This chapter summarizes key gaps in the evidence base on exposure to blast and long-term health effects and offers recommendations for scientific study to fill the gaps. Recommendations aimed at improving dissemination of information on health effects after exposure to blast throughout the Department of Veterans Affairs (VA) and the Department of Defense (DOD) also are presented.
Because of the inadequacy of evidence on long-term consequences of blast, the committee relied heavily on the literature to assess the evidence on acute effects and on its own collective medical expertise to draw conclusions regarding the plausibility of long-term consequences. Some long-term effects are obvious and well-documented consequences of acute injuries, but others will require additional study. Gaps in data collection begin while service members are on active duty and continue after they separate from the military and enter the VA health care system.
A fundamental feature of exposure to blast is that it can result in complex, multisystem injuries. Attention to the complexities has been lacking in many research studies. Research on blast should emphasize multisystem injury patterns and seek to understand the clinical importance of cross-system interactions.
Below are the committee’s recommendations for research that is most likely to provide VA with knowledge that it can use to inform decisions on how to prevent blast injuries, how to diagnose them effectively, and how to
manage, treat, and rehabilitate victims of battlefield traumas in the immediate aftermath of a blast and in the long term.
Evaluating Current Approaches to Detecting Blast Injuries and Treating and Rehabilitating the Injured
Through the literature evaluation process summarized in Chapter 4, the committee identified several long-term health outcomes on which there was sufficient evidence of an association with blast exposure. VA can begin to improve the diagnosis of and treatment for blast injuries, particularly health outcomes for which there is sufficient evidence of an association with exposure to blast, namely:
- Sufficient evidence of a causal relationship between penetrating eye injuries resulting from exposure to blast and permanent blindness and visual impairment (visual acuity of 20/40 or worse).
- Sufficient evidence of a causal relationship between exposure to blast and some long-term effects on a genitourinary organ—such as hypogonadism, infertility, voiding dysfunction, and erectile dysfunction—associated with severe injury (defined as a complete structural and functional loss that cannot be reconstructed).
- Sufficient evidence of an association between exposure to blast and posttraumatic stress disorder (PTSD); the association may be related to direct exposure of blast or to indirect exposure, such as witnessing the aftermath of a blast or being part of a community that is affected by a blast.
- Sufficient evidence of an association between severe or moderate blast-related traumatic brain injury (TBI) and endocrine dysfunction (hypopituitarism and growth hormone deficiency).
- Sufficient evidence of an association between mild blast TBI and postconcussive symptoms and persistent headache.
- Sufficient evidence of an association between severe or moderate non-blast-related TBI and permanent neurologic disability, including cognitive dysfunction, unprovoked seizures, and headache; these associations are known outcomes from TBI studies that considered blast and non-blast mechanisms together, and it is plausible that severe or moderate blast-related TBI is similarly associated with permanent neurologic disability even though studies specifically addressing blast-related TBI are lacking.
- Sufficient evidence of an association between exposure to blast and long-term dermal effects, such as cutaneous granulomas.
Recommendation 5-1. The Department of Veterans Affairs should conduct a rigorous evaluation to determine whether current approaches for detecting, treating for, and rehabilitating after health outcomes of blast exposure are adequate.
Because exposure to blast is likely to lead to polytrauma that may affect many organ systems both acutely and in the long term, VA should assess its ability to coordinate care of blast survivors who have several health conditions. VA should assess the adequacy of current approaches to management of multiple chronic conditions, such as rehabilitation, and of its long-term followup care in treating blast survivors. For example, the agency should evaluate the extent to which Patient Aligned Care Teams (PACTs) provide adequate polytrauma care of patients who have been exposed to blast.
Current or newly developed approaches for rehabilitation should be evaluated with appropriately designed studies that include adequate control groups. The impact of rehabilitation services on long-term consequences of blast exposure should be assessed according to quality of life and measures of activity and participation, such as employment status, family relations, and independence in activities of daily living.
Measuring Blast Exposure
A limitation of nearly all of the studies evaluated by the committee was inadequate information about the exposures to blast. Most of the studies used self-reported exposure data rather than objective measures. Obtaining accurate, objective measurement of exposure to blast is essential for understanding the mechanisms of injury caused by blast and for developing effective prevention and treatment strategies.
Recommendation 5-2. The Department of Defense should develop and deploy a system that measures essential components of blast and characteristics of the exposure environment, that records and stores the collected information, and that links individual blast-exposure databases with self-reported information and with demographic, medical, and operational data.
The system should measure components of primary, secondary, tertiary, quaternary, and quinary (radiation) blast. These components should include
- pressure—static, dynamic, and total;
- blast signature—impulse, primary peak, and refraction waves, intensity and duration of refraction waves;
- blast-wave frequency;
- impact and kinetic energy;
- time stamp; and
- environmental factors, such as ground configuration (open field, confined space in a vehicle or building, and complexity), gas exhaust, and noise.
The components would be measured by sensors providing 360-degree coverage; by covering critical body regions (head, chest, and abdomen); and by using individual, helmet-mounted cameras. The sensors’ and cameras’ recordings would be triggered by blast.
The data would be temporarily stored in a small storage unit worn on the body. The storage unit would collect information from multiple sensors that are triggered by blast and would incorporate the information into one identifiable event. The unit would be capable of recording data on multiple events. After completion of the military task, the information in the individual storage units would be downloaded onto computers on a military base and stored in a large database. Much of the technology for the sensors and data-storage system has been developed (for example, helmet cameras are commonly worn by service members in the field), but research is needed to combine the various parts of the system into a wearable unit.
The body’s physiologic status at the time of trauma may play a substantial role in injury outcome, so measuring hydration status, body-fat percentage, and heart-rate variability with sensors triggered by blast would provide valuable information.
The individual databases containing information about blast events should be linkable to other databases that include the following information:
- occurrence of loss of consciousness;
- subjective sensations, such as dizziness, “seeing stars,” ringing in the ears, breathing difficulties, dry cough or irritation, photophobia, and blurred near vision;
- acute post-blast medical reports, such as reports from a buddy-aid, medics, the evacuation physician at the field-hospital, and potential transport to a Level III hospital;
- previous exposures—number, intensity, complexity, and time between exposures;
- previous deployments—number, duration of each, and interval between deployments;
- previous injuries—blast and non-blast;
- previous military traumatic events—number, type, and level of distress;
- age, sex, rank, military occupational specialty code, education, and length of service;
- family status, children, and socioeconomic status;
- detailed individual and family medical history;
- results of psychologic and physical tests; and
- results of military performance evaluations.
The committee recognizes that implementing a system with those characteristics will take time, although some of the components already have been developed and fielded (personal communication, I. Cernak, University of Alberta, August 8, 2013). Until the new system is available, the following questionnaires can be used to provide an operational definition of blast exposure: Quantification of Cumulative Blast Exposure (Peskind et al., 2011), Warrior Administered Retrospective Casualty Assessment Tool (Terrio et al., 2009), and Post-deployment Health Assessment Questions 10.a and 10.b (DOD, 2012). Clearly defining those scales’ interrelationships and comparability and developing approaches to allow integration of findings from the various questionnaires should be given high priority to advance blast science. Although important, the use of self-report scales documenting exposure to blast will be subject to the usual inconsistencies that are inherent to these scales. Additionally, in cases of frontal lobe injury, the accuracy of the reports will be further diminished by known deficits in self-awareness that follow that type of injury.
A research consensus process could be applied to develop, validate, and promote the use of a self-report blast exposure scale for use in clinical and epidemiologic studies to be used prior to and in combination with deployment of blast detection technology. An important limitation of existing clinical and epidemiologic studies is the lack of validated measures of blast exposure that capture its unique, multifaceted characteristics. For many veterans, quantification of blast exposure is limited to retrospective self-report with some supplementary information from combat records. A consensus process to measure blast exposure and promoting its use is important to improve the strength of the evidence of the long-term effects of blast exposure.
Biomarkers of Blast Injury
Identification of blast injuries in service members, particularly injuries that are not acutely severe and may go undetected for long periods, presents a major challenge in both clinical and research settings. The ability to define biomarkers of blast injury that could serve as surrogates for exposure
would constitute a substantial advance in the study of long-term outcomes of exposure to blast. Biomarkers are an active area of scientific research; however, the committee recognizes that scientific consensus is lacking on the potential for blast-injury research using blood and other body fluids to identify biomarkers of sufficient sensitivity and specificity to provide clinically useful prognostic or diagnostic utility. The committee believes that biomarker research has the potential to advance the understanding of the biology of a wide range of complex diseases, including blast injury. Many of the available studies in this field focus on potential biomarkers associated with TBI. For example, as described in Chapter 4, blast TBI may confer distinctive neuroimaging patterns as measured by diffusion tensor imaging; however, the evidence is preliminary and insufficient to permit any firm conclusions to be drawn.
As described in Chapter 4, novel neuroimaging techniques can elucidate structural and functional abnormalities in neurologic circuits that are not apparent in routine magnetic resonance imaging. Data from studies of various neurodegenerative diseases have identified promising biomarkers, such as spinal fluid or blood levels of axon neurofilament proteins, that relate to late outcomes of injury (Gaiottino et al., 2013; Petzold, 2005; Shaw et al., 2005). Serum proteins have also shown promise as biomarkers for the diagnosis of non-blast mild TBI. For example, the combined use of serum S100B and apolipoprotein A-1 values increases classification accuracy for mild TBI over either marker used alone, and serum S100B alone is predictive of an abnormal head CT scan (Bazarian et al., 2013).
Other reports of the National Academies support the committee’s view on the transformative potential of modern biomarker research for many complex conditions (IOM, 2008, 2013; NRC, 2011). The 2008 Institute of Medicine (IOM) report Neuroscience Biomarkers and Biosignatures: Converging Technologies, Emerging Partnerships discusses how studies of genomic and proteomic biomarkers have shown promise in the field of neuroscience generally (IOM, 2008). The 2013 IOM report Genome-Based Diagnostics: Demonstrating Clinical Utility in Oncology notes that several genomic predictive markers of cancer treatment efficacy and safety are in clinical use and more are undergoing testing (IOM, 2013). The 2011 National Research Council report Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease discusses how the use of large data sets is a way to clarify new mechanisms, pathways, and heterogeneity of chronic diseases (NRC, 2011). Such large data sets will allow for the integration of cohorts of individuals with unexplained illness.
The committee believes that the use of biomarkers will be an important component for integrating genomic data with imaging data and clinical observation, and will move science in the blast-injury field forward.
Recommendation 5-3. The Department of Veterans Affairs should conduct epidemiologic and mechanistic studies to identify biomarkers of blast injury.
For prospective definition of biomarkers of the signature blast injury that could be applied in future assessments, the committee recommends two complementary prospective studies. In the first study, a small number of service members enrolled in the Breacher Training Course, which includes exposure to blast, would be studied in detail to measure and control for blast exposure objectively. In the second, a larger separate cohort of service members would be studied in detail before and after deployment to allow comparison of those who were exposed to blast with those who were not. Both studies would involve measuring subject-specific changes in organ-specific structure and function. In the second study, blast exposure would be determined on the basis of self-reports, and all subjects would undergo identical predeployment and postdeployment organ-specific functional assessment. The assessment would include neuropsychologic testing, imaging, and collection of serum, plasma, whole blood, and other fluids (for example, cerebrospinal fluid) to assess blast-related changes in protein, genome, and transcriptome concentration as biomarkers.
The committee recognizes that some service members may be unaware of their injuries from blast and recommends that biomarker signatures defined in the above studies be applied to groups returning from deployment (perhaps by using existing data sets) who have developed chronic unexplained health problems (for example, PTSD, addiction, diffuse pain, communication difficulties, and headache) to establish whether any relationships exist between these conditions and clinically inapparent blast exposures. In addition, service members who are relatively asymptomatic from the standpoint of organ-specific injuries can be studied. The committee recommends comparing a large cohort of returning service members who have a history of blast exposure with those who do not (that is, conducting a nested case-control study). The service members can be examined on the basis of the biomarker signatures for evidence of asymptomatic disease and then followed longitudinally to detect differences between the groups in the latent development of adverse effects of blast on which the current literature is uninformative, including some disorders that have not yet been associated with blast. Cases and controls will need to be well matched for demographic factors and for organ-specific premorbid conditions that are known to affect outcome. Postmortem pathologic correlates would be a natural extension of this longitudinal study.
Improving Collaboration in Blast-Injury Research
The committee identified substantial gaps in much of the published research on blast injuries. The gaps include inadequately powered data sets, incomplete control populations, and poor study designs; an absence of combat-relevant expertise in blast on the research team; and a need to refine and advance preclinical models so that they are adequately predictive of long-term multisystem effects of blast injuries in humans. Greater collaboration within and among institutions will expand the expertise of research teams and help to fill those gaps, and this approach should be considered a strength and not a limitation with respect to VA funding priorities.
Recommendation 5-4. To support innovation and improve the state of blast science, the Department of Veterans Affairs should develop opportunities for multidisciplinary research collaborations that cross institutional barriers between the Veterans Health Administration, the Department of Defense, and other institutions.
Improving Designs of Blast-Injury Studies
Most of the studies evaluated by the committee were limited by various aspects of their design, as described in Chapter 2. To assist VA and other researchers in improving the design of future studies, the committee offers several recommendations. In addition to the recommendations, it is important that all future studies use a standardized definition of blast exposure once it has been developed.
Recommendation 5-5. The Department of Veterans Affairs should conduct research on acute and long-term consequences of blast injury involving all service members and veterans, not just users of the Veterans Health Administration.
Recommendation 5-6. The Department of Veterans Affairs should create a registry of blast-exposed (not only blast-injured) service members to serve as a foundation for long-term studies.
Recommendation 5-7. The Department of Veterans Affairs should use existing military records to identify a cohort of service members who served in the Iraq and Afghanistan wars to enroll in a prospective study of the long-term effects of blast on health and rehabilitation. The cohort should not be limited to service members who are known to have been exposed to blast.
Recommendation 5-8. The Department of Veterans Affairs should identify and use as a resource existing longitudinal cohort studies of populations that include blast-exposed service members and veterans. This resource may include information from existing ancillary studies of these cohorts to improve the detection and measurement of adverse long-term health outcomes of blast exposure.
The existing studies include longitudinal studies that were conceptualized and designed to look at other aspects of early adult life. The advantage of such studies is that they have good prospective collection of key risk factors or outcomes of interest before military service and blast exposure. With additional supplementary data collection, the studies’ cohorts may provide important opportunities to answer specific questions about long-term health effects from exposure to blast, including the multisystem response to blast (for example, the complex relationship between TBI and PTSD). Illustrative examples include the National Longitudinal Study of Adolescent Health (2013), the Strong Star cohort (STRONG STAR, 2013), the Canadian Resilience Enhancement in Military Population longitudinal prospective study (Cernak, 2013), and selected Kaiser Permanente longitudinal studies (Kaiser Permanente, 2013).
Recommendation 5-9. The Department of Veterans Affairs should create a database linking Department of Defense records (particularly records that identify blast-injured service members) to records in the Veterans Health Administration, active-duty military treatment facilities, and TRICARE (the Department of Defense health care program) to facilitate identification of long-term health care needs after blast injury.
Recommendation 5-10. The Department of Veterans Affairs should conduct case-control studies of select adverse outcomes to test for the potential contribution of blast to them.
The case-control studies will be of particular value in incorporating biomarkers or other biologic signatures of blast that can be assessed retrospectively. The study design also will help to characterize clinically inapparent acute blast injuries.
Identifying Predictors of Risk of Blast Injury
Screening tests on entry into the military (not only before deployment) should be helpful in gathering information on predictors of increased risk of blast injury. Before enlistment in the US military, applicants are required to undergo a physical examination, which includes height and weight mea-
surements, hearing and visual examinations, urine and blood tests, muscle-group and joint maneuvers, drug and alcohol tests, a pregnancy test for women, and medical-history evaluation based on medical records or self-reported information (DOD, 2011). Specialized tests also may be required (for example, enlistees who are suspected of having epilepsy undergo a neurologic examination) (US Army, 2011). Having any of a number of pre-existing health conditions may exclude a person from serving (for example, see the Army’s Standards of Medical Fitness; US Army, 2011).
Recommendation 5-11. The Department of Defense should determine whether existing screening tests administered during the physical examination conducted on enlistment can be used to measure susceptibility to blast injury, and if additional screening tests might be helpful in determining whether a service member has an increased susceptibility to blast injury.
In making the determination, the following questions should be considered:
- Do some biologic markers predict an increased risk of long-term effects of blast injury?
- Which markers should be included? Some examples are genomic markers of susceptibility, baseline brain function and anatomy, baseline hearing function, and risk of alcohol and substance abuse.
- What tests can be conducted? Some examples are auditory testing and ocular evaluation (contrast sensitivity, reading speed, and dry-eye quantification).
- What investigative tests need to be developed? Some examples are DNA collection (such as genome-wide association studies and microarray assays) and brain imaging.
- Do some clinical characteristics predict an increased risk of the long-term effects of blast injury? The characteristics might include demographic variables, medical history, psychologic and psychiatric history or symptoms, resilience, and social and family support.
- Which clinical characteristics should be included? Some examples are early-life trauma, family history of psychopathologic conditions, social support, and perceived life threat during traumatic events.
- What questionnaires should be given? Some examples are the Early Traumatic Inventory Short Form and the Adverse Childhood Experiences Form, comprehensive medical history, family history questionnaire, and social support questionnaire.
- What investigative tests need to be developed?
As part of its charge, the committee was asked to offer recommendations for disseminating information about the health effects of blast exposure throughout VA for the purpose of improving care and benefits provided to veterans. This section briefly discusses relevant pieces of VA’s educational and communications infrastructure that could be used for that purpose, with recommendations of ways to build on the existing infrastructure to improve the dissemination of information about the health effects of blast injuries.
VA has in place several mechanisms for disseminating information to its clinicians and other health care team members, and the committee believes that the existing infrastructure can be used as the foundation for educating caregivers and others about health effects of blast exposure. It is important for VA health care teams to consider exposure to blast as a possible cause of a veteran’s health problems, and this is particularly true for veterans of the Iraq and Afghanistan wars. Proper diagnosis of health problems caused by exposure to blast will probably also lead to more effective treatment and equitable allocation of benefits.
VA has several clinical practice guidelines (CPGs) and other documents related to blast injuries. The Blasts and Explosions VA DOD General Guidance Pocket Guide (2004) provides guidance for clinicians on how to provide treatment in the immediate aftermath of an explosion. It also describes the types of injuries that are often associated with explosions. In addition, VA has developed CPGs for postdeployment health conditions, such as TBI and PTSD (VA and DOD, 2001, 2009, 2010). VA has published its method for disseminating and implementing its CPGs in Veterans Health Administration medical facilities (Nicholas et al., 2001; VA, undated). The method is summarized in Box 5-1.
VA clinicians are given military health-history pocket cards that include guidance on questions to ask veterans (VA, 2013a). Although some of the questions that are currently asked may lead a veteran to inform a clinician that he or she was exposed to blast (for example, “Did you see combat, enemy fire, or casualties?”), none of the questions mention blast specifically.
VA’s Polytrauma and Blast-Related Injuries Quality Enhancement Research Initiative (PT-BRI QUERI) focuses on conducting research to improve health outcomes in veterans who have experienced TBI. Although other types of blast-related injuries—including auditory, ocular, respiratory, gastrointestinal, and renal injuries—are within its scope, they are not being investigated as far as the committee could determine (VA, 2013c). The PT-BRI QUERI works with VA’s Physical Medicine and Rehabilitation Program Office and disseminates its findings through the VA health care system via such groups as the VHA Screening Coordination Workgroup, the VA National Polytrauma Pain Subcommittee, the VHA Tele-rehabilitation
Methods for Disseminating and Implementing Clinical Practice Guidelines in the Veterans Health Administration
- Dedicate the necessary resources (for example, staff) to make the necessary changes happen. Leadership support, local ownership, and teamwork all are essential for successful implementation of guidelines.
- Assess how current clinical practices compare to what is recommended in the guideline.
- Develop an implementation action plan to close the gaps between current clinical practice and the guideline.
- Test the implementation action plan in the clinical environment.
Monitoring and Assessing the Implementation Efforts
- Choose appropriate measures.
- Collect data.
- Interpret the results.
- Make changes as needed.
- This final step in the implementation process is made by the leadership of the Veterans Health Administration.
SOURCE: VA, undated.
Field Work Group, the Polytrauma Rehabilitation Center Family Care Collaborative, the DOD–VA Family Transition Task Force, the National Center for PTSD, the DOD Amputation Patient Care Program, and the Defense and Veterans Brain Injury Center.
VA’s Simulation Learning, Education and Research Network (SimLEARN) provides continuing education curricula and best practices on a variety of health care issues (VA, 2012). Local VA medical centers also offer training courses. However, none of the curricula offered at the national or local levels appears to address health effects specifically of exposure to blasts.
VA’s National Center for PTSD offers a number of educational materials and other products for clinicians (VA, 2013b). Examples include continuing education courses for both VA and non-VA employees, information
on how to assess PTSD, and practice recommendations for treating veterans who have PTSD and comorbid conditions.
Multiple other opportunities for dissemination of information to health care team members about blast injuries exist in the VA health care system. For example, VA has been moving to the medical home model called PACTs, and each veteran entering the VA system is assigned to a PACT (Reisinger et al., 2012). Because of the multidisciplinary, team-based approach to providing medical care, PACTs are an ideal mechanism for increasing awareness about health effects of blast exposures. Additional mechanisms include the use of clinical champions to serve as internal resources for clinicians, and learning (peer) networks to facilitate sharing of information and skills related to managing health effects of blast exposures.
Recommendation 5-12. The Department of Veterans Affairs (VA) should build on its existing educational and communication infrastructure to educate its clinicians and other health care team members further about the health effects of blast exposure. Specific actions should be taken to
- Develop clinical practice guidelines (CPGs) for blast-related injuries other than traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). The CPGs should be developed in collaboration with the Department of Defense and ideally would be used by both departments.
- Expand the focus of the Polytrauma and Blast-Related Injuries Quality Enhancement Research Initiative to include injuries other than TBI and PTSD. Blast injuries and rehabilitation after them should be viewed through a wide clinical lens.
- Offer continuing education credit courses on blast injury through the Simulation Learning, Education and Research Network and other relevant educational forums.
- Convene periodic state-of-the-science conferences (for example, every 2 or 3 years) on the health effects of blast injuries. Such conferences would be convened ideally in collaboration with the Department of Defense, and possibly with selected professional associations, and the conference proceedings would be published (for example, in special issues or supplements of professional journals).
- Establish a blast-injury literature clearinghouse or information repository that could be used as a resource for clinicians and researchers. It should be a joint effort of the VA and the Department of Defense.
- Use such mechanisms as the patient-aligned care teams, clinical champions, and learning networks to educate VA health care teams about the health effects of blast exposure.
- Encourage clinicians to ask veterans specifically about exposure to blasts. Develop standard screening questions specific to veterans’ exposures to blast for integration into the VA electronic health record and as part of veterans’ military histories. The screening questions should be listed on the military health-history pocket card.
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