Purpose
Although dozens of studies have associated vancomycin + piperacillin–tazobactam with increased acute kidney injury (AKI) risk, it is unclear whether the association represents true injury or ...a pseudotoxicity characterized by isolated effects on creatinine secretion. We tested this hypothesis by contrasting changes in creatinine concentration after antibiotic initiation with changes in cystatin C concentration, a kidney biomarker unaffected by tubular secretion.
Methods
We included patients enrolled in the Molecular Epidemiology of SepsiS in the ICU (MESSI) prospective cohort who were treated for ≥ 48 h with vancomycin + piperacillin–tazobactam or vancomycin + cefepime. Kidney function biomarkers creatinine, cystatin C, and blood urea nitrogen (BUN) were measured before antibiotic treatment and at day two after initiation. Creatinine-defined AKI and dialysis were examined through day-14, and mortality through day-30. Inverse probability of treatment weighting was used to adjust for confounding. Multiple imputation was used to impute missing baseline covariates.
Results
The study included 739 patients (vancomycin + piperacillin–tazobactam
n
= 297, vancomycin + cefepime
n
= 442), of whom 192 had cystatin C measurements. Vancomycin + piperacillin–tazobactam was associated with a higher percentage increase of creatinine at day-two 8.04% (95% CI 1.21, 15.34) and higher incidence of creatinine-defined AKI: rate ratio (RR) 1.34 (95% CI 1.01, 1.78). In contrast, vancomycin + piperacillin–tazobactam was not associated with change in alternative biomarkers: cystatin C: − 5.63% (95% CI − 18.19, 8.86); BUN: − 4.51% (95% CI − 12.83, 4.59); or clinical outcomes: dialysis: RR 0.63 (95% CI 0.31, 1.29); mortality: RR 1.05 (95%CI 0.79, 1.41).
Conclusions
Vancomycin + piperacillin–tazobactam was associated with creatinine-defined AKI, but not changes in alternative kidney biomarkers, dialysis, or mortality, supporting the hypothesis that vancomycin + piperacillin–tazobactam effects on creatinine represent pseudotoxicity.
A set of 41 nearby stars (closer than 25 pc) is investigated which have very wide binary and common proper motion (CPM) companions at projected separations between 1000 and 200,000 AU. These ...companions are identified by astrometric positions and proper motions from the NOMAD catalog. Based mainly on measures of chromospheric and X-ray activity, age estimation is obtained for most of 85 identified companions. Color-absolute magnitude diagrams are constructed to test whether CPM companions are physically related to the primary nearby stars and have the same age. Our carefully selected sample includes three remote white dwarf companions to main-sequence stars and two systems (55 Cnc and GJ 777A) of multiple planets and distant stellar companions. ten new CPM companions, including three of extreme separations, are found. Multiple hierarchical systems are abundant; more than 25% of CPM components are spectroscopic or astrometric binaries or multiples themselves. Two new astrometric binaries are discovered among nearby CPM companions, GJ 264 and HIP 59000, and preliminary orbital solutions are presented. The Hyades kinematic group (or stream) is presented broadly in the sample, but we find few possible thick-disk objects and no halo stars. It follows from our investigation that moderately young (image Gyr) thin-disk dwarfs are the dominating species in the near CPM systems, in general agreement with the premises of the dynamical survival paradigm.
BackgroundFollowing an acute myocardial infarction (MI), patients with persistently elevated biomarkers of inflammation, in particular C-reactive protein, are at significantly increased risk of ...further adverse cardiovascular events. Colchicine is a unique anti-inflammatory medication that has shown promise in reducing such events in patients with stable coronary heart disease. The current study tested the ability of low dose colchicine to reduce CRP levels at 30-days after an acute MI, a key marker of future outcome, and its safety and tolerability in this setting.MethodsWe conducted a randomised, double-blind, trial of low-dose colchicine (0.5 mg daily) or matching placebo in 237 patients admitted with an acute MI. The primary end-point was the proportion of patients with a residual CRP level ≥2 mg/L after 30 days of treatment, a threshold associated with a worse prognosis. (Figure 1).Abstract 57 Figure 1Sample group Sample groupResultsAt 30-day follow-up, 44% of patients treated with colchicine had a hsCRP level ≥2 mg/L compared to 50% of those randomised to placebo (p=0.35) and the median hsCRP in patients randomised to colchicine was 1.6 mg/L (interquartile range IQR 0.7–3.5) compared to 2.0 mg/L (IQR 0.9–4.0) in patients randomised to placebo (p=0.11). The median absolute reduction in hsCRP levels was -4.3 mg/L (IQR -1.1 to -14.1) among colchicine treated patients and -3.3 mg/L (IQR -0.9 to -14.4, p=0.44) in placebo treated patients. (Figure 2). The relative reduction was a fall of 78% compared to a fall of 64% (p=0.09). Low dose colchicine was well tolerated and did not reduce compliance with other secondary preventative medications at 30-days.Abstract 57 Figure 2The median absolute reduction in hsCRP levels The median absolute reduction in hsCRP levelsConclusionTreatment with low dose colchicine was safe and well tolerated, but was not associated with a significantly increased likelihood of achieving a CRP level <2 mg/L or lower absolute levels of CRP 30 days after an acute MI; beneficial trends were, however, observed and treatment was safe and well-tolerated. A large-scale outcome trial is required and these data suggest this will be safe and feasible. We believe, therefore, that the totality of evidence supports the need for a large scale outcome trial in patients with recent MI. Importantly in this regard the current study demonstrates the safety and tolerability of low dose colchicine after acute MI.
Amiodarone inhibits warfarin metabolism and is associated with major bleeding during warfarin therapy. Managing this drug‐drug interaction (DDI) is challenging because of substantial interpatient ...variability in DDI magnitude. Because renal dysfunction induces changes in drug metabolism and protein binding that could alter cytochrome P450 inhibition mechanisms, we hypothesized that renal dysfunction alters the impact of the warfarin‐amiodarone DDI. We tested this question in a propensity‐matched cohort study of hospitalized patients with atrial fibrillation. Patients were queried from an electronic health record database. Renal function was estimated with creatinine clearance (CrCl). Warfarin response was measured with the warfarin sensitivity index (WSI), a dose‐normalized international normalized ratio (INR) measure, and was modeled with multilevel mixed‐effects linear regression. Time to supratherapeutic INR (> 4) was modeled using Cox regression. Propensity score matching resulted in 4,518 patients administered amiodarone and 4,518 controls. Amiodarone’s effect on warfarin response varied threefold across the renal function range, increasing WSI by 36% in patients with normal renal function (CrCl 115 mL/minute), but by only 11.8% in patients with severe renal dysfunction (CrCl 15 mL/minute). Similarly, amiodarone had a strong effect in patients with normal renal function (hazard ratio (HR) 1.80; 1.23, 2.64), but a negligible effect on supratherapeutic INR hazard in patients with severe renal dysfunction (HR 1.01; 0.75, 1.37). These results suggest that renal function is a novel factor that explains substantial variability in the warfarin‐amiodarone DDI. This information could inform warfarin dosage adjustment and monitoring and may have implications for the selection of oral anticoagulation agents in patients treated with amiodarone.
ABSTRACT We describe the development and application of a Global Astrometric Solution (GAS) to the problem of Pan-STARRS1 (PS1) astrometry. Current PS1 astrometry is based on differential astrometric ...measurements using 2MASS reference stars, and thus PS1 astrometry inherits the errors of the 2MASS catalog. The GAS, based on a single, least-squares adjustment to approximately 750 k "grid stars" using over 3000 extragalactic objects as reference objects, avoids this catalog-to-catalog propagation of errors to a great extent. The GAS uses a relatively small number of quasi-stellar objects (QSOs, or distant active galactic nuclei) with very accurate (<1 mas) radio positions, referenced to the ICRF2. These QSOs provide a hard constraint in the global least-squares adjustment. Solving such a system provides absolute astrometry for all of the stars simultaneously. The concept is much cleaner than conventional astrometry but is not easy to perform for large catalogs. In this paper, we describe our method and its application to Pan-STARRS1 data. We show that large-scale systematic errors are easily corrected but our solution residuals for position (∼60 mas) are still larger than expected based on simulations (∼10 mas). We provide a likely explanation for the reason the small-scale residual errors are not corrected in our solution as would be expected.
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