Recent methodological advances in federated learning for healthcare.

For healthcare datasets, it is often impossible to combine data samples from multiple sites due to ethical, privacy, or logistical concerns. Federated learning allows for the utilization of powerful machine learning algorithms without requiring the pooling of data. Healthcare data have many simultaneous challenges, such as highly siloed data, class imbalance, missing data, distribution shifts, and non-standardized variables, that require new methodologies to address. Federated learning adds significant methodological complexity to conventional centralized machine learning, requiring distributed optimization, communication between nodes, aggregation of models, and redistribution of models. In this systematic review, we consider all papers on Scopus published between January 2015 and February 2023 that describe new federated learning methodologies for addressing challenges with healthcare data. We reviewed 89 papers meeting these criteria. Significant systemic issues were identified throughout the literature, compromising many methodologies reviewed. We give detailed recommendations to help improve methodology development for federated learning in healthcare.

COVID-19 related myocardial injury is associated with immune dysregulation in symptomatic patients with cardiac MRI abnormalities.

AIMS: While acute cardiovascular complications of COVID-19 are well-described, less is known about longer-term cardiac sequelae. For many individuals with cardiac signs or symptoms arising after COVID-19 infection, the aetiology remains unclear. We examined immune profiles associated with magnetic resonance imaging (MRI) abnormalities in patients with unexplained cardiac injury after COVID-19. METHODS AND RESULTS: Twenty-one participants (mean age 47 [SD 13] years, 71% female) with long COVID (n=17), raised troponin (n=2), or unexplained new-onset heart failure (n=2), who did not have pre-existing heart conditions or recent steroid/immunosuppression treatment were enrolled a mean 346 (SD 191) days after COVID-19 infection in a prospective observational study. Cardiac MRI and blood sampling for deep immunophenotyping using mass cytometry by time of flight and measurement of proteomic inflammatory markers was performed. Nine of 21 (43%) participants had MRI abnormalities (MRI(+)), including non-ischaemic patterns of late gadolinium enhancement and/or visually overt myocardial oedema in 8 people. One patient had mildly impaired biventricular function without fibrosis or oedema, and 2 had severe left ventricular impairment. MRI(+) individuals had higher blood CCL3, CCL7, FGF-23 and CD4 Th2 cells, and lower CD8 T effector memory (TEM) cells, than MRI(-). Cluster analysis revealed lower expression of inhibitory receptors PD1 and TIM3 in CD8 TEM cells from MRI(+) patients than MRI(-) patients, and functional studies of CD8 T αß cells showed higher proportions of cytotoxic granzyme B+ secreting cells upon stimulation. CD8 TEM cells and CCL7 were the strongest predictors of MRI abnormalities in a LASSO regression model (composite AUC 0.96, 95%CI 0.88-1.0). CCL7 was correlated with diffuse myocardial fibrosis/oedema detected by quantitative T1 mapping (r=0.47, p=0.04). CONCLUSION: COVID-19 related cardiac injury in symptomatic patients with non-ischaemic myocarditis-like MRI abnormalities is associated with immune dysregulation, including decreased peripheral CD8 TEM cells and increased CCL7, persisting long after the initial infection.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Carotid atherosclerotic plaque microcalcification is independently associated with recurrent neurovascular events: A pilot study.

BACKGROUND: Microcalcification and macrocalcification are critical processes in atherosclerotic plaque progression, though how these processes relate to the risk of stroke recurrence in symptomatic carotid atherosclerosis is poorly understood. METHODS: We performed a post hoc analysis of data from the ICARUSS (Imaging Carotid Atherosclerosis in the Recovery and Understanding of Stroke Severity) study, where individuals with acute ischemic stroke originating from ipsilateral carotid stenosis of ⩾ 50% underwent 18F-sodium fluoride positron emission tomography (NaF-PET) to measure microcalcification. Tracer uptake was quantified using maximum tissue-to-background ratio (TBRmax). Macrocalcification was measured on computed tomography (CT) using Agatston scoring. Patients were followed up for 6 months for recurrent ipsilateral neurovascular events. RESULTS: Five (27.8%) of 18 individuals had a recurrent ischemic stroke or transient ischemic attack. Ipsilateral carotid plaque NaF uptake at baseline was higher in those with recurrent events compared to those without, and this association remained after adjustment for other vascular risk factors (adjusted odds ratio (aOR) = 1.24, 1.03-1.50). Macrocalcification score in the symptomatic artery was also significantly independently associated with ipsilateral recurrence, but the effect size was relatively smaller (aOR = 1.12, 1.06-1.17 for each 100 unit increase). CONCLUSIONS: Our findings indicate that microcalcification in symptomatic carotid plaques is independently associated with ipsilateral ischemic stroke recurrence. Furthermore, differences in the extent of active microcalcification in macrocalcified plaques may help explain variation in the relationship between calcified carotid plaques and stroke recurrence reported in the literature. Our pilot study indicates that evaluation of carotid artery microcalcification using NaF-PET may be a useful method for risk-stratification of carotid atherosclerosis, though our findings require confirmation in larger cohorts.

An ecological dynamics approach to promote physical literacy and well-being of primary school children: a cluster randomised controlled trial study protocol.

BACKGROUND: Little is known about the impact of an ecological dynamics (ED) intervention (EDI) on primary school children's physical literacy and well-being in the Hong Kong context. The aim of this project is to introduce a physical literacy and well-being framework through an EDI that allows primary school children to develop good physical activity (PA) and daily behavioural habits. METHODS AND ANALYSIS: A four-arm (cluster) randomised controlled trial will be conducted to examine the effect of EDI on physical literacy and well-being in primary schools located in each of the 18 administrative districts of Hong Kong. Four classes in senior primary students (grade 4) at each school will be randomly assigned to the four different conditions. These participating schools will be equipped with sit-stand desks, PA recess facility and equipment, and sleep pillows. The research team will adopt both objective measures (aerobic fitness, fundamental movement skills, daily behaviour-physical activity and cognitive function) and self-reported measures (perceived physical literacy, quality of life, sleep quality) covering the elements and domains of physical literacy and well-being to examine the effects of EDIs at four time points, including baseline assessment, 3 months after intervention, postintervention and 3-month follow-up assessment. One-way analyses of variance (ANOVAs) will be used to test for differences in the baseline characteristics of participants between groups. Repeated measure ANOVAs and MANCOVA, with time (baseline, after intervention and follow-up) as within-subjects factor, and intervention group as between-subjects factors, will be used to evaluate the effects of different interventions on the students' physical literacy and well-being. A Bonferonni correction to the p value will be calculated to adjust for multiple tests. ETHICS AND DISSEMINATION: Ethical approval was sought from the Joint CUHK-NTEC Clinical Research Ethics Committee in Hong Kong (CREC Ref.No.:2024.027). The finding of this study will be disseminated via peer-reviewed journals, international conference presentations and academic lectures. For secondary analysis of the data, please contact the corresponding author for permission. TRIAL REGISTRATION NUMBER: ISRCTN84025914.

Coronary Atherosclerotic Plaque Activity and Risk of Myocardial Infarction.

BACKGROUND: Total coronary atherosclerotic plaque activity across the entire coronary arterial tree is associated with patient-level clinical outcomes. OBJECTIVES: We aimed to investigate whether vessel-level coronary atherosclerotic plaque activity is associated with vessel-level myocardial infarction. METHODS: In this secondary analysis of an international multicenter study of patients with recent myocardial infarction and multivessel coronary artery disease, we assessed vessel-level coronary atherosclerotic plaque activity using coronary 18F-sodium fluoride positron emission tomography to identify vessel-level myocardial infarction. RESULTS: Increased 18F-sodium fluoride uptake was found in 679 of 2,094 coronary arteries and 414 of 691 patients. Myocardial infarction occurred in 24 (4%) vessels with increased coronary atherosclerotic plaque activity and in 25 (2%) vessels without increased coronary atherosclerotic plaque activity (HR: 2.08; 95% CI: 1.16-3.72; P = 0.013). This association was not demonstrable in those treated with coronary revascularization (HR: 1.02; 95% CI: 0.47-2.25) but was notable in untreated vessels (HR: 3.86; 95% CI: 1.63-9.10; Pinteraction = 0.024). Increased coronary atherosclerotic plaque activity in multiple coronary arteries was associated with heightened patient-level risk of cardiac death or myocardial infarction (HR: 2.43; 95% CI: 1.37-4.30; P = 0.002) as well as first (HR: 2.19; 95% CI: 1.18-4.06; P = 0.013) and total (HR: 2.50; 95% CI: 1.42-4.39; P = 0.002) myocardial infarctions. CONCLUSIONS: In patients with recent myocardial infarction and multivessel coronary artery disease, coronary atherosclerotic plaque activity prognosticates individual coronary arteries and patients at risk for myocardial infarction.

Computed tomography pericoronary adipose tissue density predicts coronary allograft vasculopathy and adverse clinical outcomes after cardiac transplantation.

AIMS: To assess pericoronary adipose tissue (PCAT) density on coronary computed tomography angiography (CCTA) as a marker of inflammatory disease activity in coronary allograft vasculopathy (CAV). METHODS AND RESULTS: PCAT density, lesion volumes, and total vessel volume-to-myocardial mass ratio (V/M) were retrospectively measured in 126 CCTAs from 94 heart transplant patients [mean age 49 (SD 14.5) years, 40% female] who underwent imaging between 2010 and 2021; age- and sex-matched controls; and patients with atherosclerosis. PCAT density was higher in transplant patients with CAV [n = 40; -73.0 HU (SD 9.3)] than without CAV [n = 86; -77.9 HU (SD 8.2)], and controls [n = 12; -86.2 HU (SD 5.4)], P < 0.01 for both. Unlike patients with atherosclerotic coronary artery disease (n = 32), CAV lesions were predominantly non-calcified and comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without [32.4 mm3/g (SD 9.7) vs. 41.4 mm3/g (SD 12.3), P < 0.0001]. PCAT density and V/M improved the ability to predict CAV from area under the receiver operating characteristic curve (AUC) 0.75-0.85 when added to donor age and donor hypertension status (P < 0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality {odds ratio [OR] 18.0 [95% confidence interval (CI) 3.25-99.6], P < 0.01} and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularization [OR 7.47 (95% CI 1.8-31.6), P = 0.01] over 5.3 (SD 2.1) years. CONCLUSION: Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Increased PCAT density is associated with adverse clinical outcomes. These CCTA metrics could be useful for the diagnosis and monitoring of CAV severity.

Polygenic risk scores in atrial fibrillation: Associations and clinical utility in disease prediction.

Atrial fibrillation (AF) is a common heart arrhythmia and a major cause of cardioembolic stroke. Therefore, accurate prediction is desirable to allow high-risk individuals to be identified early and their risk lowered before complications arise. Polygenic risk scores (PRSs) have become a popular method of quantifying aggregated genetic risk from common variants, but their clinical value in AF remains uncertain. This literature review summarizes the associations between PRS and AF risk and discusses the evidence for the clinical utility of PRS for AF prediction. Stroke risk in patients with AF is also considered. Despite consistent associations between PRS and AF risk, the performance of PRS as a stand-alone tool for AF prediction was poor. However, addition of PRS to the existing AF prediction models commonly improved the predictive performance above that of the clinical models alone, including in cohorts with comorbid cardiovascular disease. Associations between PRS and cardioembolic stroke risk in patients with AF have also been reported, but improvements in stroke prediction models from PRS have been minimal. PRS are likely to add value to the existing clinical AF prediction models; however, standardization of PRS across studies and populations will likely be required before they can be meaningfully adopted into routine clinical practice.

Use of coronarycomputed tomography for cardiovascular risk assessment in immune-mediated inflammatory diseases.

Immune-mediated inflammatory diseases (IMIDs) are recognised risk factors for accelerated atherosclerotic cardiovascular disease (CVD), particularly in younger individuals and women who lack traditional CVD risk factors. Reflective of the critical role that inflammation plays in the formation, progression and rupture of atherosclerotic plaques, research into immune mechanisms of CVD has led to the identification of a range of therapeutic targets that are the subject of ongoing clinical trials. Several key inflammatory pathways implicated in the pathogenesis of atherosclerosis are targeted in people with IMIDs. However, cardiovascular risk continues to be systematically underestimated by conventional risk assessment tools in the IMID population, resulting in considerable excess CVD burden and mortality. Hence, there is a pressing need to improve methods for CVD risk-stratification among patients with IMIDs, to better guide the use of statins and other prognostic interventions. CT coronary angiography (CTCA) is the current first-line investigation for diagnosing and assessing the severity of coronary atherosclerosis in many individuals with suspected angina. Whether CTCA is also useful in the general population for reclassifying asymptomatic individuals and improving long-term prognosis remains unknown. However, in the context of IMIDs, it is conceivable that the information provided by CTCA, including state-of-the-art assessments of coronary plaque, could be an important clinical adjunct in this high-risk patient population. This narrative review discusses the current literature about the use of coronary CT for CVD risk-stratification in three of the most common IMIDs including rheumatoid arthritis, psoriasis and systemic lupus erythematosus.

Associations of physical activity dose and movement quality with executive functions in socioeconomically disadvantaged children aged 5-6 years.

BACKGROUND: Growing up in areas of high deprivation can negatively impact children's movement behaviours and cognitive development. Enhancing the quantity and quality of children's movement experiences is believed to enhance cognitive development. This study investigated the association of three different modes of movement assessment, movement proficiency and divergent movement ability (collectively understood as motor competence) and PA dose with executive function in a low socio-economic demographic. Demographics, motor competence, and a combination of motor competence and physical activity were hypothesized to be significantly predictor of executive functions. METHOD: In this cross-sectional study, 360 children aged 5-6 years from deprived areas were assessed using three movement assessments: wrist-worn accelerometery for physical activity dose, Test of Gross Motor Development-3 for movement proficiency, and divergent movement assessment. Executive function, including inhibitory control, working memory, and cognitive flexibility, was measured using the NIH Toolbox on an iPad. Multiple linear regression models were designed to evaluate the independent and combined association of demographics, movement competence and physical activity variables with executive function. RESULTS: The regression analysis, with demographic factors only, explained 12% of EF variance (r2 = 0.12 95%CI 0.06-0.18). In addition to this demographics the model with divergent movement explained 19% of EF variance (r2 = 0.19 95% CI = 0.12-0.28), the model with movement proficiency explained 16% of EF variance (r2 = 0.16 95% CI = 0.08-0.26) and the model with PA dose explained 13% of EF variance (r2 = 0.13 95% CI = 0.07-0.20). In these models both divergent movement and proficiency were significant predictors, whilst physical activity variables were not. The final models, combining motor competence and physical activity variables, explained 24% and 23% of EF variance (r2 = 0.24 CI = 0.14-0.33 and r2 = 0.23 CI = 0.14-0.32). In these models, motor competence variables were significant predictors, and only vigorous physical activity and Euclidean Norm Minus One emerged as significant PA dose predictors. DISCUSSION: These findings emphasise that motor competence and physical activity variables better predict executive functions when they are combined. When considered individually both motor competence variables were significant predictors of executive function whilst physical activity variables were not. Importantly, among the two movement competence facets, divergent movement assessment exhibited the strongest association with executive function. Future interventions should consider how to facilitate both movement and cognitive development in children. Future interventions should consider both the interplay of movement quality and quantity and the importance of environments that invite children's exploratory movement behavior.

The impact of imputation quality on machine learning classifiers for datasets with missing values.

BACKGROUND: Classifying samples in incomplete datasets is a common aim for machine learning practitioners, but is non-trivial. Missing data is found in most real-world datasets and these missing values are typically imputed using established methods, followed by classification of the now complete samples. The focus of the machine learning researcher is to optimise the classifier's performance. METHODS: We utilise three simulated and three real-world clinical datasets with different feature types and missingness patterns. Initially, we evaluate how the downstream classifier performance depends on the choice of classifier and imputation methods. We employ ANOVA to quantitatively evaluate how the choice of missingness rate, imputation method, and classifier method influences the performance. Additionally, we compare commonly used methods for assessing imputation quality and introduce a class of discrepancy scores based on the sliced Wasserstein distance. We also assess the stability of the imputations and the interpretability of model built on the imputed data. RESULTS: The performance of the classifier is most affected by the percentage of missingness in the test data, with a considerable performance decline observed as the test missingness rate increases. We also show that the commonly used measures for assessing imputation quality tend to lead to imputed data which poorly matches the underlying data distribution, whereas our new class of discrepancy scores performs much better on this measure. Furthermore, we show that the interpretability of classifier models trained using poorly imputed data is compromised. CONCLUSIONS: It is imperative to consider the quality of the imputation when performing downstream classification as the effects on the classifier can be considerable.

Many artificial intelligence (AI) methods aim to classify samples of data into groups, e.g., patients with disease vs. those without. This often requires datasets to be complete, i.e., that all data has been collected for all samples. However, in clinical practice this is often not the case and some data can be missing. One solution is to 'complete' the dataset using a technique called imputation to replace those missing values. However, assessing how well the imputation method performs is challenging. In this work, we demonstrate why people should care about imputation, develop a new method for assessing imputation quality, and demonstrate that if we build AI models on poorly imputed data, the model can give different results to those we would hope for. Our findings may improve the utility and quality of AI models in the clinic.

Common methodological pitfalls in ICI pneumonitis risk prediction studies.

Background: Pneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews. Methods: The PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools. Results: There were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets. Conclusions: Studies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies.

Associations between motor competence and physical activity levels of children with intellectual disabilities and/or autism spectrum disorder: Movement matters.

Motor competence is important for lifelong physical activity (PA). The current study aimed to examine associations between PA and motor competence. In total, 43 children aged 7-12 years with intellectual disabilities and/or autism spectrum disorder completed anthropometric measures, the Bruininks-Oseretsky Test of Motor Proficiency-2, and wore a wrist accelerometer to capture total PA, moderate-to-vigorous PA (MVPA), average acceleration, and intensity gradient. No significant associations were found between PA outcomes and motor competence. Motor competence performance was commonly 'below average' or 'average'. The weakest subtests were upper limb coordination and strength. The strongest subtest was running speed and agility. Total weekly MVPA was 336.1 ± 150.3 min, higher than UK recommendations of 120-180 per week for disabled children and young people. Larger scale studies are needed to better understand the relationship between PA and motor competence. Future research should also consider the influence of environmental factors on PA in this group.

Development of a novel workflow method to characterize and validate clinical data quality acquired through the Veterinary Committee on Trauma registry.

OBJECTIVE: To generate and apply a novel workflow method to assess the quality of data from the Veterinary Committee on Trauma (VetCOT) registry. ANIMALS: Canine and feline trauma patient data entered by identified and verified Veterinary Trauma Centers into the VetCOT registry between April 2017-December 2018 were retrieved for analysis. METHODS: Analysis software (RVetQual) was created in the R programming language to compare 5,000 cases exported from the VetCOT registry with samples of original corresponding records from 6 veterinary trauma centers. In addition, an evaluation of the consistency and completeness of the trauma registry was conducted. RESULTS: The utilization of this analysis tool allowed an assessment of the VetCOT trauma registry. Some of the variables effecting the accuracy, consistency, and completeness of the VetCOT trauma registry were canine and feline age, weight, trauma time entered, and mismatches in blood glucose. However, the completeness of the database was minimally affected. CLINICAL RELEVANCE: RVetQual is an efficient, accessible, and adjustable tool that facilitates the assessment of the data quality of the VetCOT registry. Such an assessment can lead to improvement of the quality of information serving to guide further trauma patient care.

Imaging Carotid Plaque Inflammation Using Positron Emission Tomography: Emerging Role in Clinical Stroke Care, Research Applications, and Future Directions.

Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges in standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.

A pipeline to further enhance quality, integrity and reusability of the NCCID clinical data.

The National COVID-19 Chest Imaging Database (NCCID) is a centralized UK database of thoracic imaging and corresponding clinical data. It is made available by the National Health Service Artificial Intelligence (NHS AI) Lab to support the development of machine learning tools focused on Coronavirus Disease 2019 (COVID-19). A bespoke cleaning pipeline for NCCID, developed by the NHSx, was introduced in 2021. We present an extension to the original cleaning pipeline for the clinical data of the database. It has been adjusted to correct additional systematic inconsistencies in the raw data such as patient sex, oxygen levels and date values. The most important changes will be discussed in this paper, whilst the code and further explanations are made publicly available on GitLab. The suggested cleaning will allow global users to work with more consistent data for the development of machine learning tools without being an expert. In addition, it highlights some of the challenges when working with clinical multi-center data and includes recommendations for similar future initiatives.

Examining the validity, reliability and feasibility of capturing children's physical literacy through games-based assessment in physical education.

Background: Observational tools can help refine practice design and guide the creation of effective learning environments. The intention of this study was to design and validate an observational instrument for assessing physical literacy that remains more faithful to the philosophically complex and holistic nature of the concept. Methods: Framed by concepts of ecological dynamics, the emergent games-based assessment tool enables capture of children's interactions with their environment, providing insight on the manifestation of physical literacy within physical education games. The design and validation of the instrument consisted of a multistage process: (1) design of the observational instrument and establishing face validity; (2) pilot observation study; (3) expert qualitative and quantitative review to establish content validity; (4) observation training; and (5), establishing observer reliability. Results: Following expert qualitative and quantitative evaluation, Aiken's V coefficient was used to determine content validity. Results achieved demanding levels of validity (V ≥ 0.78) for all retained measurement variables. Cohen's κ values for inter- and intra-observer reliability ranged from 0.331 to 1.00 and 0.552 to 1.00, generally reporting "substantial" agreement during inter-observer analysis and "substantial" to "almost perfect" agreement during intra-observer analysis. Conclusions: The final model of the emergent games-based assessment tool, with 9 ecological conceptualisations of behaviour, 15 measurement variables, and 44 categorical observational items was found to be valid and reliable, providing both educators and researchers with a useful mechanism to assess physical literacy during gameplay.

Coronary Atherosclerotic Plaque Activity and Future Coronary Events.

Importance: Recurrent coronary events in patients with recent myocardial infarction remain a major clinical problem. Noninvasive measures of coronary atherosclerotic disease activity have the potential to identify individuals at greatest risk. Objective: To assess whether coronary atherosclerotic plaque activity as assessed by noninvasive imaging is associated with recurrent coronary events in patients with myocardial infarction. Design, Setting, and Participants: This prospective, longitudinal, international multicenter cohort study recruited participants aged 50 years or older with multivessel coronary artery disease and recent (within 21 days) myocardial infarction between September 2015 and February 2020, with a minimum 2 years' follow-up. Intervention: Coronary 18F-sodium fluoride positron emission tomography and coronary computed tomography angiography. Main Outcomes and Measures: Total coronary atherosclerotic plaque activity was assessed by 18F-sodium fluoride uptake. The primary end point was cardiac death or nonfatal myocardial infarction but was expanded during study conduct to include unscheduled coronary revascularization due to lower than anticipated primary event rates. Results: Among 2684 patients screened, 995 were eligible, 712 attended for imaging, and 704 completed an interpretable scan and comprised the study population. The mean (SD) age of participants was 63.8 (8.2) years, and most were male (601 [85%]). Total coronary atherosclerotic plaque activity was identified in 421 participants (60%). After a median follow-up of 4 years (IQR, 3-5 years), 141 participants (20%) experienced the primary end point: 9 had cardiac death, 49 had nonfatal myocardial infarction, and 83 had unscheduled coronary revascularizations. Increased coronary plaque activity was not associated with the primary end point (hazard ratio [HR], 1.25; 95% CI, 0.89-1.76; P = .20) or unscheduled revascularization (HR, 0.98; 95% CI, 0.64-1.49; P = .91) but was associated with the secondary end point of cardiac death or nonfatal myocardial infarction (47 of 421 patients with high plaque activity [11.2%] vs 19 of 283 with low plaque activity [6.7%]; HR, 1.82; 95% CI, 1.07-3.10; P = .03) and all-cause mortality (30 of 421 patients with high plaque activity [7.1%] vs 9 of 283 with low plaque activity [3.2%]; HR, 2.43; 95% CI, 1.15-5.12; P = .02). After adjustment for differences in baseline clinical characteristics, coronary angiography findings, and Global Registry of Acute Coronary Events score, high coronary plaque activity was associated with cardiac death or nonfatal myocardial infarction (HR, 1.76; 95% CI, 1.00-3.10; P = .05) but not with all-cause mortality (HR, 2.01; 95% CI, 0.90-4.49; P = .09). Conclusions and Relevance: In this cohort study of patients with recent myocardial infarction, coronary atherosclerotic plaque activity was not associated with the primary composite end point. The findings suggest that risk of cardiovascular death or myocardial infarction in patients with elevated plaque activity warrants further research to explore its incremental prognostic implications.

Characteristics of conventional high-risk coronary plaques and a novel CT defined thin-cap fibroatheroma in patients undergoing CCTA with stable chest pain.

BACKGROUND: Coronary computed tomography angiography (CCTA) can identify high-risk coronary plaque types. However, the inter-observer variability for high-risk plaque features, including low attenuation plaque (LAP), positive remodelling (PR), and the Napkin-Ring sign (NRS), may reduce their utility, especially amongst less experienced readers. METHODOLOGY: In a prospective study, we compared the prevalence, location and inter-observer variability of both conventional CT-defined high-risk plaques with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using individualised X-ray attenuation cut-offs (the CT-defined thin-cap fibroatheroma - CT-TCFA) in 100 patients followed-up for 7 years. RESULTS: In total, 346 plaques were identified in all patients. Seventy-two (21%) of all plaques were classified by conventional CT parameters as high-risk (either NRS or PR and LAP combined), and 43 (12%) of plaques were considered high-risk using the novel CT-TCFA definition of (Necrotic Core/fibrous plaque ratio of >0.9). The majority (80%) of the high-risk plaques (LAP&PR, NRS and CT-TCFA) were located in the proximal and mid-LAD and RCA. The kappa co-efficient of inter-observer variability (k) for NRS was 0.4 and for PR and LAP combined 0.4. While the kappa co-efficient of inter-observer variability (k) for the new CT-TCFA definition was 0.7. During follow-up, patients with either conventional high-risk plaques or CT-TCFAs were significantly more likely to have MACE (Major adverse cardiovascular events) compared to patients without coronary plaques (p value 0.03 & 0.03, respectively). CONCLUSION: The novel CT-TCFA is associated with MACE and has improved inter-observer variability compared with current CT-defined high-risk plaques.