Investigating the prevalence, predictors, and prognosis of suboptimal statin use early after a non-ST elevation acute coronary syndrome

BACKGROUND:High-potency statin therapy is recommended in the secondary prevention of car-diovascular disease but discontinuation, dose reduction, statin switching, and/or nonadherence occurin practice.OBJECTIVES:To determine the prevalence and predictors of deviation from high-potency statin useearly after a non-ST elevation acute coronary syndrome (NSTE-ACS) and its association with subse-quent major adverse cardiovascular events (MACE) and all-cause mortality (ACM).METHODS:A total of 1005 patients from a UK-based prospective NSTE-ACS cohort study dis-charged on high-potency statin therapy (atorvastatin 80 mg, rosuvastatin 20 mg, or 40 mg daily)were included. At 1 month, patients were divided into constant high-potency statin users, and subop-timal users incorporating statin discontinuation, dose reduction, switching statin to a lower equivalentpotency, and/or statin nonadherence. Follow-up was a median of 16 months.RESULTS:There were 156 suboptimal (w15.5%) and 849 constant statin users. Factors associatedin multivariable analysis with suboptimal statin occurrence included female sex (odds ratio 1.75, 95%confidence interval [CI] 1.14–2.68) and muscular symptoms (odds ratio 4.28, 95% CI 1.30–14.08).Suboptimal statin use was associated with increased adjusted risks of time to MACE (hazard ratio2.10, 95% CI 1.25–3.53,P5.005) and ACM (hazard ratio 2.46, 95% CI 1.38–4.39,P5.003). Sub-group analysis confirmed that the increased MACE/ACM risks were principally attributable to statindiscontinuation or nonadherence.CONCLUSIONS:Conversion to suboptimal statin use is common early after NSTE-ACS and ispartly related to muscular symptoms. Statin discontinuation or non-adherence carries an adverse prog-nosis. Interventions that preserve and enhance statin utilization could improve post NSTE-ACSoutcomes

Inorganic speciation of dissolved elements in seawater: the influence of pH on concentration ratios

Assessments of inorganic elemental speciation in seawater span the past four decades. Experimentation, compilation and critical review of equilibrium data over the past forty years have, in particular, considerably improved our understanding of cation hydrolysis and the complexation of cations by carbonate ions in solution. Through experimental investigations and critical evaluation it is now known that more than forty elements have seawater speciation schemes that are strongly influenced by pH. In the present work, the speciation of the elements in seawater is summarized in a manner that highlights the significance of pH variations. For elements that have pH-dependent species concentration ratios, this work summarizes equilibrium data (S = 35, t = 25°C) that can be used to assess regions of dominance and relative species concentrations. Concentration ratios of complex species are expressed in the form log[A]/[B] = pH - C where brackets denote species concentrations in solution, A and B are species important at higher (A) and lower (B) solution pH, and C is a constant dependent on salinity, temperature and pressure. In the case of equilibria involving complex oxy-anions (MO(x)(OH)(y)) or hydroxy complexes (M(OH)(n)), C is written as pK(n )= -log K(n )or pK(n)* = -log K(n)* respectively, where K(n )and K(n)* are equilibrium constants. For equilibria involving carbonate complexation, the constant C is written as pQ = -log(K(2)(l)K(n )[HCO(3)(-)]) where K(2)(l )is the HCO(3 )(- )dissociation constant, K(n )is a cation complexation constant and [HCO(3)(-)] is approximated as 1.9 × 10(-3 )molar. Equilibrium data expressed in this manner clearly show dominant species transitions, ranges of dominance, and relative concentrations at any pH

Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses

Mycobacterium tuberculosis (M.tb) infection causes marked tissue inflammation leading to lung destruction and morbidity. The inflammatory extracellular microenvironment is acidic, however the effect of this acidosis on the immune response to M.tb is unknown. Using RNA-seq we show that acidosis produces system level transcriptional change in M.tb infected human macrophages regulating almost 4000 genes. Acidosis specifically upregulated extracellular matrix (ECM) degradation pathways with increased expression of Matrix metalloproteinases (MMPs) which mediate lung destruction in Tuberculosis. Macrophage MMP-1 and -3 secretion was increased by acidosis in a cellular model. Acidosis markedly suppresses several cytokines central to control of M.tb infection including TNF-α and IFN-γ. Murine studies demonstrated expression of known acidosis signaling G-protein coupled receptors OGR-1 and TDAG-8 in Tuberculosis which are shown to mediate the immune effects of decreased pH. Receptors were then demonstrated to be expressed in patients with TB lymphadenitis. Collectively, our findings show that an acidic microenvironment modulates immune function to reduce protective inflammatory responses and increase extracellular matrix degradation in Tuberculosis. Acidosis receptors are therefore potential targets for host directed therapy in patients

Don't spin the pen: two alternative methods for second-stage sampling in urban cluster surveys

In two-stage cluster surveys, the traditional method used in second-stage sampling (in which the first household in a cluster is selected) is time-consuming and may result in biased estimates of the indicator of interest. Firstly, a random direction from the center of the cluster is selected, usually by spinning a pen. The houses along that direction are then counted out to the boundary of the cluster, and one is then selected at random to be the first household surveyed. This process favors households towards the center of the cluster, but it could easily be improved. During a recent meningitis vaccination coverage survey in Maradi, Niger, we compared this method of first household selection to two alternatives in urban zones: 1) using a superimposed grid on the map of the cluster area and randomly selecting an intersection; and 2) drawing the perimeter of the cluster area using a Global Positioning System (GPS) and randomly selecting one point within the perimeter. Although we only compared a limited number of clusters using each method, we found the sampling grid method to be the fastest and easiest for field survey teams, although it does require a map of the area. Selecting a random GPS point was also found to be a good method, once adequate training can be provided. Spinning the pen and counting households to the boundary was the most complicated and time-consuming. The two methods tested here represent simpler, quicker and potentially more robust alternatives to spinning the pen for cluster surveys in urban areas. However, in rural areas, these alternatives would favor initial household selection from lower density (or even potentially empty) areas. Bearing in mind these limitations, as well as available resources and feasibility, investigators should choose the most appropriate method for their particular survey context

Choosing a Survey Sample When Data on the Population Are Limited: A Method Using Global Positioning Systems and Aerial and Satellite Photographs

Background Various methods have been proposed for sampling when data on the population are limited. However, these methods are often biased. We propose a new method to draw a population sample using Global Positioning Systems and aerial or satellite photographs. Results We randomly sampled Global Positioning System locations in designated areas. A circle was drawn around each location with radius representing 20 m. Buildings in the circle were identified from satellite photographs; one was randomly chosen. Interviewers selected one household from the building, and interviews were conducted with eligible household members. Conclusions Participants had known selection probabilities, allowing proper estimation of parameters of interest and their variances. The approach was made possible by recent technological developments and access to satellite photographs. &nbsp

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

Information management for high content live cell imaging.

BACKGROUND: High content live cell imaging experiments are able to track the cellular localisation of labelled proteins in multiple live cells over a time course. Experiments using high content live cell imaging will generate multiple large datasets that are often stored in an ad-hoc manner. This hinders identification of previously gathered data that may be relevant to current analyses. Whilst solutions exist for managing image data, they are primarily concerned with storage and retrieval of the images themselves and not the data derived from the images. There is therefore a requirement for an information management solution that facilitates the indexing of experimental metadata and results of high content live cell imaging experiments. RESULTS: We have designed and implemented a data model and information management solution for the data gathered through high content live cell imaging experiments. Many of the experiments to be stored measure the translocation of fluorescently labelled proteins from cytoplasm to nucleus in individual cells. The functionality of this database has been enhanced by the addition of an algorithm that automatically annotates results of these experiments with the timings of translocations and periods of any oscillatory translocations as they are uploaded to the repository. Testing has shown the algorithm to perform well with a variety of previously unseen data. CONCLUSION: Our repository is a fully functional example of how high throughput imaging data may be effectively indexed and managed to address the requirements of end users. By implementing the automated analysis of experimental results, we have provided a clear impetus for individuals to ensure that their data forms part of that which is stored in the repository. Although focused on imaging, the solution provided is sufficiently generic to be applied to other functional proteomics and genomics experiments. The software is available from: fhttp://code.google.com/p/livecellim/RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Giant Superfluorescent Bursts from a Semiconductor Magnetoplasma

Currently, considerable resurgent interest exists in the concept of superradiance (SR), i.e., accelerated relaxation of excited dipoles due to cooperative spontaneous emission, first proposed by Dicke in 1954. Recent authors have discussed SR in diverse contexts, including cavity quantum electrodynamics, quantum phase transitions, and plasmonics. At the heart of these various experiments lies the coherent coupling of constituent particles to each other via their radiation field that cooperatively governs the dynamics of the whole system. In the most exciting form of SR, called superfluorescence (SF), macroscopic coherence spontaneously builds up out of an initially incoherent ensemble of excited dipoles and then decays abruptly. Here, we demonstrate the emergence of this photon-mediated, cooperative, many-body state in a very unlikely system: an ultradense electron-hole plasma in a semiconductor. We observe intense, delayed pulses, or bursts, of coherent radiation from highly photo-excited semiconductor quantum wells with a concomitant sudden decrease in population from total inversion to zero. Unlike previously reported SF in atomic and molecular systems that occur on nanosecond time scales, these intense SF bursts have picosecond pulse-widths and are delayed in time by tens of picoseconds with respect to the excitation pulse. They appear only at sufficiently high excitation powers and magnetic fields and sufficiently low temperatures - where various interactions causing decoherence are suppressed. We present theoretical simulations based on the relaxation and recombination dynamics of ultrahigh-density electron-hole pairs in a quantizing magnetic field, which successfully capture the salient features of the experimental observations.Comment: 21 pages, 4 figure

The effect of mixing entire male pigs prior to transport to slaughter on behaviour, welfare and carcass lesions

peer-reviewedData set for article is also provided.Research is needed to validate lesions recorded at meat inspection as indicators of pig welfare on farm. The aims were to determine the influence of mixing pigs on carcass lesions and to establish whether such lesions correlate with pig behaviour and lesions scored on farm. Aggressive and mounting behaviour of pigs in three single sex pens was recorded on Day −5, −2, and −1 relative to slaughter (Day 0). On Day 0 pigs were randomly allocated to 3 treatments (n = 20/group) over 5 replicates: males mixed with females (MF), males mixed with males (MM), and males unmixed (MUM). Aggressive and mounting behaviours were recorded on Day 0 at holding on farm and lairage. Skin/tail lesions were scored according to severity at the farm (Day −1), lairage, and on the carcass (Day 0). Effect of treatment and time on behaviour and lesions were analysed by mixed models. Spearman rank correlations between behaviour and lesion scores and between scores recorded at different stages were determined. In general, MM performed more aggressive behaviour (50.4 ± 10.72) than MUM (20.3 ± 9.55, P < 0.05) and more mounting (30.9 ± 9.99) than MF (11.4 ± 3.76) and MUM (9.8 ± 3.74, P < 0.05). Skin lesion scores increased between farm (Day −1) and lairage (P < 0.001), but this tended to be significant only for MF and MM (P = 0.08). There was no effect of treatment on carcass lesions and no associations were found with fighting/mounting. Mixing entire males prior to slaughter stimulated mounting and aggressive behaviour but did not influence carcass lesion scores. Carcass skin/tail lesions scores were correlated with scores recorded on farm (rskin = 0.21 and rtail = 0.18, P < 0.01) suggesting that information recorded at meat inspection could be used as indicators of pig welfare on farm.This study was part of the PIGWELFIND project funded by the Department of Agriculture, Food and the Marine (DAFM), Ireland