Publications

The current tuberculosis (TB) case reporting system for the United States, the Report of Verified Case of TB (RVCT), has minimal capture of multidrug-resistant (MDR) TB treatment and adverse events. Data were abstracted in five states using the form for 13 MDR TB patients during 2012-2015. The Centers for Disease Control and Prevention Guidelines for Evaluating Public Health Surveillance Systems were used to evaluate attributes of the form. Unstructured interviews with pilot sites and stakeholders provided qualitative feedback. The form was acceptable, simple, stable, representative, and provided high-quality data but was not flexible or timely. For the 13 patients on whom data were collected, the median duration of treatment with an injectable medication was 216 days (IQR 203-252). Six (46%) patients reported a side effect requiring a medication change and eight (62%) had a side effect present at treatment completion. A standardized MDR TB supplemental surveillance form was well received by stakeholders whose feedback was critical to making modifications. The finalized form will be implemented nationally in 2020 and will provide MDR TB treatment and morbidity data in the United States to help ensure patients with MDR TB receive the most effective treatment regimens with the least toxic drugs.

OBJECTIVES

Little is known about the sexual networks of young transwomen, leaving a major gap in what we know about transmission dynamics and the elevated rates of HIV in this population. The objective of this study was to understand partnership-level factors associated with condomless anal sex among young transwomen.

METHODS

A secondary data analysis of the sexual partnerships of young transwomen was conducted using baseline data from the SHINE study. Generalised estimating equation logistic regressions were used to assess for partnership-level associations between partnership type, age, injection drug use and racial concordance, HIV seroconcordance, sexual role and condomless receptive (CRAI) and insertive anal intercourse (CIAI).

RESULTS

Our analysis included 187 young transwomen that reported a total of 464 sexual partnerships where they had at least one episode of anal sex in the past 6 months. We found casual (n=232 or 50%) and commercial partnerships (n=106 or 22.8%) to be significantly associated with a lower odds of CIAI (OR=0.53, 95% CI 0.32 to 0.86 and OR=0.39, 95% CI 0.18 to 0.82) and CRAI (OR=0.30, 95% CI 0.19 to 0.47 and OR=0.35, 95% CI 0.2 to 0.62) compared with main partnerships (n=126 or 27.2%). Additionally, HIV-positive seroconcordant (n=25 or 5.4%, OR=4.05, 95% CI 1.44 to 11.40) and injection-drug using partnerships (n=25 or 5.4%, OR=3.66, 95% CI 1.34 to 9.95) were found to be significantly associated with an increased odds of CIAI among participants compared with HIV-negative seroconcordant (n=330 or 71.1%) and non-using partnerships (n=338 or 72.8%), respectively.

CONCLUSION

Young transwomen, like other populations, engage in condomless sex more often with main than casual and commercial partners, suggesting a need for interventions that address sexual practices with steady main partners.

OBJECTIVE

To identify the association between brain vascular changes and cortical volumes on MRI and late-onset epilepsy.

METHODS

In 1993-1995, 1,920 participants (median age 62.7, 59.9% female) in the community-based Atherosclerosis Risk in Communities (ARIC) Study underwent MRI, and white matter hyperintensities were measured. In addition, in 2011-2013, 1,964 ARIC participants (median age 72.4, 61.1% female) underwent MRI, and cortical volumes and white matter hyperintensities were measured. We identified cases of late-onset epilepsy (starting at age 60 or later) from ARIC hospitalization records and Medicare claims data. Using the 1993-1995 MRI, we evaluated the association between white matter hyperintensities and subsequent epilepsy using survival analysis. We used the 2011-2013 MRI to conduct cross-sectional logistic regression to examine the association of cortical volumes and white matter hyperintensities with late-onset epilepsy. All models were adjusted for demographics, hypertension, diabetes, smoking, and ε4 allele status.

RESULTS

Ninety-seven ARIC participants developed epilepsy after having an MRI in 1993-1995 (incidence 3.34 per 1,000 person-years). The degree of white matter hyperintensities measured at ages 49-72 years was associated with the risk of late-onset epilepsy (hazard ratio 1.27 per age-adjusted SD, 95% confidence interval [CI] 1.06-1.54). Lower cortical volume scores were associated cross-sectionally with higher odds of late-onset epilepsy (odds ratio 1.87, 95% CI 1.16-3.02) per age-adjusted SD.

CONCLUSIONS

This study demonstrates associations between earlier-life white matter hyperintensities on MRI and later-life incident epilepsy, and between cortical volumes measured later in life and late-onset epilepsy. These findings may help illuminate the causes of late-onset epilepsy.

Abatacept is a CTLA-4-Ig fusion protein that binds to the costimulatory ligands CD80 and CD86 and blocks their interaction with the CD28 and CTLA-4 receptors expressed by T cells, therefore inhibiting T cell activation and function. Abatacept has shown clinical efficacy in treating some autoimmune diseases but has failed to show clinical benefit in other autoimmune conditions. The reasons for these disparate results are not clear and warrant further investigation of abatacept's mode of action. Longitudinal specimens from the Immune Tolerance Network's A Cooperative Clinical Study of Abatacept in Multiple Sclerosis trial were used to examine the effects of abatacept treatment on the frequency and transcriptional profile of specific T cell populations in peripheral blood. We found that the relative abundance of CD4 T follicular helper (Tfh) cells and regulatory T cells was selectively decreased in participants following abatacept treatment. Within both cell types, abatacept reduced the proportion of activated cells expressing CD38 and ICOS and was associated with decreased expression of genes that regulate cell-cycle and chromatin dynamics during cell proliferation, thereby linking changes in costimulatory signaling to impaired activation, proliferation, and decreased abundance. All cellular and molecular changes were reversed following termination of abatacept treatment. These data expand upon the mechanism of action of abatacept reported in other autoimmune diseases and identify new transcriptional targets of CD28-mediated costimulatory signaling in human regulatory T and Tfh cells, further informing on its potential use in diseases associated with dysregulated Tfh activity.