Publications

Amid the global economic crisis, the President's Emergency Plan for AIDS Relief (PEPFAR) and other organizations have been pressed to do more with constrained resources to meet unmet needs in the worldwide HIV/AIDS pandemic. PEPFAR has approached this challenge through the development of an Impact and Efficiency Acceleration Plan, which includes improving the collection and use of economic and financial data, increasing the efficiency of HIV/AIDS program implementation, and collaborating with governments and multilateral organizations to maximize the impact of the resources provided by the United States. For example, by linking financial data with program outputs, PEPFAR was able to help its implementing partners in Mozambique reduce mean unit expenditures for people receiving antiretroviral treatment by 45 percent, from $265 to $145 per person, between 2009 and 2011. This article describes the plan's elements, provides examples of progress and challenges to its implementation, and assesses the prospects for further improvements in efficiency and impact.

In 2011 interim results of HIV Prevention Trials Network study 052, a National Institutes of Health study designed to test the effectiveness of antiretroviral treatment against the spread of HIV, were reported. These results showed that in a stable relationship in which one member of the couple was infected with HIV, treatment of the infected partner with antiretroviral drugs, combined with couples counseling and condom use, resulted in a 96 percent reduction in sexual transmission of HIV-1. This finding led to the use of antiretroviral treatment as a cornerstone of HIV prevention. Independent advisory committees of the President's Emergency Plan for AIDS Relief (PEPFAR) and the World Health Organization (WHO) have since issued analyses that set the stage for broader use of antiretroviral agents in treatment and prevention. This article describes the separate PEPFAR and WHO recommendations and outlines the design of prospective new trials to test how best to maximize the benefits of early treatment for prevention.

Acute lung injury is a common disorder with a high mortality rate, but previous efforts to develop drugs to treat this disorder have been unsuccessful. In an effort to develop more effective treatments, we have been studying the molecular pathways that regulate the dysfunction of alveolar epithelial cells and endothelial cells that serve as a final common pathway leading to alveolar flooding. Using integrin subunit knockout mice and antibodies we developed by immunizing these mice, we have found important and distinct roles for the αvβ6 integrin on epithelial cells and the αvβ5 integrin on endothelial cells in mediating increases in alveolar permeability in multiple models of acute lung injury. We have also found therapeutic effects of αvβ5 inhibition in two models of septic shock even when the antibody was administered to animals that were obviously ill. These results identify αvβ6 and αvβ5 as promising therapeutic targets for the treatment of acute lung injury and septic shock.

BACKGROUND

As cancer care shifts from hospital to outpatient settings, the number of cancer caregivers continues to grow. However, little is known about the cancer caregiving experience. This gap in knowledge is especially evident for racially diverse caregivers.

OBJECTIVE

This study, part of a multisite study of care recipients with either lung or colorectal cancer and their caregivers, examined the caregiving experiences of African American (AA) and white caregivers.

METHODS

Caregivers were identified by cancer patients in the Cancer Care Outcomes Research and Surveillance consortium. Caregivers completed a self-administered, mailed questionnaire that assessed their characteristics and experiences. Analysis of covariance was used to compare racial groups by objective burden and caregiving resources while controlling for covariates.

RESULTS

Despite greater preparedness for the caregiving role (P = .006), AA caregivers reported more weekly hours caregiving than whites did (26.5 ± 3.1 vs 18.0 ± 1.7; P = .01). In later phases of caregiving, AAs reported having more social support (P = .02), spending more hours caregiving (31.9 ± 3.5 vs 16.9 ± 1.9; P < .001), and performing more instrumental activities of daily living on behalf of their care recipient (P = .021).

CONCLUSION

Racial differences in the caregiving experience exist.

IMPLICATIONS FOR PRACTICE

Nurses play a key role in educating cancer patients and their caregivers on how to effectively cope with and manage cancer. Because AA caregivers seem to spend more time in the caregiving role and perform more caregiving tasks, AA caregivers may benefit from interventions tailored to their specific caregiving experience.

OBJECTIVE

Item 9 of the Patient Health Questionnaire-9 (PHQ-9), which inquires about both passive thoughts of death and active ideas of self-harm, has been used to assess suicide risk. The objectives of this study were (1) to determine the proportion of patients who responded "yes" to Item 9 who endorsed active suicidal ideation in response to more direct questions from a structured clinical interview and (2) to compare the sensitivity and specificity for detecting cases of depression of the PHQ-9 and the PHQ-8, which does not include Item 9, as well as the correlation between the PHQ-8 and PHQ-9.

METHODS

Coronary artery disease (CAD) outpatients were administered the PHQ-9 and the Computerized Diagnostic Interview Schedule (C-DIS). Item 9 responses were compared to suicidal ideation and intent in the last year based on the C-DIS. Scores on the PHQ-8 were obtained by eliminating Item 9 from the PHQ-9. Test characteristics of the PHQ-9 and PHQ-8 were compared.

RESULTS

Of 1022 patients, 110 (10.8%) endorsed Item 9. Of those, only 22 (19.8%) reported thoughts about committing suicide, and only 9 of those (8.1%) reported a suicide plan any time in the last year based on the C-DIS. Correlation between PHQ-9 and PHQ-8 scores was r=0.997. Sensitivity and specificity for the PHQ-9 (54%, 90%) and PHQ-8 (50%, 91%) to detect major depression were similar.

CONCLUSION

Item 9 does not appear to be an accurate suicide screen. The PHQ-8 may be a better option than the PHQ-9 in CAD patients.

Synonymous variations, which are defined as codon substitutions that do not change the encoded amino acid, were previously thought to have no effect on the properties of the synthesized protein(s). However, mounting evidence shows that these "silent" variations can have a significant impact on protein expression and function and should no longer be considered "silent". Here, the effects of six synonymous and six non-synonymous variations, previously found in the gene of ADAMTS13, the von Willebrand Factor (VWF) cleaving hemostatic protease, have been investigated using a variety of approaches. The ADAMTS13 mRNA and protein expression levels, as well as the conformation and activity of the variants have been compared to that of wild-type ADAMTS13. Interestingly, not only the non-synonymous variants but also the synonymous variants have been found to change the protein expression levels, conformation and function. Bioinformatic analysis of ADAMTS13 mRNA structure, amino acid conservation and codon usage allowed us to establish correlations between mRNA stability, RSCU, and intracellular protein expression. This study demonstrates that variants and more specifically, synonymous variants can have a substantial and definite effect on ADAMTS13 function and that bioinformatic analysis may allow development of predictive tools to identify variants that will have significant effects on the encoded protein.

BACKGROUND

Alcohol use disorders (AUD) negatively affects adherence to and outcomes of antiretroviral treatment (ART) for HIV/AIDS patients. This study determined the prevalence of AUD and identified correlates of alcohol consumption and drinking problems during ART in large injection-driven HIV epidemics in Vietnam.

METHODS

We conducted a cross-sectional study of 1016 patients (36.2% women, mean age=35.4) in 7 hospitals in Hanoi, Hai Phong, and Ho Chi Minh City. Alcohol use problems were assessed using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C). Step-wise multivariate regression analyses determined the correlates of alcohol consumption, hazardous drinking, and binge drinking in HIV/AIDS patients.

RESULTS

There were 55.0% patients reported ever drinking, 30.1% had positive hazardous drinking and 22.3% had binge drinking. Patients who were male, drug users, working as free-lancers, asymptomatic stage, and poorer immune status were more likely to have severe alcohol consumption, hazardous drinking and binge drinking. Drug users taking both ART and Methadone Maintenance Treatment (MMT), were less likely to report AUD. In non-drug users, the longer duration of ART was also associated with lower alcohol consumption and likelihood of drinking problems. In drug users, those in the 1st year ART were more likely to be at-risk drinking than other patient groups.

CONCLUSION

AUD is highly prevalent in HIV/AIDS patients taking ART in large injection-driven HIV epidemics. ART guidelines should include AUD screening and interventions. Expanding the coverage of current services for drug users, including MMT and ART, might contribute to the reduction of AUD.