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Abstract BackgroundEmerging evidence indicates an elevated risk of post-concussion musculoskeletal injuries in collegiate athletes; however, identifying athletes at highest risk remains to be elucidated. ObjectiveThe purpose of this study was to model post-concussion musculoskeletal injury risk in collegiate athletes by integrating a comprehensive set of variables by machine learning. MethodsA risk model was developed and tested on a dataset of 194 athletes (155 in the training set and 39 in the test set) with 135 variables entered into the analysis, which included participant’s heath and athletic history, concussion injury and recovery-specific criteria, and outcomes from a diverse array of concussion assessments. The machine learning approach involved transforming variables by the weight of evidence method, variable selection using L1-penalized logistic regression, model selection via the Akaike Information Criterion, and a final L2-regularized logistic regression fit. ResultsA model with 48 predictive variables yielded significant predictive performance of subsequent musculoskeletal injury with an area under the curve of 0.82. Top predictors included cognitive, balance, and reaction at baseline and acute timepoints. At a specified false-positive rate of 6.67%, the model achieves a true-positive rate (sensitivity) of 79% and a precision (positive predictive value) of 95% for identifying at-risk athletes via a well-calibrated composite risk score. ConclusionsThese results support the development of a sensitive and specific injury risk model using standard data combined with a novel methodological approach that may allow clinicians to target high injury risk student athletes. The development and refinement of predictive models, incorporating machine learning and utilizing comprehensive datasets, could lead to improved identification of high-risk athletes and allow for the implementation of targeted injury risk reduction strategies by identifying student athletes most at risk for post-concussion musculoskeletal injury. 

Abstract BackgroundEmerging evidence indicates an elevated risk of post-concussion musculoskeletal (MSK) injuries in collegiate athletes; however, identifying athletes at highest risk remains to be elucidated. ObjectiveThe purpose of this study was to model post-concussion MSK injury risk in collegiate athletes by integrating a comprehensive set of variables by machine learning. MethodsA risk model was developed and tested on a dataset of 194 athletes (155 in the training set and 39 in the test set) with 135 variables entered into the analysis, which included participant’s heath and athletic history, concussion injury and recovery specific criteria, and outcomes from a diverse array of concussions assessments. The machine learning approach involved transforming variables by the Weight of Evidence method, variable selection using L1-penalized logistic regression, model selection via the Akaike Information Criterion, and a final L2-regularized logistic regression fit. ResultsA model with 48 predictive variables yielded significant predictive performance of subsequent MSK injury with an area under the curve of 0.82. Top predictors included cognitive, balance, and reaction at Baseline and Acute timepoints. At a specified false positive rate of 6.67%, the model achieves a true positive rate (sensitivity) of 79% and a precision (positive predictive value) of 95% for identifying at-risk athletes via a well calibrated composite risk score. ConclusionThese results support the development of a sensitive and specific injury risk model using standard data combined with a novel methodological approach that may allow clinicians to target high injury risk student-athletes. The development and refinement of predictive models, incorporating machine learning and utilizing comprehensive datasets, could lead to improved identification of high-risk athletes and allow for the implementation of targeted injury risk reduction strategies by identifying student-athletes most at risk for post-concussion MSK injury. Key PointsThere is a well-established elevated risk of post-concussion subsequent musculoskeletal injury; however, prior efforts have failed to identify risk factors.This study developed a composite risk score model with an AUC of 0.82 from common concussion clinical measures and participant demographics.By identifying athletes at elevated risk, clinicians may be able to reduce injury risk through targeted injury risk reduction programs. 

Abstract Objective:The progression of long-term diabetes complications has led to a decreased quality of life. Our objective was to evaluate the adverse outcomes associated with diabetes based on a patient’s clinical profile by utilizing a multistate modeling approach. Methods:This was a retrospective study of diabetes patients seen in primary care practices from 2013 to 2017. We implemented a five-state model to examine the progression of patients transitioning from one complication to having multiple complications. Our model incorporated high dimensional covariates from multisource data to investigate the possible effects of different types of factors that are associated with the progression of diabetes. Results:The cohort consisted of 10,596 patients diagnosed with diabetes and no previous complications associated with the disease. Most of the patients in our study were female, White, and had type 2 diabetes. During our study period, 5928 did not develop complications, 3323 developed microvascular complications, 1313 developed macrovascular complications, and 1129 developed both micro- and macrovascular complications. From our model, we determined that patients had a 0.1334 [0.1284, .1386] rate of developing a microvascular complication compared to 0.0508 [0.0479, .0540] rate of developing a macrovascular complication. The area deprivation index score we incorporated as a proxy for socioeconomic information indicated that patients who reside in more disadvantaged areas have a higher rate of developing a complication compared to those who reside in least disadvantaged areas. Conclusions:Our work demonstrates how a multistate modeling framework is a comprehensive approach to analyzing the progression of long-term complications associated with diabetes. 

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 h after hypoxia. Single-cell RNA sequencing (scRNAseq) revealed two microglia subclusters of interest following HIE. Pseudobulk analysis revealed increased microglia motility gene expression and upregulation of epigenetic machinery and neurodevelopmental genes in macrophages following HIE. No sex differences were found in any measures. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a milder phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may reveal novel targets for therapy for neonates with HIE.