Stroke clinical registries are critical for systems planning, quality improvement, advocacy and informing policy. We describe the methodology and evolution of the Registry of the Canadian Stroke Network/Ontario Stroke Registry in Canada.

At the launch of the registry in 2001, trained coordinators prospectively identified patients with acute stroke or transient ischemic attack (TIA) at comprehensive stroke centers across Canada and obtained consent for registry participation and follow-up interviews. From 2003 onward, patients were identified from administrative databases, and consent was waived for data collection on a sample of eligible patients across all hospitals in Ontario and in one site in Nova Scotia. In the most recent data collection cycle, consecutive eligible patients were included across Ontario, but patients with TIA and those seen in the emergency department without admission were excluded.

Between 2001 and 2013, the registry included 110,088 patients. Only 1,237 patients had follow-up interviews, but administrative data linkages allowed for indefinite follow-up of deaths and other measures of health services utilization. After a hiatus, the registry resumed data collection in 2019, with 13,828 charts abstracted to date with a focus on intracranial vascular imaging, identification of intracranial occlusions and treatment with thrombectomy.

The Registry of the Canadian Stroke Network/Ontario Stroke Registry is a large population-based clinical database that has evolved throughout the last two decades to meet contemporary stroke needs. Registry data have been used to monitor stroke quality of care and conduct outcomes research to inform policy.

The delivery of paediatric cardiac care across the world occurs in settings with significant variability in available resources. Irrespective of the resources locally available, we must always strive to improve the quality of care we provide to our patients and simultaneously deliver such care in the most efficient and cost-effective manner. The development of cardiac networks is used widely to achieve these aims.

This paper reports three talks presented during the 56th meeting of the Association for European Paediatric and Congenital Cardiology held in Dublin in April 2023.

The three talks describe how centres of congenital cardiac excellence can be developed in low-income countries, middle-income countries, and well-resourced environments, and also reports how centres across different countries can come together to collaborate and deliver high-quality care. It is a fact that barriers to creating effective networks may arise from competition that may exist among programmes in unregulated and especially privatised health care environments. Nevertheless, reflecting on the creation of networks has important implications because collaboration between different centres can facilitate the maintenance of sustainable programmes of paediatric and congenital cardiac care.

This article examines the delivery of paediatric and congenital cardiac care in resource limited environments, well-resourced environments, and within collaborative networks, with the hope that the lessons learned from these examples can be helpful to other institutions across the world. It is important to emphasise that irrespective of the differences in resources across different continents, the critical principles underlying provision of excellent care in different environments remain the same.

In June of 2024, Becton Dickinson experienced a blood culture bottle shortage for their BACTEC system, forcing health systems to reduce usage or risk exhausting their supply. Virginia Commonwealth University Health System (VCUHS) in Richmond, VA decided that it was necessary to implement austerity measures to preserve the blood culture bottle supply.

VCUHS includes a main campus in Richmond, VA as well as two affiliate hospitals in South Hill, VA (Community Memorial Hospital (CMH)) and Tappahannock Hospital in Tappahannock, VA. It also includes a free-standing Emergency Department in New Kent, VA.

Blood cultures from both pediatric and adult patients were included in this study.

VCUHS intervened to decrease blood culture utilization across the entire health system. Interventions included communication of blood culture guidance as well as an electronic health record order designed to guide providers and discourage wasteful ordering.

Post-implementation analyses showed that interventions reduced overall usage by 35.6% (P < .0001) and by greater than 40% in the Emergency Departments. The impact of these changes in utilization on positivity were analyzed, and it was found that the overall positivity rate increased post-intervention from 8.8% to 12.1% (P = .0115) and in the ED specifically from 10.2% to 19.5% (P < .0001).

These findings strongly suggest that some basic stewardship interventions can significantly change blood culture practice in a manner that minimizes the impact on patient care.

Dropout from healthcare interventions can negatively affect patients and healthcare providers through impaired trust in the healthcare system and ineffective use of resources. Research on this topic is still largely missing on refugees and asylum seekers. The current study aimed to characterize predictors for dropout in the Mental Health in Refugees and Asylum Seekers (MEHIRA) study, one of the largest multicentered controlled trials investigating the effectiveness and cost-effectiveness of a nationwide stepped and collaborative care model.

Predictors were multiply imputed and selected for descriptive modelling using backward elimination. The final variable set was entered into logistic regression.

The overall dropout rate was 41,7%. Dropout was higher in participants in group therapy (p = 0.001; OR = 10.7), with larger satisfaction with social relationships (p = 0.017; OR = 1.87), with difficulties in maintaining personal relationships (p = 0.005; OR = 4.27), and with higher depressive symptoms (p = 0.029; OR = 1.05). Participants living in refugee accommodation (p = 0.040; OR = 0.45), with a change in social status (p = 0.008; OR = 0.67) and with conduct (p = 0.020; OR = 0.24) and emotional problems (p = 0.013; OR = 0.31) were significantly less likely to drop out of treatment.

Overall, the outcomes of this study suggest that predictors assessing social relationships, social status, and living conditions should be considered as topics of psychological treatment to increase adherence and as predictors for future research studies (including treatment type).

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.

The Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Database Project is a multisite collaborative that includes neuropsychological evaluations of children presenting for epilepsy surgery. There is some evidence for specific neuropsychological phenotypes within epilepsy (Hermann et al, 2016); however, this is less clear in pediatric patients. As a first step, we applied an empirically-based subtyping approach to determine if there were specific profiles using indices from the Wechsler scales [Verbal IQ (VIQ), Nonverbal IQ (NVIQ), Processing Speed Index (PSI), Working Memory Index (WMI)]. We hypothesized that there would be at least four profiles that are distinguished by slow processing speed and poor working memory as well as profiles with significant differences between verbal and nonverbal reasoning abilities.

Our study included 372 children (M=12.1 years SD=4.1; 77.4% White; 48% male) who completed an age-appropriate Wechsler measure, enough to render at least two index scores. Epilepsy characteristics included 84.4% with focal epilepsy (evenly distributed between left and right focus) and 13.5% with generalized or mixed seizure types; mean age of onset = 6.7 years, SD = 4.5; seizure frequency ranged from daily to less than monthly; 53% had structural etiology; 71% had an abnormal MRI; and mean number of antiseizure medications was two. Latent profile analysis was used to identify discrete underlying cognitive profiles based on intellectual functioning. Demographic and epilepsy characteristics were compared among profiles.

Based on class enumeration procedures, a 3-cluster solution provided the best fit for the data, with profiles characterized by generally Average, Low Average, or Below Average functioning. 32.8% were in the Average profile with mean index scores ranging from 91.7-103.2; 47.6% were in the Low Average profile with mean index ranging from 80.7 to 84.5; and 19.6% were in the Below Average profile with mean index scores ranging from 55.0-63.1. Across all profiles, the lowest mean score was the PSI, followed by WMI. VIQ and NVIQ represented relatively higher scores for all three profiles. Mean discrepancy between indices within a profile was as large as 11.5 IQ points. No demographics or epilepsy characteristics were significantly different across cognitive phenotypes.

Latent cognitive phenotypes in a pediatric presurgical cohort were differentiated by general level of functioning; however, across profiles, processing speed was consistently the lowest index followed by working memory. These findings across phenotypes suggest a common relative weakness which may result from a global effect of antiseizure medications and/or the widespread impact of seizures on neural networks even in a largely focal epilepsy cohort; similar to adult studies with temporal lobe epilepsy (Hermann et al, 2007). Future work will use latent profile analysis to examine phenotypes across other domains relevant to pediatric epilepsy including attention, naming, motor, and memory functioning. These findings are in line with collaborative efforts towards cognitive phenotyping which is the aim of our PERC Epilepsy Surgery Database Project that has already established one of the largest pediatric epilepsy surgery cohorts.