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Introduction: Transgender and gender-diverse (TGD) individuals frequently encounter discrimination in health care settings. The Veterans Health Administration (VA) is committed to addressing the health disparities experienced by TGD veterans. The purpose of this study was to explore the experiences of TGD veterans with LGBTQ+ veteran care coordinators., Methods: The authors conducted semi-structured interviews with TGD veterans with depression between January and March 2022. Participants were recruited with assistance from the VA's network of LGBTQ+ veteran care coordinators. Interviews were recorded, transcribed, and analyzed., Results: Twenty-six TGD veterans participated in the study, with a range of experiences, both positive and negative, with LGBTQ+ veteran care coordinators. Veterans spoke of the role of coordinators in educating both patients and clinicians about TGD health care needs. Participants who expressed dissatisfaction with their coordinators highlighted the need for a clearer definition and communication of coordinator duties., Conclusions: This study highlights the important roles played by the VA LGBTQ+ care coordinators in addressing the needs of TGD veterans. The study also points to an immense need for clinician education in TGD care. Further training and education are recommended to improve equitable care for TGD veterans.

Importance: Compared with cisgender (CG) individuals, transgender and gender-diverse (TGD) individuals experience substantial social and economic disparities that can result in adverse mental health consequences. It is critical to understand potential barriers to care and to address the causes of the disparities in the future., Objective: To characterize mental health care utilization among TGD veterans with depression., Design, Setting, and Participants: This cohort study used electronic health record data from the US Department of Veterans Affairs (VA) to create a 1:3 age group-matched and VA facility-matched nationwide cohort of TGD and CG veterans with documentation of depression during 2018 to 2020. Data analysis was performed from January to November 2023., Exposure: TGD identity was ascertained by diagnosis of a gender identity disorder., Main Outcomes and Measures: The primary outcome was mental health care utilization, including counts of outpatient (in specialty care and primary care settings), telehealth, emergency department, and inpatient visits in this cohort. Descriptive statistics were used to characterize counts of mental health utilization, and statistically significant differences between TGD and CG veterans were tested using χ2 and Fisher exact tests. Wilcoxon rank-sum tests were used to test for differences in utilization between the 2 groups. Adjusted logistic regression, controlling for age group, administrative sex, race, Charlson Comorbidity Index, and number of mental health medications (eg, antidepressant, antipsychotic, and anxiolytic medications), was also used to compare utilization between TGD and CG veterans., Results: Among 10 564 veterans with depression (mean [SD] age, 46.4 [15.2] years; 8050 male [76.2%]), 2643 TGD veterans were matched with 7921 CG veterans. TGD veterans had 6 more specialty mental health visits per year than CG veterans (mean [SD], 13.93 [20.08] vs 8.46 [14.96] visits a year; median [range], 7.14 [0.00-246.30] vs 3.76 [0.00-202.38] visits per year). In adjusted models, compared with CG veterans, TGD veterans were 2.6 times more likely to have an outpatient mental-health visit (odds ratio, 2.60; 95% CI, 2.16-3.15)., Conclusions and Relevance: In this cohort study of veterans with depression, TGD veterans had significantly higher utilization of mental health services compared with CG veterans, even after adjusting for several relevant health factors. Different health system resources may be required to meet the needs of this population. Further studies are needed to understand the determinants of these disparities and subsequently how to address them.

Background: The Everyday Cognition scale (ECog-39) scores are associated with future cognitive decline. We investigated whether the 12-item ECog (ECog-12), which is being collected in Alzheimer's Disease Neuroimaging Initiative (ADNI)4, can predict progression., Methods: Baseline self (PT)- and study partner (SP)-ECog-12 data were extracted from the 39-item version collected in the ADNI. Weibull analysis examined the relationship between baseline ECog-12 and future clinical progression (change in Clinical Dementia Rating Sum of Boxes [CDR-SB] scores and diagnostic conversion)., Results: Higher PT- and SP-ECog-12 scores were associated with faster CDR-SB worsening, with hazard ratios in cognitively unimpaired (CU) 3.34 and 9.61, mild cognitive impairment (MCI) 1.44 and 2.82, and dementia 0.93 and 1.82. They were associated with conversion from CU to MCI 3.01 and 6.24 and MCI to dementia 1.61 and 3.07., Discussion: SP-ECog-12 provided a higher prognostic value for predicting clinical progression, so this can help identify and monitor patients at risk in research and health-care settings., Highlights: The 12-item Everyday Cognition scale (ECog-12) data obtained from both raters increased diagnostic conversion risk from cognitively unimpaired to mild cognitive impairment (MCI) and from MCI to dementia. ECog-12, rated by study partners, was associated with an increased risk of Clinical Dementia Rating Sum of Boxes worsening in all diagnostic groups. Our results provide novel information about the specific scoring outputs and rater types (participant vs. study partner) of ECog-12 that can facilitate screening, prioritization, and longitudinal monitoring of the clinical progression of participants in Alzheimer's Disease Neuroimaging Initiative 4 and other Alzheimer's disease clinical studies, clinical trials, and in health-care settings., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Introduction: We investigated the prevalence of amyloid beta (Aβ) positivity (+) and cognitive trajectories in Koreans and non-Hispanic Whites (NHWs)., Methods: We included 5121 Koreans from multiple centers across South Korea and 929 NHWs from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants underwent Aβ positron emission tomography and were categorized into cognitively unimpaired (CU), mild cognitive impairment (MCI), and dementia stages. Age, sex, education, and apolipoprotein E. genotype were adjusted using multivariable logistic regression and stabilized inverse probability of treatment weights based on the propensity scores to mitigate imbalances in these variables., Results: The prevalence of Aβ+ was lower in CU Koreans than in CU NHWs (adjusted odds ratio 0.60). Aβ+ Koreans showed a faster cognitive decline than Aβ+ NHWs in the CU (B = -0.314, p = .004) and MCI stages (B = -0.385, p < .001)., Discussion: Ethnic characteristics of Aβ biomarkers should be considered in research and clinical application of Aβ-targeted therapies in diverse populations., Highlights: Koreans have a lower prevalence of Aβ positivity compared to NHWs in the CU stage. The effects of Alzheimer's risk factors on Aβ positivity differ between Koreans and NHWs. Aβ-positive (Aβ+) Koreans show faster cognitive decline than Aβ+ NHWs in the CU and MCI stages., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Blood-based biomarkers (BBM) for Alzheimer's disease (AD) are being increasingly used in clinical practice to support an AD diagnosis. In contrast to traditional diagnostic modalities, such as amyloid positron emission tomography and cerebrospinal fluid biomarkers, BBMs offer a more accessible and lower cost alternative for AD biomarker testing. Their unique scalability addresses the anticipated surge in demand for biomarker testing with the emergence of disease-modifying treatments (DMTs) that require confirmation of amyloid pathology. To facilitate the uptake of BBMs in clinical practice, The Global CEO Initiative on Alzheimer's Disease convened a BBM Workgroup to provide recommendations for two clinical implementational pathways for BBMs: one for current use for triaging and another for future use to confirm amyloid pathology. These pathways provide a standardized diagnostic approach with guidance on interpreting BBM test results. Integrating BBMs into clinical practice will simplify the diagnostic process and facilitate timely access to DMTs for eligible patients., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Medication reconciliation is essential for optimizing medication use. In part to promote effective medication reconciliation, the Department of Veterans Affairs (VA) invested substantial resources in health information exchange (HIE) technologies. The objectives of this qualitative study were to characterize VA clinicians' use of HIE tools for medication reconciliation in their clinical practice and to identify facilitators and barriers., Methods: We recruited inpatient and outpatient prescribers (physicians, nurse practitioners, physician assistants) and pharmacists at four geographically distinct VA medical centers for observations and interviews. Participants were observed as they interacted with HIE or medication reconciliation tools during routine work. Participants were interviewed about clinical decision-making pertaining to medication reconciliation and use of HIE tools, and about barriers and facilitators to use of the tools. Qualitative data were analyzed via inductive and deductive approaches using a priori codes., Results: A total of 63 clinicians participated. Over half (58%) were female, and the mean duration of VA clinical experience was 7 (range 0-32) years. Underlying motivators for clinicians seeking data external to their VA medical center were having new patients, current patients receiving care from an external institution, and clinicians' concerns about possible medication discrepancies among institutions. Facilitators for using HIE software were clinicians' familiarity with the HIE software, clinicians' belief that medication information would be available within HIE, and their confidence in the ability to find HIE medication-related data of interest quickly. Six overarching barriers to HIE software use for medication coordination included visual clutter and information overload within the HIE display; challenges with HIE interface navigation; lack of integration between HIE and other electronic health record interfaces, necessitating multiple logins and application switching; concerns with the dependability of HIE medication information; unfamiliarity with HIE tools; and a lack of HIE data from non-VA facilities., Conclusions: This study is believed to be the first to qualitatively characterize clinicians' HIE use with respect to medication reconciliation. Results inform recommendations to optimize HIE use for medication management activities. We expect that healthcare organizations and software vendors will be able to apply the findings to develop more effective and usable HIE information displays., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

This systematic review examines the prevalence, underlying mechanisms, cohort characteristics, evaluation criteria, and cohort types in white matter hyperintensity (WMH) pipeline and implementation literature spanning the last two decades. Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we categorized WMH segmentation tools based on their methodologies from January 1, 2000, to November 18, 2022. Inclusion criteria involved articles using openly available techniques with detailed descriptions, focusing on WMH as a primary outcome. Our analysis identified 1007 visual rating scales, 118 pipeline development articles, and 509 implementation articles. These studies predominantly explored aging, dementia, psychiatric disorders, and small vessel disease, with aging and dementia being the most prevalent cohorts. Deep learning emerged as the most frequently developed segmentation technique, indicative of a heightened scrutiny in new technique development over the past two decades. We illustrate observed patterns and discrepancies between published and implemented WMH techniques. Despite increasingly sophisticated quantitative segmentation options, visual rating scales persist, with the SPM technique being the most utilized among quantitative methods and potentially serving as a reference standard for newer techniques. Our findings highlight the need for future standards in WMH segmentation, and we provide recommendations based on these observations., Competing Interests: Declarations. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Conflicts of interest: The authors declare that there are no conflicts of interest regarding the publication of this paper. This declaration is made to confirm that there has been no financial or personal relationship with other people or organizations that could inappropriately influence or bias the work presented in this manuscript. This includes, but is not limited to, employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (© 2024. The Author(s).)

Introduction: Well-chosen biomarkers have the potential to increase the efficiency of clinical trials and drug discovery and should show good precision as well as clinical validity., Methods: We suggest measures that operationalize these criteria and describe a general approach that can be used for inference-based comparisons of biomarker performance. The methods are applied to measures obtained from structural magnetic resonance imaging (MRI) from individuals with mild dementia (n = 70) or mild cognitive impairment (MCI; n = 303) enrolled in the Alzheimer's Disease Neuroimaging Initiative., Results: Ventricular volume and hippocampal volume showed the best precision in detecting change over time in both individuals with MCI and with dementia. Differences in clinical validity varied by group., Discussion: The methodology presented provides a standardized framework for comparison of biomarkers across modalities and across different methods used to generate similar measures and will help in the search for the most promising biomarkers., Highlights: A framework for comparison of biomarkers on pre-defined criteria is presented. Criteria for comparison include precision in capturing change and clinical validity. Ventricular volume has high precision in change for both dementia and mild cognitive impairment (MCI) trials. Imaging measures' performance in clinical validity varies more for dementia than for MCI., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Industrywide, primary care nurses' work is increasing in complexity and team orientation. Mobile health information technologies (HITs) designed to aid nurses with indirect care tasks, including charting, have had mixed success. Failed introductions of HIT may be explained by insufficient integration into nurses' work processes, owing to an incomplete or incorrect understanding of the underlying work systems. Despite this need for context, published evidence has focused more on inpatient settings than on primary care., Objective: This study aims to characterize nurses' and health technicians' perceptions of process inefficiencies in the primary care setting and identify related work system factors., Methods: Guided by the Systems Engineering Initiative for Patient Safety (SEIPS) 2.0 model, we conducted an exploratory work system analysis with a convenience sample of primary care nurses and health technicians. Semistructured contextual interviews were conducted in 2 sets of primary care clinics in the Midwestern United States, one in an urban tertiary care center and the other in a rural community-based outpatient facility. Using directed qualitative content analysis of transcripts, we identified tasks participants perceived as frequent, redundant, or difficult, related processes, and recommendations for improvement. In addition, we conducted configuration analyses to identify associations between process inefficiencies and work system factors., Results: We interviewed a convenience sample of 20 primary care nurses and 2 health technicians, averaging approximately 12 years of experience in their current role. Across sites, participants perceived 2 processes, managing patient calls and clinic walk-in visits, as inefficient. Among work system factors, participants described organizational and technological factors associated with inefficiencies. For example, new organization policies to decrease patient waiting invoked frequent, repetitive, and difficult tasks, including chart review and check-in using tablet computers. Participants reported that issues with policy implementation and technology usability contributed to process inefficiencies. Organizational and technological factors were also perceived among participants as the most adaptable. Suggested technology changes included new tools for walk-in triage and patient self-reporting of symptoms., Conclusions: In response to changes to organizational policy and technology, without compensative changes elsewhere in their primary care work system, participants reported process adaptations. These adaptations indicate inefficient work processes. Understanding how the implementation of organizational policies affects other factors in the primary care work system may improve the quality of such implementations and, in turn, increase the effectiveness and efficiency of primary care nurse processes. Furthermore, the design and implementation of HIT interventions should consider influential work system factors and their effects on work processes., (©Willi L Tarver, April Savoy, Himalaya Patel, Michael Weiner, Richard J Holden. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 30.09.2024.)

Phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI4) magnetic resonance imaging (MRI) protocols aim to maintain longitudinal consistency across two decades of data acquisition, while adopting new technologies. Here we describe and justify the study's design and targeted biomarkers. The ADNI4 MRI protocol includes nine MRI sequences. Some sequences require the latest hardware and software system upgrades and are continuously rolled out as they become available at each site. The main sequence additions/changes in ADNI4 are: (1) compressed sensing (CS) T1-weighting, (2) pseudo-continuous arterial spin labeling (ASL) on all three vendors (GE, Siemens, Philips), (3) multiple-post-labeling-delay ASL, (4) 1 mm 3 isotropic 3D fluid-attenuated inversion recovery, and (5) CS 3D T2-weighted. ADNI4 aims to help the neuroimaging community extract valuable imaging biomarkers and provide a database to test the impact of advanced imaging strategies on diagnostic accuracy and disease sensitivity among individuals lying on the cognitively normal to impaired spectrum. HIGHLIGHTS: A summary of MRI protocols for phase four of the Alzheimer's Disease Neuroimaging Initiative (ADNI 4). The design and justification for the ADNI 4 MRI protocols. Compressed sensing and multi-band advances have been applied to improve scan time. ADNI4 protocols aim to streamline safety screening and therapy monitoring. The ADNI4 database will be a valuable test bed for academic research., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Neurodegenerative diseases require collaborative, multisite research to comprehensively grasp their complex and diverse pathological progression; however, there is caution in aggregating global data due to data heterogeneity. In the current study, we investigated brain structure across stages of Alzheimer's disease (AD) and how relationships vary across sources of heterogeneity., Methods: Using 6 international datasets (N > 27,000), associations of structural neuroimaging markers were investigated in relation to the AD continuum via meta-analysis. We investigated whether associations varied across elements of magnetic resonance imaging acquisition, study design, and populations., Results: Modest differences in associations were found depending on how data were acquired; however, patterns were similar. Preliminary results suggested that neuroimaging marker-AD relationships differ across ethnic groups., Conclusions: Diversity in data offers unique insights into the neural substrate of AD; however, harmonized processing and transparency of data collection are needed. Global collaborations should embrace the inherent heterogeneity that exists in the data and quantify its contribution to research findings at the meta-analytical stage., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Electronic health records (EHRs) can accelerate documentation and may enhance details of notes, or complicate documentation and introduce errors. Comprehensive assessment of documentation quality requires comparing documentation to what transpires during the clinical encounter itself. We assessed outpatient primary care notes and corresponding recorded encounters to determine accuracy, thoroughness, and several additional key measures of documentation quality., Methods: Patients and primary care clinicians across five midwestern primary care clinics of the US Department of Veterans Affairs were recruited into a prospective observational study. Clinical encounters were video-recorded and transcribed verbatim. Using the Physician Documentation Quality Instrument (PDQI-9) added to other measures, reviewers scored quality of the documentation by comparing transcripts to corresponding encounter notes. PDQI-9 items were scored from 1 to 5, with higher scores indicating higher quality., Results: Encounters (N = 49) among 11 clinicians were analyzed. Most issues that patients initiated in discussion were omitted from notes, and nearly half of notes referred to information or observations that could not be verified. Four notes lacked concluding assessments and plans; nine lacked information about when patients should return. Except for thoroughness, PDQI-9 items that were assessed achieved quality scores exceeding 4 of 5 points., Conclusions: Among outpatient primary care electronic records examined, most issues that patients initiated in discussion were absent from notes, and nearly half of notes referred to information or observations absent from transcripts. EHRs may contribute to certain kinds of errors. Approaches to improving documentation should consider the roles of the EHR, patient, and clinician together., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Medical resuscitations in rugged prehospital settings require emergency personnel to perform high-risk procedures in low-resource conditions. Just-in-Time Guidance (JITG) utilizing augmented reality (AR) guidance may be a solution. There is little literature on the utility of AR-mediated JITG tools for facilitating the performance of emergent field care., Study Objective: The objective of this study was to investigate the feasibility and efficacy of a novel AR-mediated JITG tool for emergency field procedures., Methods: Emergency medical technician-basic (EMT-B) and paramedic cohorts were randomized to either video training (control) or JITG-AR guidance (intervention) groups for performing bag-valve-mask (BVM) ventilation, intraosseous (IO) line placement, and needle-decompression (Needle-d) in a medium-fidelity simulation environment. For the interventional condition, subjects used an AR technology platform to perform the tasks. The primary outcome was participant task performance; the secondary outcomes were participant-reported acceptability. Participant task score, task time, and acceptability ratings were reported descriptively and compared between the control and intervention groups using chi-square analysis for binary variables and unpaired t-testing for continuous variables., Results: Sixty participants were enrolled (mean age 34.8 years; 72% male). In the EMT-B cohort, there was no difference in average task performance score between the control and JITG groups for the BVM and IO tasks; however, the control group had higher performance scores for the Needle-d task (mean score difference 22%; P = .01). In the paramedic cohort, there was no difference in performance scores between the control and JITG group for the BVM and Needle-d tasks, but the control group had higher task scores for the IO task (mean score difference 23%; P = .01). For all task and participant types, the control group performed tasks more quickly than in the JITG group. There was no difference in participant usability or usefulness ratings between the JITG or control conditions for any of the tasks, although paramedics reported they were less likely to use the JITG equipment again (mean difference 1.96 rating points; P = .02)., Conclusions: This study demonstrated preliminary evidence that AR-mediated guidance for emergency medical procedures is feasible and acceptable. These observations, coupled with AR's promise for real-time interaction and on-going technological advancements, suggest the potential for this modality in training and practice that justifies future investigation.

The specialty referral process consists of primary care clinicians referring patients to specialty consultants. This care transition requires effective care coordination and health information exchange between care teams; however, breakdowns in workflow and information flow impede "closing the referral loop" and delay or prevent referrers from receiving the consultant's "visit notes," particularly in cross-institutional referrals. This study aimed to describe and map the referral process as it occurs in clinics and identify and characterize work system barriers affecting its performance. Referrers and consultants were interviewed about their perceived workflows, barriers, and clinical outcomes to inform a workflow analysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Michael Weiner discloses the following stock holdings: Allscripts Healthcare Solutions Inc, Apple Inc, Centene Corp, DXC Technology Co, General Electric Co, Hewlett Packard, International Business Machines, Kyndryl Holdings Inc, Micro Focus International PLC, Microsoft Corp, Oracle Cerner Corp, PerkinElmer Inc, Qualcomm Inc, Zimmer Biomet Holdings Inc, Intel Corp, Cellcom Israel Ltd, Teladoc Health Inc, Varex Imaging Corp., (Copyright © 2023. Published by Elsevier Ltd.)

White matter hyperintensities (WMH) are nearly ubiquitous in the aging brain, and their topography and overall burden are associated with cognitive decline. Given their numerosity, accurate methods to automatically segment WMH are needed. Recent developments, including the availability of challenge data sets and improved deep learning algorithms, have led to a new promising deep-learning based automated segmentation model called TrUE-Net, which has yet to undergo rigorous independent validation. Here, we compare TrUE-Net to six established automated WMH segmentation tools, including a semi-manual method. We evaluated the techniques at both global and regional level to compare their ability to detect the established relationship between WMH burden and age. We found that TrUE-Net was highly reliable at identifying WMH regions with low false positive rates, when compared to semi-manual segmentation as the reference standard. TrUE-Net performed similarly or favorably when compared to the other automated techniques. Moreover, TrUE-Net was able to detect relationships between WMH and age to a similar degree as the reference standard semi-manual segmentation at both the global and regional level. These results support the use of TrUE-Net for identifying WMH at the global or regional level, including in large, combined datasets., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

People with Alzheimer's disease or related dementias and diabetes mellitus (ADRD-DM) are at high risk for hypoglycemic events. Their cognitive impairment and psychosocial situation often hinder detection of hypoglycemia. Extending use and benefits of continuous glucose monitoring (CGM) to people with ADRD-DM could improve hypoglycemia detection, inform care, and reduce adverse events. However, cognitive impairment associated with ADRD presents unique challenges for CGM use. This commentary proposes applying the human-centered design process to CGM, investigating design solutions or interventions needed to integrate CGM into the health care of patients with ADRD-DM. With this process, we can identify and inform CGM designs for people with ADRD-DM, broadening CGM access, increasing detection and treatment of the silent threat posed by hypoglycemia., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Michael Weiner reports stock ownership in AbbVie Inc, Amgen Inc, Boston Scientific Corporation, Bristol-Myers Squibb Company, IBM, Integer Holdings Corp, Johnson & Johnson, Mallinckrodt PLC, Mead Johnson & Company, LLC, Medtronic, Mylan N.V., Novo Nordisk A/S, Perspecta Inc, Pfizer Inc, Roche Pharmaceuticals, Senseonics, Stryker Corp, Teva Pharmaceutical Industries Ltd, and Walgreens Boots Alliance, Inc. Rich Holden provides paid scientific advising to Cook Medical. April Savoy reports stock ownership in Pfizer Inc. and GSK (GlaxoSmithKline) Plc. David Klonoff is a consultant to Eoflow, Fractyl Health, Lifecare, Integrity, Rockley Photonics, and Thirdwayv. All other authors report no conflicts of interest.

Background: Chronic cough (CC) affects about 10% of adults, but opioid use in CC is not well understood., Objectives: To determine the use of opioid-containing cough suppressant (OCCS) prescriptions in patients with CC using electronic health records., Design: Retrospective cohort study., Methods: Through retrospective analysis of Midwestern U.S. electronic health records, diagnoses, prescriptions, and natural language processing identified CC - at least three medical encounters with cough, with 56-120 days between first and last encounter - and a 'non-chronic cohort'. Student's t -test, Pearson's chi-square, and zero-inflated Poisson models were used., Results: About 20% of 23,210 patients with CC were prescribed OCCS; odds of an OCCS prescription were twice as great in CC. In CC, OCCS drugs were ordered in 38% with Medicaid insurance and 15% with commercial insurance., Conclusion: Findings identify an important role for opioids in CC, and opportunity to learn more about the drugs' effectiveness.

Objectives: Alzheimer's disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden., Methods: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities., Results: In A+ category, compared with the frequency of Alzheimer's pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p<0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimer's pathological changes (A-T+, A-N+; p=0.002) and Alzheimer's pathological changes (p<0.001) categories., Conclusion: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Drug-drug interactions (DDIs) are common and can result in patient harm. Electronic health records warn clinicians about DDIs via alerts, but the clinical decision support they provide is inadequate. Little is known about clinicians' real-world DDI decision-making process to inform more effective alerts., Objective: Apply cognitive task analysis techniques to determine informational cues used by clinicians to manage DDIs and identify opportunities to improve alerts., Design: Clinicians submitted incident forms involving DDIs, which were eligible for inclusion if there was potential for serious patient harm. For selected incidents, we met with the clinician for a 60 min interview. Each interview transcript was analysed to identify decision requirements and delineate clinicians' decision-making process. We then performed an inductive, qualitative analysis across incidents., Setting: Inpatient and outpatient care at a major, tertiary Veterans Affairs medical centre., Participants: Physicians, pharmacists and nurse practitioners., Outcomes: Themes to identify informational cues that clinicians used to manage DDIs., Results: We conducted qualitative analyses of 20 incidents. Data informed a descriptive model of clinicians' decision-making process, consisting of four main steps: (1) detect a potential DDI; (2) DDI problem-solving, sensemaking and planning; (3) prescribing decision and (4) resolving actions. Within steps (1) and (2), we identified 19 information cues that clinicians used to manage DDIs for patients. These cues informed their subsequent decisions in steps (3) and (4). Our findings inform DDI alert recommendations to improve clinicians' decision-making efficiency, confidence and effectiveness., Conclusions: Our study provides three key contributions. Our study is the first to present an illustrative model of clinicians' real-world decision making for managing DDIs. Second, our findings add to scientific knowledge by identifying 19 cognitive cues that clinicians rely on for DDI management in clinical practice. Third, our results provide essential, foundational knowledge to inform more robust DDI clinical decision support in the future., Competing Interests: Competing interests: LM is co-owner of Applied Decision Science, LLC, a company that studies decision-making in complex environments and utilises the critical decision method. She aided in the design of the cognitive task analysis approach used in this study and trained the interviewer. MW has held stock in Allscripts and Express Scripts Holding Company., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cross-institutional (external) referrals are prone to communication breakdowns, increasing patient safety risks, clinician burnout, and healthcare costs. To close these external referral loops, referring primary care physicians (PCPs) need to receive patient information from consultants at different healthcare institutions. Although existing studies investigated the early phases of external referral loops, we lack sufficient knowledge about the closing phases of these loops. This knowledge could allow health care institutions to improve care coordination and rates of closed referral loops by implementing socio-technical interventions for patient information exchange throughout a referral loop. Human factors engineering (HFE) provides a systematic approach to advance our understanding of barriers perceived by physicians. Using HFE, our objective was to characterize referring and consulting physicians' barriers to closing referral loops and implications for care., Methods: This qualitative cross-sectional study included semi-structured interviews with referrers and external consultants. We used the Systems Engineering Initiative for Patient Safety 2.0 framework to conduct rapid qualitative analyses, determining perceived barriers and related implications. Main measures were consultants' and referrers' perceptions of, and experiences with, barriers to external referrals., Results: Six referring PCPs and 12 consultants participated from two healthcare systems and four medical specialties. Physicians perceived three main barriers in external referrals: receipt of excessive and unnecessary faxed documents, missing or delayed documentation, and organizational policies regarding information privacy interfering with closing the loop. Compared to internal referrals, physicians reported increased staff burden, patient frustration, and delays in diagnosis with external referrals. Consultants reported the ability to provide the same level of care to patients with internal or external referrals. However, consultants described communication breakdowns that prohibited confirmation of follow-up plan retrieval, initiation, or effectiveness., Conclusion: Physicians reported technological and organizational barriers to closing cross-institutional referral loops. Promises of HIE technology for external referrals have not fully materialized. Among physicians and patients, retrieval and exchange of medical information increases perceived workload, burden, and frustration. These increases are not accurately captured by traditional organizational metrics. This study provides evidence that informs future human factors engineering research to address perceived barriers and guide future HIE design or implementation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Majority of dementia research is conducted in non-Hispanic White participants despite a greater prevalence of dementia in other racial groups. To obtain a better understanding of biomarker presentation of Alzheimer's disease (AD) in the non-Hispanic White population, this study exclusively examined AD biomarker abnormalities in 85 Black and/or African American participants within the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were classified by the ADNI into 3 clinical groups: cognitively normal, mild cognitive impairment, or dementia. Data examined included demographics, apolipoprotein E (APOE) ε4, cerebrospinal fluid (CSF) Aβ 1-42 , CSF total tau (t-tau), CSF phosphorylated tau (p-tau), 3T magnetic resonance imaging (MRI), and measures of cognition and function. Analyses of variance and covariance showed lower cortical thickness in 5 of 7 selected MRI regions, lower hippocampal volume, greater volume of white matter hyperintensities, lower measures of cognition and function, lower measures of CSF Aβ 1 -42 , and greater measures of CSF t-tau and p-tau between clinical groups. Our findings confirmed greater AD biomarker abnormalities between clinical groups in this sample., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transitioning to a new electronic health record (EHR) presents different challenges than transitions from paper to electronic records. We synthesized the body of peer-reviewed literature on EHR-to-EHR transitions to evaluate the generalizability of published work and identify knowledge gaps where more evidence is needed., Methods: We conducted a broad search in PubMed through July 2022 and collected all publications from two prior reviews. Peer-reviewed publications reporting on data from an EHR-to-EHR transition were included. We extracted data on study design, setting, sample size, EHR systems involved, dates of transition and data collection, outcomes reported, and key findings., Results: The 40 included publications were grouped into thematic categories for narrative synthesis: clinical care outcomes (n = 15), provider perspectives (n = 11), data migration (n = 8), patient experience (n = 4), and other topics (n = 5). Many studies described single sites that are early adopters of technology with robust research resources, switching from a homegrown system to a commercial system, and emphasized the dynamic effect of transitioning on important clinical care and other outcomes over time., Discussion: The published literature represents a heterogeneous mix of study designs and outcome measures, and while some of the stronger studies in this review used longitudinal approaches to compare outcomes across more sites, the current literature is primarily descriptive and is not designed to offer recommendations that can guide future EHR transitions. Transitioning from one EHR to another constitutes a major organizational change that requires nearly every person in the organization to change how they do their work. Future research should include human factors as well as diverse methodological approaches such as mixed methods and implementation science., (© 2023. The Author(s).)

Knowing that an antibody's sensitivity and specificity is accurate is crucial for reliable data collection. This certainty is especially difficult to achieve for antibodies (Abs) which bind post-translationally modified proteins. Here we describe two validation methods using surrogate proteins in western blot and ELISA. The first method, which we termed "MILKSHAKE" is a modified maltose binding protein, hence the name, that is enzymatically conjugated to a peptide from the chosen target which is either modified or non-modified at the residue of interest. The surety of the residue's modification status can be used to confirm Ab specificity to the target's post-translational modification (PTM). The second method uses a set of surrogate proteins, which we termed "Sundae". Sundae consists of a set of modified maltose binding proteins with a genetically encoded target sequence, each of which contains a single amino acid substitution at one position of interest. With Sundae, Abs can be evaluated for binding specificities to all twenty amino acids at a single position. Combining MILKSHAKE and Sundae methods, Ab specificity can be determined at a single-residue resolution. These data improve evaluation of commercially available Abs and identify off-target effects for Research-Use-Only and therapeutic Abs., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The U.S. Department of Veterans Affairs (VA) is undergoing an enterprise-wide transition from a homegrown electronic health record (EHR) system to a commercial off-the-shelf product. Because of the far-reaching effects of the EHR transformation through all aspects of the healthcare system, VA Health Services Research and Development identified a need to develop a research agenda that aligned with health system priorities so that work may inform evidence-based improvements in implementation processes and outcomes., Objective: The purpose of this paper is to report on the development of a research agenda designed to optimize the EHR transition processes and implementation outcomes in a large, national integrated delivery system., Design: We used a sequential mixed-methods approach (portfolio assessment, literature review) combined with multi-level stakeholder engagement approach that included research, informatics, and healthcare operations experts in EHR transitions in and outside the VA. Data from each stage were integrated iteratively to identify and prioritize key research areas within and across all stakeholder groups., Participants: VA informatics researchers, regional VA health system leaders, national VA program office leaders, and external informatics experts with EHR transition experience., Key Results: Through three rounds of stakeholder engagement, priority research topics were identified that focused on operations, user experience, patient safety, clinical outcomes, value realization, and informatics innovations., Conclusions: The resulting EHR-focused research agenda was designed to guide development and conduct of rigorous research evidence aimed at providing actionable results to address the needs of operations partners, clinicians, clinical staff, patients, and other stakeholders. Continued investment in research and evaluation from both research and operations divisions of VA will be critical to executing the research agenda, ensuring its salience and value to the health system and its end users, and ultimately realizing the promise of this EHR transition., (© 2023. The Author(s).)

Background: Clinical texting systems (CTS) are widely used in hospitals for team communication about patients. With more institutions adopting such systems, there is a need to understand how texting is being used in clinical practice., Methods: We conducted content analysis of 809 randomly selected message threads sent to and from hospitalists in a 9-month window. The process, purpose and content of messages were analysed. We also examined messages for personal content (to identify whether CTS was being used for professional matters) and discussion of near miss errors. The risk levels of these near misses were also assessed., Results: Most messages focused on clinical management of patient needs (62%; n=498) and functioned to provide a notification or update regarding clinical care (64%; n=518) or make a request of the recipient (63%; n=510). Personal content was infrequent in message threads (10%; n=80). Five per cent (n=38) of message threads included discussion of a near miss, and most near misses posed low clinical risk overall (66%; n=25)., Conclusion: Most CTS communication centred around direct clinical management. Fewer messages were focused on non-clinical areas such as administrative tasks or personal communication. Further examination of care delivery, error communication and the consequences of the care discussed in messages would help clinical leaders understand the impact of clinical texting on teamwork and quality of care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Traumatic brain injury (TBI) is common among military veterans and has been associated with an increased risk of dementia. It is unclear if this is due to increased risk for Alzheimer's disease (AD) or other mechanisms. This case control study sought evidence for AD, as defined by the 2018 National Institute on Aging - Alzheimer's Association (NIA-AA) research framework, by measuring tau, β-amyloid, and glucose metabolism using positron emission tomography (PET) in veterans with service-related TBI. Seventy male Vietnam war veterans-40 with TBI (age 68.0 ± 2.5 years) and 30 controls (age 70.1 ± 5.3 years)-with no prior diagnosis of dementia or mild cognitive impairment underwent β-amyloid ( 18 F-Florbetaben), tau ( 18 F-Flortaucipir), and fluorodeoxyglucose ( 18 F-FDG) PET. The TBI cohort included 15 participants with mild, 16 with moderate, and nine with severe injury. β-Amyloid level was calculated using the Centiloid (CL) method and tau was measured by standardized uptake value ratios (SUVRs) using the cerebellar cortex as reference region. Analyses were adjusted for age and APOE-e4. The findings were validated in an independent cohort from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DOD ADNI) study. There were no significant nor trending differences in β-amyloid or tau levels or 18 F-FDG uptake between the TBI and control groups before and after controlling for covariates. The β-amyloid and tau findings were replicated in the DOD ADNI validation cohort and persisted when the Australian Imaging Biomarkers and Lifestyle study of aging-Veterans study (AIBL-VETS) and DOD ADNI cohorts were combined (114 TBI vs. 87 controls in total). In conclusion, no increase in the later life accumulation of the neuropathological markers of AD in veterans with a remote history of TBI was identified.

Importance: Emoji and emoticons are quickly becoming an omnipresent feature of virtual communication. As health care systems increasingly adopt clinical texting applications, it is critical to understand how clinicians use these ideograms with colleagues and how it may affect their interactions., Objective: To evaluate the functions that emoji and emoticons serve in clinical text messages., Design, Setting, and Participants: This qualitative study's content analysis of clinical text messages from a secure clinical messaging platform was conducted to assess the communicative function of emoji and emoticons. The analysis included messages sent by hospitalists to other health care clinicians. A subset of a random 1% sample of all message threads, which included at least 1 emoji or emoticon, on a clinical texting system used by a large, Midwestern US hospital from July 2020 until March 2021 were analyzed. A total of 80 hospitalists participated in the candidate threads., Main Outcomes: Whether and what kind of emoji or emoticon was deployed in each reviewed thread was tabulated by the study team. The communicative function of each emoji and emoticon was assessed according to a prespecified coding scheme., Results: A total of 80 hospitalists (49 [61%] male; 30 [37%] Asian, 5 [6%] Black or African American, 2 [3%] Hispanic or Latinx, 42 [53%] White; of 41 with age data, 13 [32%] aged 25-34 years, 19 [46%] aged 35-44 years) participated in the 1319 candidate threads. Within the sample of 1319 threads, 7% of threads (155 unique messages) contained at least 1 emoji or emoticon. The majority (94 [61%]) functioned emotively, that is, conveyed the internal state of the sender, and 49 (32%) served to open, maintain, or close communication. No evidence was identified that they caused confusion or were seen as inappropriate., Conclusions and Relevance: This qualitative study found that when clinicians use emoji and emoticons in secure clinical texting systems, these symbols function primarily to convey new and interactionally salient information. These results suggest that concerns about the professionalism of emoji and emoticon use may be unwarranted.

Introduction: We aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome., Methods: A consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria., Results: Consensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes., Discussion: This work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Aim: To describe adults' health-related experiences with chronic cough., Design: Survey and interviews., Methods: Participants completed questionnaires and interviews, to explore chronic cough's impact and management., Data Sources: Patients aged 18-85 years with at least three cough-related encounters within 56-120 days., Results: Forty-one patients were surveyed. Mean cough severity was 4.5 (scale 0-9). Chronic cough-related problems included embarrassment (66%), fatigue (56%), and anxiety or depression (49%). Testing was judged insufficient by 44%. Only 28% were satisfied with treatment; 20% reported abandoning treatment due to ineffectiveness. Interview themes (N = 30) included frustration with diagnostic uncertainty, and feelings of therapeutic futility. Some reported psychological distress. Work and socializing were commonly disrupted., Conclusion: Diagnostic uncertainty, perceived limitations of testing, and treatment failures suggest needs for better approaches to evaluating and treating chronic cough. Special attention to identifying and addressing mental health issues appears warranted., (© 2023 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: Major depressive disorder (MDD) has increasing prevalence with age. Both objective measures of cognitive dysfunction and subjective report of cognitive difficulties related to MDD are often thought to worsen with increasing age. However, few studies have directly evaluated these characteristics across the adult lifespan., Methods: Participants included 23,594 adults completing objective and subjective measures of cognition on an online research registry. Linear regression including interactions of age group with depression was used to evaluate the association of self-reported MDD with measures of cognition in three age groups: 21-40 years; 41-60 years; 61+ years., Results: MDD (n = 2127) demonstrated poorer objective cognitive performance and greater subjective ratings of cognitive difficulties across all domains assessed compared to non-depressed individuals (ND; n = 21,467). Significant interactions of age group and MDD status with objective and subjective measures of cognition were observed for both middle age and older adults when compared to young adults but few significant differences between middle-aged and older adults were evident., Limitations: This study relied on self-report of MDD diagnosis, utilized remotely administered and unsupervised measures of cognition, and the sample was not diverse., Conclusions: The magnitude of association between MDD and cognitive correlates appears to plateau in middle age. Our results suggest that increased rates of dementia are not due to greater cognitive consequence of MDD in older adults and that age effects, and not greater effects of depression, may lead to increased diagnosis of MDD based on subjective report of cognitive symptoms., Competing Interests: Conflict of interest During the past three years, Dr. Mackin has received research support from The National Institute of Mental Health and Janssen Research and Development, LLC. Dr. Weiner has served on the Scientific Advisory Boards for Pfizer, BOLT International, Neurotrope Bioscience, Alzheon, Inc., Alzheimer's Therapeutic Research Institute (ATRI), Eli Lilly, U. of Penn's Neuroscience of Behavior Initiative, National Brain Research Centre (NBRC), India, Dolby Family Ventures, LP, and ADNI. Dr. Neuhaus has received research support from The National Institute on Aging. Dr. Nosheny has received research support from The National Institute on Aging; the California Department of Public Health; Genentech, Inc.; and the Alzheimer's Association. Dr. Ashford has received research support from the National Institute of Aging. Drs. Rhodes, Kassel, Knight, Banh, Ashford, and Tank, and Emily Burns, Monica R. Camacho, Diana Truran, Chengshi Jin, and Joseph Eichenbaum reported no biomedical financial interests or potential conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Hypoglycemia (HG) causes symptoms that can be fatal, and confers risk of dementia. Wearable devices can improve measurement and feedback to patients and clinicians about HG events and risk., Objectives: The aim of the study is to determine whether vulnerable older adults could use wearables, and explore HG frequency over 2 weeks., Methods: First, 10 participants with diabetes mellitus piloted a continuous glucometer, physical activity monitor, electronic medication bottles, and smartphones facilitating prompts about medications, behaviors, and symptoms. They reviewed graphs of glucose values, and were asked about the monitoring experience. Next, a larger sample ( N  = 70) wore glucometers and activity monitors, and used the smartphone and bottles, for 2 weeks. Participants provided feedback about the devices. Descriptive statistics summarized demographics, baseline experiences, behaviors, and HG., Results: In the initial pilot, 10 patients aged 50 to 85 participated. Problems addressed included failure of the glucometer adhesive. Patients sought understanding of graphs, often requiring some assistance with interpretation. Among 70 patients in subsequent testing, 67% were African-American, 59% were women. Nearly one-fourth (23%) indicated that they never check their blood sugars. Previous HG was reported by 67%. In 2 weeks of monitoring, 73% had HG (glucose ≤70 mg/dL), and 42% had serious, clinically significant HG (glucose under 54 mg/dL). Eight patients with HG also had HG by home-based blood glucometry. Nearly a third of daytime prompts were unanswered. In 24% of participants, continuous glucometers became detached., Conclusion: Continuous glucometry occurred for 2 weeks in an older vulnerable population, but devices posed wearability challenges. Most patients experienced HG, often serious in magnitude. This suggests important opportunities to improve wearability and decrease HG frequency among this population., Competing Interests: M.W. reports stock ownership in AbbVie Inc., Amgen Inc., Boston Scientific Corporation, Bristol-Myers Squibb Company, IBM, Integer Hldgs Corp Com, Johnson & Johnson, Mallinckrodt PLC, Mead Johnson & Company, LLC, Medtronic, Mylan N.V., Novo Nordisk A/S, Perspecta Inc Com, Pfizer Inc., Roche Pharmaceuticals, Senseonics, Stryker Corp., Teva Pharmaceutical Industries Ltd., and Walgreens Boots Alliance, Inc., (Thieme. All rights reserved.)

Introduction: As the number of biomarkers used to study Alzheimer's disease (AD) continues to increase, it is important to understand the utility of any given biomarker, as well as what additional information a biomarker provides when compared to others., Methods: We used hierarchical clustering to group 19 cross-sectional biomarkers in autosomal dominant AD. Feature selection identified biomarkers that were the strongest predictors of mutation status and estimated years from symptom onset (EYO). Biomarkers identified included clinical assessments, neuroimaging, cerebrospinal fluid amyloid, and tau, and emerging biomarkers of neuronal integrity and inflammation., Results: Three primary clusters were identified: neurodegeneration, amyloid/tau, and emerging biomarkers. Feature selection identified amyloid and tau measures as the primary predictors of mutation status and EYO. Emerging biomarkers of neuronal integrity and inflammation were relatively weak predictors., Discussion: These results provide novel insight into our understanding of the relationships among biomarkers and the staging of biomarkers based on disease progression., (© 2022 the Alzheimer's Association.)

Background: The association between omega-3 (ω-3) PUFAs and cognition, brain imaging and biomarkers is still not fully established., Objectives: The aim was to analyze the cross-sectional and retrospective longitudinal associations between erythrocyte ω-3 index and cognition, brain imaging, and biomarkers among older adults., Methods: A total of 832 Alzheimer's Disease Neuroimaging Initiative 3 (ADNI-3) participants, with a mean (SD) age of 74.0 (7.9) y, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment, and 11.4% with Alzheimer disease (AD) were included. A low ω-3 index (%EPA + %DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests [composite score, AD Assessment Scale Cognitive (ADAS-Cog), Wechsler Memory Scale (WMS), Trail Making Test, Category Fluency, Mini-Mental State Examination, Montreal Cognitive Assessment] and brain variables [hippocampal volume, white matter hyperintensities (WMHs), positron emission tomography (PET) amyloid-β (Aβ) and tau] were considered as outcomes in regression models., Results: Low ω-3 index was not associated with cognition, hippocampal, and WMH volume or brain Aβ and tau after adjustment for demographics, ApoEε4, cardiovascular disease, BMI, and total intracranial volume in the cross-sectional analysis. In the retrospective analysis, low ω-3 index was associated with greater Aβ accumulation (adjusted β = 0.02; 95% CI: 0.01, 0.03; P = 0.003). The composite cognitive score did not differ between groups; however, low ω-3 index was significantly associated with greater WMS-delayed recall cognitive decline (adjusted β = -1.18; 95% CI: -2.16, -0.19; P = 0.019), but unexpectedly lower total ADAS-Cog cognitive decline. Low ω-3 index was cross-sectionally associated with lower WMS performance (adjusted β = -1.81, SE = 0.73, P = 0.014) and higher tau accumulation among ApoE ε4 carriers., Conclusions: Longitudinally, low ω-3 index was associated with greater Aβ accumulation and WMS cognitive decline but unexpectedly with lower total ADAS-Cog cognitive decline. Although no associations were cross-sectionally found in the whole population, low ω-3 index was associated with lower WMS cognition and higher tau accumulation among ApoE ε4 carriers. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is registered at clinicaltrials.gov as NCT00106899., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: The relationships between hoarding disorder (HD) and other neurological and psychiatric disorders remain largely unknown. Although psychiatric burden in those with HD is high, less is known about neurological disorders. Furthermore, which disorders are primarily associated with HD vs which can be better explained via a relationship with another disorder has not been determined. To address these questions, we examined comorbidity patterns of psychiatric and neurological disorders in a large online registry of adults using network analyses., Methods: We first examined psychiatric comorbidity among 252 participants completing clinician administered psychiatric assessments. Using the Brain Health Registry (BHR) (N = 15,978), we next analyzed prevalence of self-reported neurological and psychiatric disorders among participants with no/minimal hoarding, subclinical hoarding, and clinically significant hoarding and used network analyses to identify direct and indirect relationships between HD and the assessed psychiatric and neurological disorders., Results: The most prevalent comorbidity in clinically assessed participants with HD was major depressive disorder (MDD, 62%), followed by generalized anxiety disorder (GAD, 32%). Network analyses in the BHR indicated that the strongest direct relationships with HD were attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD). The relationships between HD and neurological disorders, including mild cognitive impairment, were weak or non-existent after controlling for other disorders., Conclusions: ADHD, MDD, and OCD form a triad of psychiatric disorders directly associated with HD. Despite their high comorbidity rates, the associations among anxiety disorders and HD were weak or indirect., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Mathews has received royalties from W.W. Norton and Company, and travel funding from the Tourette Association of America. She has received research funding from the National Institutes of Health, the International Obsessive Compulsive Foundation, the Tourette Association of America, and the Patient Centered Research Outcomes Institute. She is an unpaid member of several advisory boards, including the Tourette Association of America, the International OCD Foundation, and the Family Foundation for OCD Research. Dr. Mackin has received research funding from the National Institutes of Health and Janssen Research and Development LLC. Dr. Sordo Vieira has received funding from the American Mathematical Society, the US National Science Foundation, and the National Institutes of Health. Dr. Nosheny has received support grants from: NIH (grant to institution), California Department of Public Health (grant to institution), Genentech, Inc. (grant to institution), Alzheimer's Association (grant to institution). Dr. Nosheny received the following support for attending meetings: MCI 2020 symposium/Mt. Sinai: payment to her. Dr. Simpson has received royalties from the Tourette Association of America for consultation and speaking engagements. Dr. Weiner has performed paid consulting on advisory boards for Alzheon, Inc., Biogen, Cerecin, Dolby Family Ventures, Eli Lilly, Merck Sharp & Dohme Corp., Nestle/Nestec, and Roche, and University of Southern California (USC). He has provided consulting for Baird Equity Capital, BioClinica, Cerecin, Inc., Cytox, Dolby Family Ventures, Duke University, FUJIFILM-Toyama Chemical (Japan), Garfield Weston, Genentech, Guidepoint Global, Indiana University, Japanese Organization for Medical Device Development, Inc. (JOMDD), Nestle/Nestec, NIH, Peerview Internal Medicine, Roche, T3D Therapeutics, University of Southern California (USC), Medscape, Eisai, and Vida Ventures. He has acted as a speaker/lecturer for The Buck Institute for Research on Aging; China Association for Alzheimer's Disease (CAAD); Japan Society for Dementia Research; Korean Dementia Society and received travel support from University of Southern California (USC), NervGen, ASFNR, CTAD Congres. Dr. Weiner holds stock options for Alzeca, Alzheon, Inc., and Anven. Dr. Weiner receives support for his work from the National Institutes of Health, Department of Defense, Patient-Centered Outcomes Research Institute, the California Dept. of Public Health, The University of Michigan, Siemens, Biogen, Hillblom Foundation, the Alzheimer's Association, the State of California, Johnson and Johnson, Kevin and Connie Shanahan, GE, VUmc, Australian Catholic University, The Stroke Foundation and the Veterans Administration. Dr. Weiner serves on the Editorial Boards for Alzheimer's & Dementia, TMRI and MRI. Moreover, Dr. Weiner has served on Advisory Boards (paid and unpaid) for: Acumen Pharmaceutical, ADNI, Alzheon, Inc., Biogen, Brain Health Registry, Cerecin, Dolby Family Ventures, Eli Lilly, Merck Sharp & Dohme Corp., National Institute on Aging (NIA), Nestle/Nestec, PCORI/PPRN, Roche, University of Southern California (USC), and NervGen. Christian Archer, Jessica Zakrzewski, Ashley Ordway, Marie Jean Gilles, Andrea Guastello, Sara Nutley, Binh Nguyen, and Na Liu reported no biomedical financial interests or potential conflicts of interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Recently, tau PET tracers have shown strong associations with clinical outcomes in individuals with cognitive impairment and cognitively unremarkable elderly individuals. flortaucipir PET scans to measure tau deposition in multiple brain areas as the disease progresses. This information needs to be summarized to evaluate disease severity and predict disease progression. We, therefore, sought to develop a machine learning-derived index, SPARE-Tau, which successfully detects pathology in the earliest disease stages and accurately predicts progression compared to a priori-based region of interest approaches (ROI)., Methods: 587 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort had flortaucipir scans, structural MRI scans, and an Aβ biomarker test (CSF or florbetapir PET) performed on the same visit. We derived the SPARE-Tau index in a subset of 367 participants. We evaluated associations with clinical measures for CSF p-tau, SPARE-MRI, and flortaucipir PET indices (SPARE-Tau, meta-temporal, and average Braak ROIs). Bootstrapped multivariate adaptive regression splines linear regression analyzed the association between the biomarkers and baseline ADAS-Cog13 scores. Bootstrapped multivariate linear regression models evaluated associations with clinical diagnosis. Cox-hazards and mixed-effects models investigated clinical progression and longitudinal ADAS-Cog13 changes. The Aβ positive cognitively unremarkable participants, not included in the SPARE-Tau training, served as an independent validation group., Results: Compared to CSF p-tau, meta-temporal, and averaged Braak tau PET ROIs, SPARE-Tau showed the strongest association with baseline ADAS-cog13 scores and diagnosis. SPARE-Tau also presented the strongest association with clinical progression in cognitively unremarkable participants and longitudinal ADAS-Cog13 changes. Results were confirmed in the Aβ+ cognitively unremarkable hold-out sample participants. CSF p-tau showed the weakest cross-sectional associations and longitudinal prediction., Discussion: Flortaucipir indices showed the strongest clinical association among the studied biomarkers (flortaucipir, florbetapir, structural MRI, and CSF p-tau) and were predictive in the preclinical disease stages. Among the flortaucipir indices, the machine-learning derived SPARE-Tau index was the most sensitive clinical progression biomarker. The combination of different biomarker modalities better predicted cognitive performance., Competing Interests: Dr. Shaw provides quality control oversight for the Roche Electrosys immunoassay platform as part of the ADNI-3 study. Dr. Weiner has served on the Scientific Advisory Boards for Alzheon, Inc., Accera, Merck, Nestle (Nolan), PCORI (PPRN), Eli Lilly, Delfino Logic Ltd. (for Merck), Dolby Ventures, Brain Health Registry, and ADNI. He served on the editorial boards for Alzheimer’s & Dementia and MRI. He has provided consulting and/or acted as a speaker/lecturer to Synarc, Pfizer, Accera, Inc., Alzheimer’s Drug Discovery Foundation (ADDF), Merck, BioClinica, Eli Lilly, Howard University, Guidepoint, Denali Therapeutics, Nestle/Nestec, GLG Research, Atheneum Partners, BIONEST Partners, American Academy of Neurology (AAN), and Society for Nuclear Medicine and Molecular Imaging (SNMMI). This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors report no competing interests.

The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-β42, amyloid-β40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-β42, amyloid-β40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Hoarding symptoms are associated with functional impairment, though investigation of disability among individuals with hoarding disorder has largely focused on clutter-related impairment to home management activities and difficulties using space because of clutter. This analysis assesses disability among individuals with hoarding symptoms in multiple domains of everyday functioning, including cognition, mobility, self-care, interpersonal and community-level interactions, and home management. The magnitude of the association between hoarding and disability was compared to that of medical and psychiatric disorders with documented high disability burden, including major depressive disorder (MDD), diabetes, and chronic pain., Methods: Data were cross-sectionally collected from 16,312 adult participants enrolled in an internet-based research registry, the Brain Health Registry. Pearson's chi-square tests and multivariable logistic regression models were used to quantify the relationship between hoarding and functional ability relative to MDD, diabetes, and chronic pain., Results: More than one in ten participants endorsed clinical (5.7%) or subclinical (5.7%) hoarding symptoms (CHS and SCHS, respectively). After adjusting for participant demographic characteristics and psychiatric and medical comorbidity, CHS and SCHS were associated with increased odds of impairment in all domains of functioning. Moderate to extreme impairment was endorsed more frequently by those with CHS or SCHS compared to those with self-reported MDD, diabetes, and/or chronic pain in nearly all domains (e.g., difficulty with day-to-day work or school: CHS: 18.7% vs. MDD: 11.8%, p < 0.0001) except mobility and self-care. While those with current depressive symptoms endorsed higher rates of impairment than those with hoarding symptoms, disability was most prevalent among those endorsing both hoarding and comorbid depressive symptoms., Conclusions: Hoarding symptoms are associated with profound disability in all domains of functioning. The burden of hoarding is comparable to that of other medical and psychiatric illnesses with known high rates of functional impairment. Future studies should examine the directionality and underlying causality of the observed associations, and possibly identify target interventions to minimize impairment associated with hoarding symptomatology., (© 2022. The Author(s).)

Background: Transgender individuals are less likely to have had a primary care visit in the last year than cisgender individuals. While the importance of multidisciplinary clinics for transgender care has been established, little is known about the healthcare experiences of transgender patients with these clinics., Objective: To describe how patients experience transgender clinics and how these experiences compare to those experiences in other settings., Participants: Twenty-one adult patients of a gender health program., Design and Approach: Semi-structured interviews of transgender patients. The interviews focused on two domains: healthcare experiences and relationships with healthcare providers., Key Results: Overall, transgender patients expressed a need for healthcare services, particularly for primary care, that are partially met by the comprehensive care clinic model. Limitations in access included the lack of willing providers, where the patients live, and long wait times for appointments. Participants recounted a range of experiences, both positive and negative, with providers outside of the transgender clinic, but only positive experiences to share about providers from the transgender clinic., Conclusion: Outside specialty transgender settings, many patients had negative experiences with providers who were unwilling or unable to provide care. This study speaks to the need for primary care providers who can and will treat transgender patients, as well as the need for healthcare spaces that feel safe to transgender patents., (© 2022. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Introduction: The objective of this study is to evaluate the reliability and validity of the ReVeRe TM word list recall test (RWLRT), which uses speech recognition, when administered remotely and unsupervised., Methods: Prospective cohort study. Participants included 249 cognitively intact community dwelling older adults. Measures included clinician administered neuropsychological assessments at baseline and unsupervised remotely administered tests of cognition from six time-points over six months., Results: The RWLRT showed acceptable validity. Reliability coefficients varied across time points, with poor reliability between times 1 and 2 and fair-to-good reliability across the remaining five testing sessions. Practice effects were observed with repeated administration as expected., Discussion: Unsupervised computerized tests of cognition, particularly word list learning and memory tests that use speech recognition, have significant potential for large scale early detection and long-term tracking of cognitive decline due to AD.

Online registries offer many advantages for research, including the ability to efficiently assess large numbers of individuals and identify potential participants for clinical trials and genetic studies. Of particular interest is the validity and utility of self-endorsement of psychiatric disorders in online registries, which, while increasingly more common, remain understudied. We thus assessed the comparability of prevalence estimated from self-endorsement of psychiatric disorders in one such registry, the Brain Health Registry (BHR) to prevalence computed from large US-based epidemiological studies and the degree to which BHR participants report psychiatric disorders consistently. We also examined the concordance between self-report and clinically determined diagnoses of various DSM-5 psychiatric disorders in a subset of participants who underwent direct assessments and identified possible reasons for discordance. Rates of self-reported psychiatric disorders were closest to previously reported population prevalence rates when endorsed at multiple timepoints, and accuracy was at least 70% for all except Hoarding Disorder as compared to the clinical diagnoses. Clinical data suggested that self-endorsement of a given psychiatric diagnosis was indicative of the presence of a closely related condition, although not necessarily for the specific disorder, with the exception of major depressive disorder, panic disorder, and hoarding disorder, which had high positive predictive values (85%, 73%, 100%, respectively). We conclude that self-reporting of psychiatric conditions in an online setting is a fair indicator of psychopathology, but should be accompanied by more in-depth interviews if using data from a participant for a specific disorder., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Neuroimaging heterogeneity in dementia has been examined using single modalities. We evaluated the associations of magnetic resonance imaging (MRI) atrophy and flortaucipir positron emission tomography (PET) clusters across the Alzheimer's disease (AD) spectrum., Methods: We included 496 Alzheimer's Disease Neuroimaging Initiative participants with brain MRI, flortaucipir PET scan, and amyloid beta biomarker measures obtained. We applied a novel robust collaborative clustering (RCC) approach on the MRI and flortaucipir PET scans. We derived indices for AD-like (SPARE-AD index) and brain age (SPARE-BA) atrophy., Results: We identified four tau (I-IV) and three atrophy clusters. Tau clusters were associated with the apolipoprotein E genotype. Atrophy clusters were associated with white matter hyperintensity volumes. Only the hippocampal sparing atrophy cluster showed a specific association with brain aging imaging index. Tau clusters presented stronger clinical associations than atrophy clusters. Tau and atrophy clusters were partially associated., Conclusions: Each neuroimaging modality captured different aspects of brain aging, genetics, vascular changes, and neurodegeneration leading to individual multimodal phenotyping., Competing Interests: Dr. Shaw provides quality control oversight for the Roche Electrosys immunoassay platform as part of the ADNI‐3 study. Dr. Weiner has served on the Scientific Advisory Boards for Alzheon, Inc., Accera, Merck, Nestle (Nolan), PCORI (PPRN), Eli Lilly, Delfino Logic Ltd. (for Merck), Dolby Ventures, Brain Health Registry, and ADNI. He served on the editorial boards for Alzheimer's & Dementia and MRI. He has provided consulting and/or acted as a speaker/lecturer to Synarc, Pfizer, Accera, Inc., Alzheimer's Drug Discovery Foundation (ADDF), Merck, BioClinica, Eli Lilly, Howard University, Guidepoint, Denali Therapeutics, Nestle/Nestec, GLG Research, Atheneum Partners, BIONEST Partners, American Academy of Neurology (AAN), and Society for Nuclear Medicine and Molecular Imaging (SNMMI). Other authors report no competing interests., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)

Hoarding disorder often results in debilitating functional impairment and may also compromise health-related quality of life (QoL). This study investigated the association between hoarding behavior and QoL relative to six highly impairing medical and psychiatric disorders in a sample of 20,722 participants enrolled in the internet-based Brain Health Registry. Nearly 1 in 8 participants (12.2%) endorsed clinically relevant hoarding symptoms (CHS). In separate multivariable linear regression models, hoarding was more strongly associated with mental QoL than diabetes (Standardizedβ = -0.21, 95% CI: [-0.22, -0.20] vs. -0.01 [-0.02, 0.0]), heart disease (-0.22 [-0.23, -0.20] vs. 0.00 [-0.02, 0.01]), chronic pain (-0.18 [-0.19, -0.16] vs. -0.12 [-0.13, -0.10]), post-traumatic stress disorder (PTSD; -0.20 [-0.22, -0.19] vs. -0.07 [-0.09, -0.06]), and substance use disorder (SUD; -0.21 [-0.23, -0.20] vs. -0.04 [-0.05, -0.03]). Similarly, CHS was more strongly negatively associated with physical QoL than diabetes (-0.11 [-0.10, -0.12] vs. -0.08 [-0.06, -0.09]), major depressive disorder (-0.09 [-0.10, -0.08] vs. -0.05 [-0.06, 0.03]), PTSD (-0.11 [-0.12, -0.10] vs. -0.08 [-0.09, -0.07]), and SUD (-0.12 [-0.13, -0.09] vs. -0.01 [-0.02, 0.00]). Higher hoarding severity was associated with reductions in both mental (Standardizedβ = -0.28, ΔR 2  = 0.08, p < 0.0001) and physical (β = -0.12, ΔR 2  = 0.02, p < 0.0001) QoL, though the strength of the relationship between hoarding symptoms and QoL varied with depression severity. Efforts to improve the overall QoL and well-being of those with CHS are needed., (Published by Elsevier Ltd.)