Increased systemic inflammation is associated with cardiac and vascular dysfunction over the first 12 weeks of antiretroviral therapy among undernourished, HIV-infected adults in Southern Africa.

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: Persistent systemic inflammation is associated with mortality among undernourished, HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa, but the etiology of these deaths is not well understood. We hypothesized that greater systemic inflammation is accompanied by cardiovascular dysfunction over the first 12 weeks of ART. METHODS: In a prospective cohort of 33 undernourished (body mass index <18.5 kg/m2) Zambian adults starting ART, we measured C-reactive protein (CRP), tumor necrosis factor-α receptor 1 (TNF-α R1), and soluble CD163 and CD14 at baseline and 12 weeks. An EndoPAT device measured the reactive hyperemia index (LnRHI; a measure of endothelial responsiveness), peripheral augmentation index (AI; a measure of arterial stiffness), and heart rate variability (HRV; a general marker of autonomic tone and cardiovascular health) at the same time points. We assessed paired changes in inflammation and cardiovascular parameters, and relationships independent of time point (adjusted for age, sex, and CD4+ T-cell count) using linear mixed models. RESULTS: Serum CRP decreased (median change -3.5 mg/l, p=0.02), as did TNF-α R1 (-0.31 ng/ml, p<0.01), over the first 12 weeks of ART. A reduction in TNF-α R1 over 12 weeks was associated with an increase in LnRHI (p=0.03), and a similar inverse relationship was observed for CRP and LnRHI (p=0.07). AI increased in the cohort as a whole over 12 weeks, and a reduction in sCD163 was associated with a rise in the AI score (p=0.04). In the pooled analysis of baseline and 12 week data, high CRP was associated with lower HRV parameters (RMSSD, p=0.01; triangular index, p<0.01), and higher TNF- α R1 accompanied lower HRV (RMSSD, p=0.07; triangular index, p=0.06). CONCLUSIONS: Persistent inflammation was associated with impaired cardiovascular health over the first 12 weeks of HIV treatment among undernourished adults in Africa, suggesting cardiac events may contribute to high mortality in this population.This work was supported by the Vanderbilt Meharry Center for AIDS Research (NIH grant number P30 AI54999); the NIH Fogarty International Center, Office of the Director, National Institutes of Health, National Heart, Blood, and Lung Institute, and National Institute of Mental Health, through the Vanderbilt-Emory-Cornell-Duke Consortium for Global Health Fellows (grant number R25 TW009337); the National Center for Advancing Translational Sciences (CTSA award number UL1TR000445) and the European and Developing Countries Clinical Trials Partnership (grant IP.2009.33011.004)

Model study of tropospheric trace species distributions during PEM-West A

A three-dimensional mesoscale transport/photochemical model is used to study the transport and photochemical transformation of trace species over eastern Asia and western Pacific for the period from September 20 to October 6, 1991, of the Pacific Exploratory Mission-West A experiment. The influence of emissions from the continental boundary layer that was evident in the observed trace species distributions in the lower troposphere over the ocean is well simulated by the model. In the upper troposphere, species such as O3, NOy (total reactive nitrogen species), and SO2 which have a significant source in the stratosphere are also simulated well in the model, suggesting that the upper tropospheric abundances of these species are strongly influenced by stratospheric fluxes and upper tropospheric sources. In the case of SO2 the stratospheric flux is identified to be mostly from the Mount Pinatubo eruption. Concentrations in the upper troposphere for species such as CO and hydrocarbons, which are emitted in the continental boundary layer and have a sink in the troposphere, are significantly underestimated by the model. Two factors have been identified to contribute significantly to the underestimate: one is emissions upwind of the model domain (eastern Asia and western Pacific); the other is that vertical transport is underestimated in the model. Model results are also grouped by back trajectories to study the contrast between compositions of marine and continental air masses. The model-calculated altitude profiles of trace species in continental and marine air masses are found to be qualitatively consistent with observations. However, the difference in the median values of trace species between continental air and marine air is about twice as large for the observed values as for model results. This suggests that the model underestimates the outflow fluxes of trace species from the Asian continent and the Pacific rim countries to the ocean. Observed altitude profiles for species like CO and hydrocarbons show a negative gradient in continental air and a positive gradient in marine air. A mechanism which may be responsible for the altitude gradients is proposed

Nutritional status is the major factor affecting grip strength of African HIV patients before and during antiretroviral treatment.

: Low grip strength is a marker of frailty and a risk factor for mortality among HIV patients and other populations. We investigated factors associated with grip strength in malnourished HIV patients at referral to ART, and at 12 weeks and 2-3 years after starting ART. : The study involved HIV-infected Zambian and Tanzanian participants recruited to the NUSTART trial when malnourished (body mass index &lt;18.5 kg/m(2) ) and requiring ART. The relationship of grip strength to nutritional, infectious and demographic factors was assessed by multivariable linear regression at referral for ART (n=1742) and after 12 weeks (n=778) and 2-3 years of ART (n=273). : In analyses controlled only for sex, age and height, most nutrition and infection-related variables were associated with grip strength. However, in multivariable analyses, consistent associations were seen for fat-free mass index, mid-upper arm circumference, haemoglobin and systolic blood pressure, and a variable association with fat mass index in men. C-reactive protein and CD4 count had limited independent effects on grip strength, while receiving tuberculosis treatment was associated with weaker grip strength. : In this population of originally malnourished HIV patients, poor grip strength was more strongly and independently associated with nutritional than with infection and inflammation variables. Programmes to improve health and survival of HIV patients should incorporate nutritional assessment and management and could use grip strength as a functional indicator of improving nutrition. This article is protected by copyright. All rights reserved.<br/

Effects on mortality of a nutritional intervention for malnourished HIV-infected adults referred for antiretroviral therapy: a randomised controlled trial.

Malnourished HIV-infected African adults are at high risk of early mortality after starting antiretroviral therapy (ART). We hypothesized that short-course, high-dose vitamin and mineral supplementation in lipid nutritional supplements would decrease mortality

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan 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.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care

Reconciling Estimates of Cell Proliferation from Stable Isotope Labeling Experiments.

Stable isotope labeling is the state of the art technique for in vivo quantification of lymphocyte kinetics in humans. It has been central to a number of seminal studies, particularly in the context of HIV-1 and leukemia. However, there is a significant discrepancy between lymphocyte proliferation rates estimated in different studies. Notably, deuterated (2)H2-glucose (D2-glucose) labeling studies consistently yield higher estimates of proliferation than deuterated water (D2O) labeling studies. This hampers our understanding of immune function and undermines our confidence in this important technique. Whether these differences are caused by fundamental biochemical differences between the two compounds and/or by methodological differences in the studies is unknown. D2-glucose and D2O labeling experiments have never been performed by the same group under the same experimental conditions; consequently a direct comparison of these two techniques has not been possible. We sought to address this problem. We performed both in vitro and murine in vivo labeling experiments using identical protocols with both D2-glucose and D2O. This showed that intrinsic differences between the two compounds do not cause differences in the proliferation rate estimates, but that estimates made using D2-glucose in vivo were susceptible to difficulties in normalization due to highly variable blood glucose enrichment. Analysis of three published human studies made using D2-glucose and D2O confirmed this problem, particularly in the case of short term D2-glucose labeling. Correcting for these inaccuracies in normalization decreased proliferation rate estimates made using D2-glucose and slightly increased estimates made using D2O; thus bringing the estimates from the two methods significantly closer and highlighting the importance of reliable normalization when using this technique

Elevated hemostasis markers after pneumonia increases one-year risk of all-cause and cardiovascular deaths

Background: Acceleration of chronic diseases, particularly cardiovascular disease, may increase long-term mortality after community-acquired pneumonia (CAP), but underlying mechanisms are unknown. Persistence of the prothrombotic state that occurs during an acute infection may increase risk of subsequent atherothrombosis in patients with pre-existing cardiovascular disease and increase subsequent risk of death. We hypothesized that circulating hemostasis markers activated during CAP persist at hospital discharge, when patients appear to have recovered clinically, and are associated with higher mortality, particularly due to cardiovascular causes. Methods: In a cohort of survivors of CAP hospitalization from 28 US sites, we measured D-Dimer, thrombin-antithrombin complexes [TAT], Factor IX, antithrombin, and plasminogen activator inhibitor-1 at hospital discharge, and determined 1-year all-cause and cardiovascular mortality. Results: Of 893 subjects, most did not have severe pneumonia (70.6% never developed severe sepsis) and only 13.4% required intensive care unit admission. At discharge, 88.4% of subjects had normal vital signs and appeared to have clinically recovered. D-dimer and TAT levels were elevated at discharge in 78.8% and 30.1% of all subjects, and in 51.3% and 25.3% of those without severe sepsis. Higher D-dimer and TAT levels were associated with higher risk of all-cause mortality (range of hazard ratios were 1.66-1.17, p = 0.0001 and 1.46-1.04, p = 0.001 after adjusting for demographics and comorbid illnesses) and cardiovascular mortality (p = 0.009 and 0.003 in competing risk analyses). Conclusions: Elevations of TAT and D-dimer levels are common at hospital discharge in patients who appeared to have recovered clinically from pneumonia and are associated with higher risk of subsequent deaths, particularly due to cardiovascular disease. © 2011 Yende et al

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p