Publications

OBJECTIVE

To determine the predictors of elevated transaminases in an incident user cohort of older adult patients with rheumatic diseases receiving methotrexate (MTX) using elements derived from an electronic health record.

METHODS

Using a national, administrative database of patients seen through the Veterans Health Administration that included pharmacy and laboratory data, we performed an observational cohort study of veterans ages ≥65 years who were new users of MTX to identify risk factors for elevated transaminases.

RESULTS

We studied 659 incident users of MTX. We found a 6% incidence of moderate (≥1.5 × the upper limit of normal) elevations in aspartate aminotransferase or alanine aminotransferase over a mean followup period of 7 months. We identified predictors of moderate transaminase elevations to include obesity (per body mass index ≥30 kg/m(2) ), total cholesterol >240 mg/dl, pre-MTX liver function test (LFT) elevations, use of biologic agents, and lack of folic acid supplementation. A patient with these characteristics and >3 comorbid conditions would be predicted to have a 90% chance of developing a moderate transaminase elevation in the 7 months after starting MTX.

CONCLUSION

Moderate LFT abnormalities were uncommon in the first 7 months of MTX use, but were more likely to occur in patients with obesity, untreated high cholesterol, pre-MTX LFT elevations, biologic agent use, and lack of folic acid supplementation. Future work should aim to develop a robust, automated prediction rule for identifying patients at high risk for MTX-related liver toxicity.

BACKGROUND

Cross-sectional studies show that human immunodeficiency virus (HIV) stigma is negatively correlated with social support.

PURPOSE

The purpose of this study is to examine the bidirectional relationship between social support and HIV stigma.

METHODS

We collected quarterly data from a cohort of 422 people living with HIV in Uganda, followed for a median of 2.1 years. We used multilevel regression to model the contemporaneous and 3-month-lagged associations between social support and both enacted and internalized stigma.

RESULTS

Lagged enacted stigma was negatively correlated with emotional and instrumental social support, and lagged instrumental social support was negatively correlated with enacted stigma. Internalized stigma and emotional social support had reciprocal lagged associations.

CONCLUSIONS

Interventions to reduce enacted stigma may strengthen social support for people living with HIV. Improved social support may in turn have a protective influence against future enacted and internalized stigma.

RATIONALE

Nocturnal asthma is a common presentation and is associated with a more severe form of the disease. However, there are few epidemiologic studies of nocturnal asthma, particularly in minority populations.

OBJECTIVES

To identify factors associated with nocturnal asthma, including the contribution of self-identified race/ethnicity and genetic ancestry.

METHODS

The analysis included individuals from the Study for Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) cohort. Nocturnal asthma symptoms were assessed by questionnaire. Genome-wide genotype data were used to estimate genetic ancestry in a subset of African American participants. Logistic regression was used evaluate the association of various factors with nocturnal asthma, such as self-identified race/ethnicity and genetic ancestry.

MEASUREMENT AND MAIN RESULTS

The study comprised 3,380 African American and 1,818 European Americans individuals with asthma. After adjusting for other potential explanatory variables, including controller medication use, African Americans were more than twice as likely (odds ratio, 2.56; 95% confidence interval, 2.24-2.93) to report nocturnal asthma when compared with European American individuals. Among the subset of African American participants with genome-wide genotype data (n = 1,040), estimated proportion of African ancestry was also associated with an increased risk of nocturnal asthma (P = 0.007). Differences in lung function explained a small, but statistically significant (P = 0.02), proportion of the relationship between genetic ancestry and nocturnal asthma symptoms.

CONCLUSIONS

Both self-identified race/ethnicity and African ancestry appear to be independent predictors of nocturnal asthma. The mechanism by which genetic ancestry contributes to population-level differences in nocturnal asthma appears to be largely independent of lung function.

The identification of easily measured, accurate diagnostic biomarkers for active tuberculosis (TB) will have a significant impact on global TB control efforts. Because of the host and pathogen complexities involved in TB pathogenesis, identifying a single biomarker that is adequately sensitive and specific continues to be a major hurdle. Our previous studies in models of TB demonstrated that exosomes, such as those released from infected macrophages, contain mycobacterial products, including many Mtb proteins. In this report, we describe the development of targeted proteomics assays employing multiplexed multiple reaction monitoring mass spectrometry (MRM-MS) in order to allow us to follow those proteins previously identified by western blot or shotgun mass spectrometry, and enhance biomarker discovery to include detection of Mtb proteins in human serum exosomes. Targeted MRM-MS assays were applied to exosomes isolated from human serum samples obtained from culture-confirmed active TB patients to detect 76 peptides representing 33 unique Mtb proteins. Our studies revealed the first identification of bacteria-derived biomarker candidates of active TB in exosomes from human serum. Twenty of the 33 proteins targeted for detection were found in the exosomes of TB patients, and included multiple peptides from 8 proteins (Antigen 85B, Antigen 85C, Apa, BfrB, GlcB, HspX, KatG, and Mpt64). Interestingly, all of these proteins are known mycobacterial adhesins and/or proteins that contribute to the intracellular survival of Mtb. These proteins will be included as target analytes in future validation studies as they may serve as markers for persistent active and latent Mtb infection. In summary, this work is the first step in identifying a unique and specific panel of Mtb peptide biomarkers encapsulated in exosomes and reveals complex biomarker patterns across a spectrum of TB disease states.