Think twice: A cognitive perspective of an antibiotic timeout intervention to improve antibiotic use

ObjectivesTo understand clinicians' impressions of and decision-making processes regarding an informatics-supported antibiotic timeout program to re-evaluate the appropriateness of continuing vancomycin and piperacillin/tazobactam.MethodsWe implemented a multi-pronged informatics intervention, based on Dual Process Theory, to prompt discontinuation of unwarranted vancomycin and piperacillin/tazobactam on or after day three in a large Veterans Affairs Medical Center. Two workflow changes were introduced to facilitate cognitive deliberation about continuing antibiotics at day three: (1) teams completed an electronic template note, and (2) a paper summary of clinical and antibiotic-related information was provided to clinical teams. Shortly after starting the intervention, six focus groups were conducted with users or potential users. Interviews were recorded and transcribed. Iterative thematic analysis identified recurrent themes from feedback.ResultsThemes that emerged are represented by the following quotations: (1) captures and controls attention ("it reminds us to think about it"), (2) enhances informed and deliberative reasoning ("it makes you think twice"), (3) redirects decision direction ("…because [there was no indication] I just [discontinued] it without even trying"), (4) fosters autonomy and improves team empowerment ("the template… forces the team to really discuss it"), and (5) limits use of emotion-based heuristics ("my clinical concern is high enough I think they need more aggressive therapy…").ConclusionsRequiring template completion to continue antibiotics nudged clinicians to re-assess the appropriateness of specified antibiotics. Antibiotic timeouts can encourage deliberation on overprescribed antibiotics without substantially curtailing autonomy. An effective nudge should take into account clinician's time, workflow, and thought processes

Heart rate variability and inflammatory markers in neonates with hypoxic-ischemic encephalopathy

To examine heart rate variability (HRV) and inflammatory markers as predictors for neurological injury in neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). We hypothesized that HRV would differentiate between infants with no/mild injury and infants with moderate/severe injury observed on MRI. Because HRV can be associated with the inflammatory cascade, cytokine concentrations were compared with the severity of brain injury indicated by MRI. Further, we studied the effect of temperature, sex, and mechanical ventilation on HRV. HRV was prospectively collected on neonates with HIE using spectral analysis for low and high frequency components (n = 16). A subset (n = 10) of neonates had serum available for inflammatory cytokine analysis obtained during cooling. Neonates were stratified into no/mild or moderate/severe injury based on MRI obtained after rewarming. Differences in HRV were identified; lower low frequency power predicted more injury on MRI. Additionally, in neonates with HIE after cooling procedure, HRV differed by gender. Elevated RANTES (CCL5) and decreased GM-CSF (Granulocyte-macrophage colony-stimulating factor) at 96 hours predicted less severe injury. In this small study, HRV differs between no/mild and moderate/severe injury in neonates with HIE. With further study, this may aid the clinician in real-time decision making. HRV differs by gender. Finally, inflammatory biomarkers may help elucidate the pathophysiology of HIE.University of Florida Open Access Publishing FundOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

An extract from date palm fruit (&ITPhoenix dactylifera&IT) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression&IT in vitro &IT

Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPAR alpha) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis

DPE differentially regulates FXR-target gene expression <i>in vitro</i> in Caco-2 cells.

<p>Caco-2 cells were treated for 12 hours with either a negative control (DMSO), varying doses of DPE (20, 50 or 100 mg/L), 100 μM CDCA, or a combination of CDCA + DPE, as indicated. Relative gene expression is shown for <b>A.</b> <i>ASBT</i>, <b>B.</b> <i>IBABP</i>, <b>C.</b> <i>FGF19</i>, <b>D.</b> <i>OSTα</i>, <b>E.</b> <i>OSTβ</i>, and <b>F.</b> <i>FXR</i>. (Negative control (DMSO), <i>white bars</i>; DPE (20, 50 or 100 mg/L) (<i>gray bars</i>); CDCA (100 μM) (<i>black bars</i>); or in combination (<i>hatched bars</i>). Statistical differences are represented by letters. Bars with the same superscript letter are not significantly different from each other.</p

RP-HPLC-DAD and MALDI-TOF mass spec analysis of date palm extract.

<p><b>A</b>. RP-HPLC-DAD chromatograms for DPE at 280 nm (red) and 320 nm (black); and <b>B</b>. Positive reflectron mode MALDI-TOF MS spectra showing a series of peaks at m/z 734 (Δ238amu), m/z 762 (Δ266amu) and m/z 784 (Δ288amu) that may correspond to long-chain ω–hydroxyfatty acids (C16, C18, C20) esterified to the trans- Feruloyloxy octadecanoic acid. AI: absolute intensities; AU: absorbance units.</p