Patient and Regimen Characteristics Associated with Self-Reported Nonadherence to Antiretroviral Therapy

BACKGROUND: Nonadherence to antiretroviral therapy (ARVT) is an important behavioral determinant of the success of ARVT. Nonadherence may lead to virological failure, and increases the risk of development of drug resistance. Understanding the prevalence of nonadherence and associated factors is important to inform secondary HIV prevention efforts. METHODOLOGY/PRINCIPAL FINDINGS: We used data from a cross-sectional interview study of persons with HIV conducted in 18 U.S. states from 2000-2004. We calculated the proportion of nonadherent respondents (took <95% of prescribed doses in the past 48 hours), and the proportion of doses missed. We used multivariate logistic regression to describe factors associated with nonadherence. Nine hundred and fifty-eight (16%) of 5,887 respondents reported nonadherence. Nonadherence was significantly (p<0.05) associated with black race and Hispanic ethnicity; age <40 years; alcohol or crack use in the prior 12 months; being prescribed >or=4 medications; living in a shelter or on the street; and feeling "blue" >or=14 of the past 30 days. We found weaker associations with having both male-male sex and injection drug use risks for HIV acquisition; being prescribed ARVT for >or=21 months; and being prescribed a protease inhibitor (PI)-based regimen not boosted with ritonavir. The median proportion of doses missed was 50%. The most common reasons for missing doses were forgetting and side effects. CONCLUSIONS/SIGNIFICANCE: Self-reported recent nonadherence was high in our study. Our data support increased emphasis on adherence in clinical settings, and additional research on how providers and patients can overcome barriers to adherence

Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback

Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions — right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus — where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala activation using rtfMRI neurofeedback, suggesting possible applications of rtfMRI neurofeedback training in the treatment of patients with neuropsychiatric disorders

Therapeutic Goals in Patients with Refractory Angina

Refractory angina is a major clinical challenge in ­contemporary cardiovascular medicine. As therapeutic strategies evolve, there is increased life expectancy for ischemic heart disease with more patients reaching advanced stages. Due to a better understanding of the disease process and technological advances, coronary revascularization, by means of coronary by-pass grafting (CABG) and percutaneous coronary interventions (PCI), is now offered to a wide spectrum of high-risk patients. The inception of drug eluting stents in routine clinical practice has reduced the restenosis rates to single digits [1, 2], extending the indications of PCI to poor operative candidates with unprotected left main stenosis or diabetics with diffuse small vessel disease. In a similar fashion, more generalized use of major surgical revascularization breakthroughs, such as off-pump CABG and arterial grafts, have resulted in significant improvements in surgical outcomes [3]. Despite these advances, a significant proportion of patients with preserved left ventricular fraction and no life-threatening arrhythmias remain symptomatic with severe debilitating angina due to progression of native atherosclerotic disease associated with failure or unfeasibility of revascularization. In a prospective observational study, Hemingway et al. showed that at 1-year follow-up angina persists in 52% of patients treated with PCI and 40% of those treated with CABG [4]. Similar findings were observed in the multicenter international ARTS randomized trial, in which only 19% of PCI patients and 38% of CABG patients were free of angina and antianginal therapy at 1-year follow-up [5]. Moreover, in a meta-analysis of 11 randomized trials comparing PCI with medical therapy in stable patients with chronic coronary artery disease, PCI offered no survival benefit [6]