Adherence to isoniazid prophylaxis among HIV-infected children: a randomized controlled trial comparing two dosing schedules

<p>Abstract</p> <p>Background</p> <p>Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa. Isoniazid prophylaxis can reduce tuberculosis incidence in this population. However, for the treatment to be effective, adherence to the medication must be optimized. We investigated adherence to isoniazid prophylaxis administered daily, compared to three times a week, and predictors of adherence amongst HIV-infected children.</p> <p>Methods</p> <p>We investigated adherence to study medication in a two centre, randomized trial comparing daily to three times a week dosing of isoniazid. The study was conducted at two tertiary paediatric care centres in Cape Town, South Africa. Over a 5 year period, we followed 324 HIV-infected children aged ≥ 8 weeks. Adherence information based on pill counts was available for 276 children. Percentage adherence was calculated by counting the number of pills returned. Adherence ≥ 90% was considered to be optimal. Analysis was done using summary and repeated measures, comparing adherence to the two dosing schedules. Mean percentage adherence (per child during follow-up time) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90% in each group. For repeated measures, percentage adherence (per child per visit) was dichotomized at 90%. A logistic regression model with generalized estimating equations, to account for within-individual correlation, was used to evaluate the impact of the dosing schedule. Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants.</p> <p>Results</p> <p>The overall adherence to isoniazid was excellent, with a mean adherence of 94.7% (95% confidence interval [CI] 93.5-95.9); similar mean adherence was achieved by the group taking daily medication (93.8%; 95% CI 92.1-95.6) and by the three times a week group (95.5%; 95% CI 93.8-97.2). Two-hundred and seventeen (78.6%) children achieved a mean adherence of ≥ 90%. Adherence was similar for daily and three times a week dosing schedules in univariate (odds ratio [OR] 0.88; 95% CI 0.66-1.17; <it>P </it>= 0.38) and multivariate (adjusted OR 0.85; 95% CI 0.64-1.11; <it>P </it>= 0.23) models. Children from overcrowded homes were less adherent (adjusted OR 0.71; 95% CI 0.54-0.95; <it>P </it>= 0.02). Age at study visit was predictive of adherence, with better adherence achieved in children older than 4 years (adjusted OR 1.96; 95% CI 1.16-3.32; <it>P </it>= 0.01).</p> <p>Conclusion</p> <p>Adherence to isoniazid was excellent regardless of the dosing schedule used. Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing, without compromising adherence or efficacy.</p> <p>Trial registration</p> <p>Clinical Trials NCT00330304</p

Intertwining Laplace Transformations of Linear Partial Differential Equations

We propose a generalization of Laplace transformations to the case of linear partial differential operators (LPDOs) of arbitrary order in R^n. Practically all previously proposed differential transformations of LPDOs are particular cases of this transformation (intertwining Laplace transformation, ILT). We give a complete algorithm of construction of ILT and describe the classes of operators in R^n suitable for this transformation. Keywords: Integration of linear partial differential equations, Laplace transformation, differential transformationComment: LaTeX, 25 pages v2: minor misprints correcte

Prenatal evaluation of kidney function in mice using dynamic contrast-enhanced magnetic resonance imaging

Glomerular differentiation starts as soon as embryonic stage 12 in mice and suggests that kidneys may be functional at this stage. Dynamic contrast-enhanced magnetic resonance microscopy, a noninvasive imaging technique, was used to assess renal function establishment in utero. Indeed, in adults (n = 3), an intravenous injection of gadolinium-DOTA induced in a first step a massive and rapid drop in kidney signal intensity followed, in a second step, by a drop in bladder signal intensity. The delay in signal changes between kidney and bladder reflected glomerular filtration. Pregnant mice underwent anatomical and dynamic contrast-enhanced magnetic resonance microscopy on postcoital days 12-13 (n = 2), 13-14 (n = 1), 14-15 (n = 3), 15-16 (n = 2), 16-17 (n = 3), 17-18 (n = 3), and 18-19 (n = 1). Kidneys and bladder were unambiguously depicted prior to contrast agent injection on stage 15-16 embryos. Contrast agent injection allowed kidney, detection as early as stage 12-13 but not bladder. Kinetics of signal changes demonstrated that glomerular filtration is established at embryonic stage 15-16 in mice. Thus, anatomical and dynamic contrast-enhanced magnetic resonance microscopy may be a powerful noninvasive method for in vivo prenatal developmental and functional studies

EFFECTS OF A SINGLE OVERLOAD EVENT ON THE FATIGUE CRACK GROWTH RATE OF A LOW ALLOYED ROTOR STEEL

ABSTRACT The aim of this work is to study the effect of the overload on the fatigue crack growth rate properties of a low alloyed steel used for rotor disk. On one hand, experimental fatigue tests during which a single overload event is applied are performed on CT specimens. Different loading conditions are imposed in order to study the effects of these parameters on the retardation of the fatigue crack due to the overload. On the other hand, two dimensions elastic plastic Finite Element calculations of crack propagation using nodes release method were used to estimate the effects of a single overload event on the fatigue crack growth rate. Different loading conditions, as for the experimental tests, are used in order to study numerically the effects of these parameters on the retardation of the fatigue crack due to the overload. The experimental and numerical results show the decrease of the crack growth rate due to the overload. This decrease depends on different parameters as overload ratio, stress ratio used for the constant amplitude cyclic loading and ∆K at which the overload is applied. From experimental test results, it can be observed that the decrease is as significant as the overload ratio is high, and as the ∆K at which overload is applied and stress ratio are low. Numerical results show similarities with experimental results, for instance the decrease of the fatigue crack growth is linked to the increase of the overload ratio or to the decrease to the ∆K at which overload is applied. Differences are also observed i.e. the increase of the stress ratio seems to increase the effect of the overload in the numerical calculations in contrary of the experimental results. By comparing to the numerical results, the quality of the results obtained from simplified models has been assessed in regard of the overload effect. A modified Kim and al. model seems to be representative of the different effects of the overload on the fatigue crack growth rate. The future work to be done consists to improve the comparison between experimental and numerical studies

Cochlear implantation in South Africa (part 2)

Cochlear implantation is a timeous and cost-effective solution for severe-to-profound sensorineural hearing loss (SNHL) and has transformed the lives of many individuals with significant hearing loss. The advent of cochlear implantation has meant that, for the first time, one of the senses (hearing), having been entirely lost, can be restored. The previous article in this series sketched the problem of severe-toprofound SNHL, and how cochlear implantation can overcome this, how a cochlear implant (CI) works, the history of cochlear implantation and the principles of the multidisciplinary CI team. The current status of cochlear implantation in South Africa (SA) is the subject of discussion in this article, the second of this two-part series on cochlear implantation. It comprises a study of the best available current data on the status of CI in SA

Estimating the carbon content of the deep mantle with Icelandic melt inclusions

Earth’s carbon budget is central to our understanding of the long-term co-evolution of life and the planet. Direct observations of surface reservoirs allow for the detailed quantification of their carbon content. However, the carbon content of Earth’s deep interior remains poorly constrained. Here we study olivine-hosted melt inclusions from two Icelandic eruptions, with those from the Miðfell eruption allowing us to investigate the carbon content of the deep mantle. Comparison with the previously studied Borgarhraun eruption highlights the presence of deep, plume-sourced mantle material within the Miðfell source region. Miðfell contains trace element-depleted melt inclusions undersaturated in CO2, which have high CO2/Ba (= 396 ± 48) and CO2/Nb (= 1832 ± 316), though some inclusions preserve even greater relative carbon enrichment. These observations allow us to reconstruct the CO2 content of the bulk Miðfell source as being > 690 ppm. By identifying that Miðfell is a mixture of depleted and deep mantle components, we can estimate a CO2 content for the deep mantle component of 1350 ± 350 ppm; a concentration that is over ten times higher than depleted MORB mantle estimates. Assuming that the deep mantle component identified in Miðfell is representative of a global reservoir, then with our new CO2 estimate and by considering a range of representative mantle fractions for this reservoir, we calculate that it contains up to 14 times more carbon than that of the atmosphere, oceans, and crust combined. Our result of elevated CO2/Ba and CO2/Nb ratios, and carbon enrichment support geochemical bulk Earth carbon models that call for the presence of carbon-rich deep mantle domains to balance Earth’s relatively carbon-poor upper mantle and surface environment

In vitro and in vivo evaluation of superparamagnetic iron oxide nanoparticles coated by bisphosphonates: the effects of electrical charge and molecule length.

Physicochemical coating properties are often considered to be determining factors for in vivo characteristics of superparamagnetic iron oxide nanoparticles, used as contrast agent in Magnetic Resonance Imaging (MRI). To investigate the electrical charge (modified by zero, one or two ammonium groups) and the molecule length (3, 5 or 7 methylene chains) effects of bisphosphonate-type coatings, we assessed the complement activation, in vivo plasma and tissue relaxation time alterations of intravenously injected small iron oxide nanoparticles (&lt;25 nm) on male healthy Wistar rats. The presence of ammonium groups induces a weak activation of the complement whatever the size and the concentration of particles, whereas hydroxyethylenebisphosphonate (HEBP)-coated particles are poor complement activators only at the lowest concentration. In vivo, HEBP-coated nanoparticles have the greatest prolonged relaxation time effects, despite their higher negative electrical charge, contrary to two ammonium bearing coatings. No significant differences were observed between mono-ammonium molecular coatings

Data Centre for French Coastal Operational Oceanography

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