Beyond mortality: years of life lost as an underestimated outcome in traumatic brain injury

Traumatic brain injury (TBI) remains one of the leading causes of death and long-term neurological disability worldwide, disproportionately affecting adolescents and adults in their most productive years of life (1,2). Advances in acute care have significantly improved short-term survival; however, millions of individuals live for decades with the consequences of TBI (3). Despite this reality, the impact of TBI is still predominantly assessed using short-term outcomes, such as in-hospital mortality, early functional scales, and length of stay.While these indicators are essential for acute management, they fail to capture the long-term burden of TBI across the life course. Survival after the acute phase does not necessarily translate into full recovery or preservation of life expectancy. A growing body of evidence indicates that individuals who survive TBI face an increased risk of late mortality, progressive functional decline, and heightened vulnerability to neurological, psychiatric, and systemic conditions (4)(5)(6). Nevertheless, these outcomes remain largely invisible in both clinical research and health metrics that guide decision-making.In this context, years of life lost (YLL) emerge as a particularly relevant outcome to capture the longitudinal impact of TBI. By accounting for the age at death relative to a standardized life expectancy, YLL provides a more sensitive estimate of premature mortality than crude death counts alone (7). Although YLL is a core component of the Global Burden of Disease (GBD) framework, it has not been systematically incorporated into TBI-focused research (8). In this opinion article, we argue that YLL should be adopted as a central outcome in TBI research, clinical reasoning, and health policy, supported by evidence from both retrospective and prospective perspectives.YLL were developed within the framework of the GBD studies as a standardized metric to quantify premature mortality attributable to specific diseases and injuries (7,8). The YLL metric captures not only the occurrence of death but also the timing of death in relation to an optimal life expectancy, thereby providing a more comprehensive assessment of mortality-related burden. Conceptually, YLL is calculated as the difference between the age at death and a reference life expectancy obtained from standardized life tables that represent ideal survival conditions rather than country-specific mortality patterns. In the most recent GBD iterations, this reference life expectancy corresponds to a life expectancy at birth of approximately 86 years, derived from the lowest observed age-specific mortality rates across populations worldwide. The use of this normative life table ensures comparability across countries, regions, and time periods, avoiding bias introduced by local variations in mortality profiles.By assigning a higher number of lost years to deaths occurring at younger ages, YLL explicitly incorporates the disproportionate social, economic, and human impact of premature mortality. Unlike crude or age-specific mortality rates, which treat all deaths equivalently regardless of age, YLL enables meaningful comparisons across diseases and injuries with distinct epidemiological and age-distribution patterns. For this reason, YLL has become a cornerstone indicator in global health research and a central component of burden-of-disease analyses conducted by the GBD consortium and the World Health Organization (7). This perspective is particularly critical in the context of TBI. Traumatic brain injury disproportionately affects children, adolescents, and young adults, resulting in a substantial number of deaths occurring far below the reference life expectancy (1,2). Consequently, even relatively modest increases in TBIrelated mortality can lead to disproportionately large losses of potential life years. Analyses restricted to death counts or short-term survival rates therefore systematically underestimate the true magnitude of TBI-related harm, whereas YLL-based assessments more accurately capture its long-term societal and population-level impact.Mathematically, YLL were calculated by summing, across all ages, the product of the numb``er of deaths at each age and the corresponding remaining life expectancy derived from the GBD standard life table. This approach is formally expressed as:□□□□□□ = $ ( □□ □□#□□ □□ □□ × □□ □□ )where □□ % represents the number of deaths occurring at age or age group i, □□ % denotes the remaining life expectancy at that age according to the GBD reference life table, and n corresponds to the total number of age categories analyzed. When individual-level data on age at death were available, YLL was equivalently computed as the sum of the differences between the GBD reference life expectancy at birth (approximately 86 years) and the age at death for each individual, ensuring consistency with the aggregated formulation and full comparability with GBD estimates.Large population-based retrospective studies consistently demonstrate that individuals who survive a traumatic brain injury experience a sustained increase in long-term mortality compared with age-and sex-matched individuals from the general population (4,5,(9)(10)(11). Importantly, this excess mortality persists for years or even decades after the initial injury, suggesting that TBI should be understood as a chronic health condition rather than a time-limited acute event.The mechanisms underlying late mortality after TBI are multifactorial. Neurological sequelae such as epilepsy, cognitive impairment, and neurodegeneration interact with systemic consequences, including autonomic dysfunction, metabolic alterations, and increased cardiovascular risk (6,(12)(13)(14). Psychiatric disorders, substance use, and social vulnerability further amplify mortality risk, particularly among younger individuals injured during adolescence or early adulthood (4,9). Despite these findings, most clinical and epidemiological studies remain anchored to short follow-up horizons, frequently restricted to hospital discharge or 6-month functional outcomes. As a result, premature mortality occurring years after injury is rarely attributed to TBI in burden estimates, reinforcing the misconception that survival of the acute phase represents an adequate measure of success (10,11).Incorporating YLL into retrospective analyses provides a more integrative assessment of this hidden burden. By quantifying premature death relative to expected lifespan, YLL captures the cumulative downstream effects of neurological injury, comorbidity accumulation, and social disadvantage. This approach aligns TBI research with contemporary models of chronic disease burden and supports a reevaluation of outcome hierarchies traditionally used in the field. Prospective cohort designs offer a critical methodological advantage for quantifying YLL, as they allow systematic long-term follow-up and reduce the risk of misclassification of late deaths (15,16).Unlike retrospective studies that rely on administrative coding or death registries alone, prospective approaches can integrate clinical, functional, and social determinants of health across the life course.In the context of TBI, prospective measurement of YLL enables the investigation of how injury severity, secondary insults, access to rehabilitation, and post-acute care trajectories shape long-term survival (6,(17)(18)(19). Emerging evidence suggests that disparities in follow-up care and social reintegration may contribute substantially to excess mortality, particularly in low-and middle-income settings (2,20).Moreover, embedding YLL as a predefined outcome facilitates stratified analyses across clinically meaningful subgroups, such as mild versus severe TBI, pediatric versus adult injury, and isolated versus polytrauma cases. This level of granularity is essential for identifying high-risk populations and for evaluating whether specific interventions meaningfully preserve life expectancy rather than merely delaying death.From a methodological perspective, the inclusion of YLL in prospective TBI research aligns injury science with global burden-of-disease frameworks and strengthens the external validity and policy relevance of long-term outcome studies.Incorporating YLL as a clinical outcome expands the understanding of TBI beyond immediate survival. This perspective underscores the importance of long-term follow-up, secondary prevention, and integrated care models aimed at reducing late mortality. It also challenges clinicians to redefine therapeutic success, shifting from a discharge-centered view toward strategies that preserve life expectancy and long-term health.Importantly, discharge from acute care or rehabilitation should not be interpreted as the end of care or as equivalent to complete recovery. TBI may result in persistent neurological, cognitive, behavioral, and functional consequences that require continued monitoring after patients return to the community (21). Long-term follow-up should therefore be individualized according to injury severity, residual disability, comorbidities, and patient needs, with coordination across acute care, rehabilitation, primary care, and relevant multidisciplinary services. Such continuity may also facilitate the identification of late complications and deaths that would otherwise remain disconnected from the long-term trajectory following TBI. From this perspective, incorporating YLL into longitudinal outcome assessment may encourage healthcare systems to extend the concept of successful TBI care beyond hospital survival and discharge.From a research standpoint, adopting YLL as a central outcome necessitates changes in study design, follow-up duration, and analytical strategies. Future investigations should systematically quantify premature mortality and compare YLL across interventions and populations. Such an approach enables more robust evaluations of the true impact of emerging therapies and care pathways in TBI. An additional challenge is the substantial heterogeneity in post-acute TBI care across countries and healthcare systems. Following acute hospitalization, patients may return directly home, undergo inpatient or outpatient rehabilitation, transition to long-term care, or receive community-based services (21,23). The relative use and availability of these pathways vary according to healthcare organization, rehabilitation capacity, resource availability, geographic location, socioeconomic conditions, and mechanisms of healthcare financing (22,24). Consequently, no single proportion of patients returning home or receiving post-acute rehabilitation can adequately represent TBI care globally. Moreover, discharge destination alone should not be considered a surrogate for recovery, as patients returning home may continue to experience neurological, cognitive, behavioral, or functional impairments requiring ongoing care (21).These differences are particularly relevant when interpreting YLL across populations. Healthcare systems with limited access to rehabilitation, fragmented post-discharge follow-up, or incomplete linkage between hospital and mortality records may face greater difficulties in characterizing longterm outcomes after TBI (22,24). Conversely, systematic longitudinal follow-up and integration between acute, rehabilitation, primary, and community care may improve the identification of late mortality and provide a more complete understanding of the long-term burden associated with TBI.Thus, incorporating YLL into public health surveillance should be accompanied by consideration of the healthcare context in which deaths and long-term outcomes are observed.Despite its potential value, several factors may explain why YLL has not been routinely incorporated as an outcome in TBI clinical practice and research. YLL was primarily developed as a populationlevel measure of premature mortality, whereas TBI outcomes have traditionally focused on acute mortality, neurological status, functional recovery, and disability (7,8). Its broader implementation therefore requires reliable information on age at death, appropriate standardized life tables, accurate mortality ascertainment, and mechanisms for linking acute clinical information with long-term outcomes.Longitudinal follow-up represents an additional challenge. Patients with TBI may transition through multiple settings after acute hospitalization, including inpatient rehabilitation, outpatient rehabilitation, long-term care, primary care, and home -or community-based services (21). Fragmentation between these settings may hinder continuous outcome surveillance, while loss to follow-up can limit the identification and interpretation of late deaths. These challenges may be particularly relevant in healthcare systems with limited rehabilitation capacity, incomplete mortality registries, restricted access to specialized follow-up, or substantial geographic and socioeconomic inequalities (22,24).Cross-country comparisons also require caution. Although standardized reference life tables facilitate comparisons of YLL between populations, differences in healthcare organization, access to rehabilitation services, and post-acute care pathways may influence long-term outcomes following TBI (22)(23)(24). Therefore, YLL should be interpreted alongside information describing the healthcare context and the characteristics of the population being studied.Finally, YLL quantifies premature mortality but does not directly capture the substantial burden of disability, cognitive impairment, functional dependence, or reduced quality of life experienced by many TBI survivors. For this reason, we propose that YLL should complement rather than replace established clinical and functional outcomes. Integrating mortality-based measures such as YLL with disability, functional, cognitive, and quality-of-life outcomes may provide a more comprehensive representation of the lifelong burden of TBI.Traumatic brain injury has traditionally been evaluated through short-term outcomes that prioritize immediate survival (1,3). Accumulating evidence indicates that this approach substantially underestimates the long-term burden of TBI (4)(5)(6). YLL represent a critical metric for capturing premature mortality and the true impact of TBI across the lifespan (7,8). Integrating YLL into research, clinical practice, and public health policy constitutes a necessary conceptual shift to align TBI care with the complexity of its long-term consequences. The author(s) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.WGSF conceived the study, developed the conceptual framework, and wrote the manuscript.RMG contributed to the theoretical discussion and manuscript revision.MLF contributed to the literature review and manuscript revision.VCRA contributed to the literature review and manuscript revision.LJNM contributed to the literature review and manuscript revision.BVB contributed to the literature review and manuscript revision.KAK contributed to the literature review and manuscript revision.JAL contributed to the theoretical discussion and manuscript revision.JVSR contributed to the theoretical discussion and manuscript revision.RSM contributed to the theoretical discussion and manuscript revision.RFA contributed to the theoretical discussion and manuscript revision.FZSA supervised the study and critically revised the manuscript.The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.The authors would like to thank all individuals who contributed to the development of this work, directly or indirectly. We are particularly grateful to the members of the GEPENN Laboratory for their continuous scientific support and collaborative environment. We also acknowledge all affiliated institutions for providing the academic and structural conditions that made this study possible. Finally, we express our deepest respect and gratitude to all patients with traumatic brain injury, whose experiences and trajectories ultimately motivate research aimed at improving long-term outcomes and quality of life.