Drug Development.

Background: Availability of amyloid modifying therapies will dramatically increase the need for disclosure of Alzheimer's disease (AD) related genetic and/or biomarker test results. The 21st Century Cares Act requires the immediate return of most medical test results, including AD biomarkers. A shortage of genetic counselors and dementia specialists already exists, thus driving the need for scalable methods to responsibly communicate test results.

Drug Development.

Background: Although novel treatments for Alzheimer's disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects.

Drug Development.

Background: Recruitment registries are tools to decrease the time and cost required to identify and enroll eligible participants into clinical research. Despite their potential to increase the efficiency of accrual, few analyses have assessed registry effectiveness. We investigated the outcomes of study referrals from the Consent-to-Contact (C2C) registry, a recruitment registry at the University of California, Irvine.

Drug Development.

Preclinical Alzheimer's disease (AD) trials can involve multiple years of follow-up and burdensome procedures for older individuals. Optimizing the design and conduct of these trials requires input from participants and their families. Since 2020, the Alzheimer's Clinical Trials Consortium (ACTC) Research Participant Advisory Board has provided input on study attributes including: participant and study partner compensation, consent language, and result communication tools.

Drug Development.

Background: Anti-amyloid immunotherapies modestly slow disease progression in early symptomatic AD; addition of other therapeutic modalities may be necessary to achieve larger treatment effects. Therapies that directly target tau can potentially produce substantial clinical benefit because the accumulation of insoluble tau protein is strongly correlated with the progression of AD. Which tau therapies are likely to be efficacious, whether or not to combine them with anti-amyloid therapies, and which individuals are most likely to benefit are important unresolved questions that would require multiple parallel design trials to answer.

Drug Development.

Background: In Alzheimer's disease (AD) clinical trials, participants must enroll with a study partner informant who accompanies them to visits and completes validated instruments. Mid-trial informant replacement (IR) has been found to impact academic trial results. We hypothesized that a similar impact would be observed in industry-sponsored trials.

Drug Development.

Background: Participant dropout from study treatment in a clinical trial can leave a trial underpowered, produce bias in statistical analysis, and limit interpretability of study results. Retaining participants in clinical trials for the full study duration is therefore as important as participant recruitment. This analysis aims to identify the baseline characteristics of participants who discontinued during the blinded phase of one of the first and largest preclinical AD trial completed to date, the Anti-Amyloid treatment in Asymptomatic AD (A4) Study.

Drug Development.

Background: Recruiting large numbers of study participants for Alzheimer's Disease (AD) drug trials remains a significant challenge in need of more effective approaches. Advertising can be an effective way to reach large numbers of prospective participants, but can suffer from low attendance rates. This study examined the relationship between the initial behaviors of prospective AD trial participants who did not attend their first scheduled appointment and their overall likelihood of eventually attending an in-person consultation.

Drug Development.

Background: Recruitment challenges in people with and without Down syndrome (DS) can delay research progress and risk sample bias. This study identified and quantified differences in research attitudes across populations of research enrollment decision-makers for individuals with and without DS.

Method: We compared scores on the Research Attitudes Questionnaire (RAQ) of individuals enrolled in two recruitment registries: the UCI Consent to Contact [C2C (N = 4818)] and DS-Connect (N = 976).

Drug Development.

Background: Reactive astrocytes and neuron death by excitotoxicity are observed in Alzheimer's disease (AD). DHA-H (2-hydroxy-docosahexaenoic acid; 2-OH-C22:6 n-3) is a molecule under development that has demonstrated therapeutic efficacy in both cellular and 5xFAD mouse model of AD. DHA-H is metabolized through α-oxidation to yield HPA (Heneicosapentaenoic acid; C21:5 n-3).

Drug Development.

Background: Amid recent approvals, early Alzheimer's disease (AD) remains an active area of treatment development, but research on the utility of recruitment incentives in early AD trials remains limited. We examined how trial design features impact enrollment decisions among Mild Cognitive Impairment (MCI) patients and their family members.

Method: We performed a conjoint analysis experiment to compare early AD patients' preferences for trial features.

Drug Development.

Background: Prodromal Alzheimer's disease (AD) clinical trials of candidate treatments enroll individuals with mild cognitive impairment (MCI) and biomarker evidence of AD. These trials require co-enrollment with a study partner and complex decision-making, weighing potential risks and benefits of participation. Some patients with MCI lack capacity to provide trial informed consent.

Outcomes of Immunotherapy Treatment in Sinonasal Mucosal Melanoma.

Background: Sinonasal mucosal melanoma has poor survival despite multimodality treatment. While the impact of immunotherapy (IT) on metastatic cutaneous melanoma is well-defined, there are relatively little data on sinonasal mucosal melanoma.

Objective: We sought to define immunotherapy outcomes in patients with sinonasal mucosal melanoma.

Dementia Care Research and Psychosocial Factors.

Background: As the landscape of ADRD diagnoses evolves to include biomarker testing, there is a pressing need to understand the unique experiences, challenges, and support needs of families undergoing evaluations of cognitive decline, particularly in a manner that prioritizes cultural considerations from voices historically underrepresented in ADRD research. The current study aims to understand the AD biomarker disclosure journey of persons from underrepresented groups with the goal of informing culturally responsive approaches to the care of patients and their families navigating the complexities of ADRD diagnoses.

Method: Virtual focus groups are being conducted over a secure video conferencing platform, with a trained facilitator guiding the discussion.

Dementia Care Research and Psychosocial Factors.

Background: Asian American, Native Hawaiian, and Pacific Islander (AANHPI) populations are underrepresented in Alzheimer's disease and related dementias (ADRD) research, despite being the fastest growing racial group in the United States. The Collaborative Approach for AANHPI Research and Education (CARE) registry aims to create a sustainable research recruitment source to address this need.

Method: Participants can enroll online, by phone, or in-person by completing an enrollment survey in English, Chinese (Simplified/Traditional), Hindi, Korean, Samoan, or Vietnamese.

Dementia Care Research and Psychosocial Factors.

Background: Family caregivers of persons with dementia (PWD) suffer from constant caregiving burden resulting in poor sleep quality. Understanding sleep parameters (e.g.

Dementia Care Research and Psychosocial Factors.

Background: The Collaborative Approach for Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPI) Research and Education (CARE) is a recruitment registry that has enrolled over 10,000 AANHPI participants who expressed willingness to participate in Alzheimer's disease and related dementias (ADRD), aging, caregiving, and other health research. We report survey results from 24 of the 28 study principal investigators ("users") who utilized CARE between January 2021 and October 2023 to support their study recruitment.

Method: Users answered five questions on a 4-point Likert scale (0 = Strongly disagree to 3 = Strongly agree) related to (1) user experience, (2) usefulness in accelerating recruitment, (3) improving AANHPI representation, (4) whether they would use the registry again, and (5) whether they would recommend the registry to others.

Dementia Care Research and Psychosocial Factors.

Background: Amyloid imaging biomarkers serve an increasingly important role in diagnosing Alzheimer's disease and determining eligibility for treatment with new disease-modifying therapies. Yet, psychological and behavioral reactions to receiving a biomarker informed diagnosis remain relatively unstudied, especially in diverse and underserved populations where the burden of disease is high and resources for support are often insufficient. We developed the Patient And family member Reactions to biomarker-informed ADRD DiagnosEs (PARADE) Study to address two key gaps in our understanding: 1) the range and trajectory of psychological and behavioral responses to a biomarker informed diagnosis and 2) the support needs of these individuals and their families.

Dementia Care Practice.

Background: A critical need to increase Alzheimer's disease (AD) screening exists given rising incidence, new disease-modifying treatments, and ill-equipped primary care settings. This study assessed the feasibility of a novel, community-based AD screening program to increase cognitive and retinal-based assessments.

Methods: An observational study, supported by the Davos Alzheimer's Collaborative, assessed the utility of leveraging community-based settings to increase rates of cognitive assessment (conducted by Alzheimer Society (AS) social workers [SWs]) and RetiSpec's AI-based eye test in optometry settings to detect biologic signatures of AD (plus participant survey).

Technology and Dementia Preconference.

Background: Alzheimer's disease (AD) is a heterogeneous disease with different clinical phenotypes and pathophysiological subtypes. Identifying cognitive/functional subtypes in AD could elucidate the diverse clinical progression patterns. The Cognitive Function Index (CFI), a 15-item questionnaire completed by participants and study partners, captures aspects of cognitive and functional decline.

Give Peace a Chance? How Regulatory Foci Influence Organizational Conflict Events in Intractable Conflict Environments.

An intractable conflict environment (ICE) is an extreme context in which deep, unsolvable conflict between groups is central to the actors within it. While non-ICEs are typically assumed in organizational research, ICEs are increasingly common contexts for organizations. Moreover, this context influences peoples' interpretation of potential organizational conflict incidents inside the organization and therefore the likelihood and emotional intensity of organizational conflict events.

Source Characteristics Influence AI-Enabled Orthopaedic Text Simplification: Recommendations for the Future.

Background: This study assesses the effectiveness of large language models (LLMs) in simplifying complex language within orthopaedic patient education materials (PEMs) and identifies predictive factors for successful text transformation.

Methods: We transformed 48 orthopaedic PEMs using GPT-4, GPT-3.5, Claude 2, and Llama 2.

Validation of a mail-in delayed semen analysis protocol developed for home collection.

Objective: To validate a mail-in delayed semen analysis service using deidentified remnant samples from a US fertility clinic.

Design: Double-blinded prospective validation of screening/diagnostic test.

Setting: Fertility clinic and clinical reference laboratory.

Anatomic Distal Biceps Tendon Repair With All-Suture Cortical Buttons.

Acute, traumatic distal biceps tendon ruptures are a common injury in the middle-aged athletic male population, with direct anatomic surgical repair being the most effective technique to restore maximal strength. Multiple techniques for distal biceps tendon repair have been described, including single- or dual-incision approaches and tendon fixation with cortical buttons, interference screws, suture anchors, and transosseous sutures. In this Technical Note, we demonstrate an anatomic distal biceps tendon repair technique with a single-incision approach using 2 all-suture cortical buttons.

Arthroscopy-Assisted Core Decompression and Bone Grafting for Avascular Necrosis of the Hip.

Although specific techniques vary, core decompression is generally accepted as the treatment of choice for precollapse avascular necrosis (AVN) of the hip to delay or prevent progression of the disease. This can be combined with hip arthroscopy to allow visual assessment of the femoral head as well as treatment of intra-articular pathologies, which may contribute to pain and joint degeneration. We describe a technique of hip arthroscopy and concurrent core decompression using an expandable reamer and bone grafting for treatment of hip AVN.