It is well established that there is a substantial genetic component to eating disorders (EDs). Polygenic risk scores (PRSs) can be used to quantify cumulative genetic risk for a trait at an individual level. Recent studies suggest PRSs for anorexia nervosa (AN) may also predict risk for other disordered eating behaviors, but no study has examined if PRS for AN can predict disordered eating as a global continuous measure. This study aimed to investigate whether PRS for AN predicted overall levels of disordered eating, or specific lifetime disordered eating behaviors, in an Australian adolescent female population.

PRSs were calculated based on summary statistics from the largest Psychiatric Genomics Consortium AN genome-wide association study to date. Analyses were performed using genome-wide complex trait analysis to test the associations between AN PRS and disordered eating global scores, avoidance of eating, objective bulimic episodes, self-induced vomiting, and driven exercise in a sample of Australian adolescent female twins recruited from the Australian Twin Registry (N = 383).

After applying the false-discovery rate correction, the AN PRS was significantly associated with all disordered eating outcomes.

Findings suggest shared genetic etiology across disordered eating presentations and provide insight into the utility of AN PRS for predicting disordered eating behaviors in the general population. In the future, PRSs for EDs may have clinical utility in early disordered eating risk identification, prevention, and intervention.

Our aim was to explore the experiences of individuals receiving emergency department (ED) care for acute headaches.

Patients with headache exacerbations commonly present to EDs. This study explored the experiences of adult patients during the exacerbation period, specifically using photovoice.

Recruited from two urban EDs in Alberta, Canada, participants with primary headaches took photographs over 3–4 weeks and subsequently completed a 60–90 minute, one-on-one, in-person photo-elicitation interview. Interviews were audio recorded, transcribed and thematically analyzed alongside photographs.

Eight participants (six women) completed the study. The average age was 42 years (standard deviation: 16). Five themes emerged: (1) the struggle for legitimacy in light of the invisibility of their condition; (2) the importance of hope, hopelessness and fear in the day-to-day life of participants; (3) the importance of agency and becoming “your own advocate”; (4) the struggle to be and be seen as themselves despite the encroachment of their headaches; and (5) the realities of “good” and “bad” care in the ED. Participants highlighted examples of good care, specifically when they felt seen and believed. Additionally, some expressed the acute care space itself being a beacon of hope in the midst of their crisis. Others felt dismissed because providers “know it’s not life or death.”

This study highlighted the substantial emotional impact that primary headaches have on the lives of participants, particularly during times of exacerbation and while seeking acute care. This provides insight for acute care settings and practitioners on how to effectively engage with this population.

We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention.

Retrospective before-and-after study.

Tertiary and quaternary care academic medical center.

Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods.

We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020–12/2020) and post-BPA (04/15/2021–04/30/2022) periods.

774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18–65) in the pre-BPA group compared to 16 hours (IQR 2–34) in the post-BPA group (P < 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source.

Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review.

Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.

We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.

The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).

The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.

This study describes the illness burden in the first year of life for children with single-ventricle heart disease, using the metric of days alive and out of hospital to characterize morbidity and mortality.

This is a retrospective single-centre study of single-ventricle patients born between 2005 and 2021 who had their initial operation performed at our institution. Patient demographics, anatomical details, and hospitalizations were extracted from our institutional single-ventricle database. Days alive and out of hospital were calculated by subtracting the number of days hospitalized from number of days alive during the first year of life. A multivariable linear regression with stepwise variable selection was used to determine independent risk factors associated with fewer days alive and out of hospital.

In total, 437 patients were included. Overall median number of days alive and out of hospital in the first year of life for single-ventricle patients was 278 days (interquartile range 157–319 days). In a multivariable analysis, low birth weight (<2.5kg) (b = −37.55, p = 0.01), presence of a dominant right ventricle (b = −31.05, p = 0.01), moderate-severe dominant atrioventricular valve regurgitation at birth (b = −37.65, p < 0.05), index hybrid Norwood operation (b = −138.73, p < 0.01), or index heart transplant (b = −158.41, p < 0.01) were all independently associated with fewer days alive and out of hospital.

Children with single-ventricle heart defects have significant illness burden in the first year of life. Identifying risk factors associated with fewer days alive and out of hospital may aid in counselling families regarding expectations and patient prognosis.

Assessment of performance validity during neuropsychology evaluation is essential to reliably interpret cognitive test scores. Studies (Webber et al., 2018; Wisdom, et al., 2012) have validated the use of abbreviated measures, such as Trial 1 (T1) of the Test of Memory Malingering (TOMM), to detect invalid performance. Only one study (Bauer et al., 2007) known to these authors has examined the utility of Green’s Word Memory Test (WMT) immediate recall (IR) as a screening tool for invalid performance. This study explores WMT IR as an independent indicator of performance validity in a mild TBI (mTBI) veteran population.

Participants included 211 (Mage = 32.1, SD = 7.4; Medu = 13.1, SD = 1.64; 94.8% male; 67.8% White) OEF/OIF/OND veterans with a history of mTBI who participated in a comprehensive neuropsychological evaluation at one of five participating VA Medical Centers. Performance validity was assessed using validated cut scores from the following measures: WMT IR and delayed recall (DR); TOMM T1; WAIS-IV reliable digit span; CVLT-II forced choice raw score; Wisconsin Card Sorting Test failure to maintain set; and the Rey Memory for Fifteen Items test, combo score. Sensitivity and specificity were calculated for each IR score compared with failure on DR. In addition, sensitivity and specificity were calculated for each WMT IR score compared to failure of at least one additional performance validity measure (excluding DR), two or more measures, and three or more measures, respectively.

Results indicated that 46.8% participants failed to meet cut offs for adequate performance validity based on the standard WMT IR cut score (i.e., 82.5%; M = 81.8%, SD = 17.7%); however, 50.2% participants failed to meet criteria based on the standard WMT DR cut score (M = 79.8% SD = 18.6%). A cut score of 82.5% or below on WMT IR correctly identified 82.4% (i.e., sensitivity) of subjects who performed below cut score on DR, with a specificity of 94.2%. Examination of IR cutoffs compared to failure of one or more other PVTs revealed that the standardized cut score of 82.5% or below had a sensitivity of 78.2% and a specificity of 72.4%; whereas, a cut score of 65% or below had a sensitivity of 41% and a specificity of 91.3%. Similarly, examination of IR cutoffs compared to failure of two or more additional PVTs revealed that the cut score of 60% or below had a sensitivity of 45.7% and specificity of 93.1% ; whereas, a cut score of 57.5% or below had a sensitivity of 57.9% and specificity of 90.9% when using failure of three or more PVTs as the criterion.

Results indicated that a cut score of 82.5% or below on WMT IR may be sufficient to detect invalid performance when considering WMT DR as criterion. Furthermore, WMT IR alone, with adjustments to cut scores, appears to be a reasonable way to assess symptom validity compared to other PVTs. Sensitivity and specificity of WMT IR scores may have been adversely impacted by lower sensitivity of other PVTs to independently identify invalid performance.

Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.

This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.

The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).

Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.

Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).

This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.

Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.

The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.

To analyze Clostridioides difficile testing in 3 hospitals in central North Carolina to validate previous racial health-disparity findings.

We completed a retrospective analysis of inpatient C. difficile tests from 2015 to 2021 at 3 university-affiliated hospitals in North Carolina. We calculated the number of C. difficile tests per 1,000 patient days stratified by race: White, Black, and non-White, non-Black (NWNB). We defined a unique C. difficile test as one that occurred in an inpatient unit with a matching laboratory accession ID and on differing calendar days. Tests were evaluated overall, by hospital, by year, and by positivity rate.

In total, 35,160 C. difficile tests and 2,571,850 patient days across all 3 hospitals from 2015 to 2021 were analyzed. The median number of C. difficile tests per 1,000 patient days was 13.85 (interquartile range [IQR], 9.88–16.07). Among all C. difficile tests, 5,225 (15%) were positive. White patients were administered more C. difficile tests (14.46 per 1,000 patient days) than Black patients (12.96; P < .0001) or NWNB race patients (10.27; P < .0001). Black patients were administered more tests than NWNB patients (P < .0001). White patients tested positive at a similar rate to Black patients (15% vs 15%; P = .3655) and higher than NWNB individuals (12%; P = .0061), and Black patients tested positive at a higher rate than NWNB patients (P = .0024).

White patients received more C. difficile tests than Black and NWNB patient groups when controlling for race patient days. Future studies should control for comorbidities and investigate community onset of C. difficile by race and ethnicity.