Traumatic brain injury (TBI) is associated with a variety of adverse health outcomes that display complex behavior over time. The objective of this study was to investigate both the early and late health impacts of TBI within a single framework. This study evaluated TBI associations among a cohort of post-9/11 Veterans with TBI documented between 2008 and 2017 in Veteran Health Administration (VHA) records. The cohort included 108,408 post-9/11 Veterans with any history of TBI documentation between 2008-2017 who were demographically matched with 108,408 TBI negative controls. Interrupted time series (ITS) models were used to fit the prevalence of comorbidities over time (+/-6 years from index date, i.e. date of first TBI). Three ITS measures were modeled for each comorbidity: 1) The incidence rate (IR) in the month of TBI index date, 2) The incidence rate ratio (IRR) between TBI and control groups in the month of index date, and 3) Long-term changes in year-over-year diagnosis rates, i.e. the annual incidence rate difference (IRD) before vs. after index date. Overall, TBI was associated with conditions related to somatic, cognitive, and psychological outcomes including headache, cognitive dysfunction, and PTSD. Neurological events were found to be elevated within the month of TBI documentation. Conditions with the largest IR were post-traumatic stress disorder (PTSD) (+29%, p<0.001), headache (+22%, p<0.001), and adjustment disorder (+22%, p<0.001). Conditions with the highest IRR across TBI and control groups were cognitive dysfunction (474, p<0.001), vestibular dysfunction (137, p<0.001), and stroke (72, p<0.001). Long term, the conditions with the highest IRD were substance use disorders (p<0.001) and mental health conditions (p<0.001). This work demonstrates how ITS modeling can help bridge traditional divides between early and late paradigms of TBI investigation to help inform research and care for Veterans living with TBI.

The authors have declared no competing interest.

This project was funded by the Congressionally Directed Medical Research Programs Epilepsy Research Program in 2023 under award EP220089.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The institutional review board (IRB) of the University of Utah waived ethical approval of this work as IRB #00163364. This study was limited to secondary deidentified data analysis and was designated as non-human subjects research. Following ethics approval obtained for this study on June 9th 2023, data were accessed for this study on August 22nd, 2023.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Raw data is not available because it is identifying. Some deidentified data is available upon reasonable request pending appropriate study approvals and data transfer agreements between participating institutions. Code used for analysis is available upon request.