Michael Anastario

Antigen Load and Viral Sequence Diversification Determine the Functional Profile of HIV-1–Specific CD8+ T Cells

Background Virus-specific CD8+ T lymphocytes play a key role in the initial reduction of peak viremia during acute viral infections, but display signs of increasing dysfunction and exhaustion under conditions of chronic antigen persistence. It has been suggested that virus-specific CD8+ T cells with a “polyfunctional” profile, defined by the capacity to secrete multiple cytokines or chemokines, are most competent in controlling viral replication in chronic HIV-1 infection. We used HIV-1 infection as a model of chronic persistent viral infection to investigate the process of exhaustion and dysfunction of virus-specific CD8+ T cell responses on the single-epitope level over time, starting in primary HIV-1 infection. Methods and Findings We longitudinally analyzed the polyfunctional epitope-specific CD8+ T cell responses of 18 patients during primary HIV-1 infection before and after therapy initiation or sequence variation in the targeted epitope. Epitope-specific CD8+ T cells responded with multiple effector functions to antigenic stimulation during primary HIV-1 infection, but lost their polyfunctional capacity in response to antigen and up-regulated programmed death 1 (PD-1) expression with persistent viremic infection. This exhausted phenotype significantly decreased upon removal of stimulation by antigen, either in response to antiretroviral therapy or by reduction of epitope-specific antigen load in the presence of ongoing viral replication, as a consequence of in vivo selection of cytotoxic T lymphocyte escape mutations in the respective epitopes. Monofunctionality increased in CD8+ T cell responses directed against conserved epitopes from 49% (95% confidence interval 27%–72%) to 76% (56%–95%) (standard deviation [SD] of the effect size 0.71), while monofunctionality remained stable or slightly decreased for responses directed against escaped epitopes from 61% (47%–75%) to 56% (42%–70%) (SD of the effect size 0.18) (p < 0.05). Conclusion These data suggest that persistence of antigen can be the cause, rather than the consequence, of the functional impairment of virus-specific T cell responses observed during chronic HIV-1 infection, and underscore the importance of evaluating autologous viral sequences in studies aimed at investigating the relationship between virus-specific immunity and associated pathogenesis.

Quality Monitoring of Physicians: Linking Patients’ Experiences of Care to Clinical Quality and Outcomes

BackgroundPhysicians are increasingly asked to improve the delivery of clinical services and patient experiences of care.ObjectiveWe evaluated the association between clinical performance and patient experiences in a statewide sample of physician practice sites and a sample of physicians within a large physician group.Design, Setting, ParticipantsWe separately identified 373 practice sites and 119 individual primary care physicians in Massachusetts.MeasurementsUsing Health Plan Employer Data and Information Set data, we produced two composites addressing processes of care (prevention, disease management) and one composite addressing outcomes. Using Ambulatory Care Experiences Survey data, we produced seven composite measures summarizing the quality of clinical interactions and organizational features of care. For each sample (practice site and individual physician), we calculated adjusted Spearman correlation coefficients to assess the relationship between the composites summarizing patient experiences of care and those summarizing clinical performance.ResultsAmong 42 possible correlations (21 correlations involving practice sites and 21 involving individual physicians), the majority were positive in site level (71%) and physician level (67%) analyses. For the 28 possible correlations involving patient experiences and clinical process composites, 8 (29%) were significant and positive, and only 2 (7%) were significant and negative. The magnitude of the significant positive correlations ranged from 0.13 to 0.19 at the site level and from 0.28 to 0.51 at the physician level. There were no significant correlations between patient experiences and the clinical outcome composite.ConclusionsThe modest correlations suggest that clinical quality and patient experience are distinct, but related domains that may require separate measurement and improvement initiatives.

Increased Gender-based Violence Among Women Internally Displaced in Mississippi 2 Years Post–Hurricane Katrina

OBJECTIVES Although different types of gender-based violence (GBV) have been documented in disaster-affected populations, no studies have documented a quantitative increase in rates of GBV among populations living in protracted displacement after a disaster. We aimed to assess the change in rates of GBV after Hurricane Katrina among internally displaced people (IDPs) living in travel trailer parks in Mississippi. METHODS The study design included successive cross-sectional randomized surveys, conducted in 2006 and 2007, among IDPs in Mississippi using a structured questionnaire. We sampled 50 travel trailer parks in 9 counties in Mississippi in 2006, and 69 parks in 20 counties in 2007. A total of 420 female respondents comprised the final sample. We measured respondent demographics, forms of GBV including sexual and physical violence further subtyped by perpetrator, suicidal ideation, suicide attempt, and Patient Health Questionnaire-9-assessed depression. RESULTS Respondents had a mean age of 42.7 years. The crude rate of new cases of GBV among women increased from 4.6/100,000 per day to 16.3/100,000 per day in 2006, and remained elevated at 10.1/100,000 per day in 2007. The increase was primarily driven by the increase in intimate partner violence. GBV experience was significantly associated with increased risk for poor mental health outcomes. CONCLUSIONS Overall, the rate of GBV, particularly intimate partner violence, increased within the year following Hurricane Katrina and did not return to baseline during the protracted phase of displacement. Disaster planning efforts should incorporate plans to decrease the incidence of GBV following a disaster, and to ensure adequate services to people with postdisaster GBV experience.

Using Mental Health Indicators to Identify Postdisaster Gender-Based Violence among Women Displaced by Hurricane Katrina

OBJECTIVE Assessment of gender-based violence (GBV) among internally displaced persons (IDPs) is at best difficult. In complex humanitarian disasters, GBV inquiry can sometimes be dangerous and may lead to underestimation of the true prevalence. We developed a method of identifying women who have greater odds of having been exposed to postdisaster GBV (PDGBV) using mental health indicators. METHODS We systematically random sampled IDPs living in travel trailer parks in Louisiana and Mississippi and interviewed respondents using a health needs assessment survey during an 8-week period in April and May 2006. Women (n = 194) were screened for GBV and symptoms of depression. RESULTS Women were on average 43.3 years old (range 18-85). Of the nine symptoms assessed with the Patient Health Questionnaire-9 (PHQ-9), four were associated with PDGBV. Among women with sleep dysregulation, the odds of PDGBV were 2.5 times higher in comparison with women without sleep dysregulation (95% CI 1.2-5.1). Appetite dysregulation increased the odds by 3.8 (95% CI 1.4-10.3), low self-esteem increased the odds by 2.3 (95% CI 1.2-4.6), and suicidal ideation increased the odds by 2.7 (95% CI 1.1-6.7). The internal consistency reliability of this symptom cluster was higher among women with PDGBV. Women screening positive on all four symptoms were 2.7 times more likely to have experienced PDGBV (95% CI 1.03-7.1). CONCLUSIONS Several but not all symptoms of depression indicated exposure to PDGBV. Sleeping dysregulation, appetite dysregulation, low self-esteem, and suicidal ideation should be considered secondary indicators useful for identifying the prevalence of PDGBV exposure among female IDPs. This model may be useful for identifying women with exposure to PDGBV in settings where direct questioning may not be safe and reliable.

A Randomized Trial Comparing Mail versus In-Office Distribution of the CAHPS Clinician and Group Survey

OBJECTIVE To assess the effect of survey distribution protocol (mail versus handout) on data quality and measurement of patient care experiences. DATA SOURCES/STUDY SETTING Multisite randomized trial of survey distribution protocols. Analytic sample included 2,477 patients of 15 clinicians at three practice sites in New York State. DATA COLLECTION/EXTRACTION METHODS Mail and handout distribution modes were alternated weekly at each site for 6 weeks. PRINCIPAL FINDINGS Handout protocols yielded an incomplete distribution rate (74 percent) and lower overall response rates (40 percent versus 58 percent) compared with mail. Handout distribution rates decreased over time and resulted in more favorable survey scores compared with mailed surveys. There were significant mode-physician interaction effects, indicating that data cannot simply be pooled and adjusted for mode. CONCLUSIONS In-office survey distribution has the potential to bias measurement and comparison of physicians and sites on patient care experiences. Incomplete distribution rates observed in-office, together with between-office differences in distribution rates and declining rates over time suggest staff may be burdened by the process and selective in their choice of patients. Further testing with a larger physician and site sample is important to definitively establish the potential role for in-office distribution in obtaining reliable, valid assessment of patient care experiences.

Access To Care Among Displaced Mississippi Residents In FEMA Travel Trailer Parks Two Years After Katrina

The health care needs of Gulf Coast residents displaced by Hurricane Katrina in 2005 who remain in travel trailer parks nearly three years later have not been evaluated. We conducted a population-based assessment of the health care access of residents of these travel trailer parks in Mississippi. Our findings indicate a worsening of chronic disease, mental illness, and barriers to health care access since displacement. Meeting both the chronic disease and the mental health needs of people displaced by the hurricanes of 2005 is essential for ensuring their full recovery and that of the region.

Responding to gender-based violence in disasters.

To the Editor: In the editorial Responding to Gender-based Violence in Disasters: Grappling With Research Methods to Clear the Way for Planning, Rosborough et al discuss challenges to measuring and reporting on gender-based violence (GBV) in disasteraffected populations.1 The authors also comment on our research contribution, which documented an increase in GBV among female internally displaced people following Hurricane Katrina well into a protracted phase of displacement.2 We greatly appreciate the editorialists’ commentary and summary of the salient barriers to adequately assessing the prevalence of GBV in the context of disasters. Here, we seek to clarify our methods and choice of baseline GBV prevalence estimates.3

Unzip the Truth: Results from the Fort Peck Men's Sexual Health Intervention and Evaluation Study

ABSTRACT American Indian (AI) men experience sexual and reproductive health disparities including sexually transmitted infections, unplanned pregnancy, absent fatherhood, and intimate relationship violence. Using a case-control study within a community-based participatory research framework, we investigated the effectiveness of a sexual and reproductive health peer led education intervention model for AI men, ages 18–24. Intervention results demonstrated the greatest impact on attitudes regarding contraceptives, commitment in relationships, and consistency of condom use. Our study provides insights into how to access education and influence sexual risk behaviors among a diverse group of hard to reach young adult males.