centers (wriiscs) use the recommended term gulf war illness, as do va's office of research and development (va-ord) and many recent va research publications. however, va's public health website still uses gulf war veterans' medically unexplained illnesses, chronic multi-symptom illness (cmi), and undiagnosed illnesses, but explains that va doesn't use the term gulf war syndrome because of varying symptoms. the veterans health administration (vha) originally classified individuals with related ailments believed to be connected to their service in the persian gulf a special non-icd-9 code dx111, as well as icd-9 code v65.5. kansas definition in 1998, the state of kansas persian gulf veterans health initiative sponsored an epidemiological survey led by dr. lea steele of deployment-related symptoms in 2,030 gulf war veterans. the result was a "clinically based descriptive definition using correlated symptoms" in six symptom groups: fatigue and sleep problems, pain, neurologic and mood, gastrointestinal, respiratory symptoms, and skin (dermatologic) symptoms. to meet the "kansas" case definition, a veteran of the 1990–91 gulf war must have symptoms in at least three of the six symptom domains, which during the survey were scored based on severity ("severity"). symptom onset must have developed during or after deploying to the 1990–91 gulf war theatre of operations ("onset") and must have been present in the year before interview ("duration"). participants were excluded if they had a diagnosis of or were being treated for any of several conditions that might otherwise explain their symptoms ("exclusionary criteria"), including cancer, diabetes, heart disease, chronic infectious disease, lupus, multiple sclerosis, stroke, or any serious psychiatric condition. applying the kansas case definition to the original kansas study cohort resulted in a prevalence of gulf war illness of 34.2% in gulf war veterans and 8.3% in nondeployed gulf war era veterans, or an excess rate of gwi of 26.3% in gulf war veterans. cdc definition also in 1998, a study published by dr. keiji fukuda under the auspices of the u.s. centers for disease control and prevention (cdc) examined chronic multisymptom illness through a cross-sectional survey of 3,675 ill and healthy u.s. air force veterans of the 1990–91 gulf war, including from a pennsylvania-based air national guard unit and three comparison air force units. the cdc case definition was derived from clinical data and statistical analyses. the result was a symptom-category approach to a case definition, with three symptom categories: fatigue, mood–cognition, and musculoskeletal. to meet the case definition, the veteran of the 1990–91 gulf war must have symptoms in two of the three categories and have experienced the illness for six months or longer ("duration"). the original study also including a determination of severity of symptoms ("severity"). "severe cases were identified if at least one symptom in each of the required categories was rated as severe. of 1,155 participating gulf war veterans, 6% had severe cmi, and 39% had mild to moderate cmi; of the 2,520 nondeployed era veterans of 1,155 participating gulf war veterans, 6% had severe cmi, and 39% had mild to moderate cmi; of the 2,520 nondeployed era veterans, 0.7% had severe and 14% had mild to moderate cmi." treatment a 2013 report by the institute of medicine reviewed the peer-reviewed published medical literature for evidence regarding treatments for symptoms associated with chronic multisymptom illness (cmi) in 1990–91 gulf war veterans, and in other chronic multisymptom conditions. for the studies the report reviewed that were specifically regarding cmi in 1990–91 gulf war veterans (gulf war illness), the report made the following conclusions: doxycycline: "although the study of doxycycline was found to have high strength of evidence and was conducted in a group of 1991 gulf war veterans who had cmi, it did not demonstrate efficacy; that is, doxycycline did not reduce or eliminate the symptoms of cmi in the study population." cognitive behavioral therapy (cbt) and exercise: "these studies evaluated the effects of exercise and cbt in combination and individually. the therapeutic benefit of exercise was unclear in those studies. group cbt rather than exercise may confer the main therapeutic benefit with respect to physical symptoms." the report concluded: "on the basis of the evidence reviewed, the committee cannot recommend any specific therapy as a set treatment for veterans who have cmi. the committee believes that a 'one-size-fits-all' approach is not effective for managing veterans who have cmi and that individualized health care management plans are necessary." by contrast, the u.s. department of defense (dod) noted in a may 2018 publication that the primary focus of its gulf war illness research program (gwirp) "has been to fund research studies to identify treatment targets and test interventional approaches to alleviate symptoms. while most of these studies remain in progress, several have already shown varying levels of promise as gwi treatments." according to the may 2018 dod publication: published results on treatments the earliest federally funded multi-center clinical trials were va- and dod-funded trials that focused on antibiotic treatment (doxycycline) (donta, 2004) and cognitive behavioral therapy with exercise (donta, 2003). neither intervention provided long-lasting improvement for a substantial number of veterans. preliminary analysis from a placebo-controlled trial showed that 100 mg of coenzyme q10 (known as coq10 or ubiquinone) significantly improved general self-reported health and physical functioning, including among 20 symptoms, each of which was present in at least half of the study participants, with the exception of sleep. these improvements included reducing commonly reported symptoms of fatigue, dysphoric mood, and pain (golomb, 2014). these results are currently being expanded in a gwirp-funded trial of a "mitochondrial cocktail" for gwi of coq10 plus a number of nutrients chosen to support cellular energy production and defend against oxidative stress. the treatment is also being investigated in a larger, va- sponsored phase iii trial of ubiquinol, the reduced form of coq10. in a randomized, sham-controlled va-funded trial of a nasal cpap mask (amin, 2011-b), symptomatic gw veterans with sleep-disordered breathing receiving the cpap therapy showed significant improvements in fatigue scores, cognitive function, sleep quality, and measures of physical and mental health (amin, 2011a). preliminary data from a gwirp-funded acupuncture treatment study showed that veterans reported significant reductions in pain and both primary and secondary health complaints, with results being more positive in the bi-weekly versus weekly treatment group (conboy, 2012). current studies funded by the gwirp and the va are also investigating yoga as a treatment for gwi. an amino acid supplement containing l-carnosine was found to reduce irritable bowel syndrome-associated diarrhea in a randomized, controlled gwirp-funded trial in gw veterans (baraniuk, 2013). veterans receiving l-carnosine showed a significant improvement in performance in a cognitive task, but no improvement in fatigue, pain, hyperalgesia, or activity levels. results from a 26 week gwirp-funded trial comparing standard care to nasal irrigation with either saline or a xylitol solution revealed that both irrigation protocols reduced gwi respiratory (chronic rhinosinusitis) and fatigue symptoms (hayer, 2015). administration of the glucocorticoid receptor antagonist mifepristone to gw veterans in a gwirp-funded randomized trial resulted in an improvement in verbal learning, but no improvement in self-reported physical health or other self-reported measures of mental health (golier, 2016).ongoing intervention studies the gwirp is currently funding many early-phase clinical trials aimed at gwi. interventions include direct electrical nerve stimulation, repurposing fda-approved pharmaceuticals, and dietary protocols and/or nutraceuticals. both ongoing and closed gwirp-supported clinical treatment trials and pilot studies can be found at . a clinical consortium award was offered to support a group of institutions, coordinated through an operations center that will conceive, design, develop, and conduct collaborative phase i and ii clinical evaluations of promising therapeutic agents for the management or treatment of gwi. these mechanisms were designed to build on the achievements of the previously established consortia and to further promote collaboration and resource sharing. the u.s congress has made significant and continuing investment in dod's gulf war illness treatment research, with $129 million appropriated for the gwirp between federal fiscal years (fy) 2006 and 2016. the funding has risen from $5 million in fy2006, to $20 million each year from fy2013 through fy2017, and to $21 million for fy2018. prognosis according to the may 2018 dod publication cited above, "research suggests that the gwi symptomology experienced by veterans has not improved over the last 25 years, with few experiencing improvement or recovery ... . many veterans will soon begin to experience the common co-morbidities associated with aging. the effect that aging will have on this unique and vulnerable population remains a matter of significant concern, and population-based research to obtain a better understanding of mortality, morbidity, and symptomology over time is needed." prevalence the 2008 and 2014 va (rac) reports and the 2010 iom report found that the chronic multisymptom illness in gulf war veterans—gulf war illness—is more prevalent in gulf war veterans than their non-deployed counterparts or veterans of previous conflicts. while a 2009 study found the pattern of comorbidities similar for actively deployed and nondeployed australian military personnel, the large body of u.s. research reviewed in the va and iom reports showed the opposite in u.s. troops. the va's 2014 rac report found gulf war illness in "an excess of 26–32 percent of gulf war veterans compared to nondeployed era veterans" in pre-2008 studies, and "an overall multisymptom illness prevalence of 37 percent in gulf war veterans and an excess prevalence of 25 percent" in a later, larger va study. according to a may 2018 report by the u.s. department of defense, "gwi is estimated to have affected 175,000 to 250,000 of the nearly 700,000 troops deployed to the 1990–1991 gw theater of operations. twenty-seven of the 28 coalition members participating in the gw conflict have reported gwi in their troops. epidemiologic studies indicate that rates of gwi vary in different subgroups of gw veterans. gwi affects veterans who served in the u.s. army and marines corps at higher rates than those who served in the navy and air force, and u.s. enlisted personnel are affected more than officers. studies also indicate that gwi rates differ according to where veterans were located during deployment, with the highest rates among troops who served in forward areas." research epidemiologic studies have looked at many suspected causal factors for gulf war illness as seen in veteran populations. below is a summary of epidemiologic studies of veterans displaying multisymptom illness and their exposure to suspect conditions from the 2008 u.s. department of veterans affairs report. a fuller understanding of immune function in ill gulf war veterans is needed, particularly in veteran subgroups with different clinical characteristics and exposure histories. it is also important to determine the extent to which identified immune perturbations may be associated with altered neurological and endocrine processes that are associated with immune regulation. very limited cancer data have been reported for u.s. gulf war veterans in general, and no published research on cases occurring after 1999. because of the extended latency periods associated with most cancers, it is important that cancer information is brought up to date and that cancer rates be assessed in gulf war veterans on an ongoing basis. in addition, cancer rates should be evaluated in relation to identifiable exposure and location subgroups. epidemiologic studies of gulf war veterans:association of deployment exposures with multisymptom illness suspected causative agent preliminary analysis(no controls for exposure) adjusted analysis(controlled for effects of exposure) clinical evaluations gwv population in which association was ... gwv population in which association was ... assessed statistically significant assessed statistically significant dose response effect identified? pyridostigmine bromide 10 9 6 6 ✓ associated with neurocognitive and hpa differences in gw vets pesticides 10 10 6 5 physiological stressors 14 13 7 1 chemical weapons 16 13 5 3 associated with neurocognitive and hpa differences in gw vets oil wellfires 9 8 4 2 ✓ number ofvaccines 2 2 1 1 anthraxvaccine 5 5 2 1 tent heater exhaust 5 4 2 1 sand / particulates 3 3 3 1 depleteduranium 5 3 1 0 controversies an early argument in the years following the gulf war was that similar syndromes have been seen as an after effect of other conflicts — for example, "shell shock" after world war i, and post-traumatic stress disorder (ptsd) after the vietnam war. cited as evidence for this argument was a review of the medical records of 15,000 american civil war soldiers showing that "those who lost at least 5% of their company had a