127 research outputs found

    Influence of \u3cem\u3eβ\u3c/em\u3e-Lactam Infusion Strategy on Acute Kidney Injury

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    Limited literature is available assessing nephrotoxicity with prolonged β-lactam infusions. This study compared the incidence of acute kidney injury (AKI) associated with a prolonged β-lactam infusion or an intermittent infusion. This was a retrospective, matched-cohort study at an academic medical center from July 2006 to September 2015. Adult patients who received piperacillin-tazobactam (TZP), cefepime (FEP), or meropenem (MEM) for at least 48 h were evaluated. Patients were excluded for preexisting renal dysfunction or pregnancy. The primary outcome was difference in incidence of AKI evaluated using the RIFLE (risk, injury, failure, loss, and end-stage) criteria. Patients in the intermittent group were matched 3:1 to patients in the prolonged-infusion group based on the following: β-lactam agent, age, gender, Charlson comorbidity index, baseline creatinine clearance, hypotension, receipt of vancomycin, and treatment in an intensive care unit. A total of 2,390 patients were included in the matched analysis, with 1,700 receiving intermittent infusions and 690 receiving prolonged infusion. The incidence of AKI was similar in the prolonged-infusion group to that in the intermittent-infusion group (21.6% versus 18.6%; P = 0.1). After multivariate regression, prolonged infusion was not associated with increased odds of AKI (odds ratio [OR], 1.07; 95% confidence interval [95% CI], 0.83 to 1.39). Independent predictors of AKI included TZP therapy, concomitant nephrotoxins, hypotension, and heart failure. Although AKIs were numerically more common in patients receiving prolonged β-lactam infusions than those receiving intermittent infusions, prolonged infusion was not an independent risk factor for AKI

    Efficacy and Safety of Vancomycin Loading Doses in Critically Ill Patients with Methicillin-Resistant \u3ci\u3eStaphylococcus aureus\u3c/i\u3e Infection

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    Background: While vancomycin loading doses may facilitate earlier pharmacokinetic–pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults. Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent. Results: There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% versus 72.8%; p = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences. Conclusion: Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection

    Potential for diagnosis of infectious disease from the 100,000 Genomes Project Metagenomic Dataset: Recommendations for reporting results

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    The identification of microbiological infection is usually a diagnostic investigation, a complex process that is firstly initiated by clinical suspicion. With the emergence of high-throughput sequencing (HTS) technologies, metagenomic analysis has unveiled the power to identify microbial DNA/RNA from a diverse range of clinical samples (1). Metagenomic analysis of whole human genomes at the clinical/research interface bypasses the steps of clinical scrutiny and targeted testing and has the potential to generate unexpected findings relating to infectious and sometimes transmissible disease. There is no doubt that microbial findings that may have a significant impact on a patient’s treatment and their close contacts should be reported to those with clinical responsibility for the sample-donating patient. There are no clear recommendations on how such findings that are incidental, or outside the original investigation, should be handled. Here we aim to provide an informed protocol for the management of incidental microbial findings as part of the 100,000 Genomes Projectwhich may have broader application in this emerging field. As with any other clinical information, we aim to prioritise the reporting of data that are most likely to be of benefit to the patient and their close contacts. We also set out to minimize risks, costs and potential anxiety associated with the reporting of results that are unlikely to be of clinical significance. Our recommendations aim to support the practice of microbial metagenomics by providing a simplified pathway that can be applied to reporting the identification of potential pathogens from metagenomic datasets. Given that the ambition for UK sequenced human genomes over the next 5 years has been set to reach 5 million and the field of metagenomics is rapidly evolving, the guidance will be regularly reviewed and will likely adapt over time as experience develops

    Activity of ceftolozane/tazobactam against surveillance and ‘problem’ Enterobacteriaceae, Pseudomonas aeruginosa and non-fermenters from the British Isles

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    Background: We assessed the activity of ceftolozane/tazobactam against consecutive isolates collected in the BSAC Bacteraemia Surveillance from 2011 to 2015 and against ‘problem’ isolates sent to the UK national reference laboratory from July 2015, when routine testing began. Methods: Susceptibility testing was by BSAC agar dilution with resistance mechanisms identified by PCR and interpretive reading. Results: Data were reviewed for 6080 BSAC surveillance isolates and 5473 referred organisms. Ceftolozane/tazobactam had good activity against unselected ESBL producers in the BSAC series, but activity was reduced against ertapenem-resistant ESBL producers, which were numerous among reference submissions. AmpC-derepressed Enterobacter spp. were widely resistant, but Escherichia coli with raised chromosomal AmpC frequently remained susceptible, as did Klebsiella pneumoniae with acquired DHA-1-type AmpC. Carbapenemase-producing Enterobacteriaceae were mostly resistant, except for ceftazidime-susceptible isolates with OXA-48-like enzymes. Ceftolozane/tazobactam was active against 99.8% of the BSAC Pseudomonas aeruginosa isolates; against referred P. aeruginosa it was active against 99.7% with moderately raised efflux, 94.7% with strongly raised efflux and 96.6% with derepressed AmpC. Resistance in P. aeruginosa was largely confined to isolates with metallo-β-lactamases (MBLs) or ESBLs. MICs for referred Burkholderia spp. and Stenotrophomonas maltophilia were 2–4-fold lower than those of ceftazidime. Conclusions: Ceftolozane/tazobactam is active against ESBL-producing Enterobacteriaceae; gains against other problem Enterobacteriaceae groups were limited. Against P. aeruginosa it overcame the two most prevalent mechanisms (up-regulated efflux and derepressed AmpC) and was active against 51.9% of isolates non-susceptible to all other β-lactams, rising to 80.9% if ESBL and MBL producers were excluded

    Improving and Assessing Planet Sensitivity of the GPI Exoplanet Survey with a Forward Model Matched Filter

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    We present a new matched filter algorithm for direct detection of point sources in the immediate vicinity of bright stars. The stellar Point Spread Function (PSF) is first subtracted using a Karhunen-Lo\'eve Image Processing (KLIP) algorithm with Angular and Spectral Differential Imaging (ADI and SDI). The KLIP-induced distortion of the astrophysical signal is included in the matched filter template by computing a forward model of the PSF at every position in the image. To optimize the performance of the algorithm, we conduct extensive planet injection and recovery tests and tune the exoplanet spectra template and KLIP reduction aggressiveness to maximize the Signal-to-Noise Ratio (SNR) of the recovered planets. We show that only two spectral templates are necessary to recover any young Jovian exoplanets with minimal SNR loss. We also developed a complete pipeline for the automated detection of point source candidates, the calculation of Receiver Operating Characteristics (ROC), false positives based contrast curves, and completeness contours. We process in a uniform manner more than 330 datasets from the Gemini Planet Imager Exoplanet Survey (GPIES) and assess GPI typical sensitivity as a function of the star and the hypothetical companion spectral type. This work allows for the first time a comparison of different detection algorithms at a survey scale accounting for both planet completeness and false positive rate. We show that the new forward model matched filter allows the detection of 50%50\% fainter objects than a conventional cross-correlation technique with a Gaussian PSF template for the same false positive rate.Comment: ApJ accepte

    Performance of the Gemini Planet Imager Non-Redundant Mask and spectroscopy of two close-separation binaries HR 2690 and HD 142527

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    The Gemini Planet Imager (GPI) contains a 10-hole non-redundant mask (NRM), enabling interferometric resolution in complement to its coronagraphic capabilities. The NRM operates both in spectroscopic (integral field spectrograph, henceforth IFS) and polarimetric configurations. NRM observations were taken between 2013 and 2016 to characterize its performance. Most observations were taken in spectroscopic mode with the goal of obtaining precise astrometry and spectroscopy of faint companions to bright stars. We find a clear correlation between residual wavefront error measured by the AO system and the contrast sensitivity by comparing phase errors in observations of the same source, taken on different dates. We find a typical 5-σ\sigma contrast sensitivity of 23 × 1032-3~\times~10^{-3} at λ/D\sim\lambda/D. We explore the accuracy of spectral extraction of secondary components of binary systems by recovering the signal from a simulated source injected into several datasets. We outline data reduction procedures unique to GPI's IFS and describe a newly public data pipeline used for the presented analyses. We demonstrate recovery of astrometry and spectroscopy of two known companions to HR 2690 and HD 142527. NRM+polarimetry observations achieve differential visibility precision of σ0.4%\sigma\sim0.4\% in the best case. We discuss its limitations on Gemini-S/GPI for resolving inner regions of protoplanetary disks and prospects for future upgrades. We summarize lessons learned in observing with NRM in spectroscopic and polarimetric modes.Comment: Accepted to AJ, 22 pages, 14 figure

    Is music enriching for group-housed captive chimpanzees (Pan troglodytes)?

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    Many facilities that house captive primates play music for animal enrichment or for caregiver enjoyment. However, the impact on primates is unknown as previous studies have been inconclusive. We conducted three studies with zoo-housed chimpanzees (Pan troglodytes) and one with group-housed chimpanzees at the National Centre for Chimpanzee Care to investigate the effects of classical and pop/rock music on various variables that may be indicative of increased welfare. Study one compared the behaviour and use of space of 18 animals when silence, classical or pop/rock music was played into one of several indoor areas. Overall, chimpanzees did not actively avoid the area when music was playing but were more likely to exit the area when songs with higher beats per minute were broadcast. Chimpanzees showed significantly fewer active social behaviours when music, rather than silence, was playing. They also tended to be more active and engage in less abnormal behaviour during the music but there was no change to either self-grooming or aggression between music and silent conditions. The genre of music had no differential effects on the chimpanzees’ use of space and behaviour. In the second study, continuous focal observations were carried out on three individuals with relatively high levels of abnormal behaviour. No differences in behaviour between music and silence periods were found in any of the individuals. The final two studies used devices that allowed chimpanzees to choose if they wanted to listen to music of various types or silence. Both studies showed that there were no persistent preferences for any type of music or silence. When taken together, our results do not suggest music is enriching for group-housed captive chimpanzees, but they also do not suggest that music has a negative effect on welfare

    Characterizing 51 Eri b from 1-5 μ\mum: a partly-cloudy exoplanet

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    We present spectro-photometry spanning 1-5 μ\mum of 51 Eridani b, a 2-10 MJup_\text{Jup} planet discovered by the Gemini Planet Imager Exoplanet Survey. In this study, we present new K1K1 (1.90-2.19 μ\mum) and K2K2 (2.10-2.40 μ\mum) spectra taken with the Gemini Planet Imager as well as an updated LPL_P (3.76 μ\mum) and new MSM_S (4.67 μ\mum) photometry from the NIRC2 Narrow camera. The new data were combined with JJ (1.13-1.35 μ\mum) and HH (1.50-1.80 μ\mum) spectra from the discovery epoch with the goal of better characterizing the planet properties. 51 Eri b photometry is redder than field brown dwarfs as well as known young T-dwarfs with similar spectral type (between T4-T8) and we propose that 51 Eri b might be in the process of undergoing the transition from L-type to T-type. We used two complementary atmosphere model grids including either deep iron/silicate clouds or sulfide/salt clouds in the photosphere, spanning a range of cloud properties, including fully cloudy, cloud free and patchy/intermediate opacity clouds. Model fits suggest that 51 Eri b has an effective temperature ranging between 605-737 K, a solar metallicity, a surface gravity of log\log(g) = 3.5-4.0 dex, and the atmosphere requires a patchy cloud atmosphere to model the SED. From the model atmospheres, we infer a luminosity for the planet of -5.83 to -5.93 (logL/L\log L/L_{\odot}), leaving 51 Eri b in the unique position as being one of the only directly imaged planet consistent with having formed via cold-start scenario. Comparisons of the planet SED against warm-start models indicates that the planet luminosity is best reproduced by a planet formed via core accretion with a core mass between 15 and 127 M_{\oplus}.Comment: 27 pages, 19 figures, Accepted for publication in The Astronomical Journa

    Exercise in obese pregnant women: The role of social factors, lifestyle and pregnancy symptoms

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    Background Physical activity may reduce the risk of adverse maternal outcomes, yet there are very few studies that have examined the correlates of exercise amongst obese women during pregnancy. We examined which relevant sociodemographic, obstetric, and health behaviour variables and pregnancy symptoms were associated with exercise in a small sample of obese pregnant women. Methods This was a secondary analysis using data from an exercise intervention for the prevention of gestational diabetes in obese pregnant women. Using the Pregnancy Physical Activity Questionnaire (PPAQ), 50 obese pregnant women were classified as "Exercisers" if they achieved ≥900 kcal/wk of exercise and "Non-Exercisers" if they did not meet this criterion. Analyses examined which relevant variables were associated with exercise status at 12, 20, 28 and 36 weeks gestation. Results Obese pregnant women with a history of miscarriage; who had children living at home; who had a lower pre-pregnancy weight; reported no nausea and vomiting; and who had no lower back pain, were those women who were most likely to have exercised in early pregnancy. Exercise in late pregnancy was most common among tertiary educated women. Conclusions Offering greater support to women from disadvantaged backgrounds and closely monitoring women who report persistent nausea and vomiting or lower back pain in early pregnancy may be important. The findings may be particularly useful for other interventions aimed at reducing or controlling weight gain in obese pregnant women
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