The Gulf War Era Cohort and Biorepository: A Longitudinal Research Resource of Veterans of the 1990-1991 Gulf War Era.

The US Department of Veterans Affairs (VA) Gulf War Era Cohort and Biorepository (GWECB) is a nationally representative longitudinal cohort of US veterans who served during the 1990-1991 Gulf War era. The GWECB combines survey data, such as demographic, health behavior, and environmental exposure data; medical records; and a linked biorepository of blood specimens that can support a broad range of future research regarding health concerns unique to veterans of this era. To build this resource, the VA Cooperative Studies Program initiated a pilot study (2014-2016) to establish the GWECB and evaluate the processes required to build and maintain the resource. Participants (n = 1,275) consented to future sharing of their data and biospecimens for research purposes. Here we describe the pilot study, including recruitment and enrollment procedures, data collection and management, quality control, and challenges experienced. The GWECB data available to investigators under approved sharing mechanisms and the procedures for accessing them are extensively detailed. The study's consenting documents and a website link for the research survey are provided. Our hope is that new research drawing on the GWECB data and biospecimens will result in effective treatments and improved approaches to address the health concerns of Gulf War-era veterans.

Structured Approach for Evaluating Strategies for Cancer Ascertainment Using Large-Scale Electronic Health Record Data.

PURPOSE: Cancer ascertainment using large-scale electronic health records is a challenge. Our aim was to propose and apply a structured approach for evaluating multiple candidate approaches for cancer ascertainment using colorectal cancer (CRC) ascertainment within the US Department of Veterans Affairs (VA) as a use case. METHODS: The proposed approach for evaluating cancer ascertainment strategies includes assessment of individual strategy performance, comparison of agreement across strategies, and review of discordant diagnoses. We applied this approach to compare three strategies for CRC ascertainment within the VA: administrative claims data consisting of International Classification of Diseases, Ninth Revision (ICD9) diagnosis codes; the VA Central Cancer Registry (VACCR); and the newly accessible Oncology Domain, consisting of cases abstracted by local cancer registrars. The study sample consisted of 1,839,043 veterans with index colonoscopy performed from 1999 to 2014. Strategy-specific performance was estimated based on manual record review of 100 candidate CRC cases and 100 colonoscopy controls. Strategies were further compared using Cohen's κ and focused review of discordant CRC diagnoses. RESULTS: A total of 92,197 individuals met at least one CRC definition. All three strategies had high sensitivity and specificity for incident CRC. However, the ICD9-based strategy demonstrated poor positive predictive value (58%). VACCR and Oncology Domain had almost perfect agreement with each other (κ, 0.87) but only moderate agreement with ICD9-based diagnoses (κ, 0.51 and 0.57, respectively). Among discordant cases reviewed, 15% of ICD9-positive but VACCR- or Oncology Domain-negative cases had incident CRC. CONCLUSION: Evaluating novel strategies for identifying cancer requires a structured approach, including validation against manual record review, agreement among candidate strategies, and focused review of discordant findings. Without careful assessment of ascertainment methods, analyses may be subject to bias and limited in clinical impact.

The association of race with timeliness of care and survival among Veterans Affairs health care system patients with late-stage non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer is the leading cause of cancer-related mortality in the United States. Patients with late-stage disease (stage 3/4) have five-year survival rates of 2%-15%. Care quality may be measured as time to receiving recommended care and, ultimately, survival. This study examined the association between race and receipt of timely non-small cell lung cancer care and survival among Veterans Affairs health care system patients. METHODS: Data were from the External Peer Review Program, a nationwide Veterans Affairs quality-monitoring program. We included Caucasian or African American patients with pathologically confirmed late-stage non-small cell lung cancer in 2006 and 2007. We examined three quality measures: time from diagnosis to (1) treatment initiation, (2) palliative care or hospice referral, and (3) death. Unadjusted analyses used log-rank and Wilcoxon tests. Adjusted analyses used Cox proportional hazard models. RESULTS: After controlling for patient and disease characteristics using Cox regression, there were no racial differences in time to initiation of treatment (72 days for African American versus 65 days for Caucasian patients, hazard ratio 1.04, P = 0.80) or palliative care or hospice referral (129 days versus 116 days, hazard ratio 1.10, P = 0.34). However, the adjusted model found longer survival for African American patients than for Caucasian patients (133 days versus 117 days, hazard ratio 0.31, P < 0.01). CONCLUSION: For process measures of care quality (eg, time to initiation of treatment and referral to supportive care) the Veterans Affairs health care system provides racially equitable care. The small racial difference in survival time of approximately 2 weeks is not clinically meaningful. Future work should validate this possible trend prospectively, with longer periods of follow-up, in other veteran groups.

An assessment of survey measures used across key epidemiologic studies of United States Gulf War I Era veterans.

Over the past two decades, 12 large epidemiologic studies and 2 registries have focused on U.S. veterans of the 1990-1991 Gulf War Era. We conducted a review of these studies' research tools to identify existing gaps and overlaps of efforts to date, and to advance development of the next generation of Gulf War Era survey tools. Overall, we found that many of the studies used similar instruments. Questions regarding exposures were more similar across studies than other domains, while neurocognitive and psychological tools were the most variable. Many studies focused on self-reported survey results, with a range of validation practices. However, physical exams, biomedical assessments, and specimen storage were not common. This review suggests that while research may be able to pool data from past surveys, future surveys need to consider how their design can yield data comparable with previous surveys. Additionally, data that incorporate recent technologies in specimen and genetic analyses would greatly enhance such survey data. When combined with existing data on deployment-related exposures and post-deployment health conditions, longitudinal follow-up of existing studies within this collaborative framework could represent an important step toward improving the health of veterans.

Method Issues in Epidemiological Studies of Medically Unexplained Symptom-based Conditions in Veterans.

Symptom-based conditions such as chronic fatigue syndrome (CFS) and medically unexplained multi-symptom illness (MSI) are fairly common in the general population and are also important veteran's health concerns due to their higher frequency among U.S. veterans who served during the 1990-1991 Gulf War. CFS, MSI, and other symptom-based conditions are often associated with considerable morbidity due to fatigue, chronic pain, neurologic symptoms, and other symptoms that can impair the quality of life. This article discusses several important issues of methodology that arise in population studies of CFS and MSI. These include the exclusion criteria that have been used in population studies to define CFS-like illness and unexplained MSI, the potential for false positive and false negative assessments of illness status, the potential for sex differences, and the poorly understood natural history of these symptom-based conditions across the life span. As an empirical example of these methodology issues, we examined existing data from a 2005 follow-up survey. We found that 64.9% (762 of 1,175) of female Gulf War veterans and 53.4% (2,530 of 4,739) of male Gulf War veterans had 1 or more exclusionary medical conditions. The prevalence among veterans with one or more exclusionary medical conditions increased markedly by age among females and those with a low income.

Cancer incidence among patients of the U.S. Veterans Affairs Health Care System.

OBJECTIVE: Approximately 40,000 incident cancer cases are reported in the Veterans Affairs Central Cancer Registry (VACCR) annually (approximately 3% of U.S. cancer cases). Our objective was to provide the first comprehensive description of cancer incidence as reported in VACCR. METHODS: Data were obtained from VACCR for incident cancers diagnosed in VA. Analyses focused on 2007 data. Cancer incidence among VA patients was compared to the general U.S. cancer population. RESULTS: In 2007, 97.5% of VA cancers were diagnosed among men. Approximately 78.5% of newly diagnosed patients were White, 19.0% Black, and 2.5% were another race. Median age at diagnosis was 66 years. The geographic distribution of cancer patients in VA aligns that of VA users. The most commonly diagnosed cancers were similar between VA and the U.S. male cancer population. The five most frequently diagnosed cancers among VA cancer patients were: prostate (31.8%), lung/bronchus (18.8%), colon/rectum (8.6%), urinary bladder (3.6%), and skin melanomas (3.4%). VA patients were diagnosed at an earlier stage of disease for the three most commonly diagnosed cancers--lung/bronchus, colon/rectum, and prostate--compared to the U.S. male cancer population. CONCLUSIONS: Registry data indicate that incident cancers in VA in 2007 approximately mirrored those observed among U.S. men.

The cost effectiveness of radiofrequency ablation for Barrett's esophagus.

BACKGROUND & AIMS: Radiofrequency ablation (RFA) reduces the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD), but its effects in patients without dysplasia are debatable. We analyzed the effectiveness and cost effectiveness of RFA for the management of BE. METHODS: We constructed a decision analytic Markov model. We conducted separate analyses of hypothetical cohorts of patients with BE with dysplasia (HGD or low-grade [LGD]) and without dysplasia. In the analysis of the group with HGD, we compared results of initial RFA with endoscopic surveillance with surgery when cancer was detected. In analyzing the group with LGD or no dysplasia, we compared 3 strategies: endoscopic surveillance with surgery when cancer was detected (S1), endoscopic surveillance with RFA when HGD was detected (S2), and initial RFA followed by endoscopic surveillance (S3). RESULTS: Among patients with HGD, initial RFA was more effective and less costly than endoscopic surveillance. Among patients with LGD, when S3 was compared with S2, the incremental cost-effectiveness ratio was $18,231/quality-adjusted life-year, assuming an annual rate of progression rate from LGD to EAC of 0.5%/year. For patients without dysplasia, S2 was more effective and less costly than S1. In a comparison of S3 with S2, the incremental cost-effectiveness ratios were $205,500, $124,796, and $118,338/quality-adjusted life-year using annual rates of progression of no dysplasia to EAC of 0.12%, 0.33%, or 0.5% per year, respectively. CONCLUSIONS: By using updated data, initial RFA might not be cost effective for patients with BE without dysplasia, within the range of plausible rates of progression of BE to EAC, and be prohibitively expensive, from a policy perspective. RFA might be cost effective for confirmed and stable LGD. Initial RFA is more effective and less costly than endoscopic surveillance in HGD.

Improving colorectal cancer screening and care in the Veterans Affairs Healthcare system.

The Veterans Health Administration (VHA) has recently launched several nationwide initiatives to improve the quality of its colorectal cancer (CRC) screening and care. The timeliness of follow-up diagnostic tests in patients who have positive noncolonoscopic CRC screening tests is one of the target areas of these initiatives. Multiple aspects of colon cancer care are being monitored, and the degree of adherence to accepted quality measures is being assessed. The purpose of this review is to describe the background leading to these initiatives and their expected impact on CRC screening and management in the VHA.

Comorbidity, age, race and stage at diagnosis in colorectal cancer: a retrospective, parallel analysis of two health systems.

BACKGROUND: Stage at diagnosis plays a significant role in colorectal cancer (CRC) survival. Understanding which factors contribute to a more advanced stage at diagnosis is vital to improving overall survival. Comorbidity, race, and age are known to impact receipt of cancer therapy and survival, but the relationship of these factors to stage at diagnosis of CRC is less clear. The objective of this study is to investigate how comorbidity, race and age influence stage of CRC diagnosis. METHODS: Two distinct healthcare populations in the United States (US) were retrospectively studied. Using the Cancer Care Outcomes Research and Surveillance Consortium database, we identified CRC patients treated at 15 Veterans Administration (VA) hospitals from 2003-2007. We assessed metastatic CRC patients treated from 2003-2006 at 10 non-VA, fee-for-service (FFS) practices. Stage at diagnosis was dichotomized (non-metastatic, metastatic). Race was dichotomized (white, non-white). Charlson comorbidity index and age at diagnosis were calculated. Associations between stage, comorbidity, race, and age were determined by logistic regression. RESULTS: 342 VA and 340 FFS patients were included. Populations differed by the proportion of patients with metastatic CRC at diagnosis (VA 27% and FFS 77%) reflecting differences in eligibility criteria for inclusion. VA patients were mean (standard deviation; SD) age 67 (11), Charlson index 2.0 (1.0), and were 63% white. FFS patients were mean age 61 (13), Charlson index 1.6 (1.0), and were 73% white. In the VA cohort, higher comorbidity was associated with earlier stage at diagnosis after adjusting for age and race (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.58-1.00; p = 0.045); no such significant relationship was identified in the FFS cohort (OR 1.09, 95% CI 0.82-1.44; p = 0.57). In both cohorts, no association was found between stage at diagnosis and either age or race. CONCLUSION: Higher comorbidity may lead to earlier stage of CRC diagnosis. Multiple factors, perhaps including increased interactions with the healthcare system due to comorbidity, might contribute to this finding. Such increased interactions are seen among patients within a healthcare system like the VA system in the US versus sporadic interactions which may be seen with FFS healthcare.

Predicting poor outcome from acute upper gastrointestinal hemorrhage.

BACKGROUND: Uncertainty about the outcome of acute upper gastrointestinal bleeding often results in a longer-than-necessary hospital stay. METHODS: We derived and internally validated clinical prediction rules (CPRs) to predict outcome from upper gastrointestinal bleeding. This multisite, prospective cohort study involved consecutive patients admitted for acute upper gastrointestinal bleeding. Multivariate logistic regression was used to derive CPRs on two thirds of the cohort (derivation set) that predicted bleeding-specific outcomes (rebleeding, need for urgent surgery, or hospital death [poor outcome 1]) and bleeding-specific outcomes plus new or worsening comorbidity (poor outcome 2). Both CPRs were then tested on the remaining third of the cohort (validation set). RESULTS: A total of 391 individuals (99% men; mean age, 63.4 years) were enrolled, of which 4.6% rebled and 3.1% died. Independent predictors of poor outcome 1 were APACHE (Acute Physiology and Chronic Health Evaluation) II score of 11 or greater, esophageal varices, and stigmata of recent hemorrhage. Predictors of poor outcome 2 were these 3 factors plus unstable comorbidity on admission. Of patients with no risk factors, only 1 (1.1%) of 92 experienced poor outcome 1 and only 6 (6.2%) of 97 experienced poor outcome 2. Risks in the validation set were comparable. The CPRs identified 37.8% and 32.2% of patients in the derivation and validation sets, respectively, who were eligible for a shorter hospital stay. CONCLUSIONS: Patients admitted with acute upper gastrointestinal bleeding were unlikely to have a poor outcome if these risk factors were absent. These CPRs might make hospital management more efficient by identifying low-risk patients for whom early hospital discharge is possible.

Do patient preferences influence decisions on treatment for patients with steroid-refractory ulcerative colitis?

BACKGROUND & AIMS: Patients with steroid-refractory ulcerative colitis face a difficult treatment decision between colectomy and therapy with infliximab or cyclosporine. The aim of this study was to understand how individual patient preferences for the various treatment outcomes influence the optimal treatment decision for a given patient. METHODS: A Markov model was used to simulate treatment with total colectomy with an ileo pouch-anal anastomosis (TC/IPAA), cyclosporine (CSA), infliximab (INFLX), and infliximab followed by cyclosporine for treatment failures (INFLX-->CSA). Utility weights for treatment outcomes were elicited from 48 patients using both time trade-off and visual rating scale methods. Preference sets were applied to the model to identify the therapy that maximized quality-adjusted life years (QALYs) for each patient. Sensitivity analyses were performed to assess model robustness. RESULTS: Optimal treatment was highly variable among patients (INFLX-->CSA = 42%, 20/48; TC/IPAA = 37%, 18/48; CSA = 21%, 10/48; INFLX = 0%, 0/48). However, when average preference weights from our sample were applied to the model, medical treatments were superior to TC (CSA = .26 QALYs gained vs TC/IPAA; INFLX-->CSA = .25 QALYs gained vs TC/IPAA). CONCLUSIONS: Patient preferences have a clear impact on the optimal treatment for steroid-refractory ulcerative colitis. Although averaged preferences support the use of medical interventions, a third of individual patients may benefit most from proceeding directly to colectomy. Failure to fully assess individual preferences may result in suboptimal treatment for these patients.