Patient Use of Electronic Prescription Refill and Secure Messaging and Its Association With Undetectable HIV Viral Load: A Retrospective Cohort Study

BACKGROUND: Electronic personal health records (PHRs) can support patient self-management of chronic conditions. Managing human immunodeficiency virus (HIV) viral load, through taking antiretroviral therapy (ART) is crucial to long term survival of persons with HIV. Many persons with HIV have difficulty adhering to their ART over long periods of time. PHRs contribute to chronic disease self-care and may help persons with HIV remain adherent to ART. Proportionally veterans with HIV are among the most active users of the US Department of Veterans Affairs (VA) PHR, called My HealtheVet. Little is known about whether the use of the PHR is associated with improved HIV outcomes in this population. OBJECTIVE: The objective of this study was to investigate whether there are associations between the use of PHR tools (electronic prescription refill and secure messaging [SM] with providers) and HIV viral load in US veterans. METHODS: We conducted a retrospective cohort study using data from the VA\u27s electronic health record (EHR) and the PHR. We identified veterans in VA care from 2009-2012 who had HIV and who used the PHR. We examined which ones had achieved the positive outcome of suppressed HIV viral load, and whether achievement of this outcome was associated with electronic prescription refill or SM. From 18,913 veterans with HIV, there were 3374 who both had a detectable viral load in 2009 and who had had a follow-up viral load test in 2012. To assess relationships between electronic prescription refill and viral control, and SM and viral control, we fit a series of multivariable generalized estimating equation models, accounting for clustering in VA facilities. We adjusted for patient demographic and clinical characteristics associated with portal use. In the initial models, the predictor variables were included in dichotomous format. Subsequently, to evaluate a potential dose-effect, the predictor variables were included as ordinal variables. RESULTS: Among our sample of 3374 veterans with HIV who received VA care from 2009-2012, those who had transitioned from detectable HIV viral load in 2009 to undetectable viral load in 2012 tended to be older (P=.004), more likely to be white (P\u3c.001), and less likely to have a substance use disorder, problem alcohol use, or psychosis (P=.006, P=.03, P=.004, respectively). There was a statistically significant positive association between use of electronic prescription refill and change in HIV viral load status from 2009-2012, from detectable to undetectable (OR 1.36, CI 1.11-1.66). There was a similar association between SM use and viral load status, but without achieving statistical significance (OR 1.28, CI 0.89-1.85). Analyses did not demonstrate a dose-response of prescription refill or SM use for change in viral load. CONCLUSIONS: PHR use, specifically use of electronic prescription refill, was associated with greater control of HIV. Additional studies are needed to understand the mechanisms by which this may be occurring

A novel retinoblastoma therapy from genomic and epigenetic analyses.

Retinoblastoma is an aggressive childhood cancer of the developing retina that is initiated by the biallelic loss of RB1. Tumours progress very quickly following RB1 inactivation but the underlying mechanism is not known. Here we show that the retinoblastoma genome is stable, but that multiple cancer pathways can be epigenetically deregulated. To identify the mutations that cooperate with RB1 loss, we performed whole-genome sequencing of retinoblastomas. The overall mutational rate was very low; RB1 was the only known cancer gene mutated. We then evaluated the role of RB1 in genome stability and considered non-genetic mechanisms of cancer pathway deregulation. For example, the proto-oncogene SYK is upregulated in retinoblastoma and is required for tumour cell survival. Targeting SYK with a small-molecule inhibitor induced retinoblastoma tumour cell death in vitro and in vivo. Thus, retinoblastomas may develop quickly as a result of the epigenetic deregulation of key cancer pathways as a direct or indirect result of RB1 loss

Phenotypic Spectrum Caused by Transgenic Overexpression of Activated Akt in the Heart

The serine-threonine kinase, Akt, inhibits cardiomyocyte apoptosis acutely both in vitro and in vivo. However, the effects of chronic Akt activation in the heart are unknown. To address this issue, we generated transgenic mice (TG ) with cardiac-specific expression of a constitutively active mutant of Akt (myr-Akt) driven by the myosin heavy chain- promoter. Three TG founders (9–19 weeks) died suddenly with massive cardiac dilatation. Two viable TG lines (TG564 and TG20) derived from independent founders demonstrated cardiac-specific transgene expression as well as activation of Akt and p70S6 kinase. TG564 (n 19) showed cardiac hypertrophy with a heart/body weight ratio 2.3-fold greater than littermates (n 17, p < 0.005). TG20 (n 18) had less marked cardiac hypertrophy with a heart/body weight ratio 1.6-fold greater than littermates (n 17, p < 0.005). Isolated TG564 myocytes were also hypertrophic with surface areas 1.7-fold greater than littermates (p < 0.000001). Echocardiograms in both lines demonstrated concentric hypertrophy and preserved systolic function. After ischemia-reperfusion, TG had a 50% reduction in infarct size versus TG (17 3% versus 34 4%, p < 0.001). Thus, chronic Akt activation is sufficient to cause a spectrum of phenotypes from moderate cardiac hypertrophy with preserved systolic function and cardioprotection to massive cardiac dilatation and sudden death

Hemodynamic Correlates of Blood Pressure in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study

The primary aim of the present study was to identify the hemodynamic correlates of both steady and pulsatile blood pressure in community-dwelling older adults. In 3,762 adults aged 70–89 years, we observed that significant hemodynamic determinants of systolic blood pressure included arterial stiffness as measured by aortic pulse wave velocity, stroke volume (via echocardiography), arterial wave reflection, left ventricular ejection time, and upstroke time. The strongest influence was exerted by arterial stiffness. The steady state component of blood pressure, mean arterial pressure, was associated with both cardiac index and total peripheral resistance (TPR), but was more strongly associated with TPR. Results were similar when participants taking antihypertensive medications were excluded from analyses. The overall findings suggest that mean arterial pressure is associated strongly with TPR and that significant hemodynamic correlates of systolic blood pressure included arterial stiffness, stroke volume, and arterial wave reflection

Rationale and Design of a Multicenter Echocardiographic Study to Assess the Relationship Between Cardiac Structure and Function and Heart Failure Risk in a Biracial Cohort of Community-Dwelling Elderly Persons: The Atherosclerosis Risk in Communities Study

Heart failure (HF) is an important public health concern particularly among persons over 65 years of age. Women and African Americans are critically understudied populations that carry a sizeable portion of the HF burden. Limited normative and prognostic data exist regarding measures of cardiac structure, diastolic function, and novel measures of systolic deformation in older adults living in the community

Genome-wide association study of placental weight in 65,405 newborns and 113,620 parents reveals distinct and shared genetic influences between placental and fetal growth

A well-functioning placenta is essential for fetal and maternal health throughout pregnancy. Using placental weight as a proxy for placental growth, we report genome-wide association analyses in the fetal (n = 65,405), maternal (n = 61,228) and paternal (n = 52,392) genomes, yielding 40 independent association signals. Twenty-six signals are classified as fetal, four maternal and three fetal and maternal. A maternal parent-of-origin effect is seen near KCNQ1. Genetic correlation and colocalization analyses reveal overlap with birth weight genetics, but 12 loci are classified as predominantly or only affecting placental weight, with connections to placental development and morphology, and transport of antibodies and amino acids. Mendelian randomization analyses indicate that fetal genetically mediated higher placental weight is causally associated with preeclampsia risk and shorter gestational duration. Moreover, these analyses support the role of fetal insulin in regulating placental weight, providing a key link between fetal and placental growth

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data