Kyung Y. Lee

Illnesses among United States veterans of the Gulf War: a population-based survey of 30,000 veterans.

Despite numerous studies on veterans of the 1990 to 1991 Gulf War, the fundamental questions of how healthy they are and how their health compares with that of their military peers who were not deployed to the Gulf have not been fully answered. We conducted a health survey in which the health outcomes of a population-based sample of 15,000 Gulf veterans representing various military branches and unit components (regular, reserve, National Guard) were compared with those of 15,000 non-Gulf veterans who were randomly sampled to mirror the number in the same military strata in the Gulf veteran group. In comparison with their peers, Gulf veterans had a higher prevalence of functional impairment, health care utilization, symptoms, and medical conditions and a higher rate of low general health perceptions. A longitudinal follow-up of the health of these veterans will be needed to detect changes in health status and to detect diseases with a long latency period.

U.S. Food and Drug Administration Approval Summary: Brentuximab Vedotin for the Treatment of Relapsed Hodgkin Lymphoma or Relapsed Systemic Anaplastic Large-Cell Lymphoma

The U.S. Food and Drug Administration (FDA) describes the accelerated approval of brentuximab vedotin for patients with relapsed Hodgkin lymphoma and relapsed systemic anaplastic large-cell lymphoma (sALCL). FDA analyzed the results of two single-arm trials, enrolling 102 patients with Hodgkin lymphoma and 58 patients with sALCL. Both trials had primary endpoints of objective response rate (ORR) and key secondary endpoints of response duration and complete response (CR) rate. For patients with Hodgkin lymphoma, ORR was 73% (95% CI, 65–83%); median response duration was 6.7 months, and CR was 32% (95% CI, 23–42%). For patients with sALCL, ORR was 86% (95% CI, 77–95%), median response duration was 12.6 months, and CR was 57% (95% CI, 44–70%). The most common adverse reactions were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory infection, diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting. FDA granted accelerated approval of brentuximab vedotin for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplantation (ASCT) or after failure of at least two prior multiagent chemotherapy regimens in patients who are not ASCT candidates, and for the treatment of patients with sALCL after failure of at least one prior multiagent chemotherapy regimen. Clin Cancer Res; 18(21); 5845–9. ©2012 AACR.

Evidence for a Deployment-Related Gulf War Syndrome by Factor Analysis

Abstract To identify a syndrome unique to Gulf War veterans, the authors applied an exploratory factor analysis to the 47-symptom correlation matrix of 10,423 Gulf War and 8,960 non-Gulf War veteran respondents. A separate factor analysis was performed for Gulf War and non-Gulf War veterans, and the resulting 6 factors were compared between the 2 groups. Five of the factors were very similar in the 2 groups; however, 1 of the factors in the Gulf War group, but not the non-Gulf War group, contained a cluster of symptoms consistent with neurological impairment. Symptoms specific to this factor were blurred vision, loss of balance/dizziness, tremors/shaking, and speech difficulty. The Gulf War veterans who had all of the aforementioned symptoms (n = 277) also reported exposures to several putative risk factors at a rate 3 or more times higher than other Gulf War veterans. This finding suggests a possible syndrome related to Gulf War deployment, which requires objective supporting clinical evidence.

Continuing Reassessment of the Risks of Erythropoiesis-Stimulating Agents in Patients with Cancer

Purpose: Erythropoiesis-stimulating agents (ESA) are approved for the treatment of anemia in patients with nonmyeloid malignancies whose anemia is due to the effect of concomitantly administered chemotherapy. Since the 1993 approval of epoetin alfa in patients with cancer, the risk of thrombovascular events, decreased survival, and poorer tumor control have been increasingly recognized. The risks of ESAs in patients with cancer and the design of trials to assess these risks have been the topic of discussion at two Oncologic Drugs Advisory Committees in 2004 and 2007. Experimental Design: Evaluation of randomized clinical trials comparing use of ESAs to transfusion support alone in patients with active cancer. Results: Six studies (Breast Cancer Erythropoeitin Survival Trial, Evaluation of NeoRecormon on outcome in Head And Neck Cancer in Europe, Danish Head and Neck Cancer, Lymphoid Malignancy, CAN-20, and Anemia of Cancer) investigating ESAs in oncology patients showed decreased survival, decreased duration of locoregional tumor control, and/or increased risk of thrombovascular events. In these six studies, ESA dosing was targeted to achieve and maintain hemoglobin values in excess of current recommendations, and in three of the six studies, ESAs were administered to patients not receiving chemotherapy. Conclusions: ESAs increase the risk of thrombovascular events and result in decreased survival and poorer tumor control when administered to achieve hemoglobin levels of ≥12 g/dL in patients with nonmyeloid malignancies. No completed or ongoing randomized, controlled trial has addressed safety issues of ESAs in patients with chemotherapy-associated anemia using currently approved dosing regimens in an epidermal tumor type. Additional studies are needed to better characterize these risks.

Prevalence of gynecologic cancers among female Vietnam veterans.

The possibility of a gender-specific health problem associated with the Vietnam War has been a concern since the war. We targeted 4140 female Vietnam veterans and 4140 veteran controls to complete a structured telephone interview that included questions regarding any history of gynecologic cancer. As a measure of association between the risk of cancer and military service in Vietnam, odds ratios and 95% confidence intervals were calculated using multiple logistic regression models that yielded estimates of potential cofounders. Although 8% of Vietnam veterans and 7.1% of non-Vietnam veterans reported a history of gynecologic cancers, namely, breast, ovary, uterus, or cervix, the difference was not statistically significant either for the individual site or for the gynecologic cancers as a group. Female Vietnam veterans have not experienced a higher prevalence of gynecologic cancer in the 30 years since the conflict.

Missing Data in Biologic Oncology Products

The intent-to-treat principle requires analyses according to the treatment groups to which patients were randomized and that patients be followed to the occurrence of the endpoint or the end of study. This provides unbiased comparisons with valid p values. For many trials the limitations of the data will not be known until the data are analyzed. In this article, the loss-to-follow-up with respect to the intent-to-treat principle on the most important efficacy endpoints was evaluated for clinical trials of anticancer biologic products submitted to the FDA from August 2005 to October 2008. We provide recommendations in light of the results.

Pregnancy outcomes among U.S. Gulf War veterans: A population-based survey of 30,000 veterans

Anecdotal reports by veterans of the Persian Gulf War of 1990 have included concern over negative reproductive outcomes, including spontaneous abortions and birth defects. Two previous birth records studies failed to findevidence of an increased risk of defects, but a large population-based study of Gulf War veterans in the United Kingdom did suggest more miscarriages than in a control population. The present health survey examined reproductive outcomes in 15,000 Gulf War veterans and a comparable number of non-Gulf War veterans. The final study group, representing a 70% rate of response to a 16-page health survey, included 11,44] Gulf War veterans and 9476 control subjects. Nearly 30% of survey participants (6043) had index pregnancies. Male Gulf veterans reported more miscarriages and stillbirths than male non-Gulf War veterans, but the difference was statistically significant only for miscarriages. Female Gulf War veterans reported the same effects, but neither was significant. Live-born infants of male Gulf War veterans reportedly had likely birth defects nearly twice as often as control infants (adjusted odds ratio [OR], 1.94; 95% confidence interval [CI], 1.37-2.74), Female Gulf War veterans were nearly 3-fold likelier than control subjects to have a child with a likely birth defect (adjusted OR, 2.97; 95% CI, 1.47-5.99). Adjusted ORs for moderate to severe birth defects were 1.78 for males and 2.80 for females. A small excess of chromosomal defects was reported by Gulf War veterans. This large-scale population-based survey suggests that both male and female Gulf War veterans report significantly higher rates of birth defects in their live-born infants than do military control subjects. In addition, male Gulf War veterans reported significantly more miscarriages.