4

LONG-TERM OUTCOMES

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This chapter explores long-term outcomes associated with diagnoses of mild traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), or other mental-health disorders, such as depression, substance-use disorders (SUDs), and suicidal ideation. The committee focused on those outcomes as TBI and mental-health disorders were highlighted in the legislation directing its task. Not everyone who receives a diagnosis of any of those conditions will necessarily experience the sequelae discussed. Many active-duty personnel and veterans will return home and not have any adverse effects, however, others will suffer the consequences of deployment. Many of those who receive diagnoses of the outcomes discussed in this chapter will need support from family members and friends, treatment, and programs to assist them.

The committee has defined long-term outcomes as those lasting more than 6 months from the time of diagnosis. The committee did not conduct an exhaustive evidence-based review of the literature (see Chapter 2). It reviewed studies that focused on mild TBI, PTSD, and other mental-health disorders and possible outcomes in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) active-duty and veterans. If studies of OEF and OIF personnel were not available, studies of other combat veterans and civilians were included. The committee did not attempt to describe every study in detail but rather highlighted studies and reviews that demonstrated an outcome associated with the conditions of interest. The committee notes that there are difficulties in untangling long-term outcomes from preexisting disease, from diseases that have similar symptoms, and from various comorbid conditions that might occur with the conditions of interest. In its review of the literature, the committee also has summarized and included in this chapter relevant sections of recent Institute of Medicine (IOM) reports: Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment-Related Stress (IOM, 2008a), Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury (IOM, 2009), and Returning Home from Iraq and Afghanistan: Preliminary Assessment of Readjustment Needs of Veterans, Service Members, and Their Families (IOM, 2010).

Since the committee’s Phase 1 report, a large volume of government-sponsored research, statistics, reports, and peer-reviewed studies have been published and a significant portfolio of research has been funded. Despite the focused efforts of DOD and VA to increase understanding of the risk and resiliency factors, military occupational exposures, health consequences, and readjustment challenges of those who had wartime service in Iraq and Afghanistan, the committee finds that the efforts to date do not provide definitive answers sought nor do they adequately address the major concerns faced by combat veterans. Although the last decade has



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4 LONG-TERM OUTCOMES This chapter explores long-term outcomes associated with diagnoses of mild traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), or other mental-health disorders, such as depression, substance-use disorders (SUDs), and suicidal ideation. The committee focused on those outcomes as TBI and mental-health disorders were highlighted in the legislation directing its task. Not everyone who receives a diagnosis of any of those conditions will necessarily experience the sequelae discussed. Many active-duty personnel and veterans will return home and not have any adverse effects, however, others will suffer the consequences of deployment. Many of those who receive diagnoses of the outcomes discussed in this chapter will need support from family members and friends, treatment, and programs to assist them. The committee has defined long-term outcomes as those lasting more than 6 months from the time of diagnosis. The committee did not conduct an exhaustive evidence-based review of the literature (see Chapter 2). It reviewed studies that focused on mild TBI, PTSD, and other mental-health disorders and possible outcomes in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) active-duty and veterans. If studies of OEF and OIF personnel were not available, studies of other combat veterans and civilians were included. The committee did not attempt to describe every study in detail but rather highlighted studies and reviews that demonstrated an outcome associated with the conditions of interest. The committee notes that there are difficulties in untangling long-term outcomes from preexisting disease, from diseases that have similar symptoms, and from various comorbid conditions that might occur with the conditions of interest. In its review of the literature, the committee also has summarized and included in this chapter relevant sections of recent Institute of Medicine (IOM) reports: Gulf War and Health, Volume 6: Physiologic, Psychologic, and Psychosocial Effects of Deployment- Related Stress (IOM, 2008a), Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury (IOM, 2009), and Returning Home from Iraq and Afghanistan: Preliminary Assessment of Readjustment Needs of Veterans, Service Members, and Their Families (IOM, 2010). Since the committee’s Phase 1 report, a large volume of government-sponsored research, statistics, reports, and peer-reviewed studies have been published and a significant portfolio of research has been funded. Despite the focused efforts of DOD and VA to increase understanding of the risk and resiliency factors, military occupational exposures, health consequences, and readjustment challenges of those who had wartime service in Iraq and Afghanistan, the committee finds that the efforts to date do not provide definitive answers sought nor do they adequately address the major concerns faced by combat veterans. Although the last decade has 47

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48 RETURNING HOME FROM IRAQ AND AFGHANISTAN seen much advancement in the empirical documentation of combat exposures and postwar outcomes in military service members, there is still a need for further elucidation of key research questions and improvement in study design. For example, Tanielian and Jaycox (2008) reviewed 22 epidemiologic studies of returnees from deployment to OEF and OIF and found that only one included clinical diagnostic assessment for PTSD and other psychiatric disorders. The other 21 studies identified “cases” solely on the basis of brief, self-report screening scales or from medical record reviews. Although screening scales and medical records are useful for many purposes, Tanielian and Jaycox note that using either as the sole basis of estimating the prevalence of PTSD and other psychiatric disorders is fraught with hazard—a finding echoed by an earlier IOM report (2006). Our understanding of the health consequences of service in Iraq and Afghanistan remains incomplete; even simple questions such as prevalence rates of physical and psychologic morbidity after military service in Iraq or Afghanistan continue to lack precision. For example, the literature reviewed by the committee reported PTSD prevalence rates that ranged from approximately 1% to 30% in different studies. Those wide-ranging prevalence estimates have added to the public’s confusion, have not been informative for health care planning, and fail to assist in projecting long-term readjustment needs. As noted previously by the committee, these differences might be explained by variations in study design factors including, population sampling strategy (e.g., random versus nonrandom samples; deployed population versus individuals seeking health care); use of different screening instruments or the same instrument with different cutoff values; self-reports versus medical record reviews versus clinician examinations; levels of combat exposure; length, number, and time elapsed after deployment; demographic and service-related characteristics including military component (Reserve/National Guard versus active); military training and occupation (combat versus combat support); and Service (Air Force, Army, Marines versus Navy). Accounting for, understanding, and reconciling those differences to provide the insights and answers needed for effective public policy, prevention, treatment and readjustment purposes has proved difficult. ORGANIZATION OF THE CHAPTER This chapter is organized into six main sections: mild TBI, PTSD, depression, substance- use disorders, suicide and suicidal ideation, and women’s health outcomes. The TBI section begins with a definition of TBI and how its severity is measured; discusses what we have learned about TBI (of all levels of severity) from previous wars and in civilian populations (primarily summarized from Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury [IOM, 2009]); includes a rationale for the committee’s focus on mild TBI; presents the methodologic difficulties in studying mild TBI in the OEF and OIF populations; and discusses outcomes and conditions that are often comorbid with mild TBI. It also includes a subsection that focuses on the complexity in separating the effects of TBI from those due to co- morbid conditions such as PTSD, depression, and other mental-health disorders. The remaining sections of the chapter include a discussion of PTSD, associated outcomes, and comorbidities, followed by discussions of depression, substance-use disorders, and suicidal ideation and associated outcomes, comorbidities, and risk or protective factors. The final major section focuses on women’s health outcomes in active-duty and veteran populations.

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LONG-TERM OUTCOMES 49 The issue of comorbidity is a recurring theme in this chapter and adds complexity to a study of outcomes. The committee found that in many cases it was difficult or impossible to separate sequelae from comorbid conditions and often could not make the distinction accurately. In fact, the construct of comorbidity does not do justice to the complexity that clinicians and service members encounter when attempting to understand symptoms. From the perspective of an individual patient, an event that is experienced is coupled with the biopsychosocial response to the event and might lead to a constellation of symptoms that express the particular circumstances. Our diagnostic systems cannot capture that level of complexity adequately, so we apply multiple diagnoses (such as depression, PTSD, and TBI) in our attempts to capture what is observed in the individual patient. From the perspective of the population, we divide people who experience symptoms and signs of various classes (such as cognitive, mood, and anxiety) into discrete categories for a host of purposes (such as case counting and assignment to standard protocols of diagnosis and treatment); but the categorization does not do justice to the reality of the distribution of symptoms among individuals in the population. TRAUMATIC BRAIN INJURY TBI is a common injury of the wars in Iraq and Afghanistan. The Department of Defense (DOD) and Veterans Brain Injury Center estimate that brain injuries account for 22% of all OEF and OIF combat casualties, whereas in Vietnam only 12% of combat casualties were attributed to brain injuries (Summerall, 2012). Several organizations, such as the American Congress of Rehabilitation Medicine and the Brain Injury Association of America, and government agencies, such as the National Institutes of Health and the Centers for Disease Control and Prevention (CDC), have developed definitions of TBI, but the committee will focus on the definition developed by DOD and the Department of Veterans Affairs (VA) as it focuses on service members and veterans. The DOD–VA common definition of TBI is A traumatically induced structural injury and/or physiological disruption of brain function as a result of an external force that is indicated by new onset or worsening of at least one of the following clinical signs, immediately following the event (DOD, 2009a), such as  Any period of loss of or a decreased level of consciousness;  Any loss of memory for events immediately before or after the injury;  Any alteration in mental state at the time of the injury (confusion, disorientation, slowed thinking, etc.);  Neurological deficits (weakness, loss of balance, change in vision, praxis, paresis/plegia, sensory loss, aphasia, etc.) that may or may not be transient;  Intracranial lesion. The DOD–VA guidance notes that external forces may include any of the following events: the head being struck by an object, the head striking an object, the brain undergoing an acceleration/deceleration movement without direct external trauma to the head, a foreign body penetrating the brain, forces generated from events such as a blast or explosion, or other force yet to be defined. Not all individuals exposed to an external force will sustain a TBI.

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50 RETURNING HOME FROM IRAQ AND AFGHANISTAN FIGURE 4.1 TBI by severity in all armed forces, 2000–2011, as of May 16, 2012. SOURCE: DVBIC, 2012. A TBI may be closed or penetrating. TBI is often classified according to severity: mild, moderate, or severe. A mild TBI is typically referred to as a concussion, and the two terms are often used interchangeably. In a review of TBI incidence by severity, the number of mild TBIs suffered by all the armed forces far exceeds the numbers of penetrating, severe, or moderate TBIs; in fact, mild TBI accounts for 76.8% of all brain injures (see Figure 4.1). Severity TBI, as noted above, is categorized as mild, moderate, or severe. TBIs can also be penetrating or closed head injuries. Severity is typically based on measures of loss of consciousness (LOC) and posttraumatic amnesia; alteration of consciousness and structural imaging are also used to determine acute severity (see Table 4.1). TABLE 4.1 Criteria for Assessing Severity of TBI Measuring Severity Mild Moderate Severe Structural imaging Normal Normal or abnormal Normal or abnormal Loss of consciousness Up to 30 minutes 30 minutes–24 hours Over 24 hours Alteration of consciousness Up to 24 hours Over 24 hours Over 24 hours Posttraumatic amnesia Up to 1 day 1–7 days Over 7 days Glasgow Coma 13–15 9–12 3–8 Scale rating SOURCE: Adapted from VA and DOD, 2009.

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LONG-TERM OUTCOMES 51 TABLE 4.2 Glasgow Coma Scale Type of Response Type of Response Type of Response and Score and Score and Score Eye Opening: Motor: Verbal: Spontaneous 4 Obeys commands 6 Alert and oriented 5 To speech 3 Localizes pain 5 Confused, yet coherent 4 To pain 2 Withdraws from pain 5 Inappropriate words 3 No eye-opening 1 Abnormal flexion 4 Incomprehensible sounds 2 Extensor response- 3 No sounds 1 No response 2 NOTE: Overall score is the sum of all scores. SOURCE: Adapted from IOM, 2009; adapted from Teasdale and Jennett, 1974. Although the above definitions, except the Glasgow Coma Scale (GCS), rely on length of impaired consciousness, depth of impaired consciousness as measured with the GCS is another method used to classify acute severity of the injury (see Table 4.2) (Teasdale and Jennett, 1974). The GCS is useful in diagnosing moderate and severe TBI, but most civilian and combat TBIs are in the mild range (GCS 13–15) with little differentiation in outcomes. TRAUMATIC BRAIN INJURY OUTCOMES FROM PREVIOUS WARS AND THE CIVILIAN POPULATION Traumatic Brain Injury and Cognition in Active-Duty Personnel and Veterans of Previous Wars and in Civilians Over the last 30 years, much has been learned about the nature of impairments, disabilities, and participation problems that occur in the survivors of civilian closed TBI. Numerous neuropsychologic difficulties—such as problems with memory, attention, executive functions, and speed of information processing—are frequent consequences of TBI (Dikmen et al., 1990, 1995; Levin et al., 1990). Research has also determined that neuropsychologic outcome after TBI is significantly related to the severity of the brain injury (that is, whether it is penetrating or closed and whether it is mild, moderate, or severe). On the basis of review of available literature, a recent IOM report (2009) concluded that the presence, degree, and nature of cognitive impairments depend on the severity of the brain injury. The results of research on the cognitive effects of penetrating brain injuries in military populations in previous wars clearly and consistently show a decline in cognitive functioning as a result of brain injury (Corkin et al., 1989; Grafman et al., 1986, 1988, 1990; Raymont et al., 2008; Salazar et al., 1986; Teuber and Weinstein, 1954; Weinstein and Teuber, 1957). Research also indicates that the decline is related to the volume of brain tissue lost (Grafman et al., 1988) and the affected region of the brain (Corkin et al., 1989). And there is evidence from long-term longitudinal studies that over many years intellectual ability continues to decline at a greater rate in veterans who have penetrating brain injuries than in veterans who do not (Corkin et al., 1989; Raymont et al., 2008). Most studies of civilians who have mild TBI have found early neuropsychologic deficits that resolve by 1–3 months after injury in most cases (McCrea et al., 2009). Belanger et al.

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52 RETURNING HOME FROM IRAQ AND AFGHANISTAN (2005) performed a meta-analysis of 39 studies of 1,463 adults who had non-sports-related mild TBI and 1,191 control cases. They excluded sports-related injuries from their meta-analysis and included only those who sought medical attention for mild TBI. Their results indicate that the overall size of the effect of mild TBI on neuropsychologic functioning was moderate. However, the results varied by type of cognition affected, time since injury, patient characteristics, and sampling methods. Delayed memory and fluency were the types of cognition most affected by mild TBI when measured less than 3 months after injury. There were no neuropsychologic effects of mild TBI by 3 months after injury in unselected or representative, prospectively studied samples of subjects. However, clinic-based samples or groups involved in litigation showed greater cognitive sequelae of mild TBI at 3 months or more after injury. Moreover, litigation was associated with stable or worsening neuropsychologic performance. Belanger and Vanderploeg (2005) performed a separate meta-analysis of the neuropsychologic effects of sports-related concussion. They examined 21 studies that included 790 cases of sports-related concussion and 2,014 control cases. The results indicated that the overall effect size of concussion (d = 0.49) was similar to that found with mild TBI. Effect size was greater in studies that included subjects who had additional prior head injury than in studies that excluded subjects who had prior head injury. Neuropsychologic impairments were no longer found when testing occurred later than 7–10 days after injury. Such impairments are measured by psychometric testing and do not necessarily pertain to subjective neuropsychologic complaints. On the basis of the literature, TBI clearly has an effect on cognitive functions with a clear dose–response relationship. However, the findings regarding mild TBI indicate that there is insufficient evidence that a single, mild civilian TBI has long-term effects on cognition (Dikmen et al., 2009; IOM, 2009). There may be differences between civilian and military exposures, including “blast” due to improvised explosive devises and other explosive munitions. Traumatic Brain Injury and Postconcussive Symptoms in Active-Duty Personnel and Veterans of Previous Wars and in Civilians IOM recently reviewed studies that evaluated the relationship between TBI and self- reported symptoms (2009). The results of studies of mild TBI (Gerber and Schraa, 1995; Heitger et al., 2007; Mickeviciene et al., 2002, 2004; Stulemeijer et al., 2006) varied, but the majority of evidence indicated that those who had mild TBI reported significantly more symptoms than those whose injuries did not involve the head. Dikmen et al. (2010) examined rates of new or worse symptoms 1 month and 1 year after civilian TBI in a large, representative series of cases and compared symptom reports with those of people whose injuries spared the head. The TBI group reported significantly more symptoms than the control group at 1 month and 1 year after injury. Symptom reports declined from 1 month to 1 year after injury, but 53% of the TBI group and 24% of the control group continued to report three or more symptoms at 1 year after injury. The most frequently reported symptoms at 1 year were problems with memory, concentration, fatigue, anxiety, and irritability. People who had severe TBI reported significantly more problems with memory, temper, and irritability and had three or more symptoms compared with controls at 1 year after injury. There were no significant differences between the most mildly injured TBI group and controls, possibly because the TBI group was small. However, those in the mild TBI group did endorse the majority of symptoms at least 50% more often than the controls at 1 year after injury. In fact, 44% of the mild TBI group reported three or more symptoms at 1 year after injury. Similar rates were reported in a very mild TBI sample 6 months

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LONG-TERM OUTCOMES 53 after injury (Bell et al., 2008) and in a nonhospitalized population-based sample of very mild TBI 3 months after injury (Lannsjo et al., 2009). The rates are much higher than the common belief that the occurrence of three or more symptoms for more than a month after a mild TBI is rare and occurs in less than 5% of the population (McCrea et al., 2009). Traumatic Brain Injury and Depression in Active-Duty Personnel and Veterans of Previous Wars and in Civilians The recent IOM review of this literature (2009) found strong evidence of an association between TBI and depression. Regardless of the severity of the TBI (mild, moderate, or severe), the rates of major depression 6 months or more after injury are higher than in control groups. The association could not be totally explained by depression before injury (Fann et al., 2004; Jorge et al., 2004; Vanderploeg et al., 2007). In addition, there is some evidence that prior mood disorder may predispose to TBI (Fann et al., 2002; Vassallo et al., 2007), and depression after TBI is more frequent in those who had depression before the injury than in those who did not (Bombardier et al., 2010; Fann et al., 2004). For instance, Bombardier et al. (2010) found that although about 70% of the cases with preinjury depression showed major depressive disorder by 1 year after injury, only 41% of the cases with no prior history did so. The strong association between depression and TBI has also been reported in studies of World War II and Vietnam veterans. Holsinger et al. (2002) found that the odds of lifetime and current major depression were significantly higher in World War II veterans who had TBI than in controls. In addition, the odds of lifetime depression were highest in those who sustained severe TBI. The odds of depression also increased as the veterans aged. There is some evidence that depression is associated with mild TBI in veterans. A study of postdischarge Vietnam veterans found that those who reported mild TBI had a significantly higher frequency of depression than the control group (Vanderploeg et al., 2007). Traumatic Brain Injury and Social Functioning in Active-Duty Personnel and Veterans of Previous Wars and in Civilians A recent review by IOM (2009) concluded that TBI can have adverse effects on all aspects of social functioning, including employment, social relationships, independent living, functional status, and leisure activities. Research in civilians has shown that the severity of TBI decreases the probability of employment after injury and lengthens the time to return to work (Dikmen et al., 1993, 1994; Doctor et al., 2005; Oddy et al., 1978). There is evidence of an association between penetrating TBI and long-term unemployment in the military (Schwab et al., 1993), and return to work has been associated with computed-tomography findings in veterans who had penetrating head injury (Groswasser et al., 2002). For more comprehensive information about the effects of TBI on employment and other aspects of social functioning, see IOM (2009). Traumatic Brain Injury in the Operation Enduring Freedom and Operation Iraqi Freedom Populations and the Committee’s Focus on Mild Traumatic Brain Injury TBI is a common injury of the wars in Iraq (OIF) and Afghanistan (OEF). A recent report on US army soldiers deployed in 2001–2007 found that 0.14% (207 of 145,505) of those deployed to Afghanistan and 0.31% (2,241 of 722,474) of those deployed to Iraq had one or more TBI-related hospitalizations. Almost all those had moderate or severe brain injuries

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54 RETURNING HOME FROM IRAQ AND AFGHANISTAN (Wojcik et al., 2010). However, the estimated number of cases of mild TBI outweighs all the other types of brain injury. As noted early in this chapter, 76.8% of all brain injuries in OEF and OIF are considered mild TBI. The committee decided to focus its attention on mild TBI because the vast majority of TBI in OEF and OIF is considered mild, it is difficult to identify and diagnose mild TBI, and long-term outcomes of mild TBI are much less understood than those of moderate and severe TBI (see IOM, 2009). In fact, many veterans returning from OEF and OIF have presented to the VA with symptoms of mild TBI, although they had not received the diagnosis while on active duty (Elder and Cristian, 2009). In an attempt at earlier diagnosis, DOD began screening all soldiers for mild TBI on their return from deployment by using the Post-Deployment Health Assessment (PDHA) and the Post-Deployment Health Reassessment (PDHRA).1 In addition, DOD began to assess soldiers with the Military Acute Concussion Evaluation while they were still on active duty, and VA began to screen all OEF and OIF veterans for mild TBI when they were seen by VA medical care providers. The prevalence of mild TBI in the OEF- and OIF-deployed is based on a few large studies that have reported estimates of probable TBI of around 20%. For example, RAND conducted a telephone survey of 1,938 soldiers who had been deployed in OEF and OIF to determine probable TBI and other mental-health issues. Probable TBI was determined by the Brief Traumatic Brain Injury Screen, which was considered positive for probable TBI if a soldier reported being injured during deployment and experienced “being dazed, confused or seeing stars,” “not remembering the injury,” or “losing consciousness.” Results were weighted to improve the representativeness of the sample. The results of the study indicate that 19.5% had probable TBI (Tanielian and Jaycox, 2008). Finally, all 3,973 members of a brigade combat team returning to Fort Carson from a 1- year deployment to Iraq were screened with the Warrior Administered Retrospective Casualty Assessment Tool (WARCAT). The WARCAT is a self-administered tool for ascertaining detailed information regarding injury; it enables soldiers to indicate whether they were injured through mechanisms commonly associated with TBI while deployed, whether any of their injuries resulted in an altered mental state, and whether symptoms often associated with mild TBI occurred after their injury. After completing the WARCAT, all soldiers were interviewed by a clinician, all available medical records were reviewed, and information was obtained from witnesses. The results indicate that 22.8% of the brigade had sustained a probable deployment- related mild TBI (Terrio et al., 2009). A recent longitudinal study of a National Guard brigade combat team found much lower rates of mild TBI in theater than previous studies (Polusny et al., 2011). The authors administered an adapted version of the Defense and Veterans Brain Injury Center screening tool to determine probable mild TBI in a large group of soldiers still in Iraq who would be returning from deployment in about 1 month and then again 1 year after their return from deployment. Soldiers were determined to have a history of in-theater mild TBI if they endorsed an injury with altered mental status or loss of consciousness. The initial assessment, while the soldiers were still deployed, resulted in self-reporting of mild TBI in 9% of the cases. That percentage more than 1 The PDHA is given immediately on return from deployment. The PDHRA, mandated by the assistant secretary of defense for health affairs, has been used since March 2005; it provides a second health assessment and is meant to be completed 90–180 days after return to home station from deployment.

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LONG-TERM OUTCOMES 55 doubled to 22% a year after return from deployment. It is not clear whether those results are due to recall bias, to soldiers’ minimizing their reports of mild TBI so that they might remain with their units, to soldiers’ wanting to ensure that health concerns did not delay their return home, to poor reliability of the questionnaire, or to other issues associated with attribution of current psychosocial difficulties to mild TBI. Methodologic Problems in Studies of Mild Traumatic Brain Injury in Operation Enduring Freedom and Operation Iraqi Freedom Populations Most epidemiologic studies have methodologic problems, but the outcomes being studied are often easier to identify or measure than those associated with mild TBI. The methodologic problems in the existing studies of mild TBI sustained during OEF and OIF conflicts add to the complexity of understanding the outcomes. The problems include the use of convenience samples of soldiers recently returned from deployment or convenience samples of soldiers receiving clinical care many months after sustaining mild TBI. The use of convenience samples makes it difficult to generalize study results to the entire military population engaged in OEF and OIF. Furthermore, many of the studies of mild TBI have involved small groups of subjects receiving clinical services typically in the VA health care system (Belanger et al., 2009; Campbell et al., 2009; Cooper et al., 2011). Many of the groups studied have substantially different demographic features, differ in the amount of time that has passed since the mild TBI, and often comprise people who had more complex outcomes; all those factors might affect the results of the studies. In addition, many studies have low enrollment rates. For example, although Wilk et al. (2010b) studied outcomes in 3,952 soldiers after their return from Iraq, participants made up only 52% of the sample population surveyed. Similarly, the Hoge et al. (2008) study represented 59% of the sample, and Brenner et al. (2010b) approached 399 soldiers back from their second deployment to Iraq but had only a 12% enrollment rate. The effects of low enrollment rates are unknown, but one must seriously consider participation bias as having a potentially important effect on study results. Many studies of mild TBI do not include a control group. A control group is essential to rule out the effect of other factors—such as physical, emotional, and preinjury characteristics— to determine whether an outcome is due to the TBI. Some studies have compared service members returning from OEF and OIF who have no injuries (control group) with those who self- report a mild TBI and a subset of the mild-TBI group who also self-report postconcussion symptoms (Roebuck-Spencer et al., 2012) or with those who report injuries to the body but not to the head (Hoge et al., 2008). Those strategies attempt to compare people drawn from the same population (such as deployed service members), but it is unclear whether the groups are similar with respect to other relevant characteristics that might influence outcomes. The determination of probable mild TBI in an active-duty soldier is by necessity through self-reporting with little or no acute-injury information from the field to accompany or substantiate the diagnosis. And a report of mild TBI is typically related to distant events that could have occurred at any time during deployment. Retrospective recall of events is likely to introduce bias. Another complicating factor is a determination of the number of possible TBIs and when they were sustained.

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56 RETURNING HOME FROM IRAQ AND AFGHANISTAN The questions used in screening subjects for mild TBI vary among researchers, and the psychometric properties of the measures are often unknown. Other methodologic problems include lack of information about baseline neuropsychologic functioning and other information about the individual, including demographic information and preexisting psychiatric or neurologic conditions or substance-use disorders; all these can complicate the effects of mild TBI on outcomes. Traumatic Brain Injury Outcomes and Comorbidities in Operation Enduring Freedom and Operation Iraqi Freedom Populations The presence of conditions that present as comorbid with mild TBI, such as PTSD or depression, makes it difficult to separate the outcomes related to mild TBI from the outcomes related to the comorbid conditions. This issue is the subject of current research. The subsections below discuss outcomes associated with mild TBI and outcomes of conditions that appear to be comorbid with mild TBI. The overall subject of comorbidities and the difficulties presented in diagnosis and treatment is discussed in detail in the section “Mild Traumatic Brain Injury, Comorbidities, and Complicated Issues of Causality in Operation Enduring Freedom and Operation Iraqi Freedom Populations.” Mild Traumatic Brain Injury and Cognition in Operation Enduring Freedom and Operation Iraqi Freedom Populations There has been a paucity of research on the cognitive effects of mild TBI sustained during the current conflicts and assessed with formal performance measures. Most studies suffer from the methodologic problems described above. There is some evidence that mild TBI has cognitive effects soon after injury. Luethcke et al. (2011) examined 82 active-duty military personnel and a few civilian contractors referred to an outpatient TBI clinic at a combat support hospital in Iraq within 72 hours of mild TBI; they were assessed on measures of cognitive performance with the Automated Neuropsychological Assessment Metrics (ANAM).2 Subjects were divided into those who had blast injuries and those who had nonblast injuries on the basis of clinical interviews. The authors examined the magnitude of change in ANAM from baseline (before deployment) to after injury in a subsample of 53 who completed the ANAM before deployment. The results indicated significantly worse reaction time from baseline to after injury. Differences were not found between those injured by blast and those injured who had nonblast injuries. Accuracy was also significantly related to duration of loss of consciousness rather than to type of injury. Conflicting results with respect to the cognitive effects of mild TBI have been reported when cognition was evaluated months after mild TBI, that is, once the service members had returned from deployment. Brailey (2009) conducted a prospective and longitudinal study that examined the effects of mild TBI on postdeployment cognitive performance. The author examined 780 active-duty soldiers who had been deployed to Iraq before deployment (Time 1) and after deployment (Time 2) and collected data on cognitive measures by using a series of hierarchic regressions. The cognitive measures administered before and after deployment 2 The ANAM is a neurocognitive assessment tool designed to detect speed and accuracy of attention, memory, and thinking ability. It records a service member's performance through responses provided on a computer.

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LONG-TERM OUTCOMES 57 included several tests of neuropsychologic functioning, including the Trail Making Test, Wechsler Memory Scale Verbal Paired Associates and Visual Reproduction subtests (Wechsler, 2009), and the Neurobehavioral Evaluation System Continuous Performance Test (Letz, 1990) and measures from the ANAM (Reeves et al., 1992). The cognitive functions evaluated included attention, executive functioning, learning and memory, psychomotor problems, and self-reported health and cognitive problems. In the sample, 70 soldiers reported deployment-related TBI with LOC, and 87 soldiers screened positive for deployment-related PTSD. Predictors of postdeployment cognitive outcome were entered into the regression in steps starting with the relevant predeployment cognitive function; then demographics, mild TBI, and emotional status (such as PTSD or depression or deployment risk and resilience inventory); and finally interactions between mild TBI and emotional status. The results indicated that PTSD was a reliable predictor of postdeployment cognitive outcome. The pattern of results was similar when self-reported depression was substituted for PTSD. However, self-reported mild TBI was not a significant predictor of cognitive outcome. Roebuck-Spencer et al. (2012) found cognitive decline in a sample of people who reported mild TBI as a result of their most recent deployment. The authors obtained deidentified data on 10,869 service members who were deployed to OIF and OEF and who had been evaluated with the ANAM version 4 TBI battery before and less than 1 week after return from deployment. The average test–retest interval was 398 days. The 1,609 service members who reported having sustained one or more TBIs in the 4 years before deployment were excluded. The remaining subjects were divided into four groups on the basis of their responses to the TBI questionnaire. Mild TBI was defined as an injury with alteration of consciousness. Those who reported no TBI or other important injury during their most recent deployment formed the control group of 8,002. A sample of 400 of the controls was randomly selected for use in the analysis. Those who reported one or more TBIs in their most recent deployment were divided into those reporting current symptoms (197) and those who had no current symptoms (305) at the postdeployment evaluation. A small fourth group (28) consisted of those who reported an injury but not TBI during their most recent deployment and who had current symptoms. Cognitive performance was evaluated by using a composite score that covered all the ANAM tests. The results showed that there were no significant differences between the groups in predeployment ANAM performance. However, there were significant differences between the groups in postdeployment ANAM performance: the TBI group who had active symptoms performed significantly worse than controls (p < 0.0001) and worse than those who had TBI but no current symptoms (p < 0.0001). The control group and the TBI group who had no current symptoms were not significantly different in postdeployment ANAM performance. In addition, the control group showed significant predeployment–postdeployment improvement, the TBI group who had no current symptoms showed no predeployment–postdeployment change, and the TBI group who had current symptoms showed a significant predeployment–postdeployment decline in ANAM performance. Another analysis of the small group who were injured and had current symptoms but did not sustain TBI showed similar predeployment–postdeployment improvement in ANAM performance. In an analysis of reliable change using a 90% confidence interval (CI), 4.3% of the control group, 10.8% of the group who had TBI but no current symptoms, 10.7% of the non-TBI group, and 30.5% of the TBI group who had current symptoms had a clinically significant predeployment–postdeployment reduction in ANAM performance.

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