Publications

γδ T cells expressing Vδ2 may be instrumental in the control of malaria, because they inhibit the replication of blood-stage parasites in vitro and expand during acute malaria infection. However, Vδ2 T-cell frequencies and function are lower among children with heavy prior malaria exposure. It remains unclear whether malaria itself is driving this loss. Here we measure Vδ2 T-cell frequency, cytokine production, and degranulation longitudinally in Ugandan children enrolled in a malaria chemoprevention trial from 6 to 36 months of age. We observed a progressive attenuation of the Vδ2 response only among children incurring high rates of malaria. Unresponsive Vδ2 T cells were marked by expression of CD16, which was elevated in the setting of high malaria transmission. Moreover, chemoprevention during early childhood prevented the development of dysfunctional Vδ2 T cells. These observations provide insight into the role of Vδ2 T cells in the immune response to chronic malaria.

BACKGROUND

Advance care planning (ACP) is a process whereby patients prepare for medical decision-making. The traditional objective of ACP has focused on the completion of advance directives. We have developed a new paradigm of ACP focused on preparing patients and their loved ones for communication and informed medical decision-making. To operationalize this new paradigm of ACP, we created an interactive, patient-centered website called PREPARE ( www.prepareforyourcare.org ) designed for diverse older adults.

METHODS/DESIGN

This randomized controlled trial with blinded outcome assessment is designed to determine the efficacy of PREPARE to engage older Veterans in the ACP process. Veterans who are ≥ 60 years of age, have ≥ two medical conditions, and have seen a primary care physician ≥ two times in the last year are being randomized to one of two study arms. The PREPARE study arm reviews the PREPARE website and an easy-to-read advance directive. The control arm only reviews the advance directive. The primary outcome is documentation of an advance directive and ACP discussions. Other clinically important outcomes using validated surveys include ACP behavior change process measures (knowledge, contemplation, self-efficacy, and readiness) and a full range of ACP action measures (identifying a surrogate, identifying values and goals, choosing leeway or flexibility for the surrogate, communicating with clinicians and surrogates, and documenting one's wishes). We will also assess satisfaction with decision-making and Veteran activation within primary care visits by direct audio recording. To examine the outcomes at 1 week, 3 months, and 6 months between the two study arms, we will use mixed effects linear, Poisson, or negative binomial regression and mixed effects logistic regression.

DISCUSSION

This study will determine whether PREPARE increases advance directive completion rates and engagement with the ACP process. If PREPARE is efficacious, it could prove to be an easy and effective intervention to help older adults engage in the ACP process within or outside of the medical environment. PREPARE may also help older adults communicate their medical wishes and goals to their loved ones and clinicians, improve medical decision-making, and ensure their wishes are honored over the life course.

TRIAL REGISTRATION

ClinicalTrials.gov NCT01550731 . Registered on 8 December 2011.

Although poor clinic attendance is associated with increased morbidity and mortality among HIV-infected individuals, less is known about predictors of retention and the acceptability of targeted interventions to increase regular clinic attendance. To better understand which patients are at risk for irregular clinic attendance and to explore interventions to aid in retention to care, we surveyed patients attending two outpatient HIV clinics affiliated with the University of California, San Francisco. A total of 606 participants were surveyed, and the analysis was restricted to the 523 male respondents. Of this group, 45% (N = 299) reported missing at least one visit a year. Missing a clinic visit was associated with being African American (aOR = 1.99; 95%CI 1.12-3.52), being a man who has sex with both men and women (aOR=2.72; 95%CI 1.16-6.37), and reporting at least weekly methamphetamine use (aOR=5.79; 95%CI 2.47-13.57). Participants who reported a monthly income greater than $2000 were less likely to miss an appointment (aOR = 0.56; 95%CI 0.34-0.93). Regarding possible retention interventions, most patients preferred phone calls over other forms of support. These findings support the need for ongoing engagement support with particular attention to at-risk sub-groups.