Prospective study of military service and mortality from ALS
Ronnie DHorner, University of Cincinnati Medical Center, PO Box 670840; Cincinnati, OH 45267-0840Ronnie.Horner@uc.edu
John R. Feussner, Edward J. Kasarskis
Submitted March 01, 2005
We read the article by Weisskopf et al with interest. They concluded that military service is a risk factor for amyotrophic lateral sclerosis (ALS). [1] Although service during the first Gulf War was not included in the study, their view and that of the editorial [2] is that the elevated occurrence of ALS among Gulf War veterans reflects a general risk associated with military service. It also suggests that little can be learned from further inquiry into the Gulf War experience alone. [2] We believe that these conclusions are premature.
The validity of their findings is highly dependent on the nature of the cohort. Notably, the cohort was assembled from volunteers to study the risk of cancer, not the risk of a degenerative neurological disease associated with military service. As study volunteers, the participants were likely healthier than non-participants and, may yield an under-estimate of disease occurrence. Re-analysis of their Figure 1 data supports this concern. The rates for those with and without military service are less than the rates for not only a general male population but also for women of whom few would have served in the military (see Table). The exception is at the oldest ages where the rates are substantially higher which may be evidence of a survival bias in the cohort and another reason to question its validity for this study.
In our truly population-based study of Gulf War veterans, the incidence rate of ALS among the non-deployed was similar to that of a general population. [4,5] Moreover, from first principles of occupational epidemiology, the comparison group needs to be subjected to the same selection criteria as the exposed group. Those who qualify for military service are a highly selected population; hence, a better comparison group might be those with the least exposure: least number of years of service or no service during wartime. When these referents are used, the association disappears (Weisskopf’s Tables 2 and 3).
In addition, ignoring statistical power issues, Weisskopf et al find a point estimate indicative of “protection” against ALS among Marines; we found deployed Marines had an elevated risk of ALS while the non-deployed Marines had a rate lower than the non-deployed in other branches of service. [4] These findings argue against the strenuous physical exertion hypothesis suggested in the editorial. [2]
We are convinced that closing out further Gulf War research based on the Weisskopf et al findings would be premature and ill-advised. Because Gulf War veterans with ALS were relatively young, further study of their experiences may generate insights not only into ALS risk factors but also into who may be at heightened risk and potential interventions to minimize these risks.
Table
References
1. Weisskopf et al. Prospective study of military service and mortality from ALS. Neurology 2005; 64: 32-7.
2. Beghi E, Morrison KE. ALS and military service. Neurology 2005; 64: 6-7.
3. McGuire V, Longstreth WT Jr, Koepsell TD, van Belle G. Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology 1996; 47:571-3.
4. Horner RD, Kamins KG, Feussner JR et al. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 2003; 61: 742-9.
5. Coffman C, Horner RD, Grambow SC, Lindquist . Estimating the occurrence of amyotrophic lateral sclerosis among Gulf War (1990-1991) veterans using capture-recapture methodology. Neuroepidemiology 2005; 24: 141-150.
The validity of their findings is highly dependent on the nature of the cohort. Notably, the cohort was assembled from volunteers to study the risk of cancer, not the risk of a degenerative neurological disease associated with military service. As study volunteers, the participants were likely healthier than non-participants and, may yield an under-estimate of disease occurrence. Re-analysis of their Figure 1 data supports this concern. The rates for those with and without military service are less than the rates for not only a general male population but also for women of whom few would have served in the military (see Table). The exception is at the oldest ages where the rates are substantially higher which may be evidence of a survival bias in the cohort and another reason to question its validity for this study.
In our truly population-based study of Gulf War veterans, the incidence rate of ALS among the non-deployed was similar to that of a general population. [4,5] Moreover, from first principles of occupational epidemiology, the comparison group needs to be subjected to the same selection criteria as the exposed group. Those who qualify for military service are a highly selected population; hence, a better comparison group might be those with the least exposure: least number of years of service or no service during wartime. When these referents are used, the association disappears (Weisskopf’s Tables 2 and 3).
In addition, ignoring statistical power issues, Weisskopf et al find a point estimate indicative of “protection” against ALS among Marines; we found deployed Marines had an elevated risk of ALS while the non-deployed Marines had a rate lower than the non-deployed in other branches of service. [4] These findings argue against the strenuous physical exertion hypothesis suggested in the editorial. [2] We are convinced that closing out further Gulf War research based on the Weisskopf et al findings would be premature and ill-advised. Because Gulf War veterans with ALS were relatively young, further study of their experiences may generate insights not only into ALS risk factors but also into who may be at heightened risk and potential interventions to minimize these risks. Table
References
1. Weisskopf et al. Prospective study of military service and mortality from ALS. Neurology 2005; 64: 32-7.
2. Beghi E, Morrison KE. ALS and military service. Neurology 2005; 64: 6-7.
3. McGuire V, Longstreth WT Jr, Koepsell TD, van Belle G. Incidence of amyotrophic lateral sclerosis in three counties in western Washington state. Neurology 1996; 47:571-3.
4. Horner RD, Kamins KG, Feussner JR et al. Occurrence of amyotrophic lateral sclerosis among Gulf War veterans. Neurology 2003; 61: 742-9.
5. Coffman C, Horner RD, Grambow SC, Lindquist . Estimating the occurrence of amyotrophic lateral sclerosis among Gulf War (1990-1991) veterans using capture-recapture methodology. Neuroepidemiology 2005; 24: 141-150.