Referral Sources Across Racial and Ethnic Groups at Alzheimer's Disease Research Centers.

Background: Despite the need to increase engagement of underrepresented groups (URG) in Alzheimer's disease and related dementias (ADRD) studies, enrollment remains low. Objective: Compare referral sources across racial and ethnic groups among participants enrolled in ADRC studies. Methods: Data for this cross-sectional secondary analysis were extracted from the National Alzheimer's Coordinating Center Uniform Data Set. We performed mixed effects logistic regression models using generalized estimating equations for professional referral versus non-professional referral by racial and ethnic group, adjusted for age, gender, education, visit year, and Clinical Dementia Rating scale (CDR) with a random effect for study site. Results: Included in the analysis were 48,330 participants across 46 ADRCs (mean [SD] age, 71.3 [10.5] years; 20,767 female [57%]; 4,138 Hispanic [8.6%]; 1,392 non-Hispanic Asian [2.9%]; 6,766 non-Hispanic Black [14%] individuals; and 676 individuals [1.4%] of other races. Non-Hispanic Black and Asian participants had lower odds of being referred by a professional contact compared to non-Hispanic White participants (Black: adjusted OR = 0.61, 95% CI = 0.44-0.86, p = 0.005; Asian: adjusted OR = 0.65, 95% CI, p = 0.004). In participants who had completed an MRI, there was no significant difference in referral source across ethnic and racial groups. Conclusions: Further studies are needed to better understand the systemic and structural factors that contribute to differences in referral sources and disparities in recruitment of URG into ADRD studies.

Large Language Model Influence on Management Reasoning: A Randomized Controlled Trial.

Importance: Large language model (LLM) artificial intelligence (AI) systems have shown promise in diagnostic reasoning, but their utility in management reasoning with no clear right answers is unknown. Objective: To determine whether LLM assistance improves physician performance on open-ended management reasoning tasks compared to conventional resources. Design: Prospective, randomized controlled trial conducted from 30 November 2023 to 21 April 2024. Setting: Multi-institutional study from Stanford University, Beth Israel Deaconess Medical Center, and the University of Virginia involving physicians from across the United States. Participants: 92 practicing attending physicians and residents with training in internal medicine, family medicine, or emergency medicine. Intervention: Five expert-developed clinical case vignettes were presented with multiple open-ended management questions and scoring rubrics created through a Delphi process. Physicians were randomized to use either GPT-4 via ChatGPT Plus in addition to conventional resources (e.g., UpToDate, Google), or conventional resources alone. Main Outcomes and Measures: The primary outcome was difference in total score between groups on expert-developed scoring rubrics. Secondary outcomes included domain-specific scores and time spent per case. Results: Physicians using the LLM scored higher compared to those using conventional resources (mean difference 6.5 %, 95% CI 2.7-10.2, p<0.001). Significant improvements were seen in management decisions (6.1%, 95% CI 2.5-9.7, p=0.001), diagnostic decisions (12.1%, 95% CI 3.1-21.0, p=0.009), and case-specific (6.2%, 95% CI 2.4-9.9, p=0.002) domains. GPT-4 users spent more time per case (mean difference 119.3 seconds, 95% CI 17.4-221.2, p=0.02). There was no significant difference between GPT-4-augmented physicians and GPT-4 alone (-0.9%, 95% CI -9.0 to 7.2, p=0.8). Conclusions and Relevance: LLM assistance improved physician management reasoning compared to conventional resources, with particular gains in contextual and patient-specific decision-making. These findings indicate that LLMs can augment management decision-making in complex cases. Trial registration: ClinicalTrials.gov Identifier: NCT06208423; https://classic.clinicaltrials.gov/ct2/show/NCT06208423.

Neuropsychiatric symptom burden in early-onset and late-onset Alzheimer's disease as a function of age.

INTRODUCTION: We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals. METHODS: Cross-sectional data from 2940 EOAD, 8665 LOAD, and 8775 age-stratified CU individuals (early-CU, n = 2433; late-CU, n = 6342) from the National Alzheimer's Coordinating Center database were included. Fisher's exact tests compared EOAD and LOAD on the presence and severity of NPSs. Multiple logistic regression models included an age*diagnosis interaction to examine age effects. RESULTS: Presence (ps < 0.0001) and severity (ps < 0.05) of NPS were greater in EOAD than in LOAD. However, after adjusting for base rates in NPS in CU individuals (age effects), only elation and eating behaviors were more frequent in EOAD (ps < 0.05) and nighttime behaviors more frequent and severe in LOAD (ps < 0.05). DISCUSSION: Few NPSs were specific to the EOAD versus LOAD. Previous findings of greater NPS burden in EOAD may partially reflect age effects. HIGHLIGHTS: Adjusting for age effect, elation and eating problems are more frequent in EOAD. Adjusting for age effect, sleep disturbances are more frequent and severe in LOAD. Age effects underlie higher neuropsychiatric symptom presentation in EOAD than in LOAD.

Concordance Between Electronic Health Record-Recorded Race and Ethnicity and Patient Report in Emergency Department Patients.

OBJECTIVE: We assessed the concordance of patient-reported race and ethnicity for emergency department (ED) patients compared with what was recorded in the electronic health record. METHODS: We conducted a single-center, prospective, observational study of 744 ED patients (English- and/or Spanish-speaking), asking them to describe their race and ethnicity. We compared the distributions of ethnicity and race between patient-reported and electronic health record data using McNemar's test. We calculated percent agreement and Cohen's kappa, with 95% confidence intervals (CI), for the concordance of patient-reported race and ethnicity with electronic health record data. RESULTS: Of 744 ED patients, 731 participants who completed the survey reported their ethnicity, resulting in 98.2% of electronic health records obtained ethnicities matched self-reported data (kappa = 0.95; 95% CI: 0.92 to 0.98). For those who self-reported as Hispanic, only 92.3% agreement was observed between the self-reported and electronic health record values. For all patients who had race recorded, 85.4% agreement was observed (kappa = 0.75; 95% CI 0.71 to 0.79). High rates of agreement were observed for Black or African American patients (98.7%) and White patients (96.6%), with low rates for those who identified as "More than one race" (22.9%) or "Other" race (1.8%). In the subset of Hispanic patients, low rates of agreement (25.0%) were observed for race (kappa = 0.10; 95% CI 0.01 to 0.19). CONCLUSIONS: Documentation discordance regarding race and ethnicity exists between electronic health records and self-reported data for our ED patients, particularly for ethnically Hispanic and Latino/a patients. Future efforts should focus on ensuring that demographic information in the electronic health record is accurately collected.

Environmental impact of a blood test reduction intervention in adult intensive care units: A before and after quality improvement project.

BACKGROUND: Pathology testing is a very common investigation in the intensive care unit (ICU). Many tests are ordered on a routine basis rather than for a specific clinical indication, resulting in potential patient harm and unnecessary financial and environmental costs. OBJECTIVE: The objective of this study was to determine whether a multifaceted intervention based on the principles of education, audit, and feedback can result in a decrease in unnecessary pathology tests without a commensurate increase in adverse patient outcomes and to measure this decrease in terms of the associated reduction in environmental and financial costs. METHODS: A before and after quality improvement project was conducted between 2017 and 2019 across four ICUs in three 12-month phases, divided according to baseline, intervention implementation, and follow-up. Local clinician champions from each site partnered with the project coordinating centre to develop and implement a range of interventions based on the principles of education, audit, and feedback. Data were collected for the number of pathology tests performed and the clinical characteristics of patients admitted to a participating ICU across the three phases. RESULTS: A total of 196 323 arterial blood gases and 460 258 other tests across eight categories were performed on the 22 210 patients admitted to participating ICUs during the project. A decrease in testing was observed across all but one category, with the greatest reduction seen in arterial blood gases (31.2% reduction in tests per bed-day). Across all categories, this equated to a mean reduction of 1.8 tCO2e (tonnes of carbon dioxide equivalent), a potential estimated total saving of Australian dollar $918 497.50. No increase in adverse clinical outcomes was observed. CONCLUSION: A multifaceted intervention based on the principles of education, audit, and feedback can produce a significant decrease in the number of unnecessary pathology tests performed. This reduction translates to substantial environmental and financial savings without any associated increase in adverse patient outcomes.

Short-Stay Units vs Routine Admission From the Emergency Department in Patients With Acute Heart Failure: The SSU-AHF Randomized Clinical Trial.

Importance: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking. Objective: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF. Design, Setting, and Participants: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission from the ED. Patients received follow-up at 30 and 90 days post discharge. The study began December 6, 2017, and was completed on July 22, 2021. The data were analyzed between March 27, 2020, and November 11, 2023. Intervention: Randomized post-ED disposition to less than 24 hours of SSU care vs hospitalization. Main Outcomes and Measures: The study was designed to detect at least 1-day superiority for a primary outcome of days alive and out of hospital (DAOOH) at 30-day follow-up for 534 participants, with an allowance of 10% participant attrition. Due to the COVID-19 pandemic, enrollment was truncated at 194 participants. Before unmasking, the primary outcome was changed from DAOOH to an outcome with adequate statistical power: quality of life as measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The KCCQ-12 scores range from 0 to 100, with higher scores indicating better quality of life. Results: Of the 193 patients enrolled (1 was found ineligible after randomization), the mean (SD) age was 64.8 (14.8) years, 79 (40.9%) were women, and 114 (59.1%) were men. Baseline characteristics were balanced between arms. The mean (SD) KCCQ-12 summary score between the SSU and hospitalization arms at 30 days was 51.3 (25.7) vs 45.8 (23.8) points, respectively (P = .19). Participants in the SSU arm had 1.6 more DAOOH at 30-day follow-up than those in the hospitalization arm (median [IQR], 26.9 [24.4-28.8] vs 25.4 [22.0-27.7] days; P = .02). Adverse events were uncommon and similar in both arms. Conclusions and Relevance: The findings show that the SSU strategy was no different than hospitalization with regard to KCCQ-12 score, superior for more DAOOH, and safe for lower-risk patients with AHF. These findings of lower health care utilization with the SSU strategy need to be definitively tested in an adequately powered study. Trial Registration: ClinicalTrials.gov Identifier: NCT03302910.

Revisiting the Percentage of K-12 Students in Need of Preventive Interventions in Schools in a "Peri-COVID" Era: Implications for the Implementation of Tiered Programming.

As the public health framework has been implemented in schools through multi-tiered systems of support, as in Positive Behavioral Interventions and Supports (PBIS), a prominent interpretation has been that 80% of students will benefit from universal or Tier 1 schoolwide behavior support, around 15% will require added selective or Tier 2 targeted support, and 5% will require the more intensive selective or Tier 3 intervention. The PBIS framework also emphasizes the use of tiered logic, with strengthened efforts at the universal and selective levels when student behavioral or mental health needs exceed expected levels. The prediction that 5% of students will require indicated support was based mostly on students at risk for discipline encounters (i.e., office discipline referral data) and, more recently, systematic screening data, but this percentage remains an interpretation of the public health framework. Further, epidemiologic data over the past decade show that rates of childhood mental health disorders have risen and are even higher now as schools struggle to recover from the COVID-19 pandemic-much higher than 15% and 5% for selective and indicated levels. Thus, we believe it is time to revisit projections of the number of students in need of Tier 2 and Tier 3 support. In this position paper, we review the evidence for escalating youth mental health needs and discuss the implications for the tiered prevention framework in schools. We describe strategies to expand the availability of preventive intervention supports beyond Tier 1 efforts and conclude with recommendations for practice, policy, and research in this peri-COVID recovery era.

Longitudinal Associations Between Blood Biomarkers and White Matter MRI in Sport-Related Concussion: A Study of the NCAA-DoD CARE Consortium.

BACKGROUND AND OBJECTIVES: To study longitudinal associations between blood-based neural biomarkers (including total tau, neurofilament light [NfL], glial fibrillary acidic protein [GFAP], and ubiquitin C-terminal hydrolase-L1) and white matter neuroimaging biomarkers in collegiate athletes with sport-related concussion (SRC) from 24 hours postinjury to 1 week after return to play. METHODS: We analyzed clinical and imaging data of concussed collegiate athletes in the Concussion Assessment, Research, and Education (CARE) Consortium. The CARE participants completed same-day clinical assessments, blood draws, and diffusion tensor imaging (DTI) at 3 time points: 24-48 hours postinjury, point of becoming asymptomatic, and 7 days after return to play. DTI probabilistic tractography was performed for each participant at each time point to render 27 participant-specific major white matter tracts. The microstructural organization of these tracts was characterized by 4 DTI metrics. Mixed-effects models with random intercepts were applied to test whether white matter microstructural abnormalities are associated with the blood-based biomarkers at the same time point. An interaction model was used to test whether the association varies across time points. A lagged model was used to test whether early blood-based biomarkers predict later microstructural changes. RESULTS: Data from 77 collegiate athletes were included in the following analyses. Among the 4 blood-based biomarkers, total tau had significant associations with the DTI metrics across the 3 time points. In particular, high tau level was associated with high radial diffusivity (RD) in the right corticospinal tract (ß = 0.25, SE = 0.07, p FDR-adjusted = 0.016) and superior thalamic radiation (ß = 0.21, SE = 0.07, p FDR-adjusted = 0.042). NfL and GFAP had time-dependent associations with the DTI metrics. NfL showed significant associations only at the asymptomatic time point (|ß|s > 0.12, SEs <0.09, psFDR-adjusted < 0.05) and GFAP showed a significant association only at 7 days after return to play (ßs > 0.14, SEs <0.06, psFDR-adjusted < 0.05). The p values for the associations of early tau and later RD were not significant after multiple comparison adjustment, but were less than 0.1 in 7 white matter tracts. DISCUSSION: This prospective study using data from the CARE Consortium demonstrated that in the early phase of SRC, white matter microstructural integrity detected by DTI neuroimaging was associated with elevated levels of blood-based biomarkers of traumatic brain injury. Total tau in the blood showed the strongest association with white matter microstructural changes.

Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.

BACKGROUND: There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure. METHODS: TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761. FINDINGS: Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10). INTERPRETATION: Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy. FUNDING: National Institutes of Health.

APOE ε4 is associated with earlier symptom onset in LOAD but later symptom onset in EOAD.

BACKGROUND: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on age of symptom onset (AO) in early- (EO) and late- (LO) onset Alzheimer's disease (AD). METHOD: A total of 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center (NACC) were included. We used analysis of variance to examine AO differences between sexes and APOE genotypes and the effect of APOE ε4, sex, and their interaction on AO in EOAD and LOAD, separately. RESULTS: APOE ε4 carriers in LOAD had younger AO and in EOAD had older AO. Female EOAD APOE ε4 carriers had older AO compared to non-carriers (P < 0.0001). There was no difference for males. Both male and female LOAD APOE ε4 carriers had younger AO relative to non-carriers (P < 0.0001). CONCLUSION: The observed earlier AO in EOAD APOE ε4 non-carriers relative to carriers, particularly in females, suggests the presence of additional AD risk variants.

Care-home Nurses' responses to the COVID-19 pandemic: Managing ethical conundrums at personal cost: A qualitative study.

INTRODUCTION: The COVID-19 pandemic had an unprecedented effect on those living and working in care-homes for older people, as residents were particularly vulnerable to contracting the SARS-CoV-2 virus, associated with high morbidity and mortality. Often undervalued, care-home nurses (RNs) are leaders, managing complex care while working in isolation from their professional peers. The pandemic made this more apparent, when care and treatments for COVID-19 were initially unknown, isolation increased due to withdrawal of many professional health services, accompanied by staff shortages. OBJECTIVE: To explore RNs' experiences of working in older people's care-homes during the COVID-19 pandemic. DESIGN: Qualitative interview study. SETTING: Care-homes for older people in England and Scotland, UK. METHODS: Recruitment via direct contact with care-homes, social media, and links provided by national partners, then purposive sampling for age, gender, type of care-home, and location. Data collected through one-to-one online interviews using topic guide developed collaboratively with care-home nurses, focusing on how COVID-19 impacted on nurses' resilience and mental wellbeing. Data analyzed thematically using Tronto's ethics of care framework to guide development of interpretative themes. RESULTS: Eighteen nurses (16 female; 16 adult, and two mental health nurses) were interviewed March-June 2021; majority aged 46-55 years; mean time registered with Nursing and Midwifery Council: 19 years; 17 had nursed residents with COVID-19. RNs' experiences resonated with Tronto's five tenets of ethical care: attentiveness, responsibility, competence, responsiveness, and solidarity. All nurses described being attentive to needs of others, but were less attentive to their own needs, which came at personal cost. RNs were aware of their professional and leadership responsibilities, being as responsive as they could be to resident needs, processing and sharing rapidly changing guidance and implementing appropriate infection control measures, but felt that relatives and regulatory bodies were not always appreciative. RNs developed enhanced clinical skills, increasing their professional standing, but reported having to compromise care, leading to moral distress. Broadly, participants reported a sense of solidarity across care-home staff and working together to cope with the crisis. CONCLUSION: Care-home nurses felt unprepared for managing the COVID-19 pandemic, many experienced moral distress. Supporting care-home nurses to recover from the pandemic is essential to maintain a healthy, stable workforce and needs to be specific to care-home RNs, recognizing their unique pandemic experiences. Support for RNs will likely benefit other care-home workers either directly through wider roll-out, or indirectly through improved wellbeing of nurse leaders. CLINICAL RELEVANCE: The COVID-19 pandemic, an international public health emergency, created many challenges for Registered Nurses (RNs) working in long-term care facilities for older people, as residents were particularly vulnerable to the impact of the SARS-CoV-2 virus. Care-home RNs faced challenges distinct from their hospital-based nursing peers and non-nursing social care colleagues due to their isolation, leadership roles, professional legal obligations, and ethical responsibilities, leading to psychological distress on the one hand, but also a newly found confidence in their existing and newly developed skills, and increased recognition by the wider health community of their specialisms.

APOE ε4 carrier status and sex differentiate rates of cognitive decline in early- and late-onset Alzheimer's disease.

BACKGROUND: We studied the effect of apolipoprotein E (APOE) ε4 status and sex on rates of cognitive decline in early- (EO) and late- (LO) onset Alzheimer's disease (AD). METHOD: We ran mixed-effects models with longitudinal cognitive measures as dependent variables, and sex, APOE ε4 carrier status, and interaction terms as predictor variables in 998 EOAD and 2562 LOAD participants from the National Alzheimer's Coordinating Center. RESULTS: APOE ε4 carriers showed accelerated cognitive decline relative to non-carriers in both EOAD and LOAD, although the patterns of specific cognitive domains that were affected differed. Female participants showed accelerated cognitive decline relative to male participants in EOAD only. The effect of APOE ε4 was greater in EOAD for executive functioning (p < 0.0001) and greater in LOAD for language (p < 0.0001). CONCLUSION: We found APOE ε4 effects on cognitive decline in both EOAD and LOAD and female sex in EOAD only. The specific patterns and magnitude of decline are distinct between the two disease variants. HIGHLIGHTS: Apolipoprotein E (APOE) ε4 carrier status and sex differentiate rates of cognitive decline in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD). APOE ε4 in EOAD accelerated decline in memory, executive, and processing speed domains. Female sex in EOAD accelerated decline in language, memory, and global cognition. The effect of APOE ε4 was stronger for language in LOAD and for executive function in EOAD. Sex effects on language and executive function decline differed between EOAD and LOAD.

English care home staff morale and preparedness during the COVID pandemic: A longitudinal analysis.

BACKGROUND: Staff actions to prevent infection introduction and transmission in long-term care facilities (LTCFs) were key to reducing morbidity and mortality from COVID-19. Implementing infection control measures (ICMs) requires training, adherence and complex decision making while trying to deliver high quality care. We surveyed LTCF staff in England about their preparedness and morale at 3 timepoints during the COVID-19 epidemic. METHODS: Online structured survey targeted at LTCF workers (any role) administered at 3 timepoints (November 2020-January 2021; August-November 2021; March-May 2022). Narrative summary of answers, narrative and statistical summary (proportionality with Pearson's chi-square or Fisher's Exact Test) of possible differences in answers between waves. RESULTS: Across all 3 survey waves, 387 responses were received. Morale, attitudes towards working environment and perception about colleague collaboration were mostly positive at all survey points. Infection control training was perceived as adequate. Staff felt mostly positive emotions at work. The working environment remained challenging. Masks were the single form of PPE most consistently used; eye protection the least used. Mask-wearing was linked to poorer communication and resident discomfort as well as mild negative health impacts on many staff, such as dehydration and adverse skin reactions. Hand sanitizer caused skin irritation. CONCUSIONS: Staff morale and working practices were generally good even though the working environment provided many new challenges that did not exist pre-pandemic.

A How-To Guide for Open-Science Practices in Special Education Research.

Open-science reforms, which aim to increase credibility and access of research, have the potential to benefit the research base in special education, as well as practice and policy informed by that research base. Awareness of open science is increasing among special education researchers. However, relatively few researchers in the field have experience using multiple open-science practices, and few practical guidelines or resources have been tailored to special education researchers to support their exploration and adoption of open science. In this paper, we described and provided guidelines and resources for applying five core open-science practices-preregistration, registered reports, data sharing, materials sharing, and open-access publishing-in special education research.

Exploring Views and Professional Learning Needs of Comprehensive, Integrated, Three-Tiered (Ci3T) Leadership Teams Related to Universal Behavior Screening Implementation.

Research conducted to date has highlighted barriers to initial adoption of universal behavior screening in schools. However, little is known regarding the experiences of those implementing these procedures and there have been no studies conducted examining the experiences of educators in different stages of implementing various tiered systems of supports. Universal screening is foundational to a successful Comprehensive, Integrated Three-Tiered (Ci3T) model of prevention-an integrated tiered system addressing academics, behavior, and social and emotional well-being. Therefore, the perspectives of Ci3T Leadership Team members at different stages of Ci3T implementation were solicited through an online survey that sought to understand (1) current school-based screening practices and (2) individual beliefs regarding those practices. A total of 165 Ci3T Leadership Team members representing five school districts from three geographic regions across the United States, all of whom were participating in an Institute of Education Sciences Network grant examining integrated tiered systems, reported the screening procedures were generally well-understood and feasible to implement. At the same time, results highlighted continuing professional learning may be beneficial in the areas of: (1) integrating multiple sources of data (e.g., screening data with other data collected as regular school practices) and (2) using those multiple data sources to determine next steps for intervention. We discuss educational implications, limitations, and directions for future inquiry.

Initiation of Dialysis Is Associated With Impaired Cardiovascular Functional Capacity.

Background The transition to dialysis period carries a substantial increased cardiovascular risk in patients with chronic kidney disease. Despite this, alterations in cardiovascular functional capacity during this transition are largely unknown. The present study therefore sought to assess ventilatory exercise response measures in patients within 1 year of initiating dialysis. Methods and Results We conducted a cross-sectional study of 241 patients with chronic kidney disease stage 5 from the CAPER (Cardiopulmonary Exercise Testing in Renal Failure) study and from the intradialytic low-frequency electrical muscle stimulation pilot randomized controlled trial cohorts. Patients underwent cardiopulmonary exercise testing and echocardiography. Of the 241 patients (age, 48.9 [15.0] years; 154 [63.9%] men), 42 were predialytic (mean estimated glomerular filtration rate, 14 mL·min-1·1.73 m-2), 54 had a dialysis vintage ≤12 months, and 145 had a dialysis vintage >12 months. Dialysis vintage ≤12 months exhibited a significantly impaired cardiovascular functional capacity, as assessed by oxygen uptake at peak exercise (18.7 [5.8] mL·min-1·kg-1) compared with predialysis (22.7 [5.2] mL·min-1·kg-1; P<0.001). Dialysis vintage ≤12 months also exhibited reduced peak workload, impaired peak heart rate, reduced circulatory power, and increased left ventricular mass index (P<0.05 for all) compared with predialysis. After excluding those with prior kidney transplant, dialysis vintage >12 months exhibited a lower oxygen uptake at peak exercise (17.0 [4.9] mL·min-1·kg-1) compared with dialysis vintage ≤12 months (18.9 [5.9] mL·min-1·kg-1; P=0.033). Conclusions Initiating dialysis is associated with a significant impairment in oxygen uptake at peak exercise and overall decrements in ventilatory and hemodynamic exercise responses that predispose patients to functional dependence. The magnitude of these changes is comparable to the differences between low-risk New York Heart Association class I and higher-risk New York Heart Association class II to IV heart failure.

Association of the top 20 Alzheimer's disease risk genes with [18F]flortaucipir PET.

Introduction: We previously reported genetic associations of the top Alzheimer's disease (AD) risk alleles with amyloid deposition and neurodegeneration. Here, we report the association of these variants with [18F]flortaucipir standardized uptake value ratio (SUVR). Methods: We analyzed the [18F]flortaucipir scans of 352 cognitively normal (CN), 160 mild cognitive impairment (MCI), and 54 dementia (DEM) participants from Alzheimer's Disease Neuroimaging Initiative (ADNI)2 and 3. We ran step-wise regression with log-transformed [18F]flortaucipir meta-region of interest SUVR as the outcome measure and genetic variants, age, sex, and apolipoprotein E (APOE) ε4 as predictors. The results were visualized using parametric mapping at familywise error cluster-level-corrected P < .05. Results: APOE ε4 showed significant (P < .05) associations with tau deposition across all disease stages. Other significantly associated genes include variants in ABCA7 in CN, CR1 in MCI, BIN1 and CASS4 in MCI and dementia participants. Discussion: We found significant associations to tau deposition for ABCA7, BIN1, CASS4, and CR1, in addition to APOE ε4. These four variants have been previously associated with tau metabolism through model systems.

Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience.

BACKGROUND: Since 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression. METHODS: We performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort. RESULTS: No difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05). CONCLUSIONS: In this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.

An Automated Line-of-Therapy Algorithm for Adults With Metastatic Non-Small Cell Lung Cancer: Validation Study Using Blinded Manual Chart Review.

BACKGROUND: Extraction of line-of-therapy (LOT) information from electronic health record and claims data is essential for determining longitudinal changes in systemic anticancer therapy in real-world clinical settings. OBJECTIVE: The aim of this retrospective cohort analysis is to validate and refine our previously described open-source LOT algorithm by comparing the output of the algorithm with results obtained through blinded manual chart review. METHODS: We used structured electronic health record data and clinical documents to identify 500 adult patients treated for metastatic non-small cell lung cancer with systemic anticancer therapy from 2011 to mid-2018; we assigned patients to training (n=350) and test (n=150) cohorts, randomly divided proportional to the overall ratio of simple:complex cases (n=254:246). Simple cases were patients who received one LOT and no maintenance therapy; complex cases were patients who received more than one LOT and/or maintenance therapy. Algorithmic changes were performed using the training cohort data, after which the refined algorithm was evaluated against the test cohort. RESULTS: For simple cases, 16 instances of discordance between the LOT algorithm and chart review prerefinement were reduced to 8 instances postrefinement; in the test cohort, there was no discordance between algorithm and chart review. For complex cases, algorithm refinement reduced the discordance from 68 to 62 instances, with 37 instances in the test cohort. The percentage agreement between LOT algorithm output and chart review for patients who received one LOT was 89% prerefinement, 93% postrefinement, and 93% for the test cohort, whereas the likelihood of precise matching between algorithm output and chart review decreased with an increasing number of unique regimens. Several areas of discordance that arose from differing definitions of LOTs and maintenance therapy could not be objectively resolved because of a lack of precise definitions in the medical literature. CONCLUSIONS: Our findings identify common sources of discordance between the LOT algorithm and clinician documentation, providing the possibility of targeted algorithm refinement.