Citations

Background The development and evaluation of anti-amyloid beta monoclonal antibodies (mAbs) for the treatment of Alzheimer’s disease have been accompanied by extensive ethical debate spanning clinical trials, regulatory processes, prescribing practices, and healthcare delivery. This scoping review examined literature published between 2006 and 2026 to identify and clarify the landscape of ethical considerations surrounding the implementation, prescribing, and delivery of anti-amyloid mAbs across both research and clinical settings. Methods We searched PubMed, Scopus, Web of Science, Embase, and Ovid EBM Reviews (including CENTRAL and CDSR) from 2006 to March 2026 using a structured search strategy. Eligible publications focused on ethical issues associated with the clinical translation of anti-amyloid mAbs. Two reviewers independently screened titles, abstracts, and full-text articles, with duplicate extraction performed on an initial subset of publications. The review was conducted using JBI guidance and reported according to PRISMA-ScR. Results We identified 84 publications from 23 countries published between 2014 and 2026, including 12 original research studies, 1 systematic review, and 71 commentaries, narrative reviews, legal analyses, or practice guidelines. Analysis identified 32 subthemes, which were synthesized into 7 overarching themes: (1) beneficence and nonmaleficence, (2) respect for persons, (3) equity and accessibility, (4) evidence and trial integrity, (5) governance and stewardship, (6) relational and social impacts, and (7) health system readiness and sustainability. Among the 32 subthemes, uncertain clinical benefit and risk of harm (both within the beneficence and nonmaleficence theme) were discussed most frequently within the literature, each appearing in 61 publications. Conclusions The biomedical literature documents a broad range of ethical considerations relating to anti-amyloid mAbs. Despite this growing literature, it is primarily based on commentary, with few empirical studies, and even fewer incorporating the perspectives of patients, families, and clinicians. Doing so may add further context and nuance to ethical discussion about mAbs in the years ahead.

ABSTRACT Introduction Sustaining interventions implemented as part of pragmatic clinical trials requires proactive planning, but how to approach this process remains understudied. The Non‐pharmacological Options in Hospital‐based and Rehabilitation pain Management stepped‐wedge cluster‐randomized pragmatic trial tested an electronic health record‐based educational bundle (known as the Healing After Surgery [HAS] initiative) that encouraged the incorporation of non‐pharmacological pain care in perioperative pain management. The HAS initiative was implemented in multiple surgical practices and hospital sites. One year prior to trial completion, a sustainment committee was established to support the transition of intervention components to clinical ownership and to support posttrial sustainment of the HAS initiative. Methods We reviewed meeting minutes from biweekly sustainment committee meetings and conducted debriefing sessions with committee members (informed by the Clinical Sustainability Assessment Tool) to identify sustainment strategies and challenges, which were then organized into meaningful themes. Results The following six themes emerged from meeting minutes and debriefings: (1) automation of low‐touch components, (2) reliance on internal champions, (3) intentional handoff communication, (4) institutional attention, (5) relaxed fidelity, and (6) continuous evaluation. Together, they highlight the importance of early, structured planning and adaptable implementation strategies. Conclusions Sustainment of the HAS initiative required extensive communication, adaptation, and stakeholder engagement across diverse institutional contexts. Proactive sustainment planning during trial design may help ensure interventions are successfully integrated into routine clinical practice posttrial.

Alzheimer’s disease (AD), due to its multifactorial nature and complex etiology, poses challenges for research, diagnosis, and treatment, and impacts millions worldwide. To address the need for minimally invasive, repeatable measures that aid in AD diagnosis and progression monitoring, studies leveraging RNAs associated with extracellular vesicles (EVs) in human biofluids have revealed AD-associated changes. However, the validation of AD biomarkers has suffered from the collection of samples from differing points in the disease time course or a lack of confirmed AD diagnoses. Here, we integrate clinical diagnosis and postmortem pathology data to form more accurate experimental groups and use small RNA sequencing to show that EVs from plasma can serve as a potential source of RNAs that reflect disease-related changes. Importantly, we demonstrated that these changes are identifiable in the EVs of preclinical patients, years before symptom manifestation, and that machine learning models based on differentially expressed RNAs can help predict disease conversion or progression. This research offers critical insight into early disease biomarkers and underscores the significance of accounting for disease progression and pathology in human AD studies.

Extracellular RNAs (exRNAs) have been identified in all tested biofluids and have been associated with a variety of extracellular vesicles, ribonucleoprotein complexes and lipoprotein complexes. Much of the interest in exRNAs lies in the fact that they may serve as signalling molecules between cells, their potential to serve as biomarkers for prediction and diagnosis of disease and the possibility that exRNAs or the extracellular particles that carry them might be used for therapeutic purposes. Among the most significant bottlenecks to progress in this field is the lack of robust and standardized methods for collection and processing of biofluids, separation of different types of exRNA‐containing particles and isolation and analysis of exRNAs. The Sample and Assay Standards Working Group of the Extracellular RNA Communication Consortium is a group of laboratories funded by the U.S. National Institutes of Health to develop such methods. In our first joint endeavour, we held a series of conference calls and in‐person meetings to survey the methods used among our members, placed them in the context of the current literature and used our findings to identify areas in which the identification of robust methodologies would promote rapid advancements in the exRNA field.

Abstract Background & Aims Accumulating evidence indicates that micro RNA s play a role in a number of disease processes including the pathogenesis of liver fibrosis in hepatitis C infection. Our goal is to add to the accruing information regarding micro RNA deregulation in liver fibrosis to increase our understanding of the underlying mechanisms of pathology and progression. Methods We used next generation sequencing to profile all detectable micro RNA s in liver tissue and serum from patients with hepatitis C, stages F1–F4 of fibrosis. Results We found altered expression of several micro RNA s, in particular, miR‐182, miR199a‐5p, miR‐200a‐5p and miR‐183 were found to be significantly upregulated in tissue from liver biopsies of hepatitis C patients with advanced fibrosis, stage F3 and F4, when compared with liver biopsies from patients with early fibrosis, stages F1 and F2. We also found miR‐148‐5p, miR‐1260b, miR‐122‐3p and miR‐378i among the micro RNA s most significantly down‐regulated from early to advanced fibrosis of the liver. We also sequenced the serum micro RNA s; however, we were not able to detect significant changes in circulating micro RNA s associated with fibrosis stage after adjusting for multiple tests. Conclusions Adding measurements of tissue micro RNA s acquired during routine biopsies will continue to increase our knowledge of underlying mechanisms of fibrosis. Our goal is that these data, in combination with studies from other researchers and future long‐term studies, could be used to enhance the staging accuracy of liver biopsies and expand the surveillance of patients at increased risk for cancer and progression to advanced fibrosis.