Canadian, Danish, and Australian cohorts. Relatively small cohorts, such as the Canadian and Australian veterans, might not be useful for outcomes of low incidence (for example, ALS and brain cancer), but they might be very useful for tracking frequent outcomes, for example, multisymptom illness, cardiovascular and respiratory diseases, other cancer types, such neurodegenerative conditions as dementia, and some psychiatric disorders.
With regard to functional gastrointestinal disorders (irritable bowel syndrome and functional dyspepsia), recent evidence supports the need for two types of studies: to determine the role of prior acute gastroenteritis in the development of these disorders in deployed soldiers and to use symptom-specific criteria (for example, Rome criteria) to clarify the association of medical and psychosocial comorbidities with functional gastrointestinal disorders and their severity.
Uncommon genetic variants and rare environmental events may not be recognized as associated with outcomes of interest unless very large numbers of people are studied or sophisticated capture methods are used to explore them. For example, new and objective information related to exposures that becomes available in the future might improve our ability to estimate individual exposures and to stratify groups of Gulf War veterans.
A second branch of inquiry is also important. It consists of a renewed research effort to identify and treat multisymptom illness in Gulf War veterans. Given the high prevalence of persistent symptoms and the steady advances in our understanding of genetics, molecular diagnostics, and imaging, it is now possible to plan and carry out adequately powered studies to identify inherited genetic variants, molecular profiles of gene expression, other epigenetic markers (for example, modifications of DNA structure related to environmental exposures), specific viral exposures, signatures of immune activation, and brain changes identified by sensitive imaging measures that distinguish Gulf War veterans who have persistent medical symptoms from healthy deployed or nondeployed veterans. The committee is optimistic that a rigorous, adequately powered study could identify useful biomarkers that are helpful for symptomatic veterans of the Gulf War and for nondeployed veterans and civilians who have a variety of medically unexplained symptoms, including chronic fatigue, muscle and joint pain, sleep disturbance, difficulty with concentration, and depression.
Finally, the committee notes that inadequate numbers of clinical trials have been undertaken to develop more effective and evidence-based treatments for multisystem illness. Aligned with efforts to improve care pathways for veterans suffering from multisymptom illness, a focused effort should be undertaken to support high-quality clinical trials informed by the best available biologic information related to the cause of multisystem illness. The committee believes that a continued and targeted research program is the most likely path to assist VA and other health-care providers in diagnosing and treating the health problems of Gulf War veterans and preventing illness in future veterans.