Expanded polyfunctional T cell response to mycobacterial antigens in TB disease and contraction post-treatment.

BACKGROUND: T cells producing multiple factors have been shown to be required for protection from disease progression in HIV but we have recently shown this not to be the case in TB. Subjects with active disease had a greater proportion of polyfunctional cells responding to ESAT-6/CFP-10 stimulation than their infected but non-diseased household contacts (HHC). We therefore wanted to assess this profile in subjects who had successfully completed standard TB chemotherapy. METHODS: We performed a cross-sectional study using PBMC from TB cases (pre- and post-treatment) and HHC. Samples were stimulated overnight with TB antigens (ESAT-6/CFP-10 and PPD) and their CD4+ and CD8+ T cells were assessed for production of CD107a, IFN-gamma, IL-2 and TNF-alpha and the complexity of the responses was determined using SPICE and PESTLE software. RESULTS AND CONCLUSIONS: We found that an increase in complexity (i.e., production of more than 1 factor simultaneously) of the T cell profile was associated with TB disease and that this was significantly reduced following TB treatment. This implies that T cells are able to respond adequately to TB antigens with active disease (at least initially) but the ability of this response to protect the host from disease progression is hampered, presumably due to immune evasion strategies by the bacteria. These findings have implications for the development of new diagnostics and vaccine strategies.

Polyfunctional CD4(+) and CD8(+) T cell responses to tuberculosis antigens in HIV-1-infected patients before and after anti-retroviral treatment.

Tuberculosis (TB) kills 2 million people per year and infection with HIV is the most potent known risk factor for progression to active TB. An understanding of the immune response to TB Ags in HIV-infected patients is required to develop optimal TB vaccines and diagnostics. We assessed polyfunctional (IFN-gamma(+)IL-2(+)TNF-alpha(+)) T cell responses to TB Ags in three groups of HIV-1-infected patients dependent on their TB status, CD4 counts, and anti-retroviral exposure. We found that although the proportion of IFN-gamma cells in response to TB Ags was higher in patients with low CD4 counts, the responding cells changed from a polyfunctional CD4(+) to a monofunctional CD8(+) response. The overall polyfunctionality of the cells was restored by 12 mo of anti-retroviral therapy and primarily involved CD4(+) T cells with an effector memory phenotype. These findings have major implications for diagnosis of TB and in vaccine development strategies for TB in HIV-1-infected patients.

Methodology of an ongoing, randomized, controlled trial to improve drug use for elderly patients with chronic heart failure.

BACKGROUND: Medications can improve the functioning and health-related quality of life of patients with chronic heart failure (CHF) and reduce morbidity, mortality, and costs of treatment. However, patients may not adhere to therapy. Patients with complex medication regimens and low health literacy are at risk for nonadherence. OBJECTIVE: The primary goal of this project is to develop and assess a multilevel pharmacy-based program to improve patient medication adherence and health outcomes for elderly CHF patients with low health literacy. METHODS: In this 4-year, controlled trial, patients aged 50 years with a diagnosis of CHF who are being treated at Wishard Health Services (Indianapolis, Indiana) are randomly assigned to pharmacist intervention or usual care. Intervention patients receive 9 months of pharmacist support and 3 months of postintervention follow-up. The intervention involves a pharmacist providing verbal and written education, icon-based labeling of medication containers, and therapeutic monitoring. The pharmacist identifies patients' barriers to appropriate drug use, coaches them on overcoming these barriers, and coordinates medication use issues with their primary care providers. Daily updates of relevant monitoring data are delivered via an electronic medical record system and stored in a personal computer system designed to support pharmacist monitoring and facilitate documentation of interventions. To measure medication adherence objectively, electronic monitoring lids are used on all CHF medications for patients in both study groups. Other assessments include self-reported medication adherence, results of echocardiography (eg, ejection fraction), brain natriuretic peptide concentrations, and health-related quality of life. Health services utilization, refill adherence, and cost data derive from electronic medical records. After completion of this study, the data can be used to assess the effectiveness and cost-effectiveness of our intervention. RESULTS: One hundred twenty-two patients have been assigned to receive the intervention and 192 to receive usual care. CONCLUSIONS: Our study aims to improve patients' knowledge and self-management of their medication and to improve medication monitoring in a multilevel pharmacy-based intervention. By doing so, we intend that the intervention will improve the health outcomes of elderly patients with CHF.

Patient-centered instructions for medications prescribed for the treatment of heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with reduced functional capacity and quality of life, particularly among older adults. Complex medication regimens for CHF challenge older patients' ability to adhere to them, in part because of age-related cognitive decline and poor communication about medications. OBJECTIVE: This article describes patient-centered instructions for taking CHF medications that were developed as part of a multifaceted pharmacy-based intervention to improve medication adherence and health-related outcomes among older adults with CHF. The findings of 3 initial validation studies investigating patients' reactions to the instructions are reported. METHODS: Patients' responses to the instructions were measured using focus group (study 1) and questionnaire (studies 2 and 3) techniques. RESULTS: Overall, older adults with CHF in the 3 studies preferred the patient-centered instructions to the standard pharmacy instructions (93.8% in study 1, 65.0% in study 2). In addition, participants' preferences depended on their medication-related goals. A preference for patient-centered instructions reflected a focus on ease of understanding (as supported by the use of large type size, icons, and patient-centered organization), whereas a preference for the standard pharmacy instructions reflected a focus on the amount of information provided about drug interactions (studies 2 and 3). CONCLUSIONS: In the 3 validation studies, older adults with CHF tended to prefer the patient-centered instructions to the standard pharmacy instructions, although the results were not statistically significant in study 2. This suggests that the use of such instructions may improve patients' medication knowledge and their adherence to treatment regimens.