international, parallel-group, randomised controlled trial done in 143 dialysis programmes in 12 countries. Patients were aged 45 years or older, or aged 18 years or older with a history of diabetes, and were receiving maintenance dialysis for kidney failure for at least 3 months at the time of recruitment. Patients who were able to tolerate and adhere to spironolactone 25 mg daily orally during an open-label run-in were randomly assigned (1:1) to continue spironolactone or matching placebo, using a central computerised block randomisation system (block sizes of 4) stratified by centre. Participants, health-care providers, and those assessing outcomes were masked to group assignment. The primary outcome was a composite of cardiovascular mortality or hospitalisation for heart failure analysed as time-to-event in all randomly assigned participants. The trial was registered at ClinicalTrials.gov, NCT03020303. Findings: After a planned interim analysis of 75% of the expected primary outcome events, the external safety and efficacy monitoring committee recommended the trial be stopped early for futility. From Sept 19, 2017, to Oct 31, 2024, 3689 patients were screened for inclusion, 3565 of whom were enrolled in the open-label run-in phase, and 2538 were randomly assigned to spironolactone (n=1260) or placebo (n=1278). 931 (36·7%) participants were female and 1607 (63·3%) were male. Median follow-up was 1·8 years (IQR 0·85–3·35). The composite primary outcome occurred in 258 participants (10·46 events per 100 patient-years) in the spironolactone group and in 276 participants (11·33 per 100 patient-years) in the placebo group (hazard ratio [HR] 0·92 [95% CI 0·78–1·09]; p=0·35). Death from any cause was similar between groups (HR 0·95 [0·83–1·09]) as was hospitalisation for any cause (HR 0·96 [0·87–1·06]). Interpretation: Among patients receiving maintenance dialysis, spironolactone 25 mg daily orally did not reduce the composite outcome of cardiovascular mortality and hospitalisation due to heart failure compared with placebo. This trial did not identify a benefit of initiating spironolactone in patients receiving maintenance dialysis. Future research should consider alternatives to steroidal mineralocorticoid receptor antagonism to reduce cardiovascular morbidity and mortality in patients receiving maintenance haemodialysis. Funding: The Canadian Institutes of Health Research, The Medical Research Future Fund, The Health Research Council, The British Heart Foundation, Population Health Research Institute/Hamilton Health Sciences Research Institute, St Joseph's Healthcare Hamilton Division of Nephrology, Accelerating Clinical Trials Consortium, Can-SOLVE CKD Network, and the Dalhousie Department of Medicine.
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    Bending responses of graphene nanoplatelets reinforced sandwich cylindrical micro panel with piezoelectric layers
    (Informa UK Limited, 2024-08-04)
    Qian Zhang
    ;
    Mingchao Xie
    ;
    Dianyi Zhou
    ;
    Mostafa Habibi
    ;
    KHORAMI, MAJID  
    There are some inevitable challenges during the manufacturing of reinforced composite structures. Agglomeration of reinforcement and wavy reinforcement are in this category. These phenomena possess remarkable effects on the mechanical behavior of reinforced composite structures. In the current research, the effect of agglomeration and waviness of reinforcements on torsional dynamic characteristics of multi-walled carbon nanotubes (MWCNTs) reinforced composite rods subjected to two various boundary conditions have been evaluated. Three dissimilar cross-section shapes have been considered to understand the effect of cross-section shapes on torsional behavior of MWCNTs-reinforced composite rods. A new form of Halpin-Tsai homogenization model has been exerted to estimate the material properties of composite structures. Additionally, Timoshenko-Gere theory in conjunction with the Hamilton's principle has been employed to derive the partial differential governing equation of MWCNTs-reinforced composite rods. Afterward, the obtained equation was solved using an analytical approach. The precision of the methodology utilized has been evaluated against the results of previous studies documented in the literature. Ultimately, the effects of various significant parameters on the changes in natural torsional frequency have been analyzed and presented in a series of tables and figures. Based on the obtained results, the rectangular rod has the highest torsional frequency and also the effect of MWCNTs’ volume fraction depends on the consideration of waviness and agglomeration factors. At a greater volume fraction of MWCNTs, the agglomeration factor is more effective than the waviness factor and vice versa.