HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Correspondence to:

ARTICLES: M. G. Weisskopf, E. J. O’Reilly, M. L. McCullough, E. E. Calle, M. J. Thun, M. Cudkowicz, and A. Ascherio Prospective study of military service and mortality from ALS Neurology 2005; 64: 32-37 [Abstract] [Full text] [PDF]

Correspondence: Submit a response to this article

Correspondence published:

Reply to Horner et al

Alberto Ascherio, Marc G. Weisskopf, Eilis J O'Reilly, Marjie L McCullough, Eugenia E Calle, Merit Cudckowicz, Michael J Thun   (1 March 2005)

Prospective study of military service and mortality from ALS

Ronnie D Horner, John R. Feussner, Edward J. Kasarskis   (1 March 2005)

Reply to Horner et al 1 March 2005
Alberto Ascherio, Harvard School of Public Health 665 Huntington Ave, Boston, MA 02115, Marc G. Weisskopf, Eilis J O'Reilly, Marjie L McCullough, Eugenia E Calle, Merit Cudckowicz, Michael J Thun Send Correspondence to journal: Re: Reply to Horner et al aascheri{at}hsph.harvard.edu Alberto Ascherio, et al.	We do not believe that the association between military service and increased ALS mortality that we observed in our study [1] can be attributed to an artifact of self-selection of healthy volunteers into the study as proposed by Horner et al. This is because the age-specific death rates from ALS were similar in our cohort to those in the U.S. [7] (Table). Furthermore, readers may be confused that the heading of Horner's table refers to ALS mortality rates, but the data shown from McGuire et al [3] refer to ALS incidence rates, as indicated in the footnote. Any comparison between the incidence rates of ALS among men in Washington State [3], and the death rates from ALS in either our study [1] or for the U.S. general population [7] should be interpreted taking into account that the mortality rates reflect the incidence of the disease at younger ages and that there is some under-reporting of ALS in death certificates. Furthermore, the decline in ALS incidence in the oldest age group, as discussed by McGuire et al may be due to under ascertainment in older people due to greater difficulty in diagnosing the disease and shorter survival of elderly patients. Horner et al also wrote that those who qualify for the military are a “highly selected population”, and suggest that this selection may explain the higher ALS mortality rate among the military as compared with those who did not serve. Since men who served in the military (over two thirds of men in our cohort) are likely to be healthier than those who did not serve, this statement is at odds with the hypothesis of Horner et al that selection of healthy volunteers in the study resulted in lower ALS rates. Concerning the lack of increased risk among men who served in the Marine Corps, the number of men in this category is too small for any meaningful inference, as we have stated in our paper and is further indicated by the wide confidence intervals. We agree with Horner et al that the investigation of ALS among Gulf War veterans is important and further research is needed. Table References 1. Weisskopf, PhD, E. J. O’Reilly, MSc, M. L. McCullough, ScD, E. E. Calle, PhD, M. J. Thun, MD, M. Cudkowicz, MD and A. Ascherio, MD. Neurology 2005; 64: 32-37 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. 6. Weisskopf MG, McCullough ML, Calle EE, Thun MJ, Cudkowicz M, Ascherio A. Prospective study of cigarette smoking and amyotrophic lateral sclerosis. Am J Epidemiol 2004; 160:26-33. 7. National Center for Health Statistics. Compressed mortality file for 1989-1998 on CDC Wonder on-line database (http://wonder.cdc.gov/mortSQL.html).
Prospective study of military service and mortality from ALS 1 March 2005
Ronnie D Horner, University of Cincinnati Medical Center PO Box 670840; Cincinnati, OH 45267-0840, John R. Feussner, Edward J. Kasarskis Send Correspondence to journal: Re: Prospective study of military service and mortality from ALS Ronnie.Horner{at}uc.edu Ronnie D Horner, et al.	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.