Health factors impacting both the occurrence of, and recovery from traumatic brain injury (TBI) vary in complexity, and present genuine challenges to researchers and healthcare professionals seeking to characterize injury consequences and determine prognosis. However, attempts to clarify causal links between injury characteristics and clinical outcomes (including mortality) often compel researchers to exclude pre-existing health conditions (PECs) in their samples, including psychiatric history, medication usage, and other comorbid conditions. In this pre-registered population-based study (total starting n = 939,123 patients), we examined trends in PEC incidence over 22 years in the state of Pennsylvania (1997Pennsylvania ( -2019 in individuals sustaining TBI (n = 169,452) and individuals with orthopedic injury (n = 87,637). The goal was to determine how PECs interact with age and injury severity to influence short-term outcomes. A further goal was to determine whether number of PECs, or specific PEC clusters contributed to worse outcomes within the TBI cohort, compared with orthopedic injury alone. Primary findings indicate that PECs significantly influenced mortality within the TBI cohort; patients having four or more PECs were associated with approximately a two times greater likelihood of dying in acute care (odds ratio [OR] 1.9). Additionally, cluster analyses revealed four distinct PEC clusters that are age and TBI severity dependent. Overall, the likelihood of zero PECs hovers at *25%, which is critical to consider in TBI outcomes work and could potentially contribute to the challenges facing intervention science with regard to reproducibility of findings.

The replication crisis poses important challenges to modern science. Central to this challenge is re-establishing ground truths, or the most fundamental theories that serve as the bedrock to a scientific community. However, the goal to identify hypotheses with the greatest support is non-trivial given the unprecedented rate of scientific publishing. In this era of high-volume science, the goal of this study is to sample from one research community within clinical neuroscience (traumatic brain injury) and track major trends that have shaped this literature over the past 50 years. To do so, we first conduct decade-wise (1980-2019) network analysis to examine the scientific communities that shape this literature. To establish the robustness of our findings, we utilized searches from separate search engines (Web of Science; Semantic Scholar). As a second goal, we sought to determine the most highly cited hypotheses influencing the literature in each decade. In a third goal, we then searched for any papers referring to “replication” or efforts to reproduce findings within our >50,000 paper dataset. From this search, 550 papers were analyzed to determine the frequency and nature of formal replication studies over time. Finally, to maximize transparency, we provide a detailed procedure for the creation and analysis of our dataset, including a discussion of each of our major decision points, to facilitate similar efforts in other areas of neuroscience. We found that the unparalleled rate of scientific publishing within the brain injury literature combined with the scarcity of clear hypotheses in individual publications are a challenge to both evaluating accepted findings and determining paths forward to accelerate science. Additionally, while the conversation about reproducibility has increased over the past decade, the rate of published replication studies continues to be a negligible proportion of the research. Meta-science and computational methods offer the critical opportunity to assess the state of the science and illuminate pathways forward, but ultimately there is structural change needed in the brain injury literature and perhaps others.

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