Outcomes with Objective Measures or Diagnostic Medical Tests

In reviewing the studies of mortality, the committee found numerous limitations. The principal one is the short duration of followup observation. More time must elapse before investigators will be able to assess increased mortality that would result from illnesses with long latency, such as cancer, or that would have a gradually deteriorating course, such as cardiovascular disease. Another potential limitation of comparing deployed with nondeployed personnel is the healthy-warrior effect, which might result in selection bias, insofar as chronically ill or less fit members of the armed forces might be less likely to have been deployed than more fit members.

A number of studies examined rates of injuries in Gulf War veterans (Kang and Bullman 1996; Kang and Bullman 2001; Macfarlane et al. 2000). Those studies provide evidence of a modest increase in transportation-related injuries and mortality among deployed than among nondeployed Gulf War veterans in the decade immediately after deployment. However, studies with longer followup indicate that the increased injury rate was likely to have been restricted to the first several years after the war (Kang and Bullman 2001).

With regard to all causes of hospitalization, studies provide some evidence that excess hospitalizations did not occur among veterans of the Gulf War who remained on active duty through 1994 (Gray et al. 1996). Those studies have certain limitations, however, as they were largely of active-duty personnel and cannot be generalized to the entire cohort of Gulf War veterans; it has been noted that Gulf War veterans who left the military reported worse health outcomes than those who remained (Ismail et al. 2000). It also might be too soon to capture hospitalizations from illnesses that might have longer latency, such as some cancers. In addition, hospitalization data on people separated from the military and admitted to nonmilitary (Department of Veterans Affairs [VA] and civilian) hospitals or on those who used outpatient facilities might be incomplete.

Veterans are understandably concerned about increases in cancer, and the studies reviewed did not demonstrate consistent evidence of increased overall cancer in the Gulf War veterans compared with nondeployed veterans (Kang and Bullman 2001; Macfarlane et al. 2003). However, many veterans are young for cancer diagnoses, and, for most cancers, the time since the Gulf War is probably too short to expect the onset of cancer. Incidence of and mortality from cancer in general, and brain and testicular cancer in particular, have been assessed in cohort studies. An association of brain-cancer mortality with possible nerve-agent exposure (as modeled by the Department of Defense [DOD] exposure model of 2000) was observed in one study (Bullman et al. 2005), but, as discussed in more detail in Chapter 2, there were many uncertainties in the exposure model. Results for testicular cancer were mixed: one study concluded that there was no evidence of an excess risk (Knoke et al. 1998), and another, small, registry-based study (Levine et al. 2005) suggested that there might be an increased risk.

Another concern for veterans has been whether amyotrophic lateral sclerosis (ALS) is increased in Gulf War veterans. Two primary studies and one secondary study found that deployed veterans appear to be at increased risk for ALS. The primary study by Horner et al. (2003), which had the possibility of underascertainment of cases in the nondeployed population, was confirmed by a secondary analysis by Coffman et al. (2005) that documented a nearly 2-fold increase in risk. A secondary study by Haley (2003) used general population estimates as the comparison group and found a slightly higher relative risk.

Peripheral neuropathy has also been studied in Gulf War veterans. One large, well-designed study conducted by VA (Davis et al. 2004), which used a thorough and objective

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