Citations

ABSTRACT Pharmacists play a critical role in optimizing medication use, especially in vulnerable populations such as those with chronic kidney disease (CKD). Despite strong evidence and recent guideline endorsements, many pharmacists continue to rely on the Cockcroft–Gault (C‐G) equation for medication dosing. This opinion paper issues a call to action for the widespread adoption of a race‐free, body surface area–adjusted estimated glomerular filtration rate (eGFR BSAadj ) for medication‐related decision‐making, as endorsed by the 2024 Kidney Disease: Improving Global Outcomes CKD guidelines and the National Kidney Foundation and the American Society of Nephrology Taskforce. Persistent variability in pharmacy practice, institutional protocols, and pharmacy education underscores the need for coordinated change. We urge health systems to integrate eGFR BSAadj into electronic health records and clinical decision support to enhance medication decision‐making; institutions to align protocols with contemporary eGFR‐based prescribing standards; pharmacy educators to contemporize and standardize education on kidney function assessment and medication dosing; and regulatory bodies to update licensure and board examinations. The pharmacy profession must act decisively in order to align with evidence‐based, equitable kidney‐related dosing practices and ensure optimal medication management for all patients.

Introduction Tobacco use is the most significant modifiable risk factor for adverse health outcomes, and early research indicates there are also significant harms associated with vaping. National targets aim to reduce smoking and vaping during pregnancy for Aboriginal and Torres Strait Islander people. While most Aboriginal and Torres Strait Islander people want to quit, cessation is frequently attempted without support, increasing the chance of relapse. Group-based smoking cessation programmes increase quit success by 50%–130% in the general population; however, they have never been evaluated in Aboriginal and/or Torres Strait Islander communities. Methods and analysis The Gulibaa study is an Indigenous-led and community-embedded project that will co-design, implement and evaluate a group-based model of care to support Aboriginal and Torres Strait Islander women to be smoke- and vape-free. Staff of Health Services in New South Wales, Australia, will receive training to deliver a face-to-face group-based smoking and vaping cessation intervention. Aboriginal and/or Torres Strait Islander people who identify as a woman or non-binary, are pregnant or of reproductive age (16 to 49 years), currently smoke or vape at least once per day and are willing to attend the programme are eligible to participate. Up to 500 participants will be recruited. A mixed method evaluation approach will be implemented guided by the RE-AIM framework. Outcomes will include intervention reach, intervention effectiveness (determined primarily by self-reported 7-day point prevalence abstinence at 6 months follow-up), acceptability and feasibility of the intervention, programme fidelity and maintenance and cost effectiveness. Ethics and dissemination Embedding culturally safe support to quit during pregnancy can result in improved outcomes for both mother and child and immediately improve intergenerational health and well-being. Ethics approval has been provided by the Aboriginal Health and Medical Research Council and the University of Newcastle. Study findings will be disseminated to Aboriginal and Torres Strait Islander communities in ways that are meaningful to them, as well as through Aboriginal health services, key national bodies, relevant state and federal government departments. Trial registration number ACTRN12625001050448.

Abstract Two recent studies suggested that the APOE ε4 haplotype was associated with increased α-synuclein pathology in cell and mouse models. Genetic variants in the SNCA region have strong association with Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and idiopathic REM sleep behaviour disorder (iRBD), while APOE is a genetic risk determinant for only DLB. To determine if genetic-level interactions between SNCA and APOE exists that can explain the protein-level association, we investigated the genotypic interaction of APOE and SNCA in cohorts of PD, DLB and iRBD. We analysed genome-wide association study (GWAS) data from 5229 PD patients and 5480 controls, 2610 DLB patients and 1920 controls, and 1055 iRBD patients and 3667 controls. We used logistic regression interaction models across all three cohorts independently between the (i) top GWAS signals of SNCA single nucleotide polymorphisms (SNPs) and APOE haplotypes and (ii) SNP×SNP and three-way SNP interaction across the entire coding region plus 200 kb flanking each gene. No significant interactions were found to be associated with any of the synucleinopathies after correction for multiple testing. Our results do not support a role for genetic interactions between APOE and SNCA across PD, DLB and iRBD. Since the tested genetic variants affect the expression and function of these proteins, it is likely that any interactions between them do not affect the risk of PD, DLB and iRBD.

Immunotherapy has transformed oncology, yet kidney complications increasingly affect outcomes. This review summarizes nephrotoxicity from immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapies, and bispecific T-cell engagers (BiTEs). ICIs remain most used, with acute interstitial nephritis (AIN) as the hallmark lesion, while glomerular diseases and electrolyte abnormalities are less common. CAR-T therapy, though highly effective in hematologic cancers, carries risks of cytokine release syndrome, tumor lysis syndrome, and acute kidney injury (AKI). BiTEs, particularly teclistamab, show higher AKI rates than CAR-T, though mechanisms remain unclear. Early recognition, tailored management, and multidisciplinary collaboration are essential to ensure safe therapy and preserve kidney function.

Abstract Berubicin is a unique anthracycline engineered to have the ability to cross the blood-brain barrier (BBB). Herein we present the primary results from a large global trial of Berubicin vs. Lomustine randomizing patients with progressive disease after only one prior therapy, all being IDH WT and stratified for MGMT methylation. The primary endpoint was overall survival (OS), secondary endpoints included progression-free survival (PFS), overall response rates (ORR) of complete (CR) and partial (PR) responses. Eligibility was determined radiologically by central reads based on progression of disease, and in 2.5 years 252 patients were enrolled with 168 randomized to Berubicin and 84 to Lomustine. Safety assessment showed that Berubicin was well tolerated and myelosuppressive side effects were manageable with growth factors. Importantly, although anthracyclines are known to cause cardiotoxicity, evaluation with frequent troponin measurements, ECG and ECHO testing revealed no evidence of impact on cardiac function. The primary endpoint, OS, showed Berubicin and Lomustine had similar outcomes. Median overall survival for Berubicin was 8.7 months (6.7, 9.9) and for Lomustine was 9.3 months (6.7, 10.7) with a Hazard Ratio of 1.13 (p = 0.5351). PFS of Berubicin and Lomustine were also similar (1.5 vs, 1.6 months). There were no responses in the Lomustine arm and stable disease in 35.2% of patients while Berubicin had a response rate of 5.8% (PR) and stable disease of 33.6% with a combined disease control rate (DCR) of 39.4%. Additional data will be presented and discussed. Anthracyclines are characteristically used in combination for systemic therapy (e.g. leukemia, lymphoma, certain breast cancers), so there is promise that combination therapy will be the next pertinent approach to treatment of GBM. Evaluation of activity against a range of pediatric brain tumors is being pursued and preliminary results will be presented at the time of the conference.

Abstract Background The associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood. Methods We investigated associations of genetic susceptibility to type 2 diabetes (T2D), 8 T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242 283 cases, 1 569 734 controls), T1D (18 942 cases, 501 638 controls), and PDAC (10 244 cases and 360 535 controls) in individuals of European ancestry. Results Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI = 1.05 to 1.15), particularly the T2D obesity (OR = 1.28; 95% CI = 1.15 to 1.42) and lipodystrophy (OR = 1.25; 95% CI = 1.03 to 1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI = 0.99 to 1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10−8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10−4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions. Conclusions Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.

Background/Objective: Hypertension is the most prevalent chronic disease in primary care and a leading cause of cardiovascular morbidity and mortality. Despite existing guidelines, therapeutic inertia and suboptimal control persist. Large language models (LLMs) offer a potential valuable addition to augment clinical decision-making, yet their reliability for guideline-driven tasks remains unverified. This study evaluated the accuracy and safety of hypertension management recommendations generated by three LLMs compared to expert responses. Methods: Fifty-one clinical vignettes representing 17 core hypertension management concepts were constructed by hypertension experts. Each case was submitted to three LLMs (GPT-4, Gemini, MedLM) and a hypertension expert also wrote the “gold standard” answers. Three blinded expert reviewers rated each response on a 4-point accuracy scale, a binary safety (safe/unsafe) scale, and attempted to identify the source (LLM vs. expert) providing the response. Ratings were analyzed using mean scores, percentages of accurate and safe responses, and inter-rater agreement. Results: GPT-4 had the highest accuracy (83%) and safety (86%) scores among LLMs but remained inferior to expert responses (92% accuracy, 93% safety). Gemini and MedLM performed significantly worse (accuracy: 64% and 35%; safety: 73% and 39%, respectively). GPT-4 generated the most guideline-concordant responses (46%) among the three LLMs (Gemini 35%, MedLM 14%), but remains lower than experts’ responses (68%). Evaluators misidentified LLM responses as expert-written in 10 to 25% of cases, particularly with GPT-4. Inter-rater reliability for accuracy ratings was highest for expert-generated responses (ICC 0.81), with progressively lower agreement for GPT-4 (0.76), Gemini (0.70), and MedLM (0.68). A similar pattern was observed for safety and source discrimination ratings. The agreement was strongest for safety assessments and weakest for source discrimination. Conclusion: Among three tested LLMs, GPT-4 demonstrated closer agreement to expert decisions thereby showing greater potential for supporting hypertension management. However, current LLMs’ versions frequently produce inaccurate or unsafe recommendations and remain inferior to expert judgment. Human-in-the-loop supervision remains essential when deploying LLMs for clinical decision-making.