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Latent Class Analysis to Classify Injury Severity in Pediatric Traumatic Brain Injury.

ABSTRACT: Heterogeneity of injury severity among children with traumatic brain injury (TBI) classified by the Glasgow Coma Scale (GCS) makes comparisons across research cohorts, enrollment in clinical trials, and clinical predictions of outcomes difficult. The present study uses latent class analysis (LCA) to distinguish severity subgroups from a prospective cohort of 433 children 2.5-15 years of age with TBI who were recruited from two level 1 pediatric trauma centers. Indicator variables available within 48 h post-injury including emergency department (ED) GCS, hospital motor GCS, Abbreviated Injury Score (AIS), Rotterdam Score, hypotension in the ED, and pre-hospital loss of consciousness, intubation, seizures, and sedation were evaluated to define subgroups. To understand whether latent class subgroups were predictive of clinically meaningful outcomes, the Pediatric Injury Functional Outcome Scale (PIFOS) at 6 and 12 months, and the Behavior Rating Inventory of Executive Function at 12 months, were compared across subgroups. Then, outcomes were examined by GCS (primary) and AIS (secondary) classification alone to assess whether LCA provided improved outcome prediction. LCA identified four distinct increasing severity subgroups (1-4). Unlike GCS classification, mean outcome differences on PIFOS at 6 months showed decreasing function across classes. PIFOS differences relative to the lowest latent class (LC1) were: LC2 2.27 (0.83, 3.72), LC3 3.99 (1.88, 6.10), and LC4 11.2 (7.04, 15.4). Differences in 12 month outcomes were seen between the most and least severely injured groups. Differences in outcomes in relation to AIS were restricted to the most and less severely injured at both time points. This study distinguished four latent classes that are clinically meaningful, distinguished a more homogenous severe injury group, and separated children by 6-month functional outcomes better than GCS alone. Systematic reporting of these variables would allow comparisons across research cohorts, potentially improve clinical predictions, and increase sensitivity to treatment effects in clinical trials.

SUBMITTER: Keenan HT

PROVIDER: S-EPMC8024352 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: The initial injury burden from incident TBI is significantly amplified by recurrent TBI (rTBI). Unfortunately, research assessing the accuracy to conduct rTBI surveillance is not available. Accurate surveillance information on recurrent injuries is needed to justify the allocation of resources to rTBI prevention and to conduct high quality epidemiological research on interventions that mitigate this injury burden. This study evaluates the accuracy of administrative health data (AHD) surveillance case definitions for rTBI and estimates the 1-year rTBI incidence adjusted for measurement error. Methods: A 25% random sample of AHD for Montreal residents from 2000 to 2014 was used in this study. Four widely used TBI surveillance case definitions, based on the International Classification of Disease and on radiological exams of the head, were applied to ascertain suspected rTBI cases. Bayesian latent class models were used to estimate the accuracy of each case definition and the 1-year rTBI measurement-error-adjusted incidence without relying on a gold standard rTBI definition that does not exist, across children (<18 years), adults (18-64 years), and elderly (> =65 years). Results: The adjusted 1-year rTBI incidence was 4.48 (95% CrI 3.42, 6.20) per 100 person-years across all age groups, as opposed to a crude estimate of 8.03 (95% CrI 7.86, 8.21) per 100 person-years. Patients with higher severity index TBI had a significantly higher incidence of rTBI compared to patients with lower severity index TBI. The case definition that identified patients undergoing a radiological examination of the head in the context of any traumatic injury was the most sensitive across children [0.46 (95% CrI 0.33, 0.61)], adults [0.79 (95% CrI 0.64, 0.94)], and elderly [0.87 (95% CrI 0.78, 0.95)]. The most specific case definition was the discharge abstract database in children [0.99 (95% CrI 0.99, 1.00)], and emergency room visits claims in adults/elderly [0.99 (95% CrI 0.99, 0.99)]. Median time to rTBI was the shortest in adults (75 days) and the longest in children (120 days). Conclusion: Conducting accurate surveillance and valid epidemiological research for rTBI using AHD is feasible when measurement error is accounted for.

Project description:To provide an overview of the preclinical literature on progesterone for neuroprotection after traumatic brain injury and to describe unique features of developmental brain injury that should be considered when evaluating the therapeutic potential for progesterone treatment after pediatric traumatic brain injury.National Library of Medicine PubMed literature review.The mechanisms of neuroprotection by progesterone are reviewed, and the preclinical literature using progesterone treatment in adult animal models of traumatic brain injury is summarized. Unique features of the developing brain that could either enhance or limit the efficacy of neuroprotection by progesterone are discussed, and the limited preclinical literature using progesterone after acute injury to the developing brain is described. Finally, the current status of clinical trials of progesterone for adult traumatic brain injury is reviewed.Progesterone is a pleiotropic agent with beneficial effects on secondary injury cascades that occur after traumatic brain injury, including cerebral edema, neuroinflammation, oxidative stress, and excitotoxicity. More than 40 studies have used progesterone for treatment after traumatic brain injury in adult animal models, with results summarized in tabular form. However, very few studies have evaluated progesterone in pediatric animal models of brain injury. To date, two human phase II trials of progesterone for adult traumatic brain injury have been published, and two multicenter phase III trials are underway.The unique features of the developing brain from that of a mature adult brain make it necessary to independently study progesterone in clinically relevant, immature animal models of traumatic brain injury. Additional preclinical studies could lead to the development of a novel neuroprotective therapy that could reduce the long-term disability in head-injured children and could potentially provide benefit in other forms of pediatric brain injury (global ischemia, stroke, and statue epilepticus).

Project description:Background: Traumatic brain injury (TBI) is the leading cause of death and disability in children. It includes a range of different pathologies that differ considerably from adult TBI. Analyzing and understanding injury patterns of pediatric TBI is essential to establishing new preventive efforts as well as to improve clinical management. Methods: The multi-center, prospectively collected CENTER-TBI core and registry databases were screened and patients were included when younger than 18 years at enrollment and admitted to the regular ward (admission stratum) or intensive care unit (ICU stratum) following TBI. Patient demographics, injury causes, clinical findings, brain CT imaging details, and outcome (GOSE at 6 months follow-up) were retrieved and analyzed. Injury characteristics were compared between patients admitted to the regular ward and ICU and multivariate analysis of factors predicting an unfavorable outcome (GOSE 1-4) was performed. Results from the core study were compared to the registry dataset which includes larger patient numbers but no follow-up data. Results: Two hundred and twenty seven patients in the core dataset and 687 patients in the registry dataset were included in this study. In the core dataset, road-traffic incidents were the most common cause of injury overall and in the ICU stratum, while incidental falls were most common in the admission stratum. Brain injury was considered serious to severe in the majority of patients and concurrent injuries in other body parts were very common. Intracranial abnormalities were detected in 60% of initial brain CTs. Intra- and extracranial surgical interventions were performed in one-fifth of patients. The overall mortality rate was 3% and the rate of unfavorable outcome 10%, with those numbers being considerably higher among ICU patients. GCS and the occurrence of secondary insults could be identified as independent predictors for an unfavorable outcome. Injury characteristics from the core study could be confirmed in the registry dataset. Conclusion: Our study displays the most common injury causes and characteristics of pediatric TBI patients that are treated in the regular ward or ICU in Europe. Road-traffic incidents were especially common in ICU patients, indicating that preventive efforts could be effective in decreasing the incidence of severe TBI in children.

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Latent Class Analysis to Classify Injury Severity in Pediatric Traumatic Brain Injury.

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