Considerations for Designing an Epidemiologic Study for Multiple Sclerosis and Other Neurologic Disorders in Pre and Post 9/11 Gulf War Veterans (2015)

Utilization reports of pre 9/11 veterans using the VA health system. Report based on ICD-9 codes for MS, migraine, PD, and malignant neoplasms of the brain.

Provides counts for each diagnosis.

Based on visits between October 1, 2001, and September 30, 2013.

Utilization reports of post 9/11 veterans using the VA health system. Report based on ICD-9 codes for MS, migraine, PD, malignant neoplasms of the brain.

Provides counts for each diagnosis.

Based on visits between October 1, 2001, and September 30, 2014.

Evaluated the risk of developing MS and other central nervous system demyelinating diseases (ODDs) in 1990-1991 Gulf War veterans.

Cases of MS and ODD were matched to a DOD database of all active-duty personnel.

All cases evaluated for service connection.

Survey data used to report outcomes related to headaches and migraines in veterans of the 1990-1991 Gulf War.

Self-reported responses were used to calculate weighted estimates of population rates for the conditions.

Studied cancer diagnoses in Gulf War era veterans.

Using files from the DMDC and linked with 28 state cancer registries and the VA cancer registry.

An incident cohort of MS and ODD was assembled from Gulf War era veterans (1990-2007).

Cases of MS and ODD were matched to a database of all active-duty personnel from DOD.

Phase 1: 16-page structured questionnaire sent to each of the 30,000 veterans.

Phase 2: telephone interviews on the nonrespondents.

Baseline cohort: A random sample of 256,400 service members of the 2.2 million total serving as of October 1, 2000.

Approximately 77,000 completed the baseline questionnaire; those with missing outcome data were excluded.

MS (ICD-9 340): deployed 1,040; nondeployed 1,089

Migraine (ICD-9 346): deployed 16,327; nondeployed 14,115

PD (IDC-9 332.0): deployed 403; nondeployed 487

Malignant neoplasm of the brain (ICD-9 191): deployed 342; nondeployed 332

MS (ICD-9 340): 1,529 deployed

Migraine (ICD-9 346): 58,045 deployed

PD (IDC-9 332.0): 322 deployed

Malignant neoplasm of the brain (ICD-9 191): 458 deployed

There are no data on the nondeployed

For 1990-1991 Gulf War veterans:

MS and ODD: 1,841 incident cases: 387 cases among the 696,118 deployed and 1,454 cases among the 1,786,215 nondeployed

RR for MS 0.69 (95% CI: 0.61-0.78)

Migraines: 16.5% of the deployed and 9.3% of the era veterans

Recurring headaches 32.6% of deployed and 14.9% of the era veterans

Combat deployed had statistically significantly higher adjusted odds of new-onset headache disorder than nondeployed (OR = 1.72, 95% CI 1.55-1.90 for men and OR = 1.84, 95% CI 1.55-2.18 for women).

Those deployed without combat did not have statistically significantly different adjusted odds of new onset headaches compared to the nondeployed (OR = 1.07, 95% CI 0.95-1.21 for men; OR = 0.96, 95% CI 0.80-1.14 for women).

Findings indicate that the prevalence of chronic daily headache is four to five times higher in OEF and OIF than the US population.

Chronic daily headache following concussion often resembles chronic migraine and is associated with onset of headaches within the first week after concussion.

Brain cancer: 278 in deployed and 410 in era Gulf War veterans.

The PIR, comparing Gulf War deployed and era veterans: 0.86% (95% CI: 0.73-1.01).

Limited to those veterans using VA health care services.

Captures approximately 46% of deployed, 36% of nondeployed.

Based solely on a single entry of an ICD code for the disease of interest.

Limited to those veterans using VA health care services.

Captures approximately 60% of deployed.

Based solely on a single entry of an ICD code for the disease of interest.

Strengths include prospective study design, use of incident MS cases within the entire 1990-1991 Gulf War active-duty population; adequate power; and follow-up time to detect significant changes in MS risk in deployed troops.

Limitations of the study: the possibility of missing some MS cases that may have had their first symptom outside the active-duty period and 7 years thereafter.

A strength is the large number of subjects who were randomly selected.

Limitations of this study include exposure and outcomes data are based on the selfreported data that may be subject to recall bias. The differential participation rate between Gulf War veterans and era veterans could contribute to a biased prevalence estimate.

Strengths include the ability to estimate headache prevalence at baseline and new onset headache disorders at followup.

Limitations include long postdeployment time frame; possible combat exposure misclassification; types of headaches not distinguished; inability to assess the lifetime prevalence of headache disorders at follow-up.

Strengths include associating cancer incidence outcomes with the entire Gulf War veteran population; included a large and representative sample of era veterans. Outcome assessment based on cancer registry data rather than mortality, hospitalization, or self-reports.

Limitations include lack of data from all 50 states and use of different registries may have resulted in slightly different match rates.