Sherry Lassa-Claxton

Yoga lifestyle intervention reduces blood pressure in HIV-infected adults with cardiovascular disease risk factors*

People living with HIV infection are at increased risk for developing cardiovascular disease (CVD). Safe and effective interventions for lowering CVD risk in HIV infection are high priorities. We conducted a prospective, randomized, controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors, virological or immunological status, or quality of life (QOL) in HIV‐infected adults relative to standard of care treatment in a matched control group.

Human polyomaviruses in children undergoing transplantation, United States, 2008-2010

Immunocompromised patients are at risk for disease caused by infection by some polyomaviruses. To define the prevalence of polyomaviruses in children undergoing transplantation, we collected samples from a longitudinal cohort and tested for the 9 known human polyomaviruses. All were detected; several were present in previously unreported specimen types.

Insulin resistance predicts endothelial dysfunction and cardiovascular risk in HIV-infected persons on long-term highly active antiretroviral therapy.

Objective:Cardiovascular disease risk among persons with HIV is likely multifactorial, thus testing a variety of available noninvasive vascular ultrasound and other surrogate tests may yield differing results. To address this issue, we assessed multiple metabolic and clinical predictors of endothelial function and carotid intima–media thickness in HIV-infected subjects and compared results with HIV-negative controls. Design:Prospective, cross-sectional study of 50 HIV-infected, healthy adults on stable highly active antiretroviral therapy matched to 50 HIV-negative controls by age, sex, race, and body mass index. Methods:Flow-mediated vasodilation of the brachial artery, carotid intima–media thickness, dual energy X-ray absorptiometry (HIV-infected subjects), and fasting insulin, lipids, and oral glucose tolerance tests were performed. Results were compared between HIV-infected and control groups. Results:Fifty percent of subjects were African–American with 34% women. Among HIV-infected, mean CD4 cell count was 547 cells/μl; 90% had HIV RNA less than 50 copies/ml. There were no significant differences between HIV-infected and control subjects with regard to brachial artery flow-mediated vasodilation or carotid intima–media thickness. In multivariate analyses of the HIV cohort, independent predictors of endothelial dysfunction (lower flow-mediated vasodilation) were increasing insulin resistance, greater alcohol consumption, and higher baseline brachial artery diameter (P < 0.05); predictors of increased carotid intima–media thickness were hypertension, higher trunk/limb fat ratio, and insulin resistance (P < 0.05). Conclusion:In this HIV cohort on modern highly active antiretroviral therapy with well controlled HIV, there were no significant differences with regard to preclinical markers of cardiovascular disease. Insulin resistance was a strong predictor of impaired brachial artery flow-mediated vasodilation and increased carotid intima–media thickness, and may be an important cardiovascular disease risk factor in the HIV population.

Exercise training augments the peripheral insulin sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity

The prevalence and incidence of insulin resistance and type 2 diabetes mellitus (DM) are higher in people treated for human immunodeficiency virus-1 (HIV) infection than in the general population. Identifying safe and effective interventions is a high priority. We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were randomly assigned to 4 mo of pioglitazone (30 mg/day) with or without supervised, progressive aerobic, and resistance exercise training (1.5-2 h/day, 3 days/wk). The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity. Thirty-nine participants completed the study. Hepatic insulin sensitivity improved similarly in both groups. Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity. Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration. We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity. Pioglitazone alone did not significantly increase limb adipose content. Potential cardiovascular benefits of these interventions in HIV need investigation.

Post-exercise heart rate recovery in HIV-positive individuals on highly active antiretroviral therapy. Early indicator of cardiovascular disease?

HIV infection and its treatment, specifically protease inhibitor (PI) therapy, have been associated with an increased risk for cardiovascular disease. Heart rate recovery (HRR) following peak exercise is predictive of future cardiovascular events and mortality in the general population. Nothing is known regarding HRR in individuals infected with HIV on highly active antiretroviral therapy (HAART).

Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis

BackgroundIn the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC.MethodsProspective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography.ResultsMyocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/μU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/μU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001).ConclusionMen with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin.Trial RegistrationNIH Clinical Trials NCT00656851

Pilot Study of Pioglitazone and Exercise Training Effects on Basal Myocardial Substrate Metabolism and Left Ventricular Function in HIV-Positive Individuals with Metabolic Complications

Abstract Background: Individuals with HIV infection and peripheral metabolic complications have impaired basal myocardial insulin sensitivity that is related to left ventricular (LV) diastolic dysfunction. It is unknown whether interventions shown to be effective in improving peripheral insulin sensitivity can improve basal myocardial insulin sensitivity and diastolic function in people with HIV and peripheral metabolic complications. Objective: In a pilot study, we evaluated whether the peroxisome proliferator-activated receptor-gamma (PPAR-γ) agonist pioglitazone or combined endurance and resistance exercise training improves basal myocardial insulin sensitivity and diastolic function in HIV+ adults with peripheral metabolic complications. Design: Twenty-four HIV+ adults with metabolic complications including peripheral insulin resistance were randomly assigned to 4 months of pioglitazone (PIO; 30 mg/d) or supervised, progressive endurance and resistance exercise training (EXS; 90-120 min/d, 3 d/wk). Basal myocardial substrate metabolism was quantified by radioisotope tracer methodology and positron emission tomography (PET) imaging, and LV function was measured by echocardiography. Results: Twenty participants completed the study. Neither PIO nor EXS resulted in a detectable improvement in basal myocardial insulin sensitivity or diastolic function. Post hoc analyses revealed sample sizes of more than 100 participants are needed to detect significant effects of these interventions on basal myocardial insulin sensitivity and function. Conclusions: PIO or EXS alone did not significantly increase basal myocardial insulin sensitivity or LV diastolic function in HIV+ individuals with peripheral metabolic complications.

Limitations of cyclosporine C2 monitoring in pediatric heart transplant recipients

Abstract:  Monitoring CSA levels at two h after dosing (C2) has been shown effective in providing adequate CSA‐based immunosuppression in clinical trials in adult transplant recipients, but there is limited data regarding C2 monitoring in pediatric transplant recipients. Given the differences in CSA pharmacokinetics between children and adults, a cohort of stable pediatric transplant recipients was converted from monitoring CSA trough (C0) to C2 levels, to establish the clinical utility and safety of C2 monitoring. After an abbreviated AUC0–5 to establish baseline exposure, subsequent CSA dosing was adjusted based on C2 levels. Additional evaluation included monitoring for rejection, changes in CSA dose, toxicity, serum chemistries, and infection. Twelve heart transplant recipients were enrolled, with mean age 4.8 yr (range: 0.6–14.0). All patients received microemulsified CSA (Neoral®; Novartis Pharmaceuticals, East Hanover, NJ, USA) twice daily. Baseline CSA dose was 5.39 ± 2.05 mg/kg/day (mean ± s.d.), with mean C0 = 267 ± 112, C2 = 1065 ± 565, and AUC0–5 = 3817 ± 1435. Only seven participants showed clear CSA peak levels at two h, with five exhibiting delayed peaks at three to five h post‐dose. These seven participants completed 48 wk of study, with mean CSA dose decreasing to 4.55 ± 3.61 mg/kg/day, maintaining mean C2 599 ± 211 (vs. target C2 = 800). No significant change in serum creatinine was observed, although GFR increased from 76.9 to 107.6 mL/min/1.73 m2 (p = 0.11). Five patients failed to achieve target C2 levels (>800) during the first four wk, despite comparable AUC values, and were maintained on trough monitoring (C0). Mean systolic and diastolic blood pressures fell slightly, three minor infections were noted during the study period, and one episode of acute rejection occurred, despite stable CSA dosing. Nearly 50% of stable pediatric transplant recipients failed to achieve adequate peak C2 CSA levels during conversion from C0 to C2 monitoring. Age‐dependent differences in CSA absorption and/or clearance pharmacokinetics may explain these findings.

Methods for collecting paired observations from emergency medical services and emergency department providers for pediatric cervical spine injury risk factors

OBJECTIVES Cervical spine injuries (CSIs) after blunt trauma in children are rare, but cause substantial morbidity and mortality. Emergency medical services (EMS) and emergency department (ED) providers routinely use spinal precautions and cervical spine imaging, respectively, during the management of children experiencing blunt trauma. These practices lack evidence, and there is concern that they may be harmful. A pediatric CSI risk assessment tool is needed to inform EMS and ED provider decision making. Creating this tool requires prospective data collection from EMS and ED providers at the time of patient evaluation. The purpose of this article is to describe the methods used to prospectively capture paired EMS and ED provider observations of children cared for after blunt trauma. Given the rarity of prospective observational research with EMS, the novel use of Research Electronic Data Capture (REDCap) in this study, and the potential to inform future studies, we are publishing our methodology in advance of outcome data related to the risk assessment tool. METHODS The study was conducted at four tertiary childrens hospitals as a prerequisite for a planned larger study to derive a CSI risk assessment tool. We created a web-based, branch-logic questionnaire using the REDCap data collection system. The survey was administered via tablet computer to ED providers evaluating children with blunt trauma and, if applicable, to EMS providers who provided patient care at the scene. We collected information regarding factors determined a priori to be plausibly associated with CSI in children. Eligible children presenting to the ED after blunt trauma with at least one of the following one of the following were included: prehospital EMS spinal precautions, ED trauma team evaluation, or cervical spine imaging in the ED. Exclusions included penetrating trauma, language barrier, or states custody. Enrollment occurred when research coordinators (RCs) were available, generally 12-16 hours/day. RCs approached EMS providers prior to departing the ED and ED providers after they completed their patient assessments. An ED provider survey was required for enrollment. Enrolled children were followed for 28 days to determine the presence of CSI (primary outcome) by subsequent imaging or by patient/family telephone follow-up for those without imaging. RESULTS Over 18 months, we prospectively enrolled 4,144 of 5,764 (71.9%) eligible children, including 74 of 110 (67.3%) children diagnosed with CSI. Enrollment during RC hours was 85.9%. Fifty-three enrolled children were withdrawn from the study. Of those in the final study cohort, 36.5% arrived by EMS scene response in spinal precautions. The remaining 63.5% arrived by EMS scene response without spinal precautions or by private vehicle or interfacility transfer. EMS scene response providers completed surveys for 60.2% of enrolled children arriving in spinal precautions. RCs missed the EMS providers for 37.1% of children; however, EMS declined participation for only 2.6%. CONCLUSIONS Our method of data collection demonstrates the ability to prospectively capture paired observations from EMS and ED personnel for children undergoing evaluation after blunt trauma. While this methodology will be used to implement and evaluate a CSI tool in future studies, it may also be adapted to studies requiring prospective data collection from EMS and ED personnel.