Antibiotic stewardship programs (ASPs) target hospitalized children, but most do not routinely review antibiotic prescriptions at discharge, despite 30% of discharged children receiving additional antibiotics. Our objective is to describe discharge antibiotic prescribing in children hospitalized for uncomplicated community-acquired pneumonia (CAP), skin/soft tissue infection (SSTI), and urinary tract infection (UTI).

Retrospective cohort study.

Four academic children’s hospitals with established ASPs.

ICD-10 codes identified 3,847 encounters for children <18 years admitted from January 1, 2021 to December 31, 2021 and prescribed antibiotics at discharge for uncomplicated CAP, SSTI, or UTI. After excluding children with medical complexity and encounters with concomitant infections, >7 days hospital stay, or intensive care unit stay, 1,206 encounters were included.

Primary outcomes were the percentage of subjects prescribed optimal (1) total (inpatient plus outpatient) duration of therapy (DOT) and (2) antibiotic choice based on current national guidelines and available evidence.

Of 226 encounters for CAP, 417 for UTI, and 563 for SSTI, the median age was 4 years, 52% were female, and the median DOT was 9 days (8 for CAP, 10 for UTI, and 9 for SSTI). Antibiotic choice was optimal for 77%, and DOT was optimal for 26%. Only 20% of antibiotic courses included both optimal DOT and antibiotic choice.

At 4 children’s hospitals with established ASPs, 80% of discharge antibiotic courses for CAP, UTI, and SSTI were suboptimal either by choice of antibiotic or DOT. Discharge antibiotic prescribing represents an opportunity to improve antibiotic use in children.

To determine whether differences exist in antibiotic prescribing for respiratory infections in pediatric urgent cares (PUCs) by patient race/ethnicity, insurance, and language.

Multi-center cohort study.

Nine organizations (92 locations) from 22 states and Washington, DC.

Patients ages 6 months–18 years evaluated April 2022–April 2023, with acute viral respiratory infections, otitis media with effusion (OME), acute otitis media (AOM), pharyngitis, community-acquired pneumonia (CAP), and sinusitis.

We compared the use of first-line (FL) therapy as defined by published guidelines. We used race/ethnicity, insurance, and language as exposures. Multivariable logistic regression models estimated the odds of FL therapy by group.

We evaluated 396,340 ARI encounters. Among all encounters, 351,930 (88.8%) received FL therapy (98% for viral respiratory infections, 85.4% for AOM, 96.0% for streptococcal pharyngitis, 83.6% for sinusitis). OME and CAP had the lowest rates of FL therapy (49.9% and 60.7%, respectively). Adjusted odds of receiving FL therapy were higher in Black Non-Hispanic (NH) (adjusted odds ratio [aOR] 1.53 [1.47, 1.59]), Asian NH (aOR 1.46 [1.40, 1.53], and Hispanic children (aOR 1.37 [1.33, 1.41]), compared to White NH. Additionally, odds of receiving FL therapy were higher in children with Medicaid/Medicare (aOR 1.21 [1.18–1.24]) and self-pay (aOR 1.18 [1.1–1.27]) compared to those with commercial insurance.

This multicenter collaborative showed lower rates of FL therapy for children of the White NH race and those with commercial insurance compared to other groups. Exploring these differences through a health equity lens is important for developing mitigating strategies.

Being married may protect late-life cognition. Less is known about living arrangement among unmarried adults and mechanisms such as brain health (BH) and cognitive reserve (CR) across race and ethnicity or sex/gender. The current study examines (1) associations between marital status, BH, and CR among diverse older adults and (2) whether one’s living arrangement is linked to BH and CR among unmarried adults.

Cross-sectional data come from the Washington Heights-Inwood Columbia Aging Project (N = 778, 41% Hispanic, 33% non-Hispanic Black, 25% non-Hispanic White; 64% women). Magnetic resonance imaging (MRI) markers of BH included cortical thickness in Alzheimer’s disease signature regions and hippocampal, gray matter, and white matter hyperintensity volumes. CR was residual variance in an episodic memory composite after partialing out MRI markers. Exploratory analyses stratified by race and ethnicity and sex/gender and included potential mediators.

Marital status was associated with CR, but not BH. Compared to married individuals, those who were previously married (i.e., divorced, widowed, and separated) had lower CR than their married counterparts in the full sample, among White and Hispanic subgroups, and among women. Never married women also had lower CR than married women. These findings were independent of age, education, physical health, and household income. Among never married individuals, living with others was negatively linked to BH.

Marriage may protect late-life cognition via CR. Findings also highlight differential effects across race and ethnicity and sex/gender. Marital status could be considered when assessing the risk of cognitive impairment during routine screenings.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Poor cardiovascular health occurs with age and is associated with increased dementia risk, yet its impact on frontotemporal lobar degeneration (FTLD) and autosomal dominant neurodegenerative disease has not been well established. Examining cardiovascular risk in a population with high genetic vulnerability provides an opportunity to assess the impact of lifestyle factors on brain health outcomes. In the current study, we examined whether systemic vascular burden associates with accelerated cognitive and brain aging outcomes in genetic FTLD.

166 adults with autosomal dominant FTLD (C9orf72 n= 97; GRN n= 34; MAPT n= 35; 54% female; Mage = 47.9; Meducation = 15.6 years) enrolled in the Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Longitudinal FTD study (ALLFTD) were included. Participants completed neuroimaging and were screened for cardiovascular risk and functional impairment during a comprehensive neurobehavioral and medical interview. A vascular burden score (VBS) was created by summing vascular risk factors (VRS) [diabetes, hypertension, hyperlipidemia, and sleep apnea] and vascular diseases (VDS) [cerebrovascular disease (e.g., TIA, CVA), cardiac arrhythmia (e.g., atrial fibrillation, pacemaker, defibrillator), coronary artery disease (e.g., myocardial infarction, cardiac bypass, stent), and congestive heart failure] following a previously developed composite (range 0 to 8). We examined the interaction between each vascular health metric (VBS, VDS, VRS) and age (vascular health*age) on clinical severity (CDR plus NACC FTLD-SB), and white matter hyperintensity (WMH) volume outcomes, adjusting for age and sex. Vascular risk, disease, and overall burden scores were examined in separate models.

There was a statistically significant interaction between total VBS and age on both clinical severity (ß=0.20, p=0.044) and WMH burden (ß=0.20, p=0.032). Mutation carriers with higher vascular burden evidenced worse clinical and WMH outcomes for their age. When breaking down the vascular burden score into (separate) vascular risk (VRS) and vascular disease (VDS) scores, the interaction between age and VRS remained significant only for WMH (ß=0.26, p=0.009), but not clinical severity (ß=0.04, p=0.685). On the other hand, the interaction between VDS and age remained significant only for clinical severity (ß=0.20, p=0.041) but not WMH (ß=0.17, p=0.066).

Our results demonstrate that systemic vascular burden is associated with an “accelerated aging” pattern on clinical and white matter outcomes in autosomal dominant FTLD. Specifically, mutation carriers with greater vascular burden show poorer neurobehavioral outcomes for their chronological age. When separating vascular risk from disease, risk was associated with higher age-related WMH burden, whereas disease was associated with poorer age-related clinical severity of mutation carriers. This pattern suggests preferential brain-related effects of vascular risk factors, while the functional impact of such factors may be more closely aligned with fulminant vascular disease. Our results suggest cardiovascular health may be an important, potentially modifiable risk factor to help mitigate the cognitive and behavioral disturbances associated with having a pathogenic variant of autosomal dominant FTLD. Future studies should continue to examine the neuropathological processes underlying the impact of cardiovascular risk in FTLD to inform more precise recommendations, particularly as it relates to lifestyle interventions.

A common assumption in clinical neuropsychology is that cerebrovascular risk is adversely associated with executive function, while Alzheimer’s disease (AD) primarily targets episodic memory. The goal of the present study was to determine the cross-sectional and longitudinal validity of these assumptions using validated markers of cerebrovascular and AD burden.

19271 longitudinally-followed participants from the National Alzheimer Coordinating Center (NACC) database (Mean age= 72.25; SD age= 10.42; 58% women; 51.6% CDR= 0, 33.7% CDR= 0.5, 14.7% CDR> 1) were included. Cognitive outcomes were a composite memory score and an executive function composite score (UDS3-EF; Staffaroni et al., 2020). Baseline presence of cerebrovascular disease was indexed by the presence of moderate to severe white matter hyperintensities or lacunar infarct on brain MRI (yes/no), while baseline AD pathology was indexed by the presence of a positive amyloid PET scan or elevated CSF AD biomarkers (yes/no). We used linear mixed effect models to assess the effects of baseline cerebrovascular disease, baseline AD pathology, and their interactions with time in study (years post baseline) controlling for baseline age, sex, education, and baseline MoCA score.

Baseline cerebrovascular disease was significantly associated with a lower intercept on executive functioning (between-person effect) (p < -0.001, 95% CI -0.37, -0.14) but not memory, while presence of AD biomarkers was associated with a lower memory intercept (p < -0.001, 95% CI -0.52, -0.39) but not executive function. However, only presence of AD pathology at baseline was associated with faster longitudinal decline on both memory and executive functioning over time. Baseline cerebrovascular disease did not independently relate to rate of cognitive decline.

Consistent with widely held assumptions, our between-person analyses showed that MRI evidence of cerebrovascular disease was associated with worse executive functioning but not memory, while biomarker evidence of AD pathology was associated with worse memory but not executive function. Longitudinally, however, AD is the primary driver of decline in both executive and memory function. These results extend our understanding of how pathology impacts cognition in aging cohorts and highlight the importance of using longitudinal models.

The AD8 is a validated screening instrument for functional changes that may be caused by cognitive decline and dementia. It is frequently used in clinics and research studies because it is short and easy to administer, with a cut off score of 2 out of 8 items recommended to maximize sensitivity and specificity. This cutoff assumes that all 8 items provide equivalent “information” about everyday functioning. In this study, we used item response theory (IRT) to test this assumption. To determine the relevance of this measure of everyday functioning in men and women, and across race, ethnicity, and education, we conducted differential item functioning (DIF) analysis to test for item bias.

Data came from the 2021 follow up of the High School & Beyond cohort (N=8,690; mean age 57.5 ± 1.2; 55% women), a nationally representative, longitudinal study of Americans who were first surveyed in 1980 when they were in the 10th or 12th grade. Participants were asked AD8 questions about their own functioning via phone or internet survey. First, we estimated a one-parameter (i.e., differing difficulty, equal discrimination across items) and two-parameter IRT model (i.e., differing difficulty and differing discrimination across items). We compared model fit using a likelihood-ratio test. Second, we tested for uniform and non-uniform DIF on AD8 items by sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), education level (high school or less, some college, BA degree or more), and survey mode (phone or internet). We examined DIF salience by comparing the difference between original and DIF-adjusted AD8 scores to the standard error of measurement of the original score.

The two-parameter IRT model fit the data significantly better than the one-parameter model, indicating that some items were more strongly related to underlying everyday functional ability than others. For example, the “problems with judgment” item had higher discrimination (more information) than the “less interest in hobbies/activities” item. There were significant differences in item endorsement by race/ethnicity, education, and survey mode. We found significant uniform and non-uniform DIF on several items across each of these groups. For example, for a given level of functional decline (theta) White participants were more likely to endorse “Daily problems with thinking/memory” than Black and Hispanic participants. The DIF was salient (i.e., caused AD8 scores to change by greater than the standard error of measurement for a large portion of respondents) for those with a college degree and phone respondents.

In a population representative sample of Americans ∼age 57, the items on the AD8 contributed differing levels of discrimination along the range of everyday functioning that is impacted by later life cognitive impairment. This suggests that a simple cut-off or summed score may not be appropriate since some items yield more information about the underlying construct than others. Furthermore, we observed significant and salient DIF on several items by education and survey mode, AD8 scores should not be compared across education groups and assessment modes without adjustment for this measurement bias.

Recruiting underrepresented people and communities in research is essential for generalizable findings. Ensuring representative participants can be particularly challenging for practice-level dissemination and implementation trials. Novel use of real-world data about practices and the communities they serve could promote more equitable and inclusive recruitment.

We used a comprehensive primary care clinician and practice database, the Virginia All-Payers Claims Database, and the HealthLandscape Virginia mapping tool with community-level socio-ecological information to prospectively inform practice recruitment for a study to help primary care better screen and counsel for unhealthy alcohol use. Throughout recruitment, we measured how similar study practices were to primary care on average, mapped where practices’ patients lived, and iteratively adapted our recruitment strategies.

In response to practice and community data, we adapted our recruitment strategy three times; first leveraging relationships with residency graduates, then a health system and professional organization approach, followed by a community-targeted approach, and a concluding approach using all three approaches. We enrolled 76 practices whose patients live in 97.3% (1844 of 1907) of Virginia’s census tracts. Our overall patient sample had similar demographics to the state for race (21.7% vs 20.0% Black), ethnicity (9.5% vs 10.2% Hispanic), insurance status (6.4% vs 8.0% uninsured), and education (26.0% vs 32.5% high school graduate or less). Each practice recruitment approach uniquely included different communities and patients.

Data about primary care practices and the communities they serve can prospectively inform research recruitment of practices to yield more representative and inclusive patient cohorts for participation.