The charge to the committee was to determine whether the Comprehensive Clinical Evaluation Program could adequately diagnose and treat possible health problems among service personnel who may have been exposed to low levels of nerve agents. The committee reviewed extensive clinical and research results regarding the effects of nerve agents. No evidence available to the committee conclusively indicated the existence of long-term health effects of low-level exposure to nerve agents. Because firm conclusions about these effects remain elusive, the committee reviewed information about the types of health effects that might exist as a result of exposure. Leading scientists presented information suggesting that the possible effects might include neurological problems such as peripheral sensory neuropathies and psychiatric problems such as alterations in mood, cognition, or behavior.
Recent reports suggesting a possible toxic synergistic effect following exposure to multiple agents known to influence cholinesterase activity will require extensive research to determine their significance (Haley and Kurt, 1997; Haley et al., 1997a,b; Lottie et al., 1993). The results of the research to date, however, did not appear to indicate any additional possible health effects should be considered by the committee other than those already identified.
The committee concluded that the CCEP continues to provide an appropriate screening approach to the diagnosis of disease. Most CCEP patients receive a diagnosis and 80% of participants receive more than one diagnosis. Although the types of primary diagnoses commonly seen in the CCEP involve a variety of conditions, 65% of all primary diagnoses fall into three diagnostic groups (1) psychological conditions; (2) musculoskeletal diseases; and (3) symptoms, signs, ill-defined conditions or a fourth group designated as "healthy." However, in view of potential exposure to low levels of nerve agents, certain refinements in the CCEP would increase its value. These
refinements are viewed as part of a natural evolution and improvement process and, therefore, need not be applied retrospectively. The committee does encourage rapid implementation in order to provide the benefits of an improved system to new enrollees.
The committee recommends improved documentation of the screening used during Phase I for patients with psychological conditions such as depression and posttraumatic stress disorder (PTSD). The DoD (DoD, 1996) reported that depression and PTSD account for a substantial percentage of those receiving a diagnosis of a psychological condition. In addition, if there are long-term health effects of nerve agent exposure, it is possible that these effects could be manifested as changes in mood or behavior. The committee will be conducting an in-depth examination of the adequacy of the CCEP as it relates to stress and psychiatric disorders at a later time; however, because of the increased importance of ensuring that all possibilities are thoroughly checked, better documentation in this area is encouraged. Primary physicians could use any of a number of self-report screening scales, but consistent use of the same scale across facilities would ensure consistent results.
The committee recommends improved documentation of neurological screening done during both Phase I and Phase II of the CCEP. Concern about nerve agent exposure as well as the number of nonspecific, undiagnosed illnesses among CCEP patients makes documentation of neurological screening extremely important. CCEP patients are referred to neuromuscular specialists if they have complaints of severe muscle weakness, fatigue, or myalgias lasting for at least 6 months that significantly interfere with activities of daily living. These patients are evaluated by board-certified neurologists who have subspecialty training in neuromuscular disease. Based on the description of the tests administered and examinations conducted, the committee finds that the CCEP is sufficient to ensure that no chronic, well-established neurological problem is being overlooked. The documentation of the use of these tests and procedures, however, could and should be improved. Such improvements would engender confidence that neurological examinations and treatments across facilities are comparable.
Given the importance of thorough neurological and psychiatric screening, the committee recommends that Phase I primary physicians have ready access to a referral neurologist and a referral psychiatrist. As mentioned earlier, patients are referred to neuromuscular specialists if they have complaints of severe muscle weakness, fatigue, or myalgias lasting for at least 6 months that significantly interfere with activities of daily living. Appropriate psychiatric referrals could include those with chronic depression that is treatment resistant, an unexplained, persistent complaint of memory problems, or significant impairment secondary to behavioral difficulties, such as not being able to maintain productive work due to behavioral abnormalities. While patients referred for Phase II consultations with a neurologist or psychiatrist are cared for adequately, it is sometimes difficult for the primary physician to determine
whether or not a referral is appropriate. In such instances, the physician tends to refer more frequently than not. It may be that, if the primary care physician had neurological and psychiatric consultations readily available, referral decisions could be made more easily and appropriately.
The committee recommends that physicians take more complete patient histories, particularly regarding personal and family histories, the onset of health problems, and occupational and environmental exposures. While there currently is grave concern about exposure to nerve agents during deployment in the Persian Gulf, other factors affect on psychological and neurological disorders. Patients can perform below expectations on neuropsychological tests for a number of reasons. In clinical assessments, therefore, it is important to rule out alternative causes of impairment. In addition, current and past exposures to occupational and environmental toxicants are important. Detailed histories are a valuable tool in identifying the etiology of a patient's problems.
The committee recommends that, to the extent possible, predeployment physical examinations given to members of the armed forces should be standardized among the services. The lack of uniform baseline information about service members makes diagnosis and treatment of postdeployment problems more difficult. To the extent that adequate baseline information is unavailable, physicians must rely on self-reporting. Adequate predeployment physical examinations, standardized across services, could prove an important tool for both clinical assessment and structured research.
The committee recommends that DoD increase the uniformity of CCEP forms and reporting procedures across sites. The CCEP system would benefit from increased consistency and the knowledge that each service is collecting and using the same information. Currently, each branch of service and each facility use different forms to complete examinations, tests, and referrals. Increasing the consistency of such forms and procedures would provide a more reliable picture of the care given to patients in the CCEP. As was stated in the 1996 report on the Health Consequences of Service During the Persian Gulf War, it is extremely important to create a uniform, continuous, and retrievable medical record. In addition, the 1996 report stated that the information should be collected according to standardized procedures and maintained in a computer-accessible format. (IOM, 1996b) The committee concurs with those findings.
For each patient, the physician should provide written evidence that all organ systems were evaluated. The CCEP primary care physicians examine patients, and, if there are problems requiring additional expertise, the patients are referred to specialists. This is standard medical practice used across the United States. It would be appropriate, however, for the CCEP primary care physicians to document that their evaluations covered all organ systems. The committee is not recommending the use of new or sophisticated testing mechanisms. It is reinforcing the importance of the components of the basic medical examination.
This increased documentation could be completed by noting the organ systems evaluated and whether each was normal or abnormal. For those listed as abnormal, additional information could be provided.
The committee strongly urges the DoD to offer group education and counseling to soldiers and their families concerned about exposure to toxic agents. Following the revelation by the DoD of possible exposure to nerve agents due to the destruction of the munitions dump at Khamisiyah, approximately 20,000 service personnel received a letter from the DoD stating that their units were in the vicinity during the demolition. Each recipient was encouraged to contact an 800 number if he or she was experiencing health problems believed to be a result of service in the Persian Gulf. Given this revelation, there may be a heightened sense of insecurity and concern among Persian Gulf veterans and their families about possible exposure to nerve agents. Risk communication is an important clinical activity. Family and group counseling can address heightened concerns about exposure as well as other issues. Such an approach provides an appropriate public health mechanism for imparting information and addressing concerns and should be made available to all Persian Gulf veterans.
Although it is beyond the scope of the charge to this committee to determine whether low-level exposure to nerve agents causes long-term health effects, the committee believes strongly that this is an important research area that ought to be pursued. Most of the literature regarding health effects of exposure to nerve agents (i.e., sarin and cyclosarin) addresses exposures high enough to cause clinically observable effects. These clinical effects are well documented and include miosis, blurred vision, nausea, vomiting, muscular twitching, weakness, convulsions, and death. Little known research has been conducted regarding the long-term health effects of low levels of exposure to these nerve agents. The application of findings from research on organophosphate pesticide exposure to the area of nerve agent exposure has limitations. However, even in such pesticide studies, long-term health effects have been documented only for acutely poisoned individuals—that is, persons with immediate clinical symptoms.
The committee emphasizes that the CCEP is not an appropriate vehicle for scientifically assessing questions about long-term health effects of low levels of exposure to nerve agents. The CCEP is a clinical treatment program, not a research protocol. It is important, therefore, not to attempt to use the findings of the CCEP to answer research questions. Those questions must be addressed through rigorous scientific research.
The committee notes that the CCEP could be useful in identifying promising directions for separate research studies. Examinations of the health effects—if any—of various wartime exposures have been hampered by poor information about the level of exposure and an inability to identify the individuals who may have been exposed. It is often difficult to retrospectively estimate exposure levels. However, information about where individuals were and when they were there could be combined with data regarding the presence of an exposure to
develop surrogate measures. These surrogate measures could then be linked to health information and used to examine potential associations between exposures and health effects.
Although data from the CCEP can not be used to test for associations, it can be combined with other information to help identify areas for future research. For example, the DoD identified approximately 20,000 service people belonging to units that were within a 50-kilometer radius of Khamisiyah at the time of the munitions demolition. Examining the health records of these people may yield insights into whether those who participated in the CCEP (or a similar program administered by the VA) have different illnesses or patterns of illnesses than do CCEP participants outside the 50-kilometer radius. More detailed discrimination of proximity to Khamisiyah (e.g., within 20 kilometers or within the units directly responsible for the munitions destruction) may provide additional information.
It is important, however, to understand the limitations of such comparisons. The results cannot be taken as research findings and generalized to the entire population of those deployed to the Persian Gulf. Active-duty military personnel participating in the DoD health registry may be either more or less healthy than other nonparticipants on active duty. CCEP comparisons on this self-selected group of patients should not be used to draw conclusions about the entire population of Persian Gulf veterans.
More broadly, the committee notes that information that helps to identify where individuals were in the Persian Gulf and when they were there will also facilitate research into potential service-related health problems. This information is currently needed to address the question of who might have been exposed to nerve agents and who could be part of the (unexposed) comparison groups necessary for epidemiological studies. Such information could also be used to more quickly and easily identify the exposed and unexposed groups that would be required to assess any future concerns regarding this or other exposures.
Generating geographical and temporal information for all 700,000 people who served in the Persian Gulf would be an immense endeavor. It would not be prudent to undertake such a task without first thoroughly understanding the effort required to complete it. It would, however, be appropriate to take steps now to identify and preserve records that could assist in the generation of such a database in the future. Records-based information is intrinsically superior to personal recollections, especially several years after the fact.