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The unprecedented demand placed on healthcare systems from the COVID-19 pandemic has forced a reassessment of clinical trial conduct and feasibility. Consequently, the Australasian Kidney Trials Network (AKTN), an established collaborative research group known for conducting investigator-initiated global clinical trials, had to efficiently respond and adapt to the changing landscape during COVID-19. Key priorities included ensuring patient and staff safety, trial integrity and network sustainability for the kidney care community. New resources have been developed to enable a structured review and contingency plan of trial activities during the pandemic and beyond.

This randomized trial assessed whether urate-lowering treatment with allopurinol could attenuate eGFR decline in at-risk patients with stage 3 or 4 chronic kidney disease. Allopurinol did not slow the decline in eGFR as compared with placebo.

Background Delayed graft function, the requirement for dialysis due to poor kidney function post-transplant, is a frequent complication of deceased donor kidney transplantation and is associated with inferior outcomes and higher costs. Intravenous fluids given during and after transplantation may affect the risk of poor kidney function after transplant. The most commonly used fluid, isotonic sodium chloride (0.9% saline), contains a high chloride concentration, which may be associated with acute kidney injury, and could increase the risk of delayed graft function. Whether using a balanced, low-chloride fluid instead of 0.9% saline is safe and improves kidney function after deceased donor kidney transplantation is unknown. Methods BEST-Fluids is an investigator-initiated, pragmatic, registry-based, multi-center, double-blind, randomized controlled trial. The primary objective is to compare the effect of intravenous Plasma-Lyte 148 (Plasmalyte), a balanced, low-chloride solution, with the effect of 0.9% saline on the incidence of delayed graft function in deceased donor kidney transplant recipients. From January 2018 onwards, 800 participants admitted for deceased donor kidney transplantation will be recruited over 3 years in Australia and New Zealand. Participants are randomized 1:1 to either intravenous Plasmalyte or 0.9% saline peri-operatively and until 48 h post-transplant, or until fluid is no longer required; whichever comes first. Follow up is for 1 year. The primary outcome is the incidence of delayed graft function, defined as dialysis in the first 7 days post-transplant. Secondary outcomes include early kidney transplant function (composite of dialysis duration and rate of improvement in graft function when dialysis is not required), hyperkalemia, mortality, graft survival, graft function, quality of life, healthcare resource use, and cost-effectiveness. Participants are enrolled, randomized, and followed up using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Discussion If using Plasmalyte instead of 0.9% saline is effective at reducing delayed graft function and improves other clinical outcomes in deceased donor kidney transplantation, this simple, inexpensive change to using a balanced low-chloride intravenous fluid at the time of transplantation could be easily implemented in the vast majority of transplant settings worldwide. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12617000358347 . Registered on 8 March 2017. ClinicalTrials.gov: NCT03829488 . Registered on 4 February 2019.

IntroductionPatients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate improved treatment strategies and patient-level outcomes, but at present there are few large, randomised controlled clinical trials to guide management. Positive associations between serum phosphate and fibroblast growth factor 23 (FGF-23) and cardiovascular morbidity and mortality in both the general and CKD populations have resulted in clinical guidelines suggesting that serum phosphate be targeted towards the normal range, although few randomised and placebo-controlled studies have addressed clinical outcomes using interventions to improve phosphate control. Early preventive measures to reduce the development and progression of vascular calcification, left ventricular hypertrophy and arterial stiffness are crucial in patients with CKD.Methods and analysisWe outline the rationale and protocol for an international, multicentre, randomised parallel-group trial assessing the impact of the non-calcium-based phosphate binder, lanthanum carbonate, compared with placebo on surrogate markers of cardiovascular disease in a predialysis CKD population—the IM pact of P hosphate R eduction O n V ascular E nd-points (IMPROVE)-CKD study. The primary objective of the IMPROVE-CKD study is to determine if the use of lanthanum carbonate reduces the burden of cardiovascular disease in patients with CKD stages 3b and 4 when compared with placebo. The primary end-point of the study is change in arterial compliance measured by pulse wave velocity over a 96-week period. Secondary outcomes include change in aortic calcification and biochemical parameters of serum phosphate, parathyroid hormone and FGF-23 levels.Ethics and disseminationEthical approval for the IMPROVE-CKD trial was obtained by each local Institutional Ethics Committee for all 17 participating sites in Australia, New Zealand and Malaysia prior to study commencement. Results of this clinical trial will be published in peer-reviewed journals and presented at conferences.Trial registration numberACTRN12610000650099.

Biomedicine today is experiencing a shift towards decentralized data collection, which promises enhanced reproducibility and collaboration across diverse laboratory environments. This inter-laboratory study evaluates the performance of biocytometry, a method utilizing engineered bioparticles for enumerating cells based on their surface antigen patterns. In centralized and aggregated inter-lab studies, biocytometry demonstrated significant statistical power in discriminating numbers of target cells at varying concentrations as low as 1 cell per 100,000 background cells. User skill levels varied from expert to beginner capturing a range of proficiencies. Measurement was performed in a decentralized environment without any instrument cross-calibration or advanced user training outside of a basic instruction manual. The results affirm biocytometry to be a viable solution for immunophenotyping applications demanding sensitivity as well as scalability and reproducibility and paves the way for decentralized analysis of rare cells in heterogeneous samples.

Data on hypothalamic-pituitary (HP) disorders in systematically evaluated childhood cancer survivors are limited. To describe prevalence, risk factors, and associated adverse health outcomes of deficiencies in GH deficiency (GHD), TSH deficiency (TSHD), LH/FSH deficiency (LH/FSHD), and ACTH deficiency (ACTHD), and central precocious puberty (CPP). Retrospective with cross-sectional health outcomes analysis. Established cohort; tertiary care center. Participants (N = 3141; median age, 31.7 years) were followed for a median 24.1 years. Multivariable logistic regression was used to calculate ORs and 95% CIs for associations among HP disorders, tumor- and treatment-related risk factors, and health outcomes. The estimated prevalence was 40.2% for GHD, 11.1% for TSHD, 10.6% for LH/FSHD, 3.2% for ACTHD, and 0.9% for CPP among participants treated with HP radiotherapy (n = 1089), and 6.2% for GHD, and <1% for other HP disorders without HP radiotherapy. Clinical factors independently associated with HP disorders included HP radiotherapy (at any dose for GHD, TSHD, LH/FSHD, >30 Gy for ACTHD), alkylating agents (GHD, LH/FSHD), intrathecal chemotherapy (GHD), hydrocephalus with shunt placement (GHD, LH/FSHD), seizures (TSHD, ACTHD), and stroke (GHD, TSHD, LH/FSHD, ACTHD). Adverse health outcomes independently associated with HP disorders included short stature (GHD, TSHD), severe bone mineral density deficit (GHD, LH/FSHD), obesity (LH/FSHD), frailty (GHD), impaired physical health-related quality of life (TSHD), sexual dysfunction (LH/FSHD), impaired memory, and processing speed (GHD, TSHD). HP radiotherapy, central nervous system injury, and, to a lesser extent, chemotherapy are associated with HP disorders, which are associated with adverse health outcomes.

Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM 10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb 2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb 2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM 10 metal components of air pollution, that yields the generation of arrhythmias.

Background and Objectives In the absence of effective pharmacotherapy, there is an urgent need to test evidence-based dementia care interventions using pragmatic trial approaches. We present results from a study in which an evidence-based, nonpharmacologic intervention for persons living with Alzheimer’s disease and related dementia (ADRD) and their informal caregivers, Care of Persons with Dementia in their Environments (COPE), was tested in a Medicaid and state revenue-funded home and community-based service (HCBS) program. Research Design and Methods Using pragmatic trial design strategies, persons living with ADRD and their caregivers were randomly assigned as dyads to receive COPE plus usual HCBS (COPE; n = 145 dyads) or usual HCBS only (Usual Care or UC; n = 146 dyads). Outcomes were measured prerandomization, and 4 and 12 months postrandomization. Outcomes for persons living with ADRD included functional independence, activity engagement, self-reported quality of life, and behavioral and psychological symptoms. Caregiver outcomes included perceived well-being, confidence using dementia management strategies, and degree of distress caused by behavioral and psychological symptoms. Results After 4 months, caregivers receiving COPE reported greater perceived well-being (least squares mean = 3.2; 95% CI: 3.1–3.3) than caregivers receiving UC (3.0; 2.9–3.0; p < .001), and persons living with ADRD receiving COPE, compared to those receiving UC, showed a strong trend toward experiencing less frequent and less severe behavioral and psychological symptoms (9.7; 5.2–14.2 vs 12.7; 8.3–17.1; p = .07). After 12 months, persons living with ADRD receiving COPE were more engaged in meaningful activities (2.1; 2.0–2.1 vs 1.9; 1.9–2.0; p = .02) than those receiving UC. Discussion and Implications Embedding COPE in a publicly funded HCBS program yielded positive immediate effects on caregivers’ well-being, marginal positive immediate effects on behavioral and psychological symptoms, and long-term effects on meaningful activity engagement among persons living with ADRD. Findings suggest that COPE can be effectively integrated into this service system, an important step towards widespread adoption. Clinical Trials Registration Number NCT02365051.

Educators must understand current practices and gaps in knowledge regarding environmental sustainability in simulation education to reduce the environmental impact of plastic waste while still maintaining fidelity in simulation education. Therefore, a scoping review was conducted to answer the PICO question, “In healthcare institutions and hospitals, what are the environmentally sustainable practices that can be translated into simulation labs as best practice?” Fourteen studies were identified through a search of seven databases, critically appraised, and analyzed. Three key themes emerged: (1) the 5 R’s, (2) getting people motivated, and (3) larger external collaboration. These themes highlight practical strategies and motivational factors for sustainable practices. An expanded 5 R’s framework (reduce, reuse, recycle, research, and rethink) was introduced to guide a holistic approach. The literature highlights the importance of education, stakeholder engagement, and clearly defined standards as key drivers for motivating individuals and teams to engage in sustainable behaviors. These efforts are most effective when supported by interdisciplinary collaboration, regulatory frameworks, national policies, and technological innovation. Sustainability initiatives should extend beyond individual institutions to foster broader systemic change.

Pyrenoid-based CO 2 -concentrating mechanisms (pCCMs) turbocharge photosynthesis by saturating CO 2 around Rubisco. Hornworts are the only land plants with a pCCM. Owing to their closer relationship to crops, hornworts could offer greater translational potential than the green alga Chlamydomonas , the traditional model for studying pCCMs. Here we report a thorough investigation of a hornwort pCCM using the emerging model Anthoceros agrestis . The pyrenoids in A. agrestis exhibit liquid-like properties similar to those in Chlamydomonas , but they differ by lacking starch sheaths and being enclosed by multiple thylakoids. We found that the core pCCM components in Chlamydomonas , including BST, LCIB and CAH3, are conserved in A. agrestis and probably have similar functions on the basis of their subcellular localizations. The underlying chassis for concentrating CO 2 might therefore be shared between hornworts and Chlamydomonas , and ancestral to land plants. Our study presents a spatial model for a pCCM in a land plant, paving the way for future biochemical and genetic investigations. Hornworts are the only land plants with a pyrenoid-based CO 2 -concentrating mechanism. This study presents evidence that some of the key components in algal pyrenoid-based CO 2 -concentrating mechanisms are conserved in hornworts and probably serve similar functions.