To evaluate sex differences in the triage and assessment of chest pain in Dutch out-of-hours primary care (OOH-PC).

Prior research illustrated differences between women and men with confirmed cardiac ischemia. However, information on sex differences among patients with undifferentiated chest pain is limited and current protocols used to assess chest pain in urgent primary care in the Netherlands do not account for potential sex differences.

A retrospective cohort study of consecutive patients who contacted a large OOH-PC facility in the Netherlands in 2017 regarding chest pain. We performed descriptive analyses on sex differences in patient and symptom characteristics, triage assessment, and subsequent clinical outcomes, including acute coronary syndrome (ACS).

A total of 1,802 patients were included, the median age was 54 years, and 57.6% were female. Compared to men, women less often had a history of cardiovascular disease (CVD) (16.0% vs 25.8%, p < 0.001) or cardiovascular risk factors (49.3% vs 56.0%, p = 0.005). Symptom characteristics were comparable between sexes. While triage urgencies were more frequently altered in women, the resulting triage urgencies were comparable, including ambulance activation rates (31.1% and 33.5%, respectively, p = 0.33). Musculoskeletal causes were the most common in both sexes; but women were less likely to have an underlying cardiovascular condition (21.1% vs 29.6%, p < 0.001), including ACS (5.4% vs 8.5%, p = 0.019).

Women more frequently sought urgent primary care for chest pain than men. Despite a lower overall risk for cardiovascular events in women, triage assessment and ambulance activation rates were similar to those in men, indicating a potentially less efficient and overly conservative triage approach for women.

Low levels of vitamin D during pregnancy are associated with offspring behavioral problems but little is known about pre-pregnancy influences. Additionally, Black American individuals are underrepresented in studies, limiting translational impact. We tested independent and interactive effects of preconception and prenatal vitamin D in Black women in relation to positive behavioral and emotional outcomes in early childhood.

Black-identifying participants (N = 156) enrolled in the longitudinal Pittsburgh Girls Study (PGS) provided venous blood samples before and during pregnancy to measure 25-hydroxyvitamin D (25[OH]D) levels. Participants completed questionnaires assessing sociodemographic factors, depression severity and life stress, and later reported on child behavioral and emotional problems and prosocial behavior between 2 and 4 years.

Mean serum 25(OH)D concentrations were 15.5 ng/ml (s.d. = 7.7) before pregnancy and 18.0 ng/ml (s.d. = 9.2) during pregnancy; below the sufficiency threshold according to commonly used dietary guidelines. After adjusting for covariates, prenatal 25(OH)D was negatively related to behavior problems and positively related to prosocial behavior in children, although the association attenuated for behavior problems after accounting for preconception 25(OH)D, which may reflect patterns of stability. Maternal 25(OH)D was unrelated to child emotional problems, and no synergistic effects of 25(OH)D timing were observed for any child outcome.

Findings have relevance for Black women living in the northeast U.S. Results suggest specific associations between maternal vitamin D and positive behaviors in early childhood, regardless of sufficiency levels and suggest potential opportunities for early interventions to support healthy child development.

Many paediatric studies report that patients must be established on aspirin therapy for a minimum of 5 days to achieve adequate response. This is not always practical especially in critical settings. Prospective identification of patients that are unresponsive to aspirin sooner could potentially prevent thrombotic events.

The aim of this study was to investigate prospectively if the first dose of aspirin is effective in decreasing platelet aggregation, and thromboxane formation and if this can be measured after 2 hours in paediatric cardiology patients. A secondary aim was to identify a cut-off for a novel marker of aspirin responsiveness the maximum amplitude with arachidonic acid, which could potentially dramatically reduce the blood volume required. Third, we aimed to prospectively identify potentially non-responsive patients by spiking a sample of their blood ex vivo with aspirin.

The majority (92.3%) of patients were responsive, when measured 2 hours post first dose of aspirin. Non-response or inadequate response (7.7%) can also be identified at 2 hours after taking the first dose of aspirin. Additionally, we have shown a novel way to reduce blood sample volume requirements by measurement of the maximum amplitude with arachidonic acid as a marker of response, particularly for monitoring.

These findings of rapid efficacy in the majority of patients offer assurance in a sound, practical way to attending clinicians, patients, and families.

Antimicrobial resistance (AMR) causes worsening health, environmental, and financial burdens. Modelling complex issues such as AMR is important, however, how well such models and data cover the broader One Health system is unknown. Our study aimed to identify models of AMR across the One Health system (objective 1), and data to parameterize such models (objective 2) to inform a future model of the AMR in the Swedish One Health system. Based on an expert-derived qualitative description of the system, an extensive literature scan was performed to identify models and data from peer-reviewed and grey literature sources. Models and data were extracted, categorized in an Excel database, and visually represented on the existing qualitative model to illustrate coverage. The articles identidied described 106 models in various parts of the One Health system; 54 were AMR-specific. Few multi-level, multi-sector models, and models within the animal and environmental sectors, were identified. We identified 414 articles containing data to parameterize the models. Data gaps included the environment and broad, ill-defined, or abstract ideas (e.g., human behaviour). In conclusion, no models addressed the entire system, and many data gaps were found. Existing models could be integrated into a mixed-methods model in the interim.

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.

High cognitive activity possibly reduces the risk of cognitive decline and dementia.

To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.

Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.

Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.

A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.

Studies have reported mixed findings regarding the impact of the coronavirus disease 2019 (COVID-19) pandemic on pregnant women and birth outcomes. This study used a quasi-experimental design to account for potential confounding by sociodemographic characteristics.

Data were drawn from 16 prenatal cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) program. Women exposed to the pandemic (delivered between 12 March 2020 and 30 May 2021) (n = 501) were propensity-score matched on maternal age, race and ethnicity, and child assigned sex at birth with 501 women who delivered before 11 March 2020. Participants reported on perceived stress, depressive symptoms, sedentary behavior, and emotional support during pregnancy. Infant gestational age (GA) at birth and birthweight were gathered from medical record abstraction or maternal report.

After adjusting for propensity matching and covariates (maternal education, public assistance, employment status, prepregnancy body mass index), results showed a small effect of pandemic exposure on shorter GA at birth, but no effect on birthweight adjusted for GA. Women who were pregnant during the pandemic reported higher levels of prenatal stress and depressive symptoms, but neither mediated the association between pandemic exposure and GA. Sedentary behavior and emotional support were each associated with prenatal stress and depressive symptoms in opposite directions, but no moderation effects were revealed.

There was no strong evidence for an association between pandemic exposure and adverse birth outcomes. Furthermore, results highlight the importance of reducing maternal sedentary behavior and encouraging emotional support for optimizing maternal health regardless of pandemic conditions.

Alzheimer’s disease (AD) is highly comorbid with idiopathic normal pressure hydrocephalus (iNPH) and may diminish the benefits of shunting; however, findings in this area are mixed. We examined postoperative outcomes, with emphases on cognition and utilization of novel scoring procedures to enhance sensitivity.

Using participant data from an iNPH outcome study at Butler Hospital, a mixed effect model examined main and interaction effects of time since surgery (baseline, 3 months, 12 months, and 24–60 months) and AD comorbidity (20 iNPH and 11 iNPH+AD) on activities of daily living (ADLs) and iNPH symptoms. Regression modeling explored whether baseline variables predicted improvements 3 months postoperatively.

There were no group differences in gait, incontinence, and global cognition over time, and neither group showed changes in ADLs. Cognitive differences were observed postoperatively; iNPH patients showed stable improvements in working memory (p = 0.012) and response inhibition (p = 0.010), while iNPH + AD patients failed to maintain initial gains. Regarding predicting postoperative outcomes, baseline AD biomarkers did not predict shunt response at 3 months; however, older age at surgery predicted poorer cognitive outcomes (p = 0.04), and presurgical Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) (p = 0.035) and Mini-Mental Status Examination (MMSE) scores (p = 0.009) predicted improvements incontinence.

iNPH + AD may be linked with greater declines in aspects of executive functioning postoperatively relative to iNPH alone. While baseline AD pathology may not prognosticate shunt response, younger age appears linked with postsurgical cognitive improvement, and utilizing both brief and comprehensive cognitive measures may help predict improved incontinence. These results illustrate the potential benefits of surgery and inform postoperative expectations for those with iNPH + AD.

Consistent evidence from retrospective reports and case registry studies indicates that a history of depression is a major risk factor for depression in the peripartum period. However, longitudinal studies with racially and socioeconomically diverse samples of young mothers are lacking, and little is known about developmental patterns of depression across the lifespan that can inform preventive interventions.

Young primiparous mothers (n = 399, 13–25 years, 81% Black) were recruited from a population-based prospective study that began in childhood. Women reported on depression symptoms for at least 3 years prior to their pregnancy, during pregnancy, and at 4 months postpartum. Linear regression models were used to estimate change in pre-pregnancy depression severity and to evaluate associations between patterns of lifetime history and postpartum depression symptoms.

Results revealed high levels of continuity in depression from pregnancy to postpartum, and across multiple years pre-pregnancy to postpartum. Overall, depression severity leading up to pregnancy decreased over time, but patterns of worsening or improving symptoms were not associated with depression severity in the postpartum period. Instead, area under the pre-pregnancy trajectory curve, representing cumulative lifetime depression burden, was uniquely associated with postpartum depression after adjusting for prenatal depression severity.

Depression in the postpartum period should be considered within a lifespan perspective of risk that accumulates before conception. Clinical screening and early interventions are needed in adolescence and young adulthood to prevent the onset and persistence of depressive symptoms that could have long-term implications for peripartum health.