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Introduction The prevalence of mild traumatic brain injury (mTBI) is commonly estimated based on indirect metrics such as emergency department visits and self-reporting tools. The study of postconcussive symptoms faces similar challenges because of their unspecific character and indistinct causality. In this article, we compare two nonclinical, epidemiological studies that addressed these two elements and were performed within a relatively narrow period in the state of Colorado. Materials and Methods De-identified datasets were obtained from a random digit-dialed survey study conducted by the Craig Hospital and a study surveying soldiers returning from deployment by Defense and Veteran Traumatic Brain Injury Center. Information pertinent to participants’ demographics, a history of mTBI, and symptom endorsement was extracted and homogenized in order to establish a parallel comparison between the populations of the two studies. Results From the 1,558 (Warrior Strong, 679; Craig Hospital, 879) records selected for analysis, 43% reported a history of at least one mTBI. The prevalence was significantly higher among individuals from the Defense and Veteran Traumatic Brain Injury Center study independent of gender or race. Repetitive injuries were reported by 15% of the total combined cohort and were more prevalent among males. Symptom endorsement was significantly higher in individuals with a positive history of mTBI, but over 80% of those with a negative history of mTBI endorsed at least one of the symptoms interrogated. Significant differences were observed between the military and the civilian populations in terms of the types and frequencies of the symptoms endorsed. Conclusions The prevalence of mTBI and associated symptoms identified in the two study populations is higher than that of previously reported. This suggests that not all individuals sustaining concussion seek medical care and highlights the limitations of using clinical reports to assess such estimates. The lack of appropriate mechanisms to determine symptom presence and causality remains a challenge. However, the differences observed in symptom reporting between cohorts raise questions about the nature of the symptoms, the impact on the quality of life for different individuals, and the effects on military health and force readiness.

Background Post-traumatic headaches are a common sequela of mild traumatic brain injury (concussion). It is unclear whether or how these headaches differ phenotypically from primary headaches. Objective Determine whether there is an overarching unobserved latent trait that drives the expression of observed features of post-traumatic headache and other headaches. Methods Data from this post-hoc analysis come from the Warrior Strong Cohort Study conducted from 2010 through 2015. Approximately 25,000 soldiers were screened for concussion history at routine post-deployment health assessments. A random sample was invited to participate, enrolling 1567. Twelve observed headache phenotypic features were used to measure “headache complexity”, the latent trait of clinical interest, using single factor confirmatory factor analysis. We compared headache complexity between groups and determined whether headache complexity predicted accessing medical care for headache. Results Of 1094 soldiers with headaches, 198 were classified as having post-traumatic headache. These headaches were compared to those in the other soldiers (647 without concussion history and 249 with concussion history). Soldiers with post-traumatic headache had greater endorsement of all 12 headache features compared to the soldiers with non-concussive headaches. The confirmatory factor analysis showed good model fit (χ2 (51) = 95.59, p = 0.0002, RMSEA = 0.03, comparative fit index = 0.99, and Tucker-Lewis index = 0.99), providing empirical support for the headache complexity construct. Soldier groups differed in their mean headache complexity level ( p

BACKGROUND Traumatic brain injury (TBI) is a significant health issue in the US military. The purpose of this study was to estimate the probability of long-term disability among hospitalized service members (SMs) with TBIs, using the South Carolina Traumatic Brain Injury and Follow-up Registry (SCTBIFR) model developed on civilian hospitalized patients. METHODS We identified military patients in military or civilian hospitals or theater level 3 to 5 military treatment facilities (MTFs) whose first TBI occurred between October 1, 2013, and September 30, 2015. TBI-related disability at 1-year post-hospital discharge was estimated using regression coefficients from the SCTBIFR. RESULTS Among the identified 4877 SMs, an estimated 65.6% of SMs with severe TBI, 56.2% with penetrating TBI, 31.4% with moderate TBI, and 12.0% with mild TBI are predicted to develop long-term disability. TBI patients identified at theater level 4 and 5 MTFs had an average long-term disability rate of 56.9% and 61.1%, respectively. In total, we estimate that 25.2% of all SMs hospitalized with TBI will develop long-term disability. CONCLUSION Applying SCTBIFR long-term probability estimates to US SMs with TBIs provides useful disability estimates to inform providers and health systems on the likelihood that particular subgroups of TBI patients will require continued support and long-term care.

OBJECTIVE To describe and characterize the lifetime history of traumatic brain injury (TBI) among active duty soldiers returning from deployment to Afghanistan or Iraq. METHOD Data were extracted from a larger parent study that was conducted at two large United States Army bases between 2009 and 2014 during Post-Deployment Health Assessment. The sample included 1,060 soldiers who sustained at least one TBI during their lifetime. RESULTS The Ohio State University TBI-Identification Method interview was administered to characterize individuals' total lifetime history of TBI. Soldiers reported sustaining a median of 2 lifetime TBIs. Slightly more than half of the sample without a most recent deployment-related TBI still reported a history of a lifetime TBI (some of which occurred during previous deployments). Most lifetime injuries reported were of mild severity; however, 6% of individuals reported a history of moderate/severe TBI. Blast was the most frequent mechanism associated with recent deployment-related mild TBIs. CONCLUSION Findings suggest that soldiers who screened positive, as well as those who screened negative, for a history of TBI during their recent deployment still endorsed a lifetime history of TBI. Future research is needed to explore the functional impact of multiple TBIs over one's lifetime to help inform screening, assessment, and treatment among military personnel. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Objective To assess agreement between four brief computerized neurocognitive assessment tools (CNTs), ANAM, CogState, CNS Vital Signs, and ImPACT, by comparing rates of low scores. Methods Four hundred and six US Army service members (SMs) with and without acute mild traumatic brain injury completed two randomly assigned CNTs with order of administration also randomly assigned. We performed a base rate analysis for each CNT to determine the proportions of SMs in the control and mTBI groups who had various numbers of scores that were 1.0+, 1.5+, and 2.0+ standard deviations below the normative mean. We used these results to identify a hierarchy of low score levels ranging from poorest to least poor performance. We then compared the agreement between every low score level from each CNT pair administered to the SMs. Results More SMs in the mTBI group had low scores on all CNTs than SMs in the control group. As performance worsened, the association with mTBI became stronger for all CNTs. Most if not all SMs who performed at the worst level on any given CNT also had low scores on the other CNTs they completed but not necessarily at an equally low level. Conclusion These results suggest that all of the CNTs we examined are broadly similar but still retain some psychometric differences that need to be better understood. Furthermore, the base rates of low scores we present could themselves be useful to clinicians and researchers as a guide for interpreting results from the CNTs.

We analyzed data from a cohort of recently deployed soldiers from 2 US Army bases, Fort Carson and Fort Bragg (2009 to 2015). Soldiers with and without a recent history of mild traumatic brain injury (mTBI) on deployment were evaluated within days of return and at 3, 6, and 12 months. Those with mTBI were more likely than those without to endorse ≥1 postconcussive symptom as "severe" and/or "very severe" (47% vs. 21%, baseline; adjusted relative risk (RR) = 1.71, 95% confidence interval: 1.51, 1.93, all time points), which remained significant after adjusting for posttraumatic stress disorder (adjusted RR = 1.34, 95% confidence interval: 1.20, 1.50). Prevalence and relative risks for 3 of the most common baseline symptoms remained constant over time: sleep problems (RR = 2.19), forgetfulness (RR = 2.56), and irritability (RR = 2.73). The pattern was slightly different for headache (baseline, RR = 3.44; 12 months, RR = 3.26), due to increased prevalence of headache in those without mTBI. The prevalence of clinically relevant postconcussive symptoms remained relatively constant over 1 year of follow-up, whether or not symptoms were associated with concussion. Service members with recent mTBI reported more symptoms than those without at all time points.

Objective:Mild traumatic brain injury (mTBI; concussion) is common in returning service members yet limited definitive evidence exists on its prognosis.Methods:Almost 25,000 non–medically evacuated soldiers returning from Afghanistan or Iraq to 2 military bases between 2009 and 2014 were screened for mTBI. We invited a random sample to participate in the present study, oversampling those screening positive, resulting in 557 mTBI cases and 1,010 controls, of whom 366 cases and 599 controls completed 3-month follow-up evaluations. The criterion measure of screened mTBI was the Ohio State University Traumatic Brain Injury Identification Method. Postconcussive symptoms (PCS) were measured at follow-up with the Neurobehavioral Symptom Inventory. Symptoms reported at a severe or very severe level were considered clinically relevant.Results:About half (47%) of soldiers who had sustained an mTBI during this latest deployment reported PCS at 3-month follow-up vs 25% of controls: adjusted odds ratio 2.4 (1.8–3.2). The most commonly reported symptoms (cases vs controls) were sleep problems (30% vs 14%), forgetfulness (21% vs 9%), irritability (17% vs 8%), and headaches (15% vs 5%). mTBI cases were about twice as likely as controls to report receiving rehabilitative services and fair or poor health. Other predictors of PCS included posttraumatic stress, combat exposure, and noncephalic pain. A majority of both cases and controls reported traumatic brain injuries predating this latest deployment.Conclusions:In this nonclinical population of recently deployed soldiers, a substantial proportion of those who had sustained an mTBI were symptomatic 3 months postdeployment. Future studies need to include longer follow-up to measure symptom resolution.Clinicaltrials.gov identifier:NCT01847040.

Traumatic brain injury (TBI) is common,1 and survivors of moderate and severe TBI often have long-term injury-related disabilities, which prevent or interfere with their ability to support themselves and even to maintain independence in activities of daily life.2,3 The chronic disability-related consequences of traumatic brain injuries are well documented and substantial. One study by Selassie et al.2 estimated that 43.3% of civilians hospitalized with TBI in the United States in 2003 would have long-term disability related to impairment in activities of daily living, postinjury symptoms, and cognitive impairment at 12 months after discharge. Similarly, a recent study on military patients treated in hospitals, emergency departments, and theater level 3 to 5 military treatment facilities predicted that 65.6% of treated service members with severe TBI, 56.2% with penetrating TBI, 31.4% with moderate TBI, and 12.0% with mild TBI would develop long-term disability.4 Although TBI is widely recognized as an acute injury that often leads to long-term impairment, recovery and return to productive activity do occur within each injury severity category, albeit less frequently for the severely injured. One of the challenges for the TBI research and clinical communities is determining which preinjury and secondary injury conditions are mechanistically associated with outcomes after TBI. Such evidence-based determinations would inform future efforts tailored to improving outcomes for specific TBI survivor groups.

ObjectiveTo describe and compare phenotypic features of posttraumatic headaches (PTH) and headaches unrelated to concussion.MethodsParticipants are a random sample of recently deployed soldiers from the Warrior Strong cohort, consisting of soldiers with (n = 557) and without (n = 1,030) a history of a recent mild traumatic brain injury (mTBI; concussion). mTBI+ soldiers were subdivided as PTH+ (n = 230) and PTH− (n = 327). Headache classification was based on a detailed phenotypic questionnaire. Medical encounters for headache were documented for the year after deployment.ResultsThe findings here are limited to the soldiers with headaches, consisting of 94% of the mTBI+ soldiers and 76% of the mTBI− soldiers. Other than headache duration, all headache/migraine features were more common or more severe in the PTH+ group compared to the nonconcussed group (mTBI−) and compared to the concussed group with nontraumatic headaches (PTH−). Headaches were largely similar in the mTBI− and PTH− groups. The features most specific to PTH+ included allodynia, visual aura, sensory aura, daily headache, and continuous headache. Medical consultation for headache was most common in the PTH+ group (62%) vs the PTH− group (20%) or the mTBI− group (13%) (p < 0.008).ConclusionsIn this cohort of recently deployed soldiers, PTHs are more severe, frequent, and migraine-like and more often associated with medical consultation compared to headaches presumed unrelated to concussion. Future observational studies are needed to verify and characterize the PTH phenotype, which could be followed by treatment trials with appropriate and possibly novel outcomes for prespecified subgroups.ClinicalTrials.gov identifierNCT01847040.

Objective CogState is a brief computerized test battery used to assess cognitive function. We compare intra-individual agreement between CogState and a battery of traditional neuropsychological tests using rates of low scores. Methods Complete and valid data from 246 healthy soldiers and 177 soldiers ≤ 7 days from sustaining mild TBI (mTBI) were used in this analysis. All soldiers were consecutively administered CogState and a traditional test battery consisting of: TOPF, WAIS-IV, CVLT-II, RCFT, DKEFS, and CPT-II. We performed base rate analyses of both batteries to determine the proportions of soldiers who had various numbers of scores that were 1.0+, 1.5+, and 2.0+ standard deviations below the normative mean. We used those rates to place Soldiers into a “low score hierarchy” ranging from the least poor (i.e. ~ > 10th %ile) to the worst overall performance (i.e. ~ ≤ 10th %ile). We then compared agreement between the batteries at each of those levels. Results More soldiers with mTBI had low scores than healthy soldiers on both batteries. Of the soldiers who performed at the worst level on one battery, 95.1% from CogState and 70.6% from traditional had some level of poor performance on the other battery. However, of the soldiers who performed at the worst level on either battery, only 31.7% from CogState and 38.2% from traditional also performed at the worst level on the other battery. Conclusion These batteries similarly identify poor performance to a degree, though with some potentially meaningful differences still present.

OBJECTIVE Service members are frequently diagnosed with comorbid mild traumatic brain injury (mTBI) and posttraumatic stress disorder after returning from Afghanistan and Iraq. Little is known about how mTBI in the postacute and chronic phases combined with current posttraumatic stress disorder symptoms (PTS) affects performance on the Automated Neuropsychological Assessment Metrics, Version 4, Traumatic Brain Injury-Military (ANAM4) battery used by the US military. We examined postdeployment ANAM4 performance using conventional statistical methods, as well as rates of poor performance, below established cutoffs (

Product yields, efficacy, and safety of monoclonal antibodies (mAbs) are reduced by the formation of higher molecular weight aggregates during upstream processing. In-process characterization of mAb aggregate formation is a challenge since there is a lack of a fast detection method to identify mAb aggregates in cell culture. In this work, we present a rapid method to characterize mAb aggregate-containing Chinese hamster ovary (CHO) cell culture supernatants. The fluorescence dyes thioflavin T (ThT) and 4-4-bis-1-phenylamino-8-naphthalene sulfonate (Bis-ANS) enabled the detection of soluble as well as large mAb aggregates. Partial least square (PLS) regression models were used to evaluate the linearity of the dye-based mAb aggregate detection in buffer down to a mAb aggregate concentration of 2.4 μg mL(-1). Furthermore, mAb aggregates were detected in bioprocess medium using Bis-ANS and ThT. Dye binding to aggregates was stable for 60 min, making the method robust and reliable. Finally, the developed method using 10 μmol L(-1) Bis-ANS enabled discrimination between CHO cell culture supernatants containing different levels of mAb aggregates. The method can be adapted for high-throughput screening, e.g., to screen for cell culture conditions influencing mAb product quality, and hence can contribute to the improvement of production processes of biopharmaceuticals in mammalian cell culture.

OBJECTIVE: A qualitative study among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Soldiers was conducted to explore potential constructs underlying suicide according to the interpersonal-psychological theory of suicide (IPTS); these include burdensomeness, failed belonging, and acquired capability. METHODS: Qualitative semistructured interviews were conducted with 68 Soldiers at 3 months post-OEF/OIF deployment. Soldiers were asked about changes in their experiences of pain, burdensomeness, and lack of belonging. The methodology employed was descriptive phenomenological. RESULTS: Transcripts were reviewed and themes related to the IPTS constructs emerged. Soldiers' postdeployment transition experiences included higher pain tolerance, chronic pain, emotional reactivity, emotional numbing and distancing, changes in physical functioning, combat guilt, discomfort with care seeking, and difficulties reintegrating into family and society. CONCLUSIONS: Findings highlight the utility of the IPTS in understanding precursors to suicide associated with transition from deployment, as well as treatment strategies that may reduce risk in Soldiers during reintegration. Language: en

The objective of this paper is to identify the most frequent service needs, factors associated with needs, and barriers to care among Veterans and service members five or more years after moderate to severe traumatic brain injury (TBI).Survey administered via telephone 5-16 years after injury (median eight years) and subsequent acute inpatient rehabilitation at a regional Veterans Affairs (VA) medical centre.Participants were 119 Veterans and military personnel, aged 23-70 (median 35), 90% male. Demographics, injury characteristics, service needs, whether needs were addressed, barriers to care, health and general functioning were assessed.The most frequent needs were for help with memory, information about available services and managing stress. Obtaining information about services was the most consistently un-addressed need; managing stress was the most consistently addressed need. Cognitive and psychiatric symptoms and alienation from community were associated with needs going un-addressed. Participants treated after an expansion of TBI services at the study site reported fewer un-addressed needs. Not knowing where to get help was the most common barrier to care.Repeated outreach, assessment of needs and education about available services are needed throughout Veterans' lifespan after moderate to severe TBI.

Assess the prevalence of self-identified unmet service needs in a military sample an average of 5 years following noncombat traumatic brain injury (TBI). Examine relationships between unmet needs and background, injury-related and outcome variables.The study sample consisted of 89 veterans and service members who sustained non-combat TBI between 1999 and 2003, selected from enrollees in the Defense and Veterans Brain Injury Center TBI registry. Semistructured telephone interview was used to collect information about participants' self-reported unmet service needs, symptoms, and functional status.Most participants (65%) reported having at least one unmet service need. The most prevalent needs were "getting information about available post-TBI services" (47%) and "improving memory and attention" (45%). Unmet needs were associated with cognitive difficulties, physical and emotional symptoms, mental health diagnosis/treatment, and poorer functional status.Needs for services following TBI are associated with poor symptomatic and functional outcomes and may persist for years after injury in military service members and veterans. The study suggests service members' needs post TBI for improved cognition, support for emotional issues, and resources for vocational skills. Information about available services should be made accessible to those recovering from TBI to reduce the incidence of long-term unmet needs.

Base rates of low ANAM4 TBI-MIL scores were calculated in a convenience sample of 733 healthy male active duty soldiers using available military reference values for the following cutoffs: ≤2nd percentile (2 SDs), ≤5th percentile

OBJECTIVE:: To examine self-awareness 5 years or more after traumatic brain injury (TBI) and its relation to outcomes. PARTICIPANTS:: Sixty-two adults with moderate to severe TBI and significant other (SO) informants (family or close friend). SETTING:: Regional veterans medical center. MAIN MEASURES:: TBI Follow-up Interview, Community Integration Questionnaire, Satisfaction with Life Scale, and Caregiver Burden Inventory. DESIGN:: Five to 16 years after acute inpatient rehabilitation, separate staff contacted and interviewed subjects and SOs. Subject awareness was defined as inverse subject-SO discrepancy scores. RESULTS:: Subjects significantly underreported neurologic symptoms and overreported their work and home functioning; their self-ratings of emotional distress and social functioning did not differ from SO ratings. Employment was associated with greater self-awareness of cognitive deficits, even after controlling for injury severity. Subjects' life-satisfaction was associated with better self-reported neurologic functioning, which frequently did not agree with SO ratings. Caregiver burden was worse as SOs perceived subjects as having worse symptoms and poorer work and social integration. CONCLUSIONS:: Impaired self-awareness remains evident more than 5 years after TBI. People with TBI are more likely to gain employment when they are aware of their cognitive deficits and abilities. However, subjective quality of life, for subjects and SOs, was related to their own perception of the TBI outcomes. Language: en

Objective The Automated Neurological Assessment Metrics (Version 4) Traumatic Brain Injury Military (ANAM4 TBI-MIL) battery is widely used by the US military to assess cognitive function. We compare intra-individual agreement between ANAM4 TBI-MIL and a battery of traditional neuropsychological tests using rates of low scores. Methods Complete and valid data from 246 healthy soldiers and 177 soldiers ≤7 days from sustaining mild TBI (mTBI) were used in this analysis. All soldiers were consecutively administered ANAM4 TBI-MIL and a traditional test battery consisting of: TOPF, WAIS-IV, CVLT-II, RCFT, DKEFS, and CPT-II. We performed base rate analyses of both batteries to determine the proportions of soldiers who had various numbers of scores that were 1.0+, 1.5+, and 2.0+ standard deviations below the normative mean. We used those rates to place Soldiers into a “low score hierarchy” ranging from the least poor (i.e. ~≥10th %ile) to the worst overall performance (i.e. ~≤10th %ile). We then compared agreement between the batteries at each of those levels. Results More soldiers with mTBI had low scores than healthy soldiers on both batteries. Of the soldiers who performed at the worst level on one battery, 88.1% from ANAM and 100% from traditional had some level of poor performance on the other battery. However, of the soldiers who performed at the worst level on either battery, only 58.3% from ANAM and 50.0% from traditional also performed at the worst level on the other battery. Conclusion These batteries similarly identify poor performance to a degree, though with some potentially meaningful differences still present.

Objective It is not uncommon for healthy individuals to have one or more low scores on a battery of cognitive tests. The number of scores produced by the battery by itself can affect the probability of having low scores. The purpose of this study is to examine the rates of low scores on a battery of commonly used neuropsychological tests in soldiers with and without acute mTBI. Methods Data from 246 healthy soldiers and 177 soldiers evaluated within seven days of sustaining a mTBI and who had complete and valid data were used in this analysis. All soldiers completed the TOPF, WAIS-IV, CVLT-II, RCFT, DKEFS, and CPT-II. The CARB was used as a measure of effort. For each group, we determined the proportions of soldiers who had various numbers of scores that were 1.0 or more, 1.5 or more, 2.0 or more standard deviations below the normative means for each score. We used prevalence ratios to compare the proportions with low scores in each group. Results Low scores were common in both groups (93.1% and 96.0% of controls and mTBI cases, respectively, had at least one score 1.0+ SDs below norm, 57.7% and 79.1% had at least one score 1.5+ SDs below norm, while 30.5% and 48.0% had at least score 2.0+ SDs below norm). Low scores were more common in the mTBI group. Conclusion Examining rates of low scores can help identify clinically meaningful performance decrements across an entire battery when large numbers of scores are available.

Computerized neurocognitive assessment tools (NCATs) are increasingly used for baseline and post-concussion assessments. To date, NCATs have not demonstrated strong test-retest reliabilities. Most studies have used non-military populations and different methodologies, complicating the determination of the utility of NCATs in military populations. The test-retest reliability of four NCATs (Automated Neuropsychological Assessment Metrics 4 [ANAM4], CNS-Vital Signs, CogState, and Immediate Post-Concussion Assessment and Cognitive Test [ImPACT]) was investigated in a healthy active duty military sample. Four hundred and nineteen Service Members were randomly assigned to take one NCAT and 215 returned after approximately 30 days for retest. Participants deemed to have inadequate effort during one or both testing sessions, according to the NCATs scoring algorithms, were removed from analyses. Each NCAT had at least one reliability score (intraclass correlation) in the "adequate" range (.70-.79), only ImPACT had one score considered "high" (.80-.89), and no scores met "very high" criteria (.90-.99). However, overall test-retest reliabilities in four NCATs in a military sample are consistent with reliabilities reported in the literature and are lower than desired for clinical decision-making.

OBJECTIVE:: To examine the relative contributions of preinjury, injury severity, and acute postinjury variables in predicting outcomes at 1 year following moderate-severe traumatic brain injury (TBI). DESIGN:: Secondary analysis of a prospective longitudinal cohort study. SETTING:: Four Veterans Affairs Medical Center acute inpatient rehabilitation programs. PARTICIPANTS:: Active duty military or veterans with a nonpenetrating moderate-to-severe TBI. MAIN OUTCOME MEASURES:: Independent living status (N = 280) and work status (N = 248) at one year postinjury. RESULTS:: Preinjury characteristics as a group accounted for the largest amount of variance in independent living status at 1 year; however, posttraumatic amnesia (PTA) uniquely explained the largest amount of variance (8.8%). Those with less than 60 days PTA were 9 times more likely to be independent; those with less than 30 days PTA were 3 times more likely to be independent. In contrast, acute postinjury characteristics accounted for the largest amount of variance in work status, with time to rehabilitation explaining the most unique variance (10.4%). Those with less than 48 days time to rehabilitation were 2.4 times more likely to be productive. CONCLUSIONS:: This study highlights the differential contribution of variables in the prediction of 2 specific functional outcomes in a military sample, adding to our current body of knowledge to assist clinicians, patients and their families following TBI. Language: en

Objective Computerized neurocognitive assessment tools (NCATS) are often used as a screening tool to identify cognitive deficits after mild traumatic brain injury (mTBI). However, differing methodology across studies renders it difficult to identify a consensus regarding the validity of NCATs. Thus, studies where multiple NCATs are administered in the same sample using the same methodology are warranted. Method We investigated the validity of four NCATs: the ANAM4, CNS-VS, CogState, and ImPACT. Two NCATs were randomly assigned and a battery of traditional neuropsychological (NP) tests administered to healthy control active duty service members (n = 272) and to service members within 7 days of an mTBI (n = 231). Analyses included correlations between NCAT and the NP test scores to investigate convergent and discriminant validity, and regression analyses to identify the unique variance in NCAT and NP scores attributed to group status. Effect sizes (Cohen's f2) were calculated to guide interpretation of data. Results Only 37 (0.6%) of the 5,655 correlations calculated between NCATs and NP tests are large (i.e. r ≥ 0.50). The majority of correlations are small (i.e. 0.30 > r ≥ 0.10), with no clear patterns suggestive of convergent or discriminant validity between the NCATs and NP tests. Though there are statistically significant group differences across most NCAT and NP test scores, the unique variance accounted for by group status is minimal (i.e. semipartial R2 ≤ 0.033, 0.024, 0.062, and 0.011 for ANAM4, CNS-VS, CogState, and ImPACT, respectively), with effect sizes indicating small to no meaningful effect. Conclusion Though the results are not overly promising for the validity of the four NCATs we investigated, traditional methods of investigating psychometric properties may not be appropriate for computerized tests. We offer several conceptual and methodological considerations for future studies regarding the validity of NCATs.

Online monitoring of Chinese hamster ovary fed-batch cell cultures via two-dimensional fluorescence spectroscopy (2DFS) was evaluated in this work. Particular attention was directed toward different process strategies regarding the use of nutrient-rich feed media and temperature shifts. These intentionally performed process manipulations broadened the variances in the obtained fluorescence spectra and this was suspected to hamper the generation of reliable soft sensors. Principal component analysis of the obtained fluorescence data showed that temperature shift and feeding strategy had a considerable impact on the fluorescence signals. Partial least square regression models were calculated for the prediction of glucose, lactate, monoclonal antibody (mAb), and viable cell concentrations (VCC). It was aimed to integrate all 2DFS datasets in the respective calibration models regardless of the process-strategy-dependent diversity. Contrary to the expectations, it was feasible to calibrate soft sensors for the online prediction of glucose (7 latent variables (LVs), Rcal2 = 0.97, rout mean squared error of prediction (RMSEP) = 1.1 g L−1), lactate (5 LV; Rcal2 = 0.96; RMSEP = 0.5 g L−1) and mAb concentrations (4 LV; Rcal2 = 0.99; RMSEP = 11.4 mg L−1). Feeding and temperature shifts had the highest impact on the VCC model (3 LV; Rcal2 = 0.94; RMSEP 3.8 × 105 mL−1), nevertheless the prediction of VCC from the fed-batch 2DFS data was feasible. The results strongly indicate that variances in the datasets due to the process strategy can be tolerated to some extent by the respective soft sensors. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1592–1600, 2016

To assess long-term outcomes after traumatic brain injury (TBI) among veterans and service members.Regional Veterans Affairs medical centre.One hundred and eighteen veterans and military personnel, aged 23-70 years (median = 35 years), 90% male, had moderate-to-severe TBI (82% in coma1 day, 85% amnesic7 days), followed by acute interdisciplinary rehabilitation 5-16 years ago (median = 8 years).Cross-sectional analysis of live interviews conducted via telephone.TBI follow-up interview (occupational, social, cognitive, neurologic and psychiatric ratings), Community Integration Questionnaire, Disability Rating Scale (four indices of independent function) and Satisfaction with Life Scale.At follow-up, 52% of participants were working or attending school; 34% ended or began marriages after TBI, but the overall proportion married changed little. Finally, 22% were still moderately-to-severely disabled. However, 62% of participants judged themselves to be as satisfied or more satisfied with life than before injury. Injury severity, especially post-traumatic amnesia, was correlated with poorer outcomes in all functional domains.After moderate-severe TBI, most veterans assume productive roles and are satisfied with life. However, widespread difficulties and functional limitations persist. These findings suggest that veteran and military healthcare systems should continue periodic, comprehensive follow-up evaluations long after moderate-to-severe TBI.

OBJECTIVE:: To examine the relations among bodily injuries, traumatic stress, and post-concussion symptoms in a sample of combat-injured US service members who sustained a mild traumatic brain injury. PARTICIPANTS:: One hundred and thirty-seven service members evaluated and treated at Walter Reed Army Medical Center following medical evacuation from the combat theater of Operation Enduring Freedom and Operation Iraqi Freedom. All had sustained an uncomplicated mild traumatic brain injury and concurrent bodily injuries. PROCEDURE:: Participants completed 2 symptom checklists within 3 months of injury. Severity of bodily injuries was quantified with a modified version of the Injury Severity Score that excluded intracranial injuries (ISSmod). Participants were classified into 4 ISSmod groups: minor (n = 17), moderate (n = 48), serious (n = 40), severe/critical (n = 32). MAIN OUTCOME MEASURES:: Neurobehavioral Symptom Inventory (NBSI) and the Posttraumatic Stress Disorder Checklist-Civilian version (PCLC). RESULTS:: There was a significant negative association between ISSmod scores and the NBSI and PCLC total scores. There were significant main effects across the 4 groups for the NBSI and PCLC total scores. The highest NBSI and PCLC scores were consistently found in the ISSmod minor group, followed by the moderate, serious, and severe/critical groups. CONCLUSIONS:: While it might be expected that greater comorbid physical injuries would be associated with greater symptom burden, in this study as the severity of bodily injuries increased, symptom burden decreased. Hypothesized explanations include: under-reporting of symptoms; increased peer support; disruption of fear conditioning due to acute morphine use; or delayed expression of symptoms. Language: en

A clear, concise definition of traumatic brain injury (TBI) is fundamental for reporting, comparison, and interpretation of studies on TBI. Changing epidemiologic patterns, an increasing recognition of significance of mild TBI, and a better understanding of the subtler neurocognitive neuroaffective deficits that may result from these injuries make this need even more critical. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health has therefore formed an expert group that proposes the following definition: TBI is defined as an alteration in brain function, or other evidence of brain pathology, caused by an external force. In this article, we discuss criteria for considering or establishing a diagnosis of TBI, with a particular focus on the problems how a diagnosis of TBI can be made when patients present late after injury and how mild TBI may be differentiated from non-TBI causes with similar symptoms. Technologic advances in magnetic resonance imaging and the development of biomarkers offer potential for improving diagnostic accuracy in these situations.

Comparing results across studies in traumatic brain injury (TB!) has been difficult because of the variability in data coding, definitions, and collection procedures. The global aim of the Working Group on Demographics and Clinical Assessment was to develop recommendations on the coding of clinical and demographic variables for TBI studies applicable across the broad spectrum of TBI, and to classify these as core, supplemental, or emerging. The process was consensus driven, with input from experts over a broad range of disciplines. Special consideration was given to military and pediatric TBI. Categorizing clinical elements as core versus supplemental proved difficult, given the great variation in types of studies and their interests. The data elements are contained in modules, which are grouped together in categories. Three levels of detail for coding data elements were developed: basic, intermediate, and advanced, with the greatest level of detail in the advanced version. In every case, the more detailed coding can be collapsed into the basic version. Templates were produced to summarize coding formats, motivation of choices, and recommendations for procedures. Work is ongoing to include more international participation and to provide an electronic data entry format with pull-down menus and automated data checks. This proposed standardization will facilitate comparison of research findings across studies and encourage high-quality meta-analysis of individual patient data.

In civilian, military, and veteran populations, there is increased recognition of the interrelationship between traumatic brain injury (TBI) and some psychological health (PH) disorders and the need to better understand the relationships by integrating research for these topics. The use of different measures to assess similar study variables and/or assess outcomes may limit important advances in PH and TBI research. Without a set of common data elements (CDEs; to include variable definitions and recommended measures for the purpose of this discussion), comparison of findings across studies is challenging. The federal agencies involved in PH and TBI research, the National Institute of Neurological Disorders and Stroke, Department of Veterans Affairs, National Institute on Disability and Rehabilitation Research, Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury, and Defense and Veterans Brain Injury Center, therefore cosponsored a scientific initiative to develop CDEs for PH and TBI research. Scientific experts were invited to participate in 1 of 8 working groups to develop recommendations for specific topic-driven CDEs. Draft recommendations were presented and discussed in the workshop "Advancing Integrated Research in Psychological Health and Traumatic Brain Injury: Common Data Elements (CDE)" held on March 23-24, 2009, in Silver Spring, MD. The overall process leading to the workshop and subsequent recommendations by the working groups are presented in this article. Topic-driven recommendations for CDEs are presented in individual reports in this edition.

Objective: To evaluate alternative models of symptom clusters for the 22-item Neurobehavioral Symptom Inventory. Participants: Three military samples, including 2 nonclinical samples (n = 2420, n = 4244) and 1 sample of individuals with recent head injury (n = 617). Methods: In the first sample, exploratory factor analysis of Neurobehavioral Symptom Inventory responses was performed with tests of significant factors and model fit. In the other 2 samples, confirmatory factor analysis evaluated the fit of 3 models: 2- and 3-factor models based on the initial exploratory factor analysis, and a 9-factor model based on prior research. Main Outcome Measures: The exploratory factor analysis used 2 tests for the number of factors: Parallel Analysis and Minimum Average Partial test. Confirmatory factor analysis models were evaluated using 2 measures of model fit, Root Mean Square Error of Approximation and Comparative Fit Index. Results: Postconcussive symptoms can be described accurately by the 9 factors. However, the model of 3 intercorrelated factors, reflecting cognitive, affective, and somatic/sensory symptoms, fits the data more parsimoniously with little loss in model fit. Conclusion: Although the 9-cluster result from prior research provides a valid description of the relations among items of the inventory, a 3-factor model, consisting of somatic/sensory, affective, and cognitive factors, provides nearly as good a fit to the data, with greater parsimony. We encourage clinicians and researchers to conceptualize the Neurobehavioral Symptom Inventory in terms of 3 coherent clusters of symptoms rather than as 22 individual items.

The current study examined the performance of active duty soldiers on the Automated Neuropsychological Assessment Metrics (ANAM) traumatic brain injury test battery, to expand the reference data for use in military settings. The effects of age and gender on cognitive performance also were explored. The ANAM traumatic brain injury battery, consisting of six performance tests and two subjective scales, was administered to a sample of healthy active duty soldiers (N = 5,247) as part of a concussion surveillance program. Performance means and SDs, stratified according to age and gender, are reported as reference data. In addition, the impact of age and gender on performance measures was analyzed. Because ANAM is rapidly being adopted for use in many military medical and research applications, the establishment of these reference values is invaluable, particularly for assisting with rapid accurate evaluation and treatment in clinical settings.

Computerized cognitive testing with software programs such as the Automated Neuropsychological Assessment Metrics (ANAM) have long been used to assess cognition in military samples. This study desc...

OBJECTIVE: Preliminary assessment of a new instrument, the Brief Traumatic Brain Injury Screen (BTBIS). DESIGN: Cross-sectional study of 596 soldiers returning from Iraq and/or Afghanistan, comparing the consistency of their reports of traumatic brain injury (TBI) across instruments with similar TBI questions, and in a brief follow-up interview. SETTING: Military base. MEASURES: Self-reported probable TBI on the BTBIS and on 2 longer questionnaires, and a brief follow-up interview. RESULTS: Self-reports of probable TBI were higher on the BTBIS, than on the longer instruments. Participants who screened positive on the BTBIS generally provided consistent information about probable TBI in the follow-up interview. CONCLUSIONS: In this initial study, the BTBIS demonstrated promise as part of a triage process in mass casualty situations, permitting individuals with probable TBI to self-report injury and continued symptoms. Further study, including full validation and reliability assessment, is warranted and required before these screening tools can be fully evaluated. Language: en

Many factors are considered during ballistic helmet design, including comfort, weight, fit, and maintainability. These factors affect soldiers' decisions about helmet use; therefore, rigorous research about soldiers' real-life experiences with helmets is critical to assessing a helmet's overall protective efficacy. This study compared soldiers' satisfaction and problem experience with the advanced combat helmet (ACH) and the personal armor system for ground troops (PASGT) helmet. Data were obtained from surveys of soldiers at Fort Bragg, North Carolina. Ninety percent of ACH users were satisfied overall with their helmet, but only 9.5% of PASGT users were satisfied (p < 0.001). The most frequently reported problems for the ACH involved malfunctioning helmet parts. The most frequently reported problems for the PASGT involved discomfort. This analysis indicated that there was a strong soldier preference for the ACH over the PASGT, which could enhance its already superior protective qualities. It also demonstrated the usefulness of soldiers' assessments of protective equipment.

PURPOSE/OBJECTIVE: The purpose of this study was to qualitatively explore exposure to deployment-related physical and/or emotional trauma and associated symptoms among Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) soldiers. Interviews also focused on in-theater- and reintegration-related experiences. Research Method/Design: OEF/OIF soldiers (N = 103) participated in semistructured interviews, and a qualitative descriptive methodology was used to analyze the data. RESULTS: Themes were identified regarding (a) common experiences related to emotional and physical traumas and associated symptoms and strategies for coping and making meaning of experiences and (b) how combat and reintegration experiences affected soldiers' senses of self, relationships with others, and functioning. CONCLUSIONS/IMPLICATIONS: Themes identified support a rethinking of deployment-related mild traumatic brain injury and posttraumatic stress disorder as discrete conditions. Dimensional versus categorical models should be considered. The findings also highlight experiences and potentially meaningful constructs (e.g., moral injury, moral repair) that can be used to inform research and clinical efforts aimed at improving the lives of those who have served. (PsycINFO Database Record Language: en

Mild traumatic injuries to the brain (e.g., concussion) are common and have been recognized since antiquity, although definitions have varied historically. Nonetheless, studying the epidemiology of concussion helps clarify the overall importance, risk factors, and at-risk populations for this injury. The present review will focus on recent findings related to the epidemiology of concussion including definition controversies, incidence, and patterns in the population overall and in the military and athlete populations specifically. Finally, as this is an area of active research, we will discuss how future epidemiologic observations hold promise for gaining greater clarity about concussion and mild traumatic brain injury.

The Automated Neuropsychological Assessment Metrics (ANAM) is a computerized measure of processing speed, cognitive efficiency, and memory. This study describes performance and psychometric properties of ANAM in an active duty, healthy military sample (N = 2,371) composed primarily of young (18–46 years) adult males. Rarely have neuropsychological reference values for use with individuals in the military been derived from a large, active duty military population, and this is the first computerized neuropsychological test battery with military-specific reference values. Although these results do not provide demographically corrected, formal normative data, they provide reference points for neuropsychologists and other health care providers who are using ANAM data in research or clinical settings, with patients of comparable demographics to the present sample.

This is a descriptive article outlining issues in the development and implementation of a multisite randomized rehabilitation trial for brain injury treatment. The goal of this article is to present practical and theoretical considerations in designing and conducting multicenter rehabilitation trials. Practical issues discussed include (a) treatment setting, (b) patient accessibility in determining the research question of interest, as well as inclusion and exclusion criteria, (c) research protocol development in the context of rehabilitation standard of care, and (d) protocol treatments in the context of realistic cost-benefits analysis. Rehabilitation theory is discussed as playing an important role designing the specifics of the protocol interventions. The Defense and Veterans Brain Injury Center Veterans Health Administration cognitive-didactic versus functional-experiential study methodology is used for illustrative purposes. This study evaluated 2 alternative approaches to treatment: one focusing on underlying cognitive processes and the second on errorless learning in everyday functional situations. Lessons learned over the course of completing the treatment trial are discussed.

Object. Does an early Glasgow Outcome Scale (GOS) assessment provide a reliable indicator of later outcome in a patient with traumatic brain injury (TBI)? The authors examined the utility of the GOS during early treatment as a predictor of outcome score 15 months postinjury by analyzing outcome score change in a group of patients with closed head injuries. Methods. Glasgow Outcome Scale scores assessed within 3 months of injury (baseline) were compared with scores obtained at 15 months postinjury in 121 patients, primarily young military personnel. Score changes between baseline and 8 months postinjury were also studied in a subgroup of 72 patients. The impact of initial injury severity (determined by the duration of unconsciousness) on score change was also explored. The GOS scores at three time points within the 15-month period—baseline (within 3 months of injury), 8, and 15 months postinjury—were examined to ascertain when the maximal GOS score had been reached. Conclusions. Baseline GOS score was a reliable predictor of outcome in patients with an initial score of 5 (no disability) or 4 (mild disability), but not in patients with an initial score of 3 (severe disability). Patients who remained unconscious for more than 24 hours did not have significantly lower outcome scores than those who experienced loss of consciousness for less than 24 hours at 15 months postinjury. Interestingly, the duration of unconsciousness did not affect the likelihood of an improved score during the study period in patients with a GOS score of 3 or 4 at baseline. An updated evaluation conducted after the early phases of treatment is needed to provide a realistic prognosis of severe TBI.

Objective: Changes in health care delivery required substitution of a number of alternatives for the traditional inpatient clerkship used in the neurology education of fourth-year medical students at the Uniformed Services University of the Health Sciences and for third-year medical students from Georgetown University. Methods: We retrospectively analyzed grades on a locally generated multiple-choice examination based on a student objective list. Scores from students rotating on ambulatory neurology, neurosurgery, child neurology, neurorehabilitation, and rotations at other military hospitals over a 2-year period were compared with those achieved by students in a traditional clerkship at Walter Reed Army Medical Center. Results: There were no significant differences in the grades between any of the groups. Conclusions: Student acquisition of factual material was not influenced by the type of clinical experience or by whether the student is in the third or fourth year of medical school.

We review the literature on two long-term functional outcomes of traumatic brain injury (TBI) important to patients, family members, and rehabilitation treatment teams: work for pay and driving outcomes. Estimates on the percentages working after TBI have ranged widely, and few consistent prognostic indicators of long-term outcomes have been identified. The few large randomized controlled treatment trials of these long-term productive outcomes have been negative, but have identified promising subgroup results that bear further investigation. Salazar et al. (2000) identified patients with loss of consciousness of 1 hour or longer as a subgroup that benefited from intensive in-hospital treatment. Vanderploeg et al. (2008) found that the cognitive treatment arm resulted in improved cognitive performance, and that younger patients benefited more from the cognitive treatment; whereas older patients (31 plus) benefited from a more functional approach to treatment. The research evidence on driving post TBI is sparse - relying upon small studies, and lacking follow-up data. This review included only published research studies of 100 or more subjects, with control groups, and outcomes 6 months or longer after injury. The inclusion of more reliable studies narrowed return to work estimates and provided evidence that type of control group affects findings about return to work after mild TBI (mTBI). Prognostic indicators remain inconsistently measured among these more reliable studies. Heeding the frequent recommendation that research in this area be more stringently conducted, well powered, and use shared measures of critical variables would improve evidence. Adequately powered treatment trials of existing and innovative treatment modalities remain a priority.

Functional outcome in relation to CT findings in traumatic brain injured (TBI) patients is not well established in relation to cognitive and vocational outcome.To investigate the possible correlation between relatively simple quantitative radiological measurements and cognitive and vocational outcome.Retrospective analysis of quantitative assessment of CT studies in relation to post-injury cognitive changes and vocational outcome.US Army Medical Centre.74 penetrating head injured (PHI) and 37 closed head injured (CHI) Vietnam war veterans.The Armed Forces Qualification Test (AFQT); Disability score; Return to work.Total brain volume loss, third ventricle width (3VW), ventricular score (VS), and septum-caudate distance (SCD) were significantly related to cognitive change and return to work in PHI patients. Volume loss and 3VW were the most valuable radiologic predictors of outcome in multivariate linear and logistic regression models for both CHI and PHI.3VW on late CT scans following traumatic brain injury is a powerful predictor of overall long-term cognitive outcomes and potential for return to work.

OBJECTIVE:: To investigate the impact of traumatic brain injury (TBI) on the experience and expression of anger in a military sample. PARTICIPANTS:: A total of 661 military personnel with a history of TBI and 1204 military personnel with no history of TBI. DESIGN:: Cross-sectional, between-group design, using multivariate analysis of variance. MAIN MEASURE:: State-Trait Anger Expression Inventory-2 (STAXI-2). RESULTS:: Participants with a history of TBI had higher scores on the STAXI-2 than controls and were 2 to 3 times more likely than the participants in the control group to have at least 1 clinically significant elevation on the STAXI-2. Results suggested that greater time since injury (ie, months between TBI and assessment) was associated with lower scores on the STAXI-2 State Anger scale. CONCLUSION:: Although the results do not take into account confounding psychiatric conditions and cannot address causality, they suggest that a history of TBI increases the risk of problems with the experience, expression, and control of anger. This bolsters the need for proper assessment of anger when evaluating TBI in a military cohort. Language: en

We have recently reported the results of a prospective controlled randomized trial comparing home versus inpatient cognitive rehabilitation for patients with moderate to severe head injury. That study showed no overall difference in outcomes between the two groups.(1) In this article, we provide further details of the home program arm of the study. All patients in the home program received medical treatment as needed, a multidisciplinary in-hospital evaluation, and TBI counseling before entering the eight-week home program, which then included guidance on home activities, as well as weekly telephone calls from a psychiatric nurse.