Determinants of long-term physical and mental health outcomes after intensive care admission for trauma survivors.

INTRODUCTION: Collectively, studies from medical and surgical intensive care units (ICU) suggest that long-term outcomes are poor for patients who have spent significant time in an ICU. We sought to identify determinants of post-intensive care physical and mental health outcomes 6-12 months after injury. METHODS: Adult trauma patients [ISS ≥9] admitted to one of three Level-1 trauma centers were interviewed 6-12 months post-injury to evaluate patient-reported outcomes. Patients requiring ICU admission â€‹≥ â€‹3 days ("ICU patients") were compared with those who did not require ICU admission ("non-ICU patients"). Multivariable regression models were built to identify factors associated with poor outcomes among ICU survivors. RESULTS: 2407 patients were followed [598 (25%) ICU and 1809 (75%) non-ICU patients]. Among ICU patients, 506 (85%) reported physical or mental health symptoms. Of them, 265 (52%) had physical symptoms only, 15 (3%) had mental symptoms only, and 226 (45%) had both physical and mental symptoms. In adjusted analyses, compared to non-ICU patients, ICU patients were more likely to have new limitations for ADLs (OR â€‹= â€‹1.57; 95% CI â€‹= â€‹1.21, 2.03), and worse SF-12 mental (mean Δ â€‹= â€‹-1.43; 95% CI â€‹= â€‹-2.79, -0.09) and physical scores (mean Δ â€‹= â€‹-2.61; 95% CI â€‹= â€‹-3.93, -1.28). Age, female sex, Black race, lower education level, polytrauma, ventilator use, history of psychiatric illness, and delirium during ICU stay were associated with poor outcomes in the ICU-admitted group. CONCLUSIONS: Physical impairment and mental health symptoms following ICU stay are highly prevalent among injury survivors. Modifiable ICU-specific factors such as early liberation from ventilator support and prevention of delirium are potential targets for intervention.

Intersection of Race, Ethnicity, and Sex in New Functional Limitations after Injury: Black and Hispanic Female Survivors at Greater Risk.

BACKGROUND: The impact of disparities at the intersection of multiple marginalized social identities is poorly understood in trauma. We sought to evaluate the joint effect of race, ethnicity, and sex on new functional limitations 6 to 12 months postinjury. STUDY DESIGN: Moderately to severely injured patients admitted to one of three Level I trauma centers were asked to complete a phone-based survey assessing functional outcomes 6 to 12 months postinjury. Multivariate adjusted regression analyses were used to compare functional limitations by race and ethnicity alone, sex alone, and the interaction between both race and ethnicity and sex. The joint disparity and its composition were calculated across race and sex strata. RESULTS: Included were 4,020 patients: 1,621 (40.3%) non-Hispanic White male patients, 1,566 (39%) non-Hispanic White female patients, 570 (14.2%) Black or Hispanic/Latinx male patients, and 263 (6.5%) Black or Hispanic/Latinx female patients (BHF). The risk-adjusted incidence of functional limitations was highest among BHF (50.6%) vs non-Hispanic White female patients (39.2%), non-Hispanic White male patients (35.8%), and Black or Hispanic male patients (34.6%; p < 0.001). In adjusted analysis, women (odds ratio 1.35 [95% CI 1.16 to 1.57]; p < 0.001) and Blacks or Hispanic patients (odds ratio 1.28 [95% CI 1.03 to 1.58]; p = 0.02) were more likely to have new functional limitations 6 to 12 months postinjury. When sex and race were analyzed together, BHF were more likely to have new functional limitations compared with non-Hispanic White male patients (odds ratio 2.12 [1.55 to 2.90]; p < 0.001), with 63.5% of this joint disparity being explained by the intersection of race and ethnicity and sex. CONCLUSION: More than half of the race and sex disparity in functional limitations experienced by BHF is explained by the unique experience of being both minority and a woman. Intermediate modifiable factors contributing to this intersectional disparity must be identified.

Core outcome measures for research in traumatic injury survivors: The National Trauma Research Action Plan modified Delphi consensus study.

BACKGROUND: Until recently, survival has been the main outcome measure for injury research. Given the impact of injury on quality of life, the National Academies of Science, Engineering, and Medicine has called for advancing the science of research evaluating the long-term outcomes of trauma survivors. This is necessary so that treatments and interventions can be assessed for their impact on a trauma patients' long-term functional and psychosocial outcomes. We sought to propose a set of core domains and measurement instruments that are best suited to evaluate long-term outcomes after traumatic injury with a goal for these measures to be adopted as a national standard. METHODS: As part of the development of a National Trauma Research Action Plan, we conducted a two-stage, five-round modified online Delphi consensus process with a diverse panel of 50 key stakeholders including clinicians, researchers, and trauma survivors from more than 9 professional areas across the United States. Before voting, panelists reviewed the results of a scoping review on patient-reported outcomes after injury and standardized information on measurement instruments following the Consensus-based Standards for the Selection of Health Measurement Instruments guidelines. RESULTS: The panel considered a preliminary list of 74 outcome domains (patient-reported outcomes) and ultimately reached the a priori consensus criteria for 29 core domains that encompass aspects of physical, mental, social, and cognitive health. Among these 29 core domains, the panel considered a preliminary list of 199 patient-reported outcome measures and reached the a priori consensus criteria for 14 measures across 13 core domains. Participation of panelists ranged from 65% to 98% across the five Delphi rounds. CONCLUSION: We developed a core outcome measurement set that will facilitate the synthesis, comparison, and interpretation of long-term trauma outcomes research. These measures should be prioritized in all future studies in which researchers elect to evaluate long-term outcomes of traumatic injury survivors. LEVEL OF EVIDENCE: Diagnostic Test or Criteria, Level IV.

A Global Loss of Dio2 Leads to Unexpected Changes in Function and Fiber Types of Slow Skeletal Muscle in Male Mice.

The type 2 iodothyronine-deiodinase (D2) enzyme converts T4 to T3, and mice deficient in this enzyme [D2 knockout (D2KO) mice] have decreased T3 derived from T4 in skeletal muscle despite normal circulating T3 levels. Because slow skeletal muscle is particularly susceptible to changes in T3 levels, we expected D2 inactivation to result in more pronounced slow-muscle characteristics in the soleus muscle, mirroring hypothyroidism. However, ex vivo studies of D2KO soleus revealed higher rates of twitch contraction and relaxation and reduced resistance to fatigue. Immunostaining of D2KO soleus showed that these properties were associated with changes in muscle fiber type composition, including a marked increase in the number of fast, glycolytic type IIB fibers. D2KO soleus muscle fibers had a larger cross-sectional area, and this correlated with increased myonuclear accretion in myotubes formed from D2KO skeletal muscle precursor cells differentiated in vitro. Consistent with our functional findings, D2KO soleus gene expression was markedly different from that in hypothyroid wild-type (WT) mice. Comparison of gene expression between euthyroid WT and D2KO mice indicated that PGC-1α, a T3-dependent regulator of slow muscle fiber type, was decreased by ∼50% in D2KO soleus. Disruption of Dio2 in the C2C12 myoblast cell line led to a significant decrease in PGC-1α expression and a faster muscle phenotype upon differentiation. These results indicate that D2 loss leads to significant changes in soleus contractile function and fiber type composition that are inconsistent with local hypothyroidism and suggest that reduced levels of PCG-1α may contribute to the observed phenotypical changes.