B
CONCLUSIONS AND RECOMMENDATIONS: GULF WAR AND HEALTH, VOLUME 1

The conclusions and research recommendations of the IOM report Gulf War and Health, Volume 1, Literature Review of Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines are provided below.

CONCLUSIONS

Sufficient Evidence of a Causal Relationship

Evidence is sufficient to conclude that a causal relationship exists between the exposure to a specific agent and a health outcome in humans. The evidence fulfills the criteria for sufficient evidence of an association (below) and satisfies several of the criteria used to assess causality: strength of association, dose-response relationship, consistency of association, temporal relationship, specificity of association, and biological plausibility.

Exposure to sarin and a dose-dependent acute cholinergic syndrome that is evident seconds to hours subsequent to sarin exposure and resolves in days to months.

Sufficient Evidence of an Association

Evidence is sufficient to conclude that there is a positive association. That is, a positive association has been observed between an exposure to a specific agent and a health outcome in human studies in which chance, bias, and confounding could be ruled out with reasonable confidence.

  • Pyridostigmine bromide and transient acute cholinergic effects in doses normally used in treatment and for diagnostic purposes.

  • Anthrax vaccination and transient acute local and systemic effects.

  • Botulinum toxoid vaccination and transient acute local and systemic effects.



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Gulf War and Health: Insecticides and Solvents, Volume 2 B CONCLUSIONS AND RECOMMENDATIONS: GULF WAR AND HEALTH, VOLUME 1 The conclusions and research recommendations of the IOM report Gulf War and Health, Volume 1, Literature Review of Depleted Uranium, Pyridostigmine Bromide, Sarin, Vaccines are provided below. CONCLUSIONS Sufficient Evidence of a Causal Relationship Evidence is sufficient to conclude that a causal relationship exists between the exposure to a specific agent and a health outcome in humans. The evidence fulfills the criteria for sufficient evidence of an association (below) and satisfies several of the criteria used to assess causality: strength of association, dose-response relationship, consistency of association, temporal relationship, specificity of association, and biological plausibility. Exposure to sarin and a dose-dependent acute cholinergic syndrome that is evident seconds to hours subsequent to sarin exposure and resolves in days to months. Sufficient Evidence of an Association Evidence is sufficient to conclude that there is a positive association. That is, a positive association has been observed between an exposure to a specific agent and a health outcome in human studies in which chance, bias, and confounding could be ruled out with reasonable confidence. Pyridostigmine bromide and transient acute cholinergic effects in doses normally used in treatment and for diagnostic purposes. Anthrax vaccination and transient acute local and systemic effects. Botulinum toxoid vaccination and transient acute local and systemic effects.

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Gulf War and Health: Insecticides and Solvents, Volume 2 Limited/Suggestive Evidence of an Association Evidence is suggestive of an association between exposure to a specific agent and a health outcome in humans, but is limited because chance, bias, and confounding could not be ruled out with confidence. Exposure to sarin at doses sufficient to cause acute cholinergic signs and symptoms and subsequent long-term health effects. Inadequate/Insufficient Evidence to Determine Whether an Association Does or Does Not Exist The available studies are of insufficient quality, consistency, or statistical power to permit a conclusion regarding the presence or absence of an association between an exposure to a specific agent and a health outcome in humans. Exposure to uranium and lung cancer at higher levels of cumulative exposure (>200 mSv or 25 cGy). Exposure to uranium and lymphatic cancer; bone cancer; nervous system disease; nonmalignant respiratory disease; or other health outcomes (gastrointestinal disease, immune-mediated disease, effects on hematological parameters, reproductive or developmental dysfunction, genotoxic effects, cardiovascular effects, hepatic disease, dermal effects, ocular effects, or musculoskeletal effects). Pyridostigmine bromide and long-term adverse health effects. Exposure to sarin at low doses insufficient to cause acute cholinergic signs and symptoms and subsequent long-term adverse health effects. Anthrax vaccination and long-term adverse health effects. Botulinum toxoid vaccination and long-term adverse health effects. Multiple vaccinations and long-term adverse health effects. Limited/Suggestive Evidence of No Association There are several adequate studies covering the full range of levels of exposure that humans are known to encounter, that are mutually consistent in not showing a positive association between exposure to a specific agent and a health outcome at any level of exposure. A conclusion of no association is inevitably limited to the conditions, levels of exposure, and length of observation covered by the available studies. In addition, the possibility of a very small elevation in risk at the levels of exposure studied can never be excluded. Exposure to uranium and lung cancer at cumulative internal dose levels lower than 200 mSv or 25 cGy. Exposure to uranium and clinically significant renal dysfunction.

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Gulf War and Health: Insecticides and Solvents, Volume 2 RESEARCH RECOMMENDATIONS Biological, Chemical, and Psychological Interactions Research on the interactions among the multiple agents and stressors to which military personnel were exposed as a result of the Gulf War conflict. Depleted Uranium Continued followup of the Baltimore cohort of Gulf War veterans with DU exposure. Long-term studies of the health of other Gulf War veterans at high risk for DU exposure (e.g., cleanup or radiation control units). Continued followup of the cohorts of uranium processing workers. Additional studies of the effects of DU in animals. Sarin Long-term followup of populations exposed to sarin in the Matsumoto and Tokyo terrorist attacks. Studies in experimental animals to investigate the long-term effects of an acute, short-term exposure to sarin at doses that do not cause overt cholinergic effects and minimal acetylcholinesterase inhibition. Research on genetic factors that may alter susceptibility to sarin toxicity. Pyridostigmine Bromide Research on chemical interactions between PB and other agents such as stress, and certain insecticides. Research on genetic factors (e.g., genetic polymorphisms of butyrylcholinesterase, paraoxonase) that may alter susceptibility to the effects of PB. Epidemiologic studies on the possible long-term health effects of PB. Vaccines Long-term longitudinal studies of participants in the Anthrax Vaccine Immunization Program that would actively monitor and systematically collect and analyze data about symptoms, functional status, and disease status. Long-term systematic research to examine potential adverse effects of anthrax and botulinum toxoid vaccination in multiple species and strains of animals. Careful study of current symptoms, functional status, and disease status in cohorts of Gulf War veterans and Gulf War-era veterans for whom vaccination records exist.