epidemiologic literature on all the possible environmental agents to which Gulf War veterans might have been exposed was not conducted.

For each health effect presented in this chapter, the committee first summarizes the primary studies and secondary or supporting studies that were included in Gulf War and Health, Volume 4: Health Effects of Serving in the Gulf War (referred to as Volume 4). The committee then identifies additional primary and secondary studies from its updated literature searches and reconsiders the studies described in Volume 4 taking into account these updates. Although many of the studies are new and were published after Volume 4 was completed in 2006, some of the additional studies cited by the Update committee were published before or during 2006 but were not discussed in Volume 4. Because the Volume 4 committee was tasked with identifying those health effects seen at greater prevalence in deployed versus nondeployed Gulf War veterans and not with determining the strength of the association between deployment and the development of a particular health effect, not every study that examined an association between a health effect and Gulf War exposures was included in Volume 4. Therefore, the Update committee reviewed the categorization (primary or secondary) of all of the studies considered for Volume 4 as well as any new studies identified from an updated literature search. All studies for each health outcome, including those originally cited in Volume 4, were reviewed and categorized as primary or secondary by the entire committee in plenary session, before it came to a consensus on the appropriate category of association to be assigned to each health outcome. Consistent with previous volumes of the Gulf War and Health series, the primary studies on which the committee based its conclusions are detailed in the evidence table at the end of each health outcome section. Using this weight-of-the-evidence approach required that the Update committee be more rigorous in its review of the studies in Volume 4; as a result some studies considered to be primary in Volume 4 were recategorized as secondary for this report and vice versa. Thus, the Update committee summarizes de novo the information from both Volume 4 and any new literature to arrive at its conclusions on the strength of the association between deployment to the Gulf War and a health outcome.

As described in Chapter 2, a primary study had to include information about the putative exposure (generally deployment) and specific health outcomes, demonstrate rigorous methods, include adequate details of its methods to allow a thorough assessment, include an appropriate control or reference group, and provide appropriate adjustment for confounders. It is of note that many of the large cohort studies examined multiple outcomes and so might be referred to in more than one place in this report. A given study might be deemed a primary study for one or more health outcome and be a secondary study for another outcome, based on how each health outcome was defined and measured. For example, a particular study might be well designed for assessing diabetes because the authors used a strong indicator such as blood glucose levels to identify this disorder, but the same study might not be well designed for assessing a psychiatric disorder because the authors used only a screening instrument to identify the disorder. In general, only primary studies appear in the evidence tables that accompany the discussion of each health outcome.

A secondary study typically had methodological limitations, such as not including a rigorous or well-defined method of diagnosis, or a lack of an appropriate control group. The secondary studies were reviewed and included in the discussion because they evaluated the same health outcomes and in some cases provided useful information on veteran populations from the same conflicts as the primary studies. For this reason it was felt that secondary studies add information that might modify (increase or decrease) confidence in the conclusions, which are

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