Publications

We evaluated ABO associated outcomes in 1737 patients who underwent allogeneic hematopoietic cell transplantation (allo-HCT) at Stanford University between January 1986 and July 2011. Grafts were 61% ABO matched, 18% major mismatched (MM), 17% minor MM, and 4% bidirectional MM. Median follow-up was 6 years. In multivariate analysis, overall survival (OS) was inferior in minor MM hematopoietic cell transplantations (median 2.1 versus 6.3 years; hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.19 to 2.05; P = .001) in comparison with ABO-matched grafts. ABO minor MM was associated with an increase in early nonrelapse mortality (NRM) (18% versus 13%; HR, 1.48; 95% CI, 1.06 to 2.06; P = .02). In an independent Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 435 lymphoma patients receiving mobilized peripheral blood grafts, impairment of OS (HR, 1.55; 95% CI, 1.07 to 2.25; P = .021) and increased NRM (HR, 1.72; 95% CI, 1.11 to 2.68; P = .03) were observed in recipients of ABO minor-MM grafts. A second independent analysis of a CIBMTR data set including 5179 patients with acute myeloid leukemia and myelodysplastic syndrome identified a nonsignificant trend toward decreased OS in recipients of ABO minor-MM grafts and also found ABO major MM to be significantly associated with decreased OS (HR, 1.19; 95% CI, 1.08 to 1.31; P < .001) and increased NRM (HR, 1.23; 95% CI, 1.08 to 1.4; P = .002). ABO minor and major MM are risk factors for worse transplantation outcomes, although the associated hazards may not be uniform across different transplantation populations. Further study is warranted to determine which patient populations are at greatest risk, and whether this risk can be modified by anti-B cell therapy or other peri-transplantation treatments.

OBJECTIVE

Oral communication between health care providers and patients--the "oral exchange"--greatly impacts patient health outcomes; however, only recently have health literacy inquiries been incorporated into this field. This review examines the intersection between oral and aural literacy and the oral exchange.

METHODS

A systematic literature search was carried out. Papers published in English since 2003 that specifically examine oral/aural literacy and oral patient-provider communication were included.

RESULTS

The search yielded 999 articles, 12 of which were included in this review. Three tools have been developed to measure either patient or provider oral/aural literacy. There is a discrepancy between patient and provider oral/aural literacy levels, and high literacy demand is associated with reduced patient learning. Low patient oral/aural literacy is associated with poor health outcomes. Two interventions have been developed to reduce literacy demand.

CONCLUSION

This review demonstrates the critical role of oral and aural literacy in the oral exchange, the importance of reducing literacy demand, and the need for future research in this field.

PRACTICE IMPLICATIONS

Recommendations include the use of plain language and teach-back by providers, as well as incorporation of awareness of oral and aural literacy into community programs and health care provider education and training.

OBJECTIVE

The objectives of this study were to determine the rate of testosterone replacement therapy (TRT) initiation, TRT predictors and associated monitoring in HIV-infected men.

DESIGN

A multisite cohort study.

METHODS

We examined TRT initiation rates and monitoring among adult HIV-infected men in routine care at seven sites in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) from 1996 to 2011. We determined TRT predictors using Cox regression modelling.

RESULTS

Of 14 454 men meeting inclusion criteria, TRT was initiated in 1482 (10%) with an initiation rate of 19.7/1000 person-years [95% confidence interval (95% CI) 18.7-20.7]. In the multivariable model, TRT was significantly associated with age at least 35 years, white race, diagnosis of AIDS wasting, hepatitis C coinfection, protease inhibitor based antiretroviral therapy and nadir CD4 cell count of 200 cells/μl or less. Overall, 1886 out of 14 454 (13%) had testosterone deficiency. Among those initiating TRT, 992 out of 1482 (67%) had a pre-TRT serum total testosterone measured, and deficiency [<300 ng/dl (10.4 nmol/l)] was found in 360 out of 1482 (24%). Post-TRT serum total testosterone was measured within 6 months of TRT initiation in 377 out of 1482 (25%) men.

CONCLUSION

TRT was common in HIV-infected men, though evidence for pre-TRT testosterone deficiency was lacking in 76%. Endocrine guidelines for post-TRT monitoring were uncommonly followed. Given cardiovascular and other risks associated with TRT, efforts should focus on understanding factors driving these TRT practices in HIV-infected men.

OBJECTIVE

Programme implementers have argued that the increasing availability of antiretroviral therapy (ART) will reduce the stigma of HIV. We analyzed data from Uganda to assess how HIV-related stigma has changed during a period of ART expansion.

DESIGN

Serial cross-sectional surveys.

METHODS

We analyzed data from the Uganda AIDS Rural Treatment Outcomes study during 2007-2012 to estimate trends in internalized stigma among people living with HIV (PLHIV) at the time of treatment initiation. We analyzed data from the Uganda Demographic and Health Surveys from 2006 to 2011 to estimate trends in stigmatizing attitudes and anticipated stigma in the general population. We fitted regression models adjusted for sociodemographic characteristics, with year of data collection as the primary explanatory variable.

RESULTS

We estimated an upward trend in internalized stigma among PLHIV presenting for treatment initiation [adjusted b = 0.18; 95% confidence interval (CI), 0.06-0.30]. In the general population, the odds of reporting anticipated stigma were greater in 2011 compared with 2006 [adjusted odds ratio (OR) = 1.80; 95% CI, 1.51-2.13], despite an apparent decline in stigmatizing attitudes (adjusted OR = 0.62; 95% CI, 0.52-0.74).

CONCLUSION

Internalized stigma has increased over time among PLHIV in the setting of worsening anticipated stigma in the general population. Further study is needed to better understand the reasons for increasing HIV-related stigma in Uganda and its impact on HIV prevention efforts.

OBJECTIVE

Microbial translocation and innate immune action characterize HIV infection. Continued gut mucosal dysfunction during treatment and its relationship to CD4 T-cell recovery has not been well described.

DESIGN

A cross-sectional study was performed of antiretroviral therapy (ART)-suppressed (immunologic responders with CD4 > 500 cells/μl and immunologic nonresponders with CD4 < 350 cells/μl), untreated HIV-infected, and seronegative participants consenting to gut biopsies and a blood draw.

METHODS

Neutrophil infiltration as a surrogate response to epithelial breach, colorectal epithelial proliferation as a measure of repair, and mucosal apoptosis by immunohistochemistry were determined in gut biopsies. Plasma markers of monocyte activation (sCD14), immune activation (interleukin-6), and indoleamine 2,3-dioxygenase-1 activity (plasma kynurenine/tryptophanratio) were concurrently measured.

RESULTS

Each HIV-infected group had greater neutrophil infiltration than controls. Similarly, untreated HIV-infected participants and ART-suppressed immunologic responders had increased epithelial proliferation compared with controls, but immunologic nonresponders had no appreciable increase in epithelial proliferation despite elevated neutrophil infiltration. The CD4 T-cell count was positively correlated with epithelial proliferation and was modestly negatively correlated with neutrophil infiltration in ART-suppressed patients. Epithelial proliferation was inversely correlated with mucosal apoptosis, and apoptosis was linked to plasma sCD14 and modestly to kynurenine/tryptophan ratio.

CONCLUSIONS

Neutrophil infiltration and mucosal apoptosis remain abnormally high despite ART. Epithelial proliferation increases in HIV, but may be impaired in immunologic nonresponders. Whether mucosal apoptosis is a cause or consequence of epithelial proliferative defects is unclear, but appears to be associated with systemic inflammation. The impact of ART and interventions targeting the gut epithelial barrier in treated HIV infection warrant further investigation.

Interest in "Emerging Adulthood" (EA) as a unique developmental period has increased. This study examined the heterogeneity of EA among at-risk youth (N=1,677) by identifying trajectories of development across individuals. First, an 8-item version of the Inventory of Dimensions of EA (IDEA) measure was tested for factorial invariance across three time points; the 5-item EA measure was found to be factorially invariant. Next, latent class growth modeling identified three unique developmental trajectories. Lastly, classes were compared on demographics and health-risk behaviors. Class 1 represented a large, low-risk class (highest on EA). Classes 2 and 3 were comparably sized (~5% of the sample). Class 2 appears to be a high-risk class that decreases in EA, while Class 3 appears to be a medium-risk class that increases in EA. This study confirms that not everyone experiences EA similarly and that continuation high school students do not circumvent EA (move directly to adulthood).

Monocytes and macrophages are key components of the innate immune system yet they are often the victims of attack by infectious agents. This review examines the significance of viral infection of macrophages. The central hypothesis is that macrophage tropism enhances viral dissemination and persistence, but these changes may come at the cost of reduced replication in cells other than macrophages.