AN INVESTIGATION OF THE RELIABILITY AND VALIDITY OF THE CENTER FOR EPIDEMIOLOGIC STUDIES DEPRESSION SCALE IN THREE ETHNIC GROUPS

Epidemiologic studies of mental disorder have called attention to the need for identifying untreated cases and to the inadequacies of the instruments available for this purpose. Accurate case ascertainment devices are the basis of sound epidemiology. Without these, neither case classification nor analytic studies of risk factors is possible.^ The purpose of this research was to examine the reliability and validity of an instrument designed to measure depressive symptoms in community populations--the Center for Epidemiologic Studies Depression Scale (CES-D Scale). Two particular foci of the study were whether or not the scale had the same statistical structure across three ethnic groups and whether or not the magnitude and pattern of rates of symptoms for these groups were affected by one source of response error, that due to response tendencies. The effects of age and education on the pattern and magnitude of rates also were examined. In addition, the reliability and validity of the measures of response tendencies were assessed.^ The study population consisted of residents of Alameda County, California. A stratified sample of approximately 700 whites, blacks and Mexican-Americans was interviewed in the summer and fall of 1978.^ The results of the analysis indicated that the scale was reliable and measured a similar content domain across the three ethnic groups. The unadjusted sex- and ethnic-specific rates of depressive symptoms showed an ethnic pattern for both sexes: rates for whites were lowest, those for Mexican-Americans were highest, and those for blacks were intermediate. Measures of response tendencies--need for social approval, trait desirability, and acquiescence--affected the magnitude of the rates for most comparisons. Likewise, the pattern of rates changed somewhat from that originally observed. The one fairly consistent observation was that rates for Mexican-American women were higher than those for the other two female subgroups in most of the comparisons. These results must be considered in the context of the reliability and validity assessment of the measures of response tendencies which indicated the tenuousness of these measures.^ Age affected the ethnic pattern of rates for men in an inconsistent way; for women, Mexican-Americans continued to have higher rates than whites or blacks in all age categories. Education affected the magnitude of rates for women but not for men. For both men and women, Mexican-Americans had higher rates in all educational strata. Rates for women showed an inverse association with education while those for men did not. ^

Parental substance abuse as a risk factor for physical child abuse and neglect: A systematic review of the literature

Case control and retrospective studies have identified parental substance abuse as a risk factor for physical child abuse and neglect (Dore, Doris, & Wright, 1995, May; S. R. Dube et al., 2001; Guterman & Lee, 2005, May; Walsh, MacMillan, & Jamieson, 2003). The purpose of this paper is to present the findings of a systematic review of prospective studies from 1975 through 2005 that include parental substance abuse as a risk factor for physical child abuse or neglect. Characteristics of each study such as the research question, sample information, data collection methods and results, including the parent assessed and definitions of substance abuse and physical child abuse and neglect, are discussed. Five studies were identified that met the search criteria. Four of five studies found that parental substance abuse was a significant variable in predicting physical child abuse and neglect.^

Incident hypertension among pre-hypertensive adolescents: Evaluation of pre-hypertension as an independent risk factor among secondary school students in the Houston area

Cardiovascular disease has been the leading cause of death in the United States for over fifty years. While multiple risk factors for cardiovascular disease have been identified, hypertension is one of the most commonly recognized and treatable. Recent studies indicate that the prevalence of hypertension among children and adolescents is between 3-5%, much higher than originally estimated and likely rising due to the epidemic of obesity in the U.S. In 2004, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents published new guidelines for the diagnosis and treatment of hypertension in this population. Included in these recommendations was the creation of a new diagnosis, pre-hypertension, aimed at identifying children at-risk for hypertension to provide early lifestyle interventions in an effort to prevent its ultimate development. In order to determine the risk associated with pre-hypertension for the development of incident HTN, a secondary analysis of a repeated cross-sectional study measuring blood pressure in Houston area adolescents from 2000 to 2007 was performed. Of 1006 students participating in the blood pressure screening on more than one occasion not diagnosed with hypertension at initial encounter, eleven were later found to have hypertension providing an overall incident rate of 0.5% per year. Incidence rates were higher among overweight adolescents–1.9% per year [IRR 8.6 (1.97, 51.63)]; students “at-risk for hypertension” (pre-hypertensive or initial blood pressure in the hypertensive range but falling on subsequent measures)–1.4% per year [IRR 4.77 (1.21, 19.78)]; and those with blood pressure ≥90th percentile on three occasions–6.6% per year [IRR 21.87 (3.40, 112.40)]. Students with pre-hypertension as currently defined by the Task Force did have an increased rate of hypertension (1.1% per year) but it did not reach statistical significance [IRR 2.44 (0.42, 10.18)]. Further research is needed to determine the morbidity and mortality associated with pre-hypertension in this age group as well as the effectiveness of various interventions for preventing the development of hypertensive disease among these at-risk individuals. ^

Exploring race/ethnicity as a risk factor for mortality in newborns following congenital heart surgery at a center of excellence

The purpose of this study was to determine if race/ethnicity was a significant risk factor for hospital mortality in children following congenital heart surgery in a contemporary sample of newborns with congenital heart disease. Unlike previous studies that utilized administrative databases, this study utilized clinical data collected at the point of care to examine racial/ethnic outcome differences in the context of the patients' clinical condition and their overall perioperative experience. A retrospective cohort design was used. The study sample consisted of 316 newborns (<31 days of age) who underwent congenital heart surgery between January 2007 through December 2009. A multivariate logistic regression model was used to determine the impact of race/ethnicity, insurance status, presence of a spatial anomaly, prenatal diagnosis, postoperative sepsis, cardiac arrest, respiratory failure, unplanned reoperation, and total length of stay in the intensive care unit on outcomes following congenital heart surgery in newborns. The study findings showed that the strongest predictors of hospital mortality following congenital heart surgery in this cohort were postoperative cardiac arrest, postoperative respiratory failure, having a spatial anomaly, and total ICU LOS. Race/ethnicity and insurance status were not significant risk factors. The institution where this study was conducted is designated as a center of excellence for congenital heart disease. These centers have state-of-the-art facilities, extensive experience in caring for children with congenital heart disease, and superior outcomes. This study suggests that optimal care delivery for newborns requiring congenital heart surgery at a center of excellence portends exceptional outcomes and this benefit is conferred upon the entire patient population despite the race/ethnicity of the patients. From a public health and health services view, this study also contributes to the overall body of knowledge on racial/ethnic disparities in children with congenital heart defects and puts forward the possibility of a relationship between quality of care and racial/ethnic disparities. Further study is required to examine the impact of race/ethnicity on the long-term outcomes of these children as they encounter the disparate components of the health care delivery system. There is also opportunity to study the role of race/ethnicity on the hospital morbidity in these patients considering current expectations for hospital survival are very high, and much of the current focus for quality improvement rests in minimizing the development of patient morbidities.^

Is obesity a possible risk factor for Clostridium difficile infection

Aims: Obesity is a state of chronic inflammation characterized by depressed Th2 immune response. Animal studies have shown decreased IgA levels in obese rats and Leptin an adipose cell origin cytokine have been shown to enhance the activity of Clostridium difficile Toxin A. Hence we hypothesized that obesity is a risk factor for C. difficile infection (CDI) ^ Methods: 33 cases of CDI and 131 controls matched by age and HORNS index were identified from an IRB approved observational study at St. Luke's Episcopal Hospital in Houston. Variables like age, gender, height, weight, chronic antibiotic use, proton pump inhibitor use, diabetes mellitus, myocardial infarction, inflammatory bowel disease, diverticulitis, transfer from nursing home, hospital or home, nasogastric tube use and use of hemodialysis were provided in the dataset. Height and weight of the patient were used to calculate the BMI, based on which the study subjects were classified as obese and non-obese. Using STATA these variables were analyzed using test, chi square test followed by conditional logistic regression. ^ Results: On univariate analysis and conditional logistic regression, no significant increase in risk was associated with obesity (OR: 1.24; 95% CI: 0.46 - 3.36; p = 0.67) or BMI (OR: 0.98; CI: 0.92 - 1.04; p = 0.92). Hence, we cannot reject our hypothesis and conclude that "obesity is a risk factor associated with higher incidence of CDI in hospitalized patients. On univariate analysis using hemodialysis, nursing home transfer, home transfer, PPI and chronic antibiotics were found to be significantly different (p<0.05) in the cases and controls. On conditional logistic regression home (OR: 3.4; 95% CI: 1.15 - 9.61) and hemodialysis (OR: 4.1; 95% CI: 1.14 - 15.57) were found to be significantly different (p<0.05) between the case and control groups. ^ Conclusion: Our results show that obesity is not a significant risk factor for CDI. Our sample size was small and hence this may need conformation with a larger study. Patients transferred from home to the hospital and patients on hemodialysis had significantly higher incidence of CDI.^

Human TOB, an antiproliferative transcription factor, is a poly(A)-binding protein-dependent positive regulator of cytoplasmic mRNA deadenylation.

In mammalian cells, mRNA decay begins with deadenylation, which involves two consecutive phases mediated by the PAN2-PAN3 and the CCR4-CAF1 complexes, respectively. The regulation of the critical deadenylation step and its relationship with RNA-processing bodies (P-bodies), which are thought to be a site where poly(A)-shortened mRNAs get degraded, are poorly understood. Using the Tet-Off transcriptional pulsing approach to investigate mRNA decay in mouse NIH 3T3 fibroblasts, we found that TOB, an antiproliferative transcription factor, enhances mRNA deadenylation in vivo. Results from glutathione S-transferase pull-down and coimmunoprecipitation experiments indicate that TOB can simultaneously interact with the poly(A) nuclease complex CCR4-CAF1 and the cytoplasmic poly(A)-binding protein, PABPC1. Combining these findings with those from mutagenesis studies, we further identified the protein motifs on TOB and PABPC1 that are necessary for their interaction and found that interaction with PABPC1 is necessary for TOB's deadenylation-enhancing effect. Moreover, our immunofluorescence microscopy results revealed that TOB colocalizes with P-bodies, suggesting a role of TOB in linking deadenylation to the P-bodies. Our findings reveal a new mechanism by which the fate of mammalian mRNA is modulated at the deadenylation step by a protein that recruits poly(A) nuclease(s) to the 3' poly(A) tail-PABP complex.

Dengue risk factor distribution in Harris County, Texas

As an important emerging arboviral disease in Texas and throughout the world, dengue fever has the potential to make a re-emergence in the Harris County/Houston metropolitan area. Harris County has seen dengue epidemics in the past. The area has a competent vector, Aedes aegypti, capable of transmission of the virus should it be introduced. It is important to examine areas of highest risk for dengue emergence and transmission in Harris County so that surveillance and educational programs can be properly implemented. This study uses mapping software to visually represent risk factor information with areas of known Ae. aegypti populations. This study focused on known demographic risk factors such as race/ethnicity, place of birth, gender as well as socioeconomic status represented by educational attainment and income. This study found that there are several areas, particularly in central Harris County that are at particular risk for dengue transmission. The findings support the hypothesis that in areas of lower socioeconomic status there were increased populations of foreign born populations, Hispanic populations, and identified locations of a competent vector present. These findings suggest that more specific surveillance of Ae. aegypti, testing of the mosquitoes for dengue virus, and active surveillance for human cases should be implemented in these areas. ^

Ethnicity as a risk factor for diabetes incidence in a population of diagnosed hypertensives

Significant racial/ethnic differences exist in prevalence of hypertension (HTN) and non-insulin dependent diabetes mellitus (NIDDM). Hypertension is more common in diabetics than in non-diabetics, and an etiologic link between the two conditions has been proposed. Since there are few longitudinal studies of persons with both HTN and NIDDM, a retrospective cohort study was conducted to determine if ethnicity (Black, Hispanic (Mexican-American), and non-Hispanic White) was related to NIDDM incidence in a low-SES, multi-ethnic clinic population of diagnosed hypertensives. Two thousand nine hundred forty-one hypertensives free of NIDDM at baseline were followed for up to 10 years. Mean baseline age was 56 $\pm$ 12 years, M:F percent was 33:67, and Black:Hispanic:White percent was 63:17:20. There were 236 incident cases of NIDDM. In Cox proportional hazards analysis, the risk of developing NIDDM over 10 years was not related to ethnicity after controlling for significant covariates, including age, baseline blood glucose and body mass index (adjusted RR for Blacks compared to Whites =.82, 95 percent CI =.57-1.18; adjusted RR for Hispanics compared to Whites =.84, 95 percent CI =.51-1.38). This result contrasts with the increased risk of NIDDM among Blacks and Hispanics compared to Whites found in the general population. The study suggests that a diagnosis of hypertension equalizes the risk of developing NIDDM among the three ethnic groups. ^

Identification, purification, sequencing and characterization of human lung fibroblast motility -stimulating factor for human soft tissue sarcoma cells

Paracrine motogenic factors, including motility cytokines and extracellular matrix molecules secreted by normal cells, can stimulate metastatic cell invasion. For extracellular matrix molecules, both the intact molecules and the degradative products may exhibit these activities, which in some cases are not shared by the intact molecules. We found that human peritumoral and lung fibroblasts secrete motility-stimulating activity for several recently established human sarcoma cell strains. The motility of lung metastasis-derived human SYN-1 sarcoma cells was preferentially stimulated by human lung and peritumoral fibroblast motility-stimulating factors (FMSFs). FMSFs were nondialyzable, susceptible to trypsin, and sensitive to dithiothreitol. Cycloheximide inhibited accumulation of FMSF activity in conditioned medium; however, addition of cycloheximide to the migration assay did not significantly affect motility-stimulating activity. Purified hepatocyte growth factor/scatter factor (HGF/SF), rabbit anti-hHGF, and RT-PCR analysis of peritumoral and lung fibroblast HGF/SF mRNA expression indicated that FMSF activity was unrelated to HGF/SF. Partial purification of FMSF by gel exclusion chromatography revealed several peaks of activity, suggesting multiple FMSF molecules or complexes.^ We purified the fibroblast motility-stimulating factor from human lung fibroblast-conditioned medium to apparent homogeneity by sequential heparin affinity chromatography and DEAE anion exchange chromatography. Lysylendopeptidase C digestion of FMSF and sequencing of peptides purified by reverse phase HPLC after digestion identified it as an N-terminal fragment of human fibronectin. Purified FMSF stimulated predominantly chemotaxis but chemokinesis as well of SYN-1 sarcoma cells and was chemotactic for a variety of human sarcoma cells, including fibrosarcoma, leiomyosarcoma, liposarcoma, synovial sarcoma and neurofibrosarcoma cells. The motility-stimulating activity present in HLF-CM was completely eliminated by either neutralization or immunodepletion with a rabbit anti-human-fibronectin antibody, thus further confirming that the fibronectin fragment was the FMSF responsible for the motility stimulation of human soft tissue sarcoma cells. Since human soft tissue sarcomas have a distinctive hematogenous metastatic pattern (predominantly lung), FMSF may play a role in this process. ^

Genetics and epidemiology of gallbladder disease in New World native peoples.

Native peoples of the New World, including Amerindians and admixed Latin Americans such as Mexican-Americans, are highly susceptible to diseases of the gallbladder. These include cholesterol cholelithiasis (gallstones) and its complications, as well as cancer of the gallbladder. Although there is clearly some necessary dietary or other environmental risk factor involved, the pattern of disease prevalence is geographically associated with the distribution of genes of aboriginal Amerindian origin, and levels of risk generally correspond to the degree of Amerindian admixture. This pattern differs from that generally associated with Westernization, which suggests a gene-environment interaction, and that within an admixed population there is a subset whose risk is underestimated when admixture is ignored. The risk that an individual of a susceptible New World genotype will undergo a cholecystectomy by age 85 can approach 40% in Mexican-American females, and their risk of gallbladder cancer can reach several percent. These are heretofore unrecognized levels of risk, especially of the latter, because previous studies have not accounted for admixture or for the loss of at-risk individuals due to cholecystectomy. A genetic susceptibility may, thus, be as "carcinogenic" in New World peoples as any known major environmental exposure; yet, while the risk has a genetic basis, its expression as gallbladder cancer is so delayed as to lead only very rarely to multiply-affected families. Estimates in this paper are derived in part from two studies of Mexican-Americans in Starr County and Laredo, Texas.

Childhood sexual victimization: Risk factor for drug use and sexual risk behaviors

The purpose of this dissertation was to survey men in the Harris County Jail (HCJ) to establish a more valid estimate of childhood sexual abuse (CSA) prevalence in a jailed-based population; to assess whether inmates with a history of CSA were at greater risk for use of drugs and alcohol and engaging in high-risk sexual behaviors than those without histories of childhood sexual abuse. ^ The first study determined the prevalence of childhood sexual abuse among incarcerated males in a county jail. In this study, sixty-three percent of the subjects reported having been sexually abused. Sixty-one percent reported abuse pre-puberty and 10% reported abuse post puberty. In pre-puberty abuse the initiation of first abuse occurred at a mean age of 5.6 years (SD 5.096, range: 2–13 years). ^ The second study explored the association between inmates with histories of CSA as a risk factor for sexual risk behaviors. A history of sexual abuse did not appear to be associated with an elevated risk of sexual risk behaviors. ^ The third study explored a history of drug use and a history of CSA among the inmates. A chi-square test showed that the inmates who reported a history of CSA, was significantly greater for the following drugs: Marijuana (02), Crack (03), Heroin/Morphine (.03), Amphetamines/Speed (01), Downers/Barbiturates (.001), Methamphetamine/Crystal Meth (.001), Valium .02), LSD/Acid (.001), and Inhalants (.001), p < .05). Significance was not found in alcohol, tobacco, cocaine, Quaaludes and methadone. ^ The research from this study provides empirical data supporting previous research. The current data shows that incarcerated inmates have a high prevalence of childhood sexual abuse and drug use. Sexual victimization as a child does not appear to be associated with an elevated risk of unsafe sexual behaviors. However, men who used drugs were twice as likely to have engaged in unprotected sex with casual and regular partners, and rarely used condoms with paid sex. Although our study methods do not permit a causal explanation for this association, we believe it is of concern. Finally, data in this study shows that sexually abused children are likely candidates for adult criminal behavior. ^

Prior history of atopy or autoimmunity increases risk for alopecia areata

Background. The association between a prior history of atopy or other autoimmune diseases and risk of alopecia areata is not well established. ^ Objective. Purpose of this study was to use the National Alopecia Areata Registry database to further investigate the association between history of atopy or other autoimmune diseases and risk of alopecia areata. ^ Methods. A total of 2,613 self-registered sporadic cases (n = 2,055) and controls (n = 558) were included in the present analysis. ^ Results. Possessing a history of any atopy (OR = 2.00; 95% CI 1.50-2.54) or autoimmune disease (OR = 1.73; 95% CI 1.10-2.72) was associated with an increased risk of alopecia areata. There was no trend for possessing a history of more than one atopy or autoimmune disease and increasing risk of alopecia areata. ^ Limitations. Recall, reporting, and recruiting bias are potential sources of limitations in this analysis. ^ Conclusion. This analysis revealed that a prior history of atopy and autoimmune disease was associated with an increased risk of alopecia areata and that the results were consistent for both the severe subtype of alopecia areata (i.e., alopecia totalis and alopecia universalis) and the localized subtype (i.e., alopecia areata persistent).^

EMPLOYMENT AND EXPOSURES IN THE PETROLEUM REFINING AND PETROCHEMICAL INDUSTRIES AND THE RISK OF LUNG CANCER (EPIDEMIOLOGY, ASSESSMENT)

This dissertation addresses the risk of lung cancer associated with occupational exposures in the petroleum refining and petrochemical industries. Earlier epidemiologic studies of this association did not adjust for cigarette smoking or have specific exposure classifications. The Texas EXposure Assessment System (TEXAS) was developed with data from a population-based, case-comparison study conducted in five southeast Texas counties between 1976 and 1980. The Texas Exposure Assessment System uses job and process categories developed by the American Petroleum Institute, as well as time-oriented variables to identify high risk groups.^ An industry-wide, increased risk for lung cancer was associated with jobs having low-level hydrocarbon exposure that also include other occupational inhalation exposures (OR = 2.0--adjusted for smoking and latency effects). The prohibition of cigarette smoking for jobs with high-level hydrocarbon exposure might explain part of the increased risk for jobs with low-level hydrocarbon exposures. Asbestos exposure comprises a large part of the risk associated with jobs having other inhalation exposures besides hydrocarbons. Workers in petroleum refineries were not shown to have an increased, occupational risk for lung cancer. The increased risk for lung cancer among petrochemical workers (OR = 3.1--smoking and latency adjusted) is associated with all jobs that involve other inhalation exposure characteristics (not only low-level hydrocarbon exposures). Findings for contract workers and workers exposed to specific chemicals were inconclusive although some hypotheses for future research were identified.^ The study results demonstrate that the predominant risk for lung cancer is due to cigarette smoking (OR = 9.8). Cigarette smoking accounts for 86.5% of the incident lung cancer cases within the study area. Workers in the petroleum industry smoke significantly less than persons employed in other industries (p << 0.001). Only 2.2% of the incident lung cancer cases may be attributed to petroleum industry jobs; lifestyle factors (e.g., nutrition) may be associated with the balance of the cases. The results from this study also suggest possible high risk time periods (OR = 3.9--smoking and occupation adjusted). Artifacts in time-oriented findings may result because of the latency interval for lung cancer, secular peaks in age-, sex-specific incidence rates, or periods of hazardous exposures in the petroleum industry. ^

Molecular markers of human papillomavirus (HPV) infection and epidemiologic risk factors for squamous intraepithelial lesions (SIL) of the cervix

Infection with certain types of HPV is a necessary event in the development of cervical carcinoma; however, not all women who become infected will progress. While much is known about the molecular influence of HPV E6 and E7 proteins on the malignant transformation, little is known about the additional factors needed to drive the process. Currently, conventional cervical screening is insufficient at identifying women who are likely to progress from premalignant lesions to carcinoma. Aneuploidy and chromatin texture from image cytometry have been suggested as quantitative measures of nuclear damage in premalignant lesions and cancer, and traditional epidemiologic studies have identified potential factors to aid in the discrimination of those lesions likely to progress. ^ In the current study, real-time PCR was used to quantitate mRNA expression of the E7 gene in women exhibiting normal epithelium, LSIL, and HSIL. Quantitative cytometry was used to gather information about the DNA index and chromatin features of cells from the same women. Logistic regression modeling was used to establish predictor variables for histologic grade based on the traditional epidemiologic risk factors and molecular markers. ^ Prevalence of mRNA transcripts was lower among women with normal histology (27%) than for women with LSIL (40%) and HSIL (37%) with mean levels ranging from 2.0 to 4.2. The transcriptional activity of HPV 18 was higher than that of HPV 16 and increased with increasing level of dysplasia, reinforcing the more aggressive nature of HPV 18. DNA index and mRNA level increased with increasing histological grade. Chromatin score was not correlated with histology but was higher for HPV 18 samples and those with both HPV 18 and HPV 16. However, chromatin score and DNA index were not correlated with mRNA levels. The most predictive variables in the regression modeling were mRNA level, DNA index, parity, and age, and the ROC curves for LSIL and HSIL indicated excellent discrimination. ^ Real-time PCR of viral transcripts could provide a more efficient method to analyze the oncogenic potential within cells from cervical swabs. Epidemiological modeling of malignant progression in the cervix should include molecular markers, as well as the traditional epidemiological risk factors. ^

Interferon-gamma release assays for latent tuberculosis infection in child and young adult candidates or recipients of tumor necrosis factor inhibitor therapy

Background. Inhibition of tumor necrosis factor (TNF) is associated with progression of latent tuberculosis infection (LTBI) to active disease. LTBI screening prior to starting TNF inhibitor therapy is recommended. Blood tests, collectively known as interferon-gamma release assays (IGRAs), offer a means other than the tuberculin skin test (TST) of screening for LTBI. However, in the setting of immune compromise, anergy may limit the clinical utility of IGRAs. ^ Methods. A cross-sectional study was conducted in children and young adults ≤ 21 years of age who were cared for at Texas Children's Hospital in Houston, TX, during 2011 and who were candidates for, or were receiving, tumor necrosis factor (TNF)-inhibitor therapy. All subjects answered a risk factor questionnaire and were tested for LTBI by two commercially available IGRAs (QuantiFERON-Gold In-Tube assay and the T-SPOT.TB assay), along with the TST. T-cell phenotypes were evaluated through flow cytometry, both at baseline and after antigen stimulation. ^ Results. Twenty-eight subjects were enrolled. All were TST negative and none were IGRA positive. Results were negative for the 27 subjects who were tested with QuantiFERON-Gold In-Tube. However, 26% of subjects demonstrated anergy in the T-SPOT.T. Patients with T-SPOT. TB anergy had lower quantitative IFN-γ responses to mitogen in the QFT assay—the mean IFN-γ level to mitogen in patients without T-SPOT.TB anergy was 9.84 IU/ml compared to 6.91 IU/ml in patients with T-SPOT.TB anergy (P = 0.046). Age and use of TNF inhibitors, corticosteroids, or methotrexate use were not significantly associated with T-SPOT.TB anergy. Antigen stimulation revealed depressed expression of intracellular IFN-γ in subjects with T-SPOT. TB anergy. ^ Conclusions. The frequency of anergy in this population is higher than would be expected from studies in adults. There appears to be inappropriate IFN-γ responses to antigen in subjects with T-SPOT. TB anergy. This immune defect was detected by the T-SPOT. TB assay but not by the QuantiFERON-Gold In-Tube assay. Further data are needed to clarify the utility of IGRAs in this population.^