The lived experience of military beneficiaries with amputations at the hip and pelvic level.

BACKGROUND: Hip- and pelvic-level amputations are devastating injuries that drastically alter patient function and quality of life. This study examined the experience of military beneficiaries with a hip- or pelvic-level amputation to better characterize their challenges and specific needs and to optimize treatment in the future. METHODS: We conducted a retrospective review of the Military Health System and identified 118 patients with a history of one or more amputation(s) at the hip or pelvic level between October 2001 and September 2017. Surviving participants (n = 97) were mailed a letter which explained the details of the study and requested participation in a telephonic interview. A total of six individuals (one female, five males) participated in structured interviews. RESULTS: The study group included four participants with hip disarticulations and two participants with hemipelvectomies (one internal, one external). All six participants reported significant challenges with activities related to prosthetic use, mobility, residual limb health, pain, gastrointestinal and genitourinary function, psychiatric health, and sexual function. CONCLUSIONS: These interviews highlight the unique needs of individuals with hip- and pelvic-level amputations and may improve access to higher echelons of care that would enhance the function and quality of life for these participants.

Research Letter: Relationship of Blood Biomarkers of Inflammation With Acute Concussion Symptoms and Recovery in the CARE Consortium.

OBJECTIVE: Determine the association of inflammatory biomarkers with clinical measures and recovery in participants with concussion. SETTING: Multicenter study in National Collegiate Athletic Association member institutions including military service academies. PARTICIPANTS: Four hundred twenty-two participants with acute concussion. DESIGN: Clinical visits and blood draws were completed preinjury and at multiple visits postconcussion (0-12 hours, 12-36 hours, and 36-60 hours postinjury). Clinical measures included Sport Concussion Assessment Tool (SCAT) symptom severity, Balance Error Scoring System, Standardized Assessment of Concussion (SAC), Brief Symptom Inventory-18 (BSI-18) scores, time to initiation of graduated return-to-play (RTP) protocol, and time to RTP. Interleukin (IL)-6, IL-10, IL-8, IL-1 receptor antagonist (RA), tumor necrosis factor (TNF), c-reactive protein, and vascular endothelial growth factor (VEGF) were measured in serum. Prespecified analyses focused on IL-6 and IL-1RA at 0 to 12 hours; exploratory analyses were conducted with false discovery rate correction. RESULTS: For prespecified analyses, IL-1RA at 0 to 12 hours in female participants was positively associated with more errors on the SAC (B(standard error, SE) = 0.58(0.27), P < .05) and worse SCAT symptom severity (B(SE) = 0.96(0.44), P < .05). For exploratory analyses, higher levels of IL-1RA at 12 to 36 hours were associated with higher global (B(SE) = 0.55(0.14), q < 0.01), depression (B(SE) = 0.45(0.10), q < 0.005), and somatization scores on the BSI (B(SE) = 0.46(0.12), q < 0.01) in participants with concussion; Higher TNF at 12 to 36 hours was associated with fewer errors on the SAC (B(SE) = - 0.46(0.14), q < 0.05). Subanalyses showed similar results for male participants and participants who were athletes. No associations were discovered in nonathlete cadets. Higher IL-8 at 0 to 12 hours was associated with slower RTP in female participants (OR = 14.47; 95% confidence interval, 2.96-70.66, q < 0.05); no other associations with recovery were observed. CONCLUSIONS: Peripheral inflammatory markers are associated with clinical symptoms following concussion and potentially represent one mechanism for psychological symptoms observed postinjury. Current results do not provide strong support for a potential prognostic role for these markers.

The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium.

BACKGROUND: Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes. HYPOTHESIS: New or worsened neck pain is common after a concussion (>30%), negatively influences recovery, and is associated with patient sex and level of contact in sport. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Varsity-level athletes from 29 National Collegiate Athletic Association member institutions as well as nonvarsity sport athletes at military service academies were eligible for enrollment. Participants completed a preseason baseline assessment and follow-up assessments at 6 and 24 to 48 hours after a concussion, when they were symptom-free, and when they returned to unrestricted play. Data collection occurred between January 2014 and September 2018. RESULTS: A total of 2163 injuries were studied. New or worsened neck pain was reported with 47.0% of injuries. New or worsened neck pain was associated with patient sex (higher in female athletes), an altered mental status after the injury, the mechanism of injury, and what the athlete collided with. The presence of new/worsened neck pain was associated with delayed recovery. Those with new or worsened neck pain had 11.1 days of symptoms versus 8.8 days in those without (P < .001). They were also less likely to have a resolution of self-reported symptoms in ≤7 days (P < .001). However, the mean duration of the return-to-play protocol was not significantly different for those with new or worsened neck pain (7.5 ± 7.7 days) than those without (7.4 ± 8.3 days) (P = .592). CONCLUSION: This novel study shows that neck pain was common in collegiate athletes sustaining a concussion, was influenced by many factors, and negatively affected recovery.

Mechanisms of Injury Leading to Concussions in Collegiate Soccer Players: A CARE Consortium Study.

BACKGROUND: Few previous studies have investigated how different injury mechanisms leading to sport-related concussion (SRC) in soccer may affect outcomes. PURPOSE: To describe injury mechanisms and evaluate injury mechanisms as predictors of symptom severity, return to play (RTP) initiation, and unrestricted RTP (URTP) in a cohort of collegiate soccer players. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: The Concussion Assessment, Research and Education (CARE) Consortium database was used. The mechanism of injury was categorized into head-to-ball, head-to-head, head-to-body, and head-to-ground/equipment. Baseline/acute injury characteristics-including Sports Concussion Assessment Tool-3 total symptom severity (TSS), loss of consciousness (LOC), and altered mental status (AMS); descriptive data; and recovery (RTP and URTP)-were compared. Multivariable regression and Weibull models were used to assess the predictive value of the mechanism of injury on TSS and RTP/URTP, respectively. RESULTS: Among 391 soccer SRCs, 32.7% were attributed to a head-to-ball mechanism, 27.9% to a head-to-body mechanism, 21.7% to a head-to-head mechanism, and 17.6% to a head-to-ground/equipment mechanism. Event type was significantly associated with injury mechanism [χ2(3) = 63; P < .001), such that more head-to-ball concussions occurred in practice sessions (n = 92 [51.1%] vs n = 36 [17.1%]) and more head-to-head (n = 65 [30.8%] vs n = 20 [11.1]) and head-to-body (n = 76 [36%] vs n = 33 [18.3%]) concussions occurred in competition. The primary position was significantly associated with injury mechanism [χ2(3) = 24; P < .004], with goalkeepers having no SRCs from the head-to-head mechanism (n = 0 [0%]) and forward players having the least head-to-body mechanism (n = 15 [19.2%]). LOC was also associated with injury mechanism (P = .034), with LOC being most prevalent in head-to-ground/equipment. Finally, AMS was most prevalent in head-to-ball (n = 54 [34.2%]) and head-to-body (n = 48 [30.4%]) mechanisms [χ2(3) = 9; P = .029]. In our multivariable models, the mechanism was not a predictor of TSS or RTP; however, it was associated with URTP (P = .044), with head-to-equipment/ground injuries resulting in the shortest mean number of days (14 ± 9.1 days) to URTP and the head-to-ball mechanism the longest (18.6 ± 21.6 days). CONCLUSION: The mechanism of injury differed by event type and primary position, and LOC and AMS were different across mechanisms. Even though the mechanism of injury was not a significant predictor of acute symptom burden or time until RTP initiation, those with head-to-equipment/ground injuries spent the shortest time until URTP, and those with head-to-ball injuries had the longest time until URTP.

Determining Which Combinatorial Combat-Relevant Factors Contribute to Heterotopic Ossification Formation in an Ovine Model.

Traumatic heterotopic ossification (HO) is frequently observed in Service Members following combat-related trauma. Estimates suggest that ~65% of wounded warriors who suffer limb loss or major extremity trauma will experience some type of HO formation. The development of HO delays rehabilitation and can prevent the use of a prosthetic. To date there are limited data to suggest a standard mechanism for preventing HO. This may be due to inadequate animal models not producing a similar bone structure as human HO. We recently showed that traumatic HO growth is possible in an ovine model. Within that study, we demonstrated that 65% of sheep developed a human-relevant hybrid traumatic HO bone structure after being exposed to a combination of seven combat-relevant factors. Although HO formed, we did not determine which traumatic factor contributed most. Therefore, in this study, we performed individual and various combinations of surgical/traumatic factors to determine their individual contribution to HO growth. Outcomes showed that the presence of mature biofilm stimulated a large region of bone growth, while bone trauma resulted in a localized bone response as indicated by jagged bone at the linea aspera. However, it was not until the combinatory factors were included that an HO structure similar to that of humans formed more readily in 60% of the sheep. In conclusion, data suggested that traumatic HO growth can develop following various traumatic factors, but a combination of known instigators yields higher frequency size and consistency of ectopic bone.

Profile of brief symptom inventory-18 (BSI-18) scores in collegiate athletes: A CARE Consortium study.

Objective: The goal of this study was to characterize normative scores for the Brief Symptom Inventory (BSI-18) in collegiate athletes to inform decision making about the need for psychological health services in this group. Methods: Collegiate student-athletes (N = 20,034) from 25 universities completed the BSI-18 at their preseason baseline assessment. A subgroup (n = 5,387) underwent multiple baseline assessments. Global Severity Index (GSI) scores were compared to community norms and across multiple timepoints. Results: Collegiate athletes reported significantly lower GSI scores than published community norms (p<.001). Published GSI threshold scores for "caseness", identified only 2 per 100 athletes (≥ the 98th percentile) as needing further evaluation. Using a GSI score ≥ than the cohort's 90th percentile, 11.4 per 100 athletes would merit additional evaluation. These individuals were more likely to report a history of psychiatric diagnosis (Odds ratio [95% CI] 2.745 [2.480, 3.039]), as well as ≥ 2 prior concussions (p<.001). GSI scores were not highly correlated across timepoints. Suicidal ideation was rare (n = 230; 1.15%). Conclusions: For collegiate student-athletes, published BSI-18 threshold scores identify only extreme outliers who might benefit from additional behavioral health evaluation. Alternatively, use of threshold scores ≥ the 90th percentile identifies a more realistic 11.4% of the population, with higher likelihood of prior concussion and/or psychiatric disorders.

Factors Influencing Time to Return to Learn Among NCAA Student-Athletes Enrolled in the Concussion Assessment, Research, and Education (CARE) Study.

PURPOSE: The aim was to describe the demographic and post-injury factors that influence time to return to learn (RTL) among student-athletes enrolled in the Concussion Assessment, Research and Education (CARE) Consortium. METHODS: A total of 47,860 student-athletes enrolled in the National Collegiate Athletic Association-Department of Defense (NCAA-DoD) CARE Consortium study from 2014 to 2020, with 1485 sport-related concussions (SRCs) analyzed in the present dataset. Demographic and post-injury characteristics were calculated using descriptive statistics, followed by Kaplan-Meier estimates to examine median time to return to normal academic performance (i.e., RTL) by sex (male, female), baseline psychiatric conditions (depression, anxiety) and/or learning disorder, NCAA division (I, II, III), SRC history (0, 1, 2, 3+), NCAA sport category (contact, limited contact, non-contact sport), and median difference in baseline/post-injury symptom severity scores (< 21, ≥ 21). Further, a multivariable zero-inflated negative binomial (ZINB) regression model was used to examine their association with RTL. RESULTS: Overall, time to RTL (mean = 4.96 ± 8.24 days, median = 3.0 [interquartile range = 0.0, 6.0] days) was found to be influenced by several factors resulting in earlier trajectories. Notably, nearly 25% of the sample demonstrated immediate RTL (i.e., 0 days). Among student-athletes who did not immediately RTL, males demonstrated a decreased rate in RTL (rate = 0.79; 95% CI 0.66-0.96) compared to females. Further, student-athletes with a ≥ 21 change in symptom severity score (post-injury baseline) demonstrated a higher rate of RTL (rate = 1.47; 95% CI 1.21-1.79) compared to student-athletes with a symptom severity change score < 21. Lastly, male student-athletes demonstrated two times higher odds (odds ratio = 1.95; 95% CI 1.02-3.73) of immediate RTL compared to female student-athletes. No other covariates were associated with time to RTL. CONCLUSION: Collectively, the present findings suggest a rapid return to the classroom following concussion. Specifically, males demonstrated higher odds of time to RTL, whereas those with greater differences in symptom severity resulted in a higher rate of time to RTL among those who did not immediately RTL. Ultimately, these findings support prior work emphasizing an individualized approach to SRC management.

Association of Blood Biomarkers of Inflammation With Acute Concussion in Collegiate Athletes and Military Service Academy Cadets.

BACKGROUND AND OBJECTIVES: The objective was to characterize the acute effects of concussion (a subset of mild traumatic brain injury) on serum interleukin (IL)-6 and IL-1 receptor antagonist (RA) and 5 additional inflammatory markers in athletes and military service academy members from the Concussion Assessment, Research, and Education Consortium and to determine whether these markers aid in discrimination of concussed participants from controls. METHODS: Athletes and cadets with concussion and matched controls provided blood at baseline and postinjury visits between January 2015 and March 2020. Linear models investigated changes in inflammatory markers measured using Meso Scale Discovery assays across time points (baseline and 0-12, 12-36, 36-60 hours). Subanalyses were conducted in participants split by sex and injury population. Logistic regression analyses tested whether acute levels of IL-6 and IL-1RA improved discrimination of concussed participants relative to brain injury markers (glial fibrillary acidic protein, tau, neurofilament light, ubiquitin c-terminal hydrolase-L1) or clinical data (Sport Concussion Assessment Tool-Third Edition, Standardized Assessment of Concussion, Balance Error Scoring System). RESULTS: Participants with concussion (total, N = 422) had elevated IL-6 and IL-1RA at 0-12 hours vs controls (n = 345; IL-6: mean difference [MD] (standard error) = 0.701 (0.091), p < 0.0001; IL-1RA: MD = 0.283 (0.042), p < 0.0001) and relative to baseline (IL-6: MD = 0.656 (0.078), p < 0.0001; IL-1RA: MD = 0.242 (0.038), p < 0.0001), 12-36 hours (IL-6: MD = 0.609 (0.086), p < 0.0001; IL-1RA: MD = 0.322 (0.041), p < 0.0001), and 36-60 hours (IL-6: MD = 0.818 (0.084), p < 0.0001; IL-1RA: MD = 0.317 (0.040), p < 0.0001). IL-6 and IL-1RA were elevated in participants with sport (IL-6: MD = 0.748 (0.115), p < 0.0001; IL-1RA: MD = 0.304 (0.055), p < 0.0001) and combative-related concussions (IL-6: MD = 0.583 (0.178), p = 0.001; IL-1RA: MD = 0.312 (0.081), p = 0.0001). IL-6 was elevated in male (MD = 0.734 (0.105), p < 0.0001) and female participants (MD = 0.600 (0.177), p = 0.0008); IL-1RA was only elevated in male participants (MD = 0.356 (0.047), p < 0.0001). Logistic regression showed the inclusion of IL-6 and IL-1RA at 0-12 hours improved the discrimination of participants with concussion from controls relative to brain injury markers (χ2(2) = 17.855, p = 0.0001; area under the receiver operating characteristic curve [AUC] 0.73 [0.66-0.80] to 0.78 [0.71-0.84]), objective clinical measures (balance and cognition; χ2(2) = 40.661, p < 0.0001; AUC 0.81 [0.76-0.86] to 0.87 [0.83-0.91]), and objective and subjective measures combined (χ2(2) = 13.456, p = 0.001; AUC 0.97 [0.95-0.99] to 0.98 [0.96-0.99]), although improvement in AUC was only significantly relative to objective clinical measures. DISCUSSION: IL-6 and IL-1RA (male participants only) are elevated in the early-acute window postconcussion and may aid in diagnostic decisions beyond traditional blood markers and common clinical measures. IL-1RA results highlight sex differences in the immune response to concussion which should be considered in future biomarker work.

Cortical Reorganization after Limb Loss: Bridging the Gap between Basic Science and Clinical Recovery.

Despite the increasing incidence and prevalence of amputation across the globe, individuals with acquired limb loss continue to struggle with functional recovery and chronic pain. A more complete understanding of the motor and sensory remodeling of the peripheral and central nervous system that occurs postamputation may help advance clinical interventions to improve the quality of life for individuals with acquired limb loss. The purpose of this article is to first provide background clinical context on individuals with acquired limb loss and then to provide a comprehensive review of the known motor and sensory neural adaptations from both animal models and human clinical trials. Finally, the article bridges the gap between basic science researchers and clinicians that treat individuals with limb loss by explaining how current clinical treatments may restore function and modulate phantom limb pain using the underlying neural adaptations described above. This review should encourage the further development of novel treatments with known neurological targets to improve the recovery of individuals postamputation.Significance Statement In the United States, 1.6 million people live with limb loss; this number is expected to more than double by 2050. Improved surgical procedures enhance recovery, and new prosthetics and neural interfaces can replace missing limbs with those that communicate bidirectionally with the brain. These advances have been fairly successful, but still most patients experience persistent problems like phantom limb pain, and others discontinue prostheses instead of learning to use them daily. These problematic patient outcomes may be due in part to the lack of consensus among basic and clinical researchers regarding the plasticity mechanisms that occur in the brain after amputation injuries. Here we review results from clinical and animal model studies to bridge this clinical-basic science gap.

Collegiate Athletes With Diabetes: Baseline Medical Comorbidities and Preseason Concussion Testing Performance.

CONTEXT: People with diabetes mellitus (DM) are at increased risk for adverse health events and complications throughout their lifetime. Whether DM significantly affects collegiate athletes' concussion baseline testing performance remains unclear. OBJECTIVES: To (1) describe the prevalence of DM and associated comorbidities and (2) compare concussion baseline testing performance between student-athletes with DM and student-athletes without DM (NoDM). DESIGN: Retrospective, cross-sectional study. SETTING: University. PATIENTS OR OTHER PARTICIPANTS: Using the Concussion, Assessment, Research and Education (CARE) Consortium research database, we matched athletes with self-reported DM (N = 229) by institution, sex, age, sport, position, testing year, and concussion history to athletes with NoDM (N = 229; total sample mean age = 19.6 ± 1.4 years, women = 42%). MAIN OUTCOME MEASURE(S): Descriptive statistics and χ2 tests of independence with subsequent odds ratios were calculated. Independent-samples t tests compared baseline symptoms, neurocognitive testing, and balance performance between athletes with DM and athletes with NoDM. Effect sizes were determined for significant group differences. RESULTS: At baseline, athletes with DM had higher rates of self-reported pre-existing balance disorders, sleep disorders, seizure disorders, motion sickness, learning disorders, vision and hearing problems, psychiatric disorders, depression, bipolar disorder, nonmigraine headaches, and meningitis than athletes with NoDM (P values < .05). We found balance differences between groups (P = .032, Cohen d = 0.17) such that, on average, athletes with DM had 1 additional error on the Balance Error Scoring System (DM = 13.4 ± 6.5; NoDM = 12.1 ± 5.9). No other comparisons yielded significant results. CONCLUSIONS: Although athletes with DM had high rates of self-reported balance disorders, sleep disorders, seizures, and meningitis, their baseline neurocognitive testing results were largely identical to those of athletes with NoDM. Our findings suggested that nonclinically meaningful differences were present in concussion baseline balance testing but no significant differences were noted in cognitive testing; however, the effect of DM on concussion recovery remains unknown.

Healthcare Utilization Following Hemipelvectomy or Hip Disarticulation in the Military Health System.

INTRODUCTION: Amputations at the hip and pelvic level are often performed secondary to high-energy trauma or pelvic neoplasms and are frequently associated with a prolonged postoperative rehabilitation course that involves a multitude of health care providers. The purpose of this study was to examine the health care utilization of patients with hip- and pelvic-level amputations that received care in the U.S. Military Health System. MATERIALS AND METHODS: We performed a retrospective review of all patients who underwent a hip- or pelvic-level amputation in the Military Health System between 2001 and 2017. We compiled and reviewed all inpatient and outpatient encounters during three time points: (1) 3 months pre-amputation to 1 day pre-amputation, (2) the day of amputation through 12 months post-amputation, and (3) 13-24 months post-amputation. Health care utilization was defined as the average number of encounter days/admissions for each patient. Concomitant diagnoses following amputation including post-traumatic stress disorder, traumatic brain injury, anxiety, depression, and chronic pain were also recorded. RESULTS: A total of 106 individuals with hip- and pelvic-level amputations were analyzed (69 unilateral hip disarticulation, 6 bilateral hip disarticulations, 27 unilateral hemipelvectomy, 2 bilateral hemipelvectomies, and 2 patients with a hemipelvectomy and contralateral hip disarticulation). Combat trauma contributed to 61.3% (n = 65) of all amputations. During the time period of 3 months pre-amputation, patients had an average of 3.8 encounter days. Following amputation, health care utilization increased in both the year following amputation and the time period of 13-24 months post-amputation, averaging 170.8 and 77.4 encounter days, respectively. Patients with trauma-related amputations averaged more total encounter days compared to patients with disease-related amputations in the time period of 12 months following amputation (203.8 vs.106.7, P < .001) and the time period of 13-24 months post-amputation (92.0 vs. 49.0, P = .005). PTSD (P = .02) and traumatic brain injuries (P < .001) were more common following combat-related amputations. CONCLUSIONS: This study highlights the increased health care resource demand following hip- and pelvic-level amputations in a military population, particularly for those patients who sustained combat-related trauma. Additionally, patients with combat-related amputations had significantly higher rates of concomitant PTSD and traumatic brain injury. Understanding the extensive needs of this unique patient population helps inform providers and policymakers on the requirements for providing high-quality care to combat casualties.

Postinjury Outcomes After Non-Sport-Related Concussion: A CARE Consortium Study.

CONTEXT: Concussion research has primarily focused on sport-related mechanisms and excluded non-sport-related mechanisms. In adult populations, non-sport-related concussions (non-SRCs) demonstrated worse clinical outcomes compared with sport-related concussions (SRCs); however, investigations of non-SRCs in college-aged patients are limited. OBJECTIVES: To examine clinical outcomes in collegiate athletes with non-SRCs compared with SRCs and explore sex differences in outcomes among collegiate athletes with non-SRCs. DESIGN: Prospective cohort study. SETTING: Clinical setting. PATIENTS OR OTHER PARTICIPANTS: A total of 3500 athletes were included (n = 555 with non-SRCs, 42.5% female) from colleges or universities and service academies participating in the National Collegiate Athletic Association Department of Defense Concussion Assessment, Research and Education (CARE) Consortium. MAIN OUTCOME MEASURE(S): Dichotomous outcomes (yes or no) consisted of immediate reporting, mental status alterations, loss of consciousness, posttraumatic amnesia, retrograde amnesia, motor impairments, delayed symptom presentation, and required hospital transport. Continuous outcomes were symptom severity, days with concussion symptoms, and days lost to injury. Data were collected within 24 to 48 hours of injury and at return to play. Adjusted relative risks (ARRs) compared the likelihood of dichotomous outcomes by mechanism and by sex within patients with non-SRCs. Multivariate negative binomial regressions were used to assess group differences in continuous variables. RESULTS: Athletes with non-SRCs were less likely to report immediately (ARR = 0.73, 95% CI = 0.65, 0.81) and more likely to report delayed symptom presentation (ARR = 1.17, 95% CI = 1.03, 1.32), loss of consciousness (ARR = 3.15, 95% CI = 2.32, 4.28), retrograde amnesia (ARR = 1.77, 95% CI = 1.22, 2.57), and motor impairment (ARR = 1.45, 95% CI = 1.14, 1.84). Athletes with non-SRCs described greater symptom severity, more symptomatic days, and more days lost to injury (P < .001) compared with those who had SRCs. Within the non-SRC group, female athletes indicated greater symptom severity, more symptomatic days, and more days lost to injury (P < .03) than male athletes. CONCLUSIONS: Athletes with non-SRCs had worse postinjury outcomes compared with those who had SRCs, and female athletes with non-SRCs had worse recovery metrics than male athletes. Our findings suggest that further investigation of individuals with non-SRCs is needed to improve concussion reporting and management.

Health Care Utilization After Major Limb Loss in Adults (18-64) Receiving Care in the Military Health System From 2001 to 2017.

OBJECTIVE: To characterize and quantify health care utilization of Military Health System beneficiaries with major limb loss. DESIGN: Retrospective cohort study. SETTING: Military treatment facilities and civilian health care facilities that accept TRICARE insurance across the United States. PARTICIPANTS: A total 5950 adult Military Health System beneficiaries with major limb amputation(s) acquired between January 1st, 2001, and September 30th, 2017 (N=5950). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: This study was an exploratory analysis designed to identify common care specialties, services, and devices utilized by Military Health System beneficiaries with major limb loss. RESULTS: Most beneficiaries were retirees/dependents (63.3%), men (73.1%), and had a single amputation (88.7%), with a mean age of 42 years. Differences between beneficiary categories were found. Active-duty service members used a larger proportion of inpatient, emergency, primary care, physical and occupational therapy, prosthetics and orthotics, physical medicine and rehabilitation, and psychiatry services than retirees/dependents. Most common procedures included "revision of amputation stump" (57.2%) for the active-duty population and "other amputation below knee" (24.3%) for the retirees/dependents. CONCLUSIONS: These findings highlight the rehabilitation trajectories of beneficiaries receiving treatment for major limb loss in military and civilian care settings. The results could inform staffing decisions and training programs for military treatment facilities, American trauma centers, rehabilitation hospitals, and outpatient health care providers treating individuals with amputation.

Concussion Risk and Recovery in Athletes With Psychostimulant-Treated Attention-Deficit/Hyperactivity Disorder: Findings From the NCAA-DOD CARE Consortium.

The aim of the present study was to examine the effects of attention-deficit/hyperactivity disorder (ADHD) -related psychostimulant use in the context of concussion risk and symptom recovery. Data were obtained from the National Collegiate Athletic Association Department of Defense Grand Alliance Concussion Assessment, Research, and Education (NCAA-DOD CARE) Consortium from 2014 to 2017. Relative to individuals without diagnosed ADHD (i.e., control), both ADHD diagnosis and the combination of ADHD diagnosis and psychostimulant use were associated with a greater risk of incurring a concussive injury. Following a concussive injury, ADHD diagnosis was associated with longer symptom recovery time relative to the control group. However, individuals with ADHD who use psychostimulants did not take longer to resolve symptoms than controls, suggesting that psychostimulants may have a positive influence on recovery. Regardless of time point, ADHD diagnosis was associated with an elevated number of concussion-related symptoms; however, this effect appears mitigated by having used ADHD-related psychostimulants.

Sex Differences in Recovery Trajectories of Assessments for Sport-Related Concussion Among NCAA Athletes: A CARE Consortium Study.

OBJECTIVES: The purpose of this study was to determine sex differences in recovery trajectories of assessments for sport-related concussion using Concussion Assessment, Research and Education (CARE) Consortium data. METHODS: National Collegiate Athletic Association athletes (N = 906; 61% female) from sex-comparable sports completed a pre-season baseline assessment and post-sport-related concussion assessments within 6 h of injury, 24-48 h, when they initiated their return to play progression, when they were cleared for unrestricted return to play, and 6 months post-injury. Assessments included the Standardized Assessment of Concussion, Balance Error Scoring System, Brief Symptom Inventory-18, Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), Sport Concussion Assessment Tool-3 symptom evaluation, Clinical Reaction Time, King-Devick test, Vestibular Ocular Motor Screen, 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale. RESULTS: Only the Vestibular Ocular Motor Screen Total Symptom Score at the 24-48 h timepoint (p = 0.005) was statistically significantly different between sexes. Specifically, female athletes (mean = 60.2, 95% confidence interval [CI] 51.5-70.4) had higher Vestibular Ocular Motor Screen Total Symptom Scores than male athletes (mean = 36.9, 95% CI 27.6-49.3), but this difference resolved by the time of return-to-play initiation (female athletes, mean = 1.8, 95% CI 1.1-2.9; male athletes, mean = 4.1, 95% CI 1.5-10.9). CONCLUSIONS: Sport-related concussion recovery trajectories for most assessments were similar for female and male National Collegiate Athletic Association athletes except for Vestibular Ocular Motor Screen symptoms within 48 h of sport-related concussion, which was greater in female athletes. Female athletes had a greater symptom burden across all timepoints, suggesting that cross-sectional observations may indicate sex differences despite similar recovery trajectories.

Sport-Specific Recovery Trajectories for NCAA Collegiate Athletes Following Concussion.

The recovery trajectories of collegiate athletes with sport-related concussion (SRC) are well characterized in contact/collision sports but are less well understood in limited contact sports with lower risk, reducing the ability of clinicians to effectively manage the return-to-play (RTP) process. The current study investigated the time to asymptomatic and RTP across a broad range of male and female collegiate sports and sought to group sports by recovery intervals. Data from the Concussion Assessment, Research and Education (CARE) Consortium included 1049 collegiate athletes who sustained a SRC while participating in game or practice/training of their primary sport. Injury setting and subsequent clinical presentation data were obtained. Survival analysis using the Cox Proportional Hazard model estimated the median recovery times for each sport. Optimal univariate K-means clustering grouped sports into recovery categories. Across all sports, median time to asymptomatic following SRC ranged from 5.9 (female basketball) to 8.6 days (male wrestling). Median RTP protocol duration ranged from 4.9 days (female volleyball) to 6.3 days (male wrestling). Median total RTP days ranged from 11.2 days (female lacrosse) to 16.9 days (male wrestling). Sport clusters based on recovery differences in time to asymptomatic (3) and RTP protocol duration (2) were identified. The findings from this study of a large sample of more than 1000 NCAA collegiate athletes with SRC show there exists ranges in recovery trajectories. Clinicians can thus manage athletes with similar guidelines, with individualized treatment and recovery plans.

Gene Expression Alterations in Peripheral Blood Following Sport-Related Concussion in a Prospective Cohort of Collegiate Athletes: A Concussion Assessment, Research and Education (CARE) Consortium Study.

BACKGROUND: Molecular-based approaches to understanding concussion pathophysiology provide complex biological information that can advance concussion research and identify potential diagnostic and/or prognostic biomarkers of injury. OBJECTIVE: The aim of this study was to identify gene expression changes in peripheral blood that are initiated following concussion and are relevant to concussion response and recovery. METHODS: We analyzed whole blood transcriptomes in a large cohort of concussed and control collegiate athletes who were participating in the multicenter prospective cohort Concussion Assessment, Research, and Education (CARE) Consortium study. Blood samples were collected from collegiate athletes at preseason (baseline), within 6 h of concussion injury, and at four additional prescribed time points spanning 24 h to 6 months post-injury. RNA sequencing was performed on samples from 230 concussed, 130 contact control, and 102 non-contact control athletes. Differential gene expression and deconvolution analysis were performed at each time point relative to baseline. RESULTS: Cytokine and immune response signaling pathways were activated immediately after concussion, but at later time points these pathways appeared to be suppressed relative to the contact control group. We also found that the proportion of neutrophils increased and natural killer cells decreased in the blood following concussion. CONCLUSIONS: Transcriptome signatures in the blood reflect the known pathophysiology of concussion and may be useful for defining the immediate biological response and the time course for recovery. In addition, the identified immune response pathways and changes in immune cell type proportions following a concussion may inform future treatment strategies.

Optimizing baseline and post-concussion assessments through identification, confirmation, and equivalence of latent factor structures: findings from the NCAA-DoD CARE Consortium.

Objective: Concussion evaluations use a multidimensional assessment to evaluate unique patient function dimensions (e.g., subjective symptoms differ from balance assessments), but the overarching latent factor structure has not been empirically substantiated. Our objective was to determine the cumulative latent factor structure of pre-injury baseline and acute (<48-h) post-concussion assessment battery outcomes, and determine measurement equivalence among common factors in collegiate student-athletes. Methods: Collegiate student-athletes at baseline (n = 21,865) and post-concussion (n = 1,537) across 25-institutions completed standardized assessments. Individual items were used from the baseline and post-concussion assessments and consisted of: Sport Concussion Assessment Tool, Brief Symptom Inventory-18, Standardized Assessment of Concussion, Balance Error Scoring System, Immediate Post-Concussion Assessment and Cognitive Test, and vestibular-ocular motor screening. Exploratory factor analysis was used on half the baseline data, and confirmatory factor analysis on the remaining baseline data and post-concussion data separately. Measurement equivalence was assessed between sex, sport contact classification, concussion history, and time. Results: A 10-factor exploratory model was established and comprised of: depression, somatic, vestibulo-ocular, headache, postural stability, neurocognition, emotional, fatigue, cognitive, consciousness clouding. The 10-factor model was confirmed at baseline and post-concussion with strong measurement equivalence between timepoints. Strong to strict measurement equivalence was observed for sex, sport contact classification, and concussion history at both timepoints separately. Conclusion: Our findings established a robust 10-factor latent factor model equivalent across timepoints and common factors among healthy and concussed collegiate athletes. Clinicians can use these findings to target specific factors while reducing redundant elements to provide efficient, comprehensive post-concussion assessments.

Initial Mild Traumatic Brain Injury Characteristics and Recovery Patterns Among Females Across the United States Military Service Academies: A Report from the NCAA-DoD CARE Consortium.

Mild traumatic brain injury (mTBI) has been described in the United States (US) military service academy cadet population, but female-specific characteristics and recovery outcomes are poorly characterized despite sex being a confounder. Our objective was to describe female cadets' initial characteristics, assessment performance, and return-to-activity outcomes post-mTBI. Female cadets (n = 472) from the four US military service academies who experienced a mTBI completed standardized mTBI assessments from pre-injury to acute initial injury and unrestricted return-to-duty (uRTD). Initial injury presentation characteristics (e.g., delayed symptoms, retrograde amnesia) and return-to-activity outcomes [i.e., return-to-learn, initiate return-to-duty protocol (iRTD), uRTD] were documented. Descriptive statistics summarized female cadets' injury characteristics, return-to-activity outcomes, and post-mTBI assessment performance change categorization (worsened, unchanged, improved) relative to pre-injury baseline using established change score confidence rank criteria for each assessment score. The median (interquartile range) days to return-to-learn (n = 157) was 7.0 (3.0-14.0), to iRTD (n = 412) was 14.7 (8.6-25.8), and to uRTD (n = 431) was 26.0 (17.7-41.8). The majority experienced worse SCAT total symptom severity (77.8%) and ImPACT reaction time (97.0%) acutely < 24-h versus baseline, but unchanged BESS total errors (75.2%), SAC total score (72%), BSI-18 total score (69.6%), and ImPACT verbal memory (62.3%), visual memory (58.4%), and visual motor speed (52.5%). We observed similar return-to-activity times in the present female cadet cohort relative to the existing female-specific literature. Confidence ranks categorizing post-mTBI performance were heterogenous and indicate multimodal assessments are necessary. Our findings provide clinically relevant insights to female cadets experiencing mTBI across the US service academies for stakeholders providing healthcare.

Plasma phosphorylated tau181 as a biomarker of mild traumatic brain injury: findings from THINC and NCAA-DoD CARE Consortium prospective cohorts.

Objective: The aim of this study was to investigate phosphorylated tau (p-tau181) protein in plasma in a cohort of mild traumatic brain injury (mTBI) patients and a cohort of concussed athletes. Methods: This pilot study comprised two independent cohorts. The first cohort-part of a Traumatic Head Injury Neuroimaging Classification (THINC) study-with a mean age of 46 years was composed of uninjured controls (UIC, n = 30) and mTBI patients (n = 288) recruited from the emergency department with clinical computed tomography (CT) and research magnetic resonance imaging (MRI) findings. The second cohort-with a mean age of 19 years-comprised 133 collegiate athletes with (n = 112) and without (n = 21) concussions. The participants enrolled in the second cohort were a part of a multicenter, prospective, case-control study conducted by the NCAA-DoD Concussion Assessment, Research and Education (CARE) Consortium at six CARE Advanced Research Core (ARC) sites between 2015 and 2019. Blood was collected within 48 h of injury for both cohorts. Plasma concentration (pg/ml) of p-tau181 was measured using the Single Molecule Array ultrasensitive assay. Results: Concentrations of plasma p-tau181 in both cohorts were significantly elevated compared to controls within 48 h of injury, with the highest concentrations of p-tau181 within 18 h of injury, with an area under the curve (AUC) of 0.690-0.748, respectively, in distinguishing mTBI patients and concussed athletes from controls. Among the mTBI patients, the levels of plasma p-tau181 were significantly higher in patients with positive neuroimaging (either CT+/MRI+, n = 74 or CT-/MRI+, n = 89) compared to mTBI patients with negative neuroimaging (CT-/MRI-, n = 111) findings and UIC (P-values < 0.05). Conclusion: These findings indicate that plasma p-tau181 concentrations likely relate to brain injury, with the highest levels in patients with neuroimaging evidence of injury. Future research is needed to replicate and validate this protein assay's performance as a possible early diagnostic biomarker for mTBI/concussions.