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.

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.

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.

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.

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.

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.

Lung Ultrasound-Guided Emergency Department Management of Acute Heart Failure (BLUSHED-AHF): A Randomized Controlled Pilot Trial.

OBJECTIVES: The goal of this study was to determine whether a 6-hour lung ultrasound (LUS)-guided strategy-of-care improves pulmonary congestion over usual management in the emergency department (ED) setting. A secondary goal was to explore whether early targeted intervention leads to improved outcomes. BACKGROUND: Targeting pulmonary congestion in acute heart failure remains a key goal of care. LUS B-lines are a semi-quantitative assessment of pulmonary congestion. Whether B-lines decrease in patients with acute heart failure by targeting therapy is not well known. METHODS: A multicenter, single-blind, ED-based, pilot trial randomized 130 patients to receive a 6-hour LUS-guided treatment strategy versus structured usual care. Patients were followed up throughout hospitalization and 90 days' postdischarge. B-lines ≤15 at 6 h was the primary outcome, and days alive and out of hospital (DAOOH) at 30 days was the main exploratory outcome. RESULTS: No significant difference in the proportion of patients with B-lines ≤15 at 6 hours (25.0% LUS vs 27.5% usual care; P = 0.83) or the number of B-lines at 6 hours (35.4 ± 26.8 LUS vs 34.3 ± 26.2 usual care; P = 0.82) was observed between groups. There were also no differences in DAOOH (21.3 ± 6.6 LUS vs 21.3 ± 7.1 usual care; P = 0.99). However, a significantly greater reduction in the number of B-lines was observed in LUS-guided patients compared with those receiving usual structured care during the first 48 hours (P = 0.04). CONCLUSIONS: In this pilot trial, ED use of LUS to target pulmonary congestion conferred no benefit compared with usual care in reducing the number of B-lines at 6 hours or in 30 days DAOOH. However, LUS-guided patients had faster resolution of congestion during the initial 48 hours. (B-lines Lung Ultrasound-Guided ED Management of Acute Heart Failure Pilot Trial; NCT03136198).

Mobility Impairment in Patients New to Dialysis.

BACKGROUND: Impaired mobility is associated with functional dependence, frailty, and mortality in prevalent patients undergoing dialysis. We investigated risk factors for mobility impairment, (poor gait speed) in patients incident to dialysis, and changes in gait speed over time in a 2-year longitudinal study. METHODS: One hundred eighty-three patients enrolled within 6 months of dialysis initiation were followed up 6, 12, and 24 months later. Grip strength, health-related quality of life, and comorbidities were assessed at baseline. Outcomes were (a) baseline gait speed and (b) change in gait speed over time. Gait speed was assessed by 4-meter walk. Multivariate linear regression was used to identify risk factors for low gait speed at baseline. For longitudinal analyses, linear mixed effects modeling with gait speed modeled over time was used as the outcome. RESULTS: Participants were 54.7 ± 12.8 years old, 52.5% men, 73.9% black with mean dialysis vintage of 100.1 ± 46.9 days and median gait speed 0.78 (0.64-0.094) m/s. Lower health utility and grip strength, diabetic nephropathy, and walking aids were associated with lower baseline gait speed. Loss of 0.1 m/s gait speed occurred in 24% of subjects at 1 year. In multivariate mixed effects models, only age, walking aid use, lower health utility, and lower handgrip strength were significantly associated with gait speed loss. CONCLUSIONS: In our cohort of incident dialysis patients, overall gait speed is very low and 54.2% of the subjects continue to lose gait speed over 2 years. Older age, lower handgrip strength, and quality of life are risk factors for slowness. Patients at highest risk of poor gait speed can be identified at dialysis initiation to allow targeted implementation of therapeutic options.

Novel Markers of Angiogenesis in the Setting of Cognitive Impairment and Dementia.

BACKGROUND: Aberrant angiogenesis may play a role in the development of Alzheimer's disease and related dementia. OBJECTIVE: To explore the relationship between angiogenesis activity and evidence of neurodegeneration among older adults. METHODS: Cross-sectional study of 49 older adults clinically characterized as cognitively normal, mild cognitive impairment, or early Alzheimer's disease. In addition to neuroimaging, we completed assays on peripheral blood, including: vascular endothelial growth factor, tumor necrosis factor, fibroblast growth factor, and amyloid-ß peptide 40. We used advanced polychromatic flow cytometry to phenotype circulating mononuclear cells to assess angiogenesis activity. RESULTS: Although we documented differences in cognitive performance, structural changes on neuroimaging, and burden of amyloid and tau on positron emission tomography, angiogenesis activity did not vary by group. Interestingly, VEGF levels were shown to be increased among subjects with mild cognitive impairment. In ANCOVA models controlling for age, sex, intracranial volume, and monocyte subpopulations, angiogenesis activity was correlated with increased white matter hyperintensities. CONCLUSION: We demonstrate a significant association between angiogenesis activity and cerebrovascular disease. To better understand the potential of angiogenesis as an intervention target, longitudinal studies are needed.

Beyond Discharge Summaries: Communication Preferences in Care Transitions Between Hospitalists and Primary Care Providers Using Electronic Medical Records.

BACKGROUND: Ineffective transitions of care continue to be a source of risk for patients. Although there has been widespread implementation of electronic medical record (EMR) systems, little is currently known about hospitalists' and primary care providers' (PCPs) direct communication preferences at discharge using messaging capabilities in a shared EMR system. OBJECTIVE: We examined how hospitalists and PCPs with a shared EMR prefer to directly communicate at the time of hospital discharge by identifying preferred modes, information prioritization, challenges, facilitators, and proposed solutions. DESIGN: A sequential, explanatory mixed methods study with surveys and semi-structured interviews. PARTICIPANTS: Thirty-eight academic hospitalists and 63 PCPs working in outpatient clinics in a single safety net hospital system with a shared EMR. MAIN APPROACH: Descriptive statistics were used to analyze survey responses. Interviews were analyzed using immersion/crystallization and a mixture of inductive and deductive thematic analysis. KEY RESULTS: PCPs preferred direct communication at discharge through a message within the EMR while hospitalists preferred a message within the EMR and email. Qualitative results identified key themes related to patient care and direct communication: value of direct communication, safety, social determinants of health, and clinical judgment. Both groups prioritized direct communication for high-risk medications, pending and follow-up studies, and high-risk patients that hospitalists were concerned about. Overall, both hospitalists and PCPs reported that ensuring patient safety, flagging patients with social challenges, and expressing concerns about patients based on clinical judgment were key communication priorities. CONCLUSIONS: Hospitalists and primary care providers report considerable overlap in preferences for direct communication at the time of hospital discharge through a shared EMR. Specifically, both groups reported similar concerns regarding patient safety and continuity during transitions. Direct messaging within the EMR could enable "closed loop" communication that helps ensure safe transitions of care for high-risk patients.

A Time Motion Study Evaluating the Impact of Geographic Cohorting of Hospitalists.

BACKGROUND: Geographic cohorting (GCh) localizes hospitalists to a unit. Our objective was to compare the GCh and non-GCh workday. METHODS: In an academic, Midwestern hospital we observed hospitalists in GCh and non-GCh teams. Time in patient rooms was considered direct care; other locations were considered 'indirect' care. Geotracking identified time spent in each location and was obtained for 17 hospitalists. It was supplemented by in-person observation of four GCh and four non-GCh hospitalists for a workday each. Multilevel modeling was used to analyze associations between direct and indirect care time and team and workday characteristics. RESULTS: Geotracking yielded 10,522 direct care episodes. GCh was associated with longer durations of patient visits while increasing patient loads were associated with shorter visits. GCh, increasing patient loads, and increasing numbers of units visited were associated with increased indirect care time. In-person observations yielded 3,032 minutes of data. GCh hospitalists were observed spending 56% of the day in computer interactions vs non-GCh hospitalists (39%; P < .005). The percentage of time spent multitasking was 18% for GCh and 14% for non-GCh hospitalists (P > .05). Interruptions were pervasive, but the highest interruption rate of once every eight minutes in the afternoon was noted in the GCh group. CONCLUSION: GCh may have the potential to increase patient-hospitalist interactions but these gains may be attenuated if patient loads and the structure of cohorting are suboptimal. The hospitalist workday is cognitively intense. The interruptions noted may increase the time taken for time-intensive tasks like electronic medical record interactions.

TACIT (High Sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial).

BACKGROUND: Identifying low-risk acute heart failure patients safe for discharge from the emergency department is a major unmet need. METHODS AND RESULTS: A prospective, observational, multicenter pilot study targeting lower risk acute heart failure patients to determine whether hsTnT (high-sensitivity troponin T) identifies emergency department acute heart failure patients at low risk for rehospitalization and mortality. hsTnT was drawn at baseline and 3 hours. Phone follow-up occurred at 30 and 90 days. The primary end point composite of all-cause mortality, rehospitalization, and emergency department visits at 90 days (changed from 30 days because of lack of mortality events), analyzed using logistic regression. Secondary end points: 30- and 90-day all-cause mortality. hsTnT values less than the 99th percentile were defined as low hsTnT. Out of 527 enrolled patients, 499 comprised the initial analysis set. Of these, 332 had both 0- and 3-hour hsTnT drawn, of whom 319 completed 30 day follow-up. The average age was 62, 60% male, and 57% black. Median hsTnT was 26.4 ng/L (interquartile range, 15.1-44.3). There were 99 (21%) 30-day composite events, 13 (2.7%) deaths at 30 days, and 25 deaths (8.2%) at 90 days. Serial hsTnT values below the 99th percentile were not associated with a lower risk for the 90-day primary composite end point (odds ratio, 0.79; 95% CI, 0.42-1.50; P=0.4736). However, no deaths occurred in the low hsTnT group at 30 days with 1 death at 90 days. CONCLUSIONS: hsTnT did not identify patients at low risk for the primary outcome of rehospitalization, emergency department visits, and mortality at 90 days. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02592135.

Telomere Shortening in the Alzheimer's Disease Neuroimaging Initiative Cohort.

BACKGROUND: Although shorter telomeres have been associated with Alzheimer's disease (AD), it is unclear whether longitudinal change in telomere length is associated with AD progression. OBJECTIVE: To investigate the association of telomere length change with AD diagnosis and progression. METHODS: In 653 individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, T/S ratio (telomere versus single copy gene), a proxy of telomere length, was measured for up to five visits per participant (N = 1918 samples post-QC) using quantitative PCR (qPCR). T/S ratio was adjusted for batch effects and DNA storage time. A mixed effects model was used to evaluate association of telomere length with AD diagnostic group and interaction of age and diagnosis. Another mixed effects model was used to compare T/S ratio changes pre- to post-conversion to MCI or AD to telomere change in participants with stable diagnoses. RESULTS: Shorter telomeres were associated with older age (Effect Size (ES) = -0.23) and male sex (ES = -0.26). Neither baseline T/S ratio (ES = -0.036) nor T/S ratio change (ES = 0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ES = -0.186). CONCLUSIONS: Although AD compared to controls showed small, non-significant effects for baseline T/S ratio and T/S ratio shortening, we did observe a larger, though still non-significant effect for greater telomere shortening in converters compared to non-converters. Although our results do not support telomere shortening as a robust biomarker of AD progression, further investigation in larger samples and for subgroups of participants may be informative.

Neurodegenerative Patterns of Cognitive Clusters of Early-Onset Alzheimer's Disease Subjects: Evidence for Disease Heterogeneity.

BACKGROUND/AIMS: Alzheimer's disease (AD) with onset before 65 (early-onset AD [EOAD]) occurs in approximately 6% of cases and can affect nonmemory domains. Here, we analyze patterns of impairment in amnestic EOAD individuals using data-driven statistical analyses. METHODS: Cognitive data of 146 EOAD subjects were Z-normalized to 395 cognitively normal (CN) individuals. Domain-averaged Z-scores were adjusted for age, sex, and education followed by Wald cluster analysis of residuals. Magnetic resonance imaging and positron emission tomography comparisons of EOAD clusters to age-matched CN were done using Statistic Parametric Mapping 8. Cluster-level-family-wise error (p < 0.05) correction was applied. Mixed-effect models were used to compute longitudinal change across clusters. RESULTS: Scree plot using the pseudo-T-squared suggested a 4-cluster solution. Cluster 1 (memory-predominant impairment) showed atrophy/hypometabolism in medial/lateral temporal, lateral parietal, and posterior cingulate regions. Cluster 2 (memory/visuospatial-predominant) showed atrophy/hypometabolism of medial temporal, temporoparietal, and frontal cortices. Cluster 3 (memory, language, and executive function) and Cluster 4 (globally impaired) manifested atrophy and hypometabolism throughout the brain. Longitudinally between-cluster differences in the visuospatial and language/executive domains were significant, suggesting phenotypic variation. CONCLUSION: We observed significant heterogeneity in cognitive presentation among amnestic EOAD subjects and patterns of atrophy/hypometabolism in each cluster in agreement with the observed cognitive phenotype.

Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial.

BACKGROUND: Medical treatment for acute heart failure (AHF) has not changed substantially over the last four decades. Emergency department (ED)-based evidence for treatment is limited. Outcomes remain poor, with a 25% mortality or re-admission rate within 30days post discharge. Targeting pulmonary congestion, which can be objectively assessed using lung ultrasound (LUS), may be associated with improved outcomes. METHODS: BLUSHED-AHF is a multicenter, randomized, pilot trial designed to test whether a strategy of care that utilizes a LUS-driven treatment protocol outperforms usual care for reducing pulmonary congestion in the ED. We will randomize 130 ED patients with AHF across five sites to, a) a structured treatment strategy guided by LUS vs. b) a structured treatment strategy guided by usual care. LUS-guided care will continue until there are ≤15 B-lines on LUS or 6h post enrollment. The primary outcome is the proportion of patients with B-lines ≤ 15 at the conclusion of 6 h of management. Patients will continue to undergo serial LUS exams during hospitalization, to better understand the time course of pulmonary congestion. Follow up will occur through 90days, exploring days-alive-and-out-of-hospital between the two arms. The study is registered on ClinicalTrials.gov (NCT03136198). CONCLUSION: If successful, this pilot study will inform future, larger trial design on LUS driven therapy aimed at guiding treatment and improving outcomes in patients with AHF.