Symptomatic relief precedes improvement of myocardial blood flow in patients under spinal cord stimulation

BACKGROUND: Spinal cord electrical stimulation (SCS) has shown to be a treatment option for patients suffering from angina pectoris CCS III-IV although being on optimal medication and not suitable for conventional treatment strategies, e.g. CABG or PTCA. Although many studies demonstrated a clear symptomatic relief under SCS therapy, there are only a few short-term studies that investigated alterations in cardiac ischemia. Therefore doubts remain whether SCS has a direct effect on myocardial perfusion. METHODS: A prospective study to investigate the short- and long-term effect of spinal cord stimulation (SCS) on myocardial ischemia in patients with refractory angina pectoris and coronary multivessel disease was designed. Myocardial ischemia was measured by MIBI-SPECT scintigraphy 3 months and 12 months after the beginning of neurostimulation. To further examine the relation between cardiac perfusion and functional status of the patients we measured exercise capacity (bicycle ergometry and 6-minute walk test), symptoms and quality of life (Seattle Angina Questionnaire [SAQ]), as well. RESULTS: 31 patients (65 ± 11 SEM years; 25 male, 6 female) were included into the study. The average consumption of short acting nitrates (SAN) decreased rapidly from 12 ± 1.6 times to 3 ± 1 times per week. The walking distance and the maximum workload increased from 143 ± 22 to 225 ± 24 meters and 68 ± 7 to 96 ± 12 watt after 3 months. Quality of life increased (SAQ) significantly after 3 month compared to baseline, as well. No further improvement was observed after one year of treament. Despite the symptomatic relief and the improvement in maximal workload computer based analysis (Emory Cardiac Toolbox) of the MIBI-SPECT studies after 3 months of treatment did not show significant alterations of myocardial ischemia compared to baseline (16 patients idem, 7 with increase and 6 with decrease of ischemia, 2 patients dropped out during initial test phase). Interestingly, in the long-term follow up after one year 16 patients (of 27 who completed the one year follow up) showed a clear decrease of myocardial ischemia and only one patient still had an increase of ischemia compared to baseline. CONCLUSION: Thus, spinal cord stimulation not only relieves symptoms, but reduces myocardial ischemia as well. However, since improvement in symptoms and exercise capacity starts much earlier, decreased myocardial ischemia might not be a direct effect of neurostimulation but rather be due to a better coronary collateralisation because of an enhanced physical activity of the patients

Sexual Behaviors of US Women at Risk of HIV Acquisition: A Longitudinal Analysis of Findings from HPTN 064

We describe the sexual behaviors of women at elevated risk of HIV acquisition who reside in areas of high HIV prevalence and poverty in the US. Participants in HPTN 064, a prospective HIV incidence study, provided information about participants’ sexual behaviors and male sexual partners in the past 6 months at baseline, 6- and 12-months. Independent predictors of consistent or increased temporal patterns for three high-risk sexual behaviors were assessed separately: exchange sex, unprotected anal intercourse [UAI] and concurrent partnerships. The baseline prevalence of each behavior was >30% among the 2,099 participants, 88% reported partner(s) with > one HIV risk characteristic and both individual and partner risk characteristics decreased over time. Less than high school education and food insecurity predicted consistent/increased engagement in exchange sex and UAI, and partner's concurrency predicted participant concurrency. Our results demonstrate how interpersonal and social factors may influence sustained high-risk behavior by individuals and suggest that further study of the economic issues related to HIV risk could inform future prevention interventions

Daily and Nondaily Oral Preexposure Prophylaxis in Men and Transgender Women Who Have Sex With Men: The Human Immunodeficiency Virus Prevention Trials Network 067/ADAPT Study

Background: Nondaily dosing of oral preexposure prophylaxis (PrEP) may provide equivalent coverage of sex events compared with daily dosing. Methods: At-risk men and transgender women who have sex with men were randomly assigned to 1 of 3 dosing regimens: 1 tablet daily, 1 tablet twice weekly with a postsex dose (time-driven), or 1 tablet before and after sex (event-driven), and were followed for coverage of sex events with pre- and postsex dosing measured by weekly self-report, drug concentrations, and electronic drug monitoring. Results: From July 2012 to May 2014, 357 participants were randomized. In Bangkok, the coverage of sex events was 85% for the daily arm compared with 84% for the time-driven arm (P = .79) and 74% for the event-driven arm (P = .02). In Harlem, coverage was 66%, 47% (P = .01), and 52% (P = .01) for these groups. In Bangkok, PrEP medication concentrations in blood were consistent with use of ≥2 tablets per week in >95% of visits when sex was reported in the prior week, while in Harlem, such medication concentrations occurred in 48.5% in the daily arm, 30.9% in the time-driven arm, and 16.7% in the event-driven arm (P < .0001). Creatinine elevations were more common in the daily arm (P = .050), although they were not dose limiting. Conclusions: Daily dosing recommendations increased coverage and protective drug concentrations in the Harlem cohort, while daily and nondaily regimens led to comparably favorable outcomes in Bangkok, where participants had higher levels of education and employment

Tuberculosis and HIV co-infection: its impact on quality of life

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Quality of life in patients treated with first-line antiretroviral therapy containing nevirapine or efavirenz in Uganda: A prospective non-randomized study

© 2015 Mwesigire et al. Background: The goal of antiretroviral therapy (ART) is to suppress viral replication, reduce morbidity and mortality, and improve quality of life (QoL). For resource-limited settings, the World Health Organization recommends a first-line regimen of two-nucleoside reverse-transcriptase inhibitors and one non-nucleoside transcriptase inhibitor (nevirapine (NVP) or efavirenz (EFV)). There are few data comparing the QoL impact of NVP versus EFV. This study assessed the change in QoL and factors associated with QoL among HIV patients receiving ART regimens based on EFV or NVP. Methods: We enrolled 640 people with HIV eligible for ART who received regimens including either NVP or EFV. QoL was assessed at baseline, three months and six months using Physical Health Summary (PHS) and Mental Health Summary (MHS) scores and the Global Person Generated Index (GPGI). Data were analyzed using generalized estimating equations, with ART regimen as the primary exposure, to identify associations between patient and disease factors and QoL. Results: QoL increased on ART. The mean QoL scores did not differ significantly for regimens based on NVP versus EFV during follow-up for MHS and GPGI regardless of CD4 stratum and for PHS among patients with a CD4 count >250 cells/μL. The PHS-adjusted β coefficients for ART regimens based on EFV versus NVP by CD4 count strata were as follows: -1.61 (95 % CI -2.74, -0.49) for CD4 count 250 cells/μL. The corresponding MHS-adjusted β coefficients were as follows: -0.39 (-1.40, 0.62) for CD4∈250 cells/μL. The GPGI-adjusted odds ratios for EFV versus NVP were 0.51 (0.25, 1.04) for CD4 count ∈250 cells/μL. QoL improved among patients on EFV over the 6-month follow-up period (MHS p

Characterization of HIV seroconverters in a TDF/FTC PrEP study: HPTN 067/ADAPT

Background: HPTN 067/ADAPT evaluated tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) pre-exposure prophylaxis (PrEP) in women (South Africa) and men who have sex with men (Thailand, US). Participants received once-weekly directly observed TDF/FTC (DOT), and were then randomized to daily, time-driven, or event-driven PrEP. This report describes characterization of 12 HIV seroconversion events in this trial. Methods: HIV rapid testing was performed at study sites. Retrospective testing included: 4th generation assays; HIV RNA testing; Western blot; an HIV-1/2 discriminatory assay; resistance testing; and antiretroviral (ARV) drug testing. Results: Six of the 12 seroconverters received TDF/FTC in the DOT phase, but were not randomized (3 were acutely infected at enrollment; 2 were infected during the DOT phase; one was not randomized due to pregnancy). One of the six randomized participants had acute infection at randomization but was not diagnosed for 3–4 months because HIV rapid tests were non-reactive; continued daily PrEP use was associated with false-negative antibody tests and low HIV RNA levels. The five participants infected after randomization included four with low adherence to the PrEP regimen, and one who reported a 7-day period without dosing prior to infection. Three participants had TDF/FTC resistance (M184I, K65R), including two who received only four once-weekly TDF/FTC doses; most TDF/FTC mutations were detected by next generation sequencing only. Conclusions: In HPTN 067/ADAPT, participants who acquired HIV infection had infrequent PrEP dosing or low/suboptimal adherence. Sensitive assays improved detection of HIV infection and drug resistance. Drug resistance was observed with limited PrEP exposure

Factors that affect quality of life among people living with HIV attending an urban clinic in Uganda: A cohort study

© 2015 Mutabazi-Mwesigire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction: With the availability of antiretroviral therapy (ART) and primary general care for people living with HIV (PLHIV) in resource limited settings, PLHIV are living longer, and HIV has been transformed into a chronic illness. People are diagnosed and started on treatment when they are relatively well. Although ART results in clinical improvement, the ultimate goal of treatment is full physical functioning and general well-being, with a focus on quality of life rather than clinical outcomes. However, there has been little research on the relationship of specific factors to quality of life in PLHIV. The objective of this study was to investigate factors associated with quality of life among PLHIV in Uganda receiving basic care and those on ART. Methods: We enrolled 1274 patients attending an HIV outpatient clinic into a prospective cohort study. Of these, 640 received ART. All were followed up at 3 and 6 months. Health related quality of life was assessed with the MOS-HIV Health Survey and the Global Person Generated Index (GPGI). Multivariate linear regression and logistic regression with generalized estimating equations were used to examine the relationship of social behavioral and disease factors with Physical Health Summary (PHS) score, Mental Health Summary (MHS) score, and GPGI. Results: Among PLHIV receiving basic care, PHS was associated with: sex (p=0.045) - females had lower PHS; age in years at enrollment (p=0.0001) - older patients had lower PHS; and depression (

Knowledge brokering between researchers and policymakers in Fiji to develop policies to reduce obesity: a process evaluation

The importance of using research evidence in decision making at the policy level has been increasingly recognized. However, knowledge brokering to engage researchers and policymakers in government and non-government organizations is challenging. This paper describes and evaluates the knowledge exchange processes employed by the Translational Research on Obesity Prevention in Communities (TROPIC) project that was conducted from July 2009 to April 2012 in Fiji. TROPIC aimed to enhance: the evidence-informed decision making skills of policy developers; and awareness and utilization of local and other obesity-related evidence to develop policies that could potentially improve the nation&rsquo;s food and physical activity environments. The specific research question was: Can a knowledge brokering approach advance evidence-informed policy development to improve eating and physical activity environments in Fiji. <br /

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