Jacob Kean

Structured Background/Objective: Headache following traumatic brain injury (TBI) is a common, yet disabling, disorder with diverse mechanisms and treatment needs that remain poorly defined. Pharmacological regimens are the primary source of remedies for individuals with post-traumatic headaches (PTH). The main objective of this review is to describe the efficacy of pharmacological medications for the treatment of PTH with a specific focus on the effect of these medications on headache characteristics and patients’ quality of life (QoL). Methods: This systematic review (CRD42024537710) followed PRISMA and SWiM guidelines. PubMed, CINAHL, Scopus, PsycINFO, and the Cochrane Library were searched in April 2024 for peer-reviewed articles published in English between 2009 and 2024. Eligible studies included randomized controlled trials, controlled cohort studies, and systematic reviews or meta-analyses evaluating pharmacological treatments for PTH in adults. Studies were excluded if they did not assess outcomes related to PTH pain, included pediatric populations, used animal models, investigated only non-pharmacological interventions, were case reports, narrative reviews, editorials, or conference abstracts, or did not involve human participants with TBI- or whiplash-related headache. Risk of bias was assessed using RoB-2 for RCTs and the Newcastle-Ottawa Scale (NOS) for controlled cohort studies. Result: Sixteen studies were included in the final review. Most studies reported some improvements in headache frequency and intensity, with some also noting benefits in headache burden and QoL. Study designs included retrospective observational (n=7), non-randomized prospective (n=4), and randomized controlled trials (n=6). Of the RCTs, only three had a low risk of bias, and just one focused specifically on PTH. Conclusion: Erenumab showed potential benefits for persistent headache symptoms and improved quality of life in civilian populations, while Prazosin demonstrated similar benefits in military populations, both with minimal side effects. Metoclopramide, co-administered with diphenhydramine to minimize side effects, demonstrated short-term efficacy as an abortive treatment for headache in emergency settings. However, due to the limited high-quality evidence, current pharmacological treatments for PTH should be used with caution. Future research should prioritize rigorous, controlled studies—particularly comparative effectiveness trials—and explore holistic, personalized approaches that incorporate treatment of psychiatric comorbidities and consider patient context.

Health care value, quantified as outcome per unit cost, requires knowing which outcomes are influenced by which intervention at what cost. The value of rehabilitation is still largely unknown. Much of the reason for this limited evidence is historically poor standardization and collection of rehabilitation interventions, and objectively measured outcomes across care settings, care providers, and health care systems. The purposeful standardization and aggregation of rehabilitation-relevant data about interventions, cost, and outcomes from routine clinical practices offers potential to understand and improve the value of rehabilitation. This perspective details the critical need for rehabilitation-relevant data that are aggregated across settings, providers, and systems and proposes 3 options to meet this need, including (1) integrating rehabilitation-relevant data into existing research registry databases that are condition specific, (2) adding rehabilitation-relevant data to federally funded research networks, and (3) creating a novel rehabilitation registry database. There must be continued pursuit of discovering which rehabilitation interventions achieve which specific outcomes, in which settings, for which patients, and at what costs. Successfully aggregating rehabilitation-relevant data is critical for generating evidence that answers these key questions about the value of rehabilitation.

Background: All federal agencies are required to support appropriation requests with evidence and evaluation (US Public Law 115-435; the Evidence Act). The StrAtegic PoLicy EvIdence-Based Evaluation CeNTer (SALIENT) is 1 of 6 centers that help the Department of Veterans Affairs (VA) meet this requirement. Objective: Working with the existing VA evaluation structure, SALIENT evaluations will contribute to (1) optimize policies and programs for veteran populations; (2) improve outcomes regarding health, equity, cost, and provider well-being; (3) advance the science of dissemination and knowledge translation; and (4) expand the implementation and dissemination science workforce. Methods: We leverage the Lean Sprint methodology (iterative, incremental, rule-governed approach to clearly defined, and time-boxed work) and 3 cores to develop our evaluation plans collaboratively with operational partners and key stakeholders including veterans, policy experts, and clinicians. The Operations Core will work with evaluation teams to develop timelines, facilitate work, monitor progress, and guide quality improvement within SALIENT. The Methods Core will work with evaluation teams to identify the most appropriate qualitative, quantitative, and mixed methods approaches to address each evaluation, ensure that the analyses are conducted appropriately, and troubleshoot when problems with data acquisition and analysis arise. The Knowledge Translation (KT) Core will target key partners and decision makers using a needs-based market segmentation approach to ensure that needs are incorporated in the dissemination of knowledge. The KT Core will create communications briefs, playbooks, and other materials targeted at these market segments to facilitate implementation of evidence-based practices and maximize the impact of evaluation results. Results: The SALIENT team has developed a center infrastructure to support high-priority evaluations, often to be responsive to shifting operational needs and priorities. Our team has engaged in our core missions and operations to rapidly evaluate a high-priority areas, develop a comprehensive Lean Sprint systems redesign approach to training, and accelerate rapid knowledge translation. Conclusions: With an array of interdisciplinary expertise, operational partnerships, and integrated resources, SALIENT has an established and evolving infrastructure to rapidly develop and implement high-impact evaluations. Projects are developed with sustained efficiency approaches that can pivot to new priorities as needed and effectively translate knowledge for key stakeholders and policy makers, while creating a learning health system infrastructure to foster the next generation of evaluation and implementation scientists. International Registered Report Identifier (IRRID): PRR1-10.2196/59830

BACKGROUND All federal agencies are required to support appropriation requests with evidence and evaluation (US Public Law 115-435; the Evidence Act). The StrAtegic PoLicy EvIdence-Based Evaluation CeNTer (SALIENT) is 1 of 6 centers that help the Department of Veterans Affairs (VA) meet this requirement. OBJECTIVE Working with the existing VA evaluation structure, SALIENT evaluations will contribute to (1) optimize policies and programs for veteran populations; (2) improve outcomes regarding health, equity, cost, and provider well-being; (3) advance the science of dissemination and knowledge translation; and (4) expand the implementation and dissemination science workforce. METHODS We leverage the Lean Sprint methodology (iterative, incremental, rule-governed approach to clearly defined, and time-boxed work) and 3 cores to develop our evaluation plans collaboratively with operational partners and key stakeholders including veterans, policy experts, and clinicians. The Operations Core will work with evaluation teams to develop timelines, facilitate work, monitor progress, and guide quality improvement within SALIENT. The Methods Core will work with evaluation teams to identify the most appropriate qualitative, quantitative, and mixed methods approaches to address each evaluation, ensure that the analyses are conducted appropriately, and troubleshoot when problems with data acquisition and analysis arise. The Knowledge Translation (KT) Core will target key partners and decision makers using a needs-based market segmentation approach to ensure that needs are incorporated in the dissemination of knowledge. The KT Core will create communications briefs, playbooks, and other materials targeted at these market segments to facilitate implementation of evidence-based practices and maximize the impact of evaluation results. RESULTS The SALIENT team has developed a center infrastructure to support high-priority evaluations, often to be responsive to shifting operational needs and priorities. Our team has engaged in our core missions and operations to rapidly evaluate a high-priority areas, develop a comprehensive Lean Sprint systems redesign approach to training, and accelerate rapid knowledge translation. CONCLUSIONS With an array of interdisciplinary expertise, operational partnerships, and integrated resources, SALIENT has an established and evolving infrastructure to rapidly develop and implement high-impact evaluations. Projects are developed with sustained efficiency approaches that can pivot to new priorities as needed and effectively translate knowledge for key stakeholders and policy makers, while creating a learning health system infrastructure to foster the next generation of evaluation and implementation scientists. INTERNATIONAL REGISTERED REPORT PRR1-10.2196/59830

Introduction: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements. Material and Methods: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor. Results: After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non–blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus. Conclusions: In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.

Background and Objectives: Traumatic brain injury (TBI) is a well-established epilepsy risk factor and is common among service members. Deployment related TBI, where combat/blast may be more common, may have different outcomes than non-deployment related TBI. This work examined associations of all TBI exposures (not just combat), and epilepsy, while adjusting for comorbidities associated with epilepsy, among Veterans by deployment status. Methods: The cohort included post-9/11 Veterans with ≥ 2 years of care in both Veterans Health Administration (VHA) and Defense Health Agency (DHA) systems. We identified epilepsy using ICD-9/10-CM codes, anti-seizure medication, and service-connected disability for epilepsy. We conducted a logistic regression model with interaction terms for conditions by deployment history that adjusted for demographics and military characteristics. Results: The cohort (n=938,890) included post-9/11 Veterans of which 27,436 (2.92%) had epilepsy. Most Veterans had a history of deployment (70.64%), referred to as “deployed”. Epilepsy was more common among Veterans who were never deployed (“non-deployed”) (3.85% vs. 2.54%). Deployed Veterans were more likely to have had TBI, compared to the non-deployed (33.94% vs. 4.24%), but non-deployed Veterans with moderate/severe TBI had higher odds of epilepsy compared to deployed Veterans (aOR=2.92, 95% CI: 2.68-3.17 vs. aOR=2.01, 95% CI: 1.91-2.11). Penetrating TBI had higher odds of epilepsy among the deployed (aOR=5.33, 95% CI: 4.89-5.81), whereas the odds of epilepsy for mild TBI did not significantly differ by deployment status. Though most neurological conditions were more prevalent among non-deployed, they were often associated with higher odds of epilepsy in the deployed. Discussion: Deployment history had a significant differential impact on epilepsy predictors. As expected, penetrating TBI had a greater epilepsy impact among deployed Veterans perhaps due to combat/blast. Some epilepsy predictors (moderate/severe TBI, MS, Parkinson’s disease) had a stronger association in the non-deployed suggesting a potential healthy warrior effect in which such conditions preclude deployment. Other neurological conditions (e.g., brain tumor, Alzheimer9s disease/frontotemporal dementia) had a greater epilepsy impact in the deployed. This may be attributable to deployment related exposures (combat injury, occupational exposures). A better understanding of deployment effects is critical to provide targeted epilepsy prevention in Veterans and military service members.

Variation in availability, format, and standardization of patient attributes across health care organizations impacts patient-matching performance. We report on the changing nature of patient-matching features available from 2010–2020 across diverse care settings. We asked 38 health care provider organizations about their current patient attribute data-collection practices. All sites collected name, date of birth (DOB), address, and phone number. Name, DOB, current address, social security number (SSN), sex, and phone number were most commonly used for cross-provider patient matching. Electronic health record queries for a subset of 20 participating sites revealed that DOB, first name, last name, city, and postal codes were highly available (>90%) across health care organizations and time. SSN declined slightly in the last years of the study period. Birth sex, gender identity, language, country full name, country abbreviation, health insurance number, ethnicity, cell phone number, email address, and weight increased over 50% from 2010 to 2020. Understanding the wide variation in available patient attributes across care settings in the United States can guide selection and standardization efforts for improved patient matching in the United States.

Background: The traumatic brain injury (TBI) Intensive Evaluation and Treatment Program (IETP) is an innovative modality for delivering evidence-based treatments in a residential, inpatient format to special operational forces service members and veterans with mild TBI. IETPs provide bundled evidence-based assessment, treatment, referral, and case management in concordance with the existing guidelines for mild TBI and commonly co-occurring comorbidities. To date, there has been no formal characterization or evaluation of the IETP to understand the determinants of implementation across the system of care. The goal of our partnered evaluation initiative (PEI) with an operational partner, the Physical Medicine and Rehabilitation National Program Office, is to facilitate the full implementation of the IETP across all 5 Veterans Health Administration TBI–Centers of Excellence (TBI-COE) and to inform minimum standards while supporting the unique characteristics of each site. Objective: This IETP partnered evaluation will describe each of the 5 TBI-COE IETP services and state of implementation to identify opportunities for adaptation and scale, characterize the relationship between patient characteristics and clinical services received, evaluate the outcomes for participants in the IETP, and inform ongoing implementation and knowledge translation efforts to support IETP expansion. In alignment with the goals of the protocol, ineffective treatment components will be targeted for deimplementation. Methods: A 3-year concurrent mixed methods evaluation using a participatory approach in collaboration with the operational partner and TBI-COE site leadership will be conducted. Qualitative observations, semistructured focus groups, and interviewing methods will be used to describe IETP, stakeholder experiences and needs, and suggestions for IETP implementation. Quantitative methods will include primary data collection from patients in the IETP at each site to characterize long-term outcomes and patient satisfaction with treatment and secondary data collection to quantitatively characterize patient-level and care system–level data. Finally, data sets will be triangulated to share data findings with partners to inform ongoing implementation efforts. Results: Data collection began in December 2021 and is currently ongoing. The results and deliverables will inform IETP characterization, evaluation, implementation, and knowledge translation. Conclusions: The results of this evaluation seek to provide an understanding of the determinants affecting the implementation of IETPs. Service member, staff, and stakeholder insights will inform the state of implementation at each site, and quantitative measures will provide options for standardized outcome measures. This evaluation is expected to inform national Physical Medicine and Rehabilitation Office policies and processes and knowledge translation efforts to improve and expand the IETP. Future work may include cost evaluations and rigorous research, such as randomized controlled trials. International Registered Report Identifier (IRRID): DERR1-10.2196/44776

BACKGROUND The traumatic brain injury (TBI) Intensive Evaluation and Treatment Program (IETP) is an innovative modality for delivering evidence-based treatments in a residential, inpatient format to special operational forces service members and veterans with mild TBI. IETPs provide bundled evidence-based assessment, treatment, referral, and case management in concordance with the existing guidelines for mild TBI and commonly co-occurring comorbidities. To date, there has been no formal characterization or evaluation of the IETP to understand the determinants of implementation across the system of care. The goal of our partnered evaluation initiative (PEI) with an operational partner, the Physical Medicine and Rehabilitation National Program Office, is to facilitate the full implementation of the IETP across all 5 Veterans Health Administration TBI–Centers of Excellence (TBI-COE) and to inform minimum standards while supporting the unique characteristics of each site. OBJECTIVE This IETP partnered evaluation will describe each of the 5 TBI-COE IETP services and state of implementation to identify opportunities for adaptation and scale, characterize the relationship between patient characteristics and clinical services received, evaluate the outcomes for participants in the IETP, and inform ongoing implementation and knowledge translation efforts to support IETP expansion. In alignment with the goals of the protocol, ineffective treatment components will be targeted for deimplementation. METHODS A 3-year concurrent mixed methods evaluation using a participatory approach in collaboration with the operational partner and TBI-COE site leadership will be conducted. Qualitative observations, semistructured focus groups, and interviewing methods will be used to describe IETP, stakeholder experiences and needs, and suggestions for IETP implementation. Quantitative methods will include primary data collection from patients in the IETP at each site to characterize long-term outcomes and patient satisfaction with treatment and secondary data collection to quantitatively characterize patient-level and care system–level data. Finally, data sets will be triangulated to share data findings with partners to inform ongoing implementation efforts. RESULTS Data collection began in December 2021 and is currently ongoing. The results and deliverables will inform IETP characterization, evaluation, implementation, and knowledge translation. CONCLUSIONS The results of this evaluation seek to provide an understanding of the determinants affecting the implementation of IETPs. Service member, staff, and stakeholder insights will inform the state of implementation at each site, and quantitative measures will provide options for standardized outcome measures. This evaluation is expected to inform national Physical Medicine and Rehabilitation Office policies and processes and knowledge translation efforts to improve and expand the IETP. Future work may include cost evaluations and rigorous research, such as randomized controlled trials. INTERNATIONAL REGISTERED REPORT DERR1-10.2196/44776