To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed ...academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
Significance Currently there are no targeted therapies for KRAS mutant cancer. Our study uncovers a critical role of the small ubiquitin-like modifier (SUMO) E2 ligase Ubc9 in sustaining the ...transformation growth of KRAS mutant colorectal cancer cells, thus establishing a functional link between the SUMO pathway and the KRAS oncogene. SUMO ligases are poorly explored drug targets; our work suggests that targeting the SUMO pathway, and Ubc9 in particular, could be potentially useful for the treatment of KRAS mutant colorectal cancers.
The small GTPase KRAS is frequently mutated in human cancer and currently there are no targeted therapies for KRAS mutant tumors. Here, we show that the small ubiquitin-like modifier (SUMO) pathway is required for KRAS-driven transformation. RNAi depletion of the SUMO E2 ligase Ubc9 suppresses 3D growth of KRAS mutant colorectal cancer cells in vitro and attenuates tumor growth in vivo. In KRAS mutant cells, a subset of proteins exhibit elevated levels of SUMOylation. Among these proteins, KAP1, CHD1, and EIF3L collectively support anchorage-independent growth, and the SUMOylation of KAP1 is necessary for its activity in this context. Thus, the SUMO pathway critically contributes to the transformed phenotype of KRAS mutant cells and Ubc9 presents a potential target for the treatment of KRAS mutant colorectal cancer.
The bioMérieux BacT/Alert Virtuo blood culture system used in combination with resin-containing media may enhance the growth of microorganisms. Our objective was to assess the impact of transitioning ...to the Virtuo system in comparison to the VersaTREK blood culture system at a tertiary care medical center. We retrospectively reviewed all blood cultures performed at a 1,250-bed academic medical center between January and December 2018 (VersaTREK) and January and December 2019 (Virtuo). Blood culture positivity rates and contamination rates were compared before and after Virtuo implementation. Of 101,438 blood cultures performed during the study period, 48,839 (48.1%) were processed preimplementation and 52,599 (51.9%) postimplementation. The blood culture positivity rate increased from 8.1% preimplementation to 11.7% postimplementation (
< 0.001). Staphylococcus aureus was the most frequently isolated species in both time periods and had a higher recovery rate postimplementation (1.5% of all blood cultures obtained preimplementation versus 3.4% postimplementation;
< 0.001). A higher recovery rate in the postimplementation period was also noted for coagulase-negative staphylococci (1.9% preimplementation versus 2.7% postimplementation;
< 0.001), as well as modest but statistically significant changes for Escherichia coli (0.8% versus 1.0%;
< 0.001), Klebsiella pneumoniae (0.4% versus 0.5%;
= 0.005), and Candida albicans. (0.1% versus 0.2%;
= 0.038). The inpatient blood culture contamination rate was higher postimplementation (1.5% preimplementation versus 1.9% postimplementation;
< 0.001). The Virtuo blood culture system was associated with a higher observed proportion of positive blood cultures than the VersaTREK system. Future studies are needed to assess whether an increased rate of positive blood cultures is associated with changes in clinical outcomes.
Orbital gamma‐ray measurements obtained by the MESSENGER spacecraft have been analyzed to determine the abundances of the major elements Al, Ca, S, Fe, and Na on the surface of Mercury. The Si ...abundance was determined and used to normalize those of the other reported elements. The Na analysis provides the first abundance estimate of 2.9 ± 0.1 wt% for this element on Mercury's surface. The other elemental results (S/Si = 0.092 ± 0.015, Ca/Si = 0.24 ± 0.05, and Fe/Si = 0.077 ± 0.013) are consistent with those previously obtained by the MESSENGER X‐Ray Spectrometer, including the high sulfur and low iron abundances. Because of different sampling depths for the two techniques, this agreement indicates that Mercury's regolith is, on average, homogenous to a depth of tens of centimeters. The elemental results from gamma‐ray and X‐ray spectrometry are most consistent with petrologic models suggesting that Mercury's surface is dominated by Mg‐rich silicates. We also compare the results with those obtained during the MESSENGER flybys and with ground‐based observations of Mercury's surface and exosphere.
Key Points
Abundances of the major elements on the surface of Mercury
MESSENGER mission orbital gamma ray measurements
The first abundance measurements of sodium
This consensus statement by the Society for Healthcare Epidemiology of America (SHEA) and the Society for Post-Acute and Long-Term Care Medicine (AMDA), the Association for Professionals in ...Epidemiology and Infection Control (APIC), the HIV Medicine Association (HIVMA), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP) recommends that coronavirus disease 2019 (COVID-19) vaccination should be a condition of employment for all healthcare personnel in facilities in the United States. Exemptions from this policy apply to those with medical contraindications to all COVID-19 vaccines available in the United States and other exemptions as specified by federal or state law. The consensus statement also supports COVID-19 vaccination of nonemployees functioning at a healthcare facility (eg, students, contract workers, volunteers, etc).
Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, ...and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 6956 VLBW (401-1500 g) neonates admitted to the clinical centers of the National Institute of Child Health and Human Development Neonatal Research Network over a 2-year period (1998-2000).
The National Institute of Child Health and Human Development Neonatal Research Network maintains a prospective registry of all VLBW neonates admitted to participating centers within 14 days of birth. Expanded infection surveillance was added in 1998.
Of 6215 infants who survived beyond 3 days, 1313 (21%) had 1 or more episodes of blood culture-proven late-onset sepsis. The vast majority of infections (70%) were caused by Gram-positive organisms, with coagulase-negative staphylococci accounting for 48% of infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of late-onset sepsis included patent ductus arteriosus, prolonged ventilation, prolonged intravascular access, bronchopulmonary dysplasia, and necrotizing enterocolitis. Infants who developed late-onset sepsis had a significantly prolonged hospital stay (mean length of stay: 79 vs 60 days). They were significantly more likely to die than those who were uninfected (18% vs 7%), especially if they were infected with Gram-negative organisms (36%) or fungi (32%).
Late-onset sepsis remains an important risk factor for death among VLBW preterm infants and for prolonged hospital stay among VLBW survivors. Strategies to reduce late-onset sepsis and its medical, social, and economic toll need to be addressed urgently.
The speed-accuracy trade-off (SAT), whereby faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during the performance of almost all daily tasks. ...To date, computational modeling has implicated the latent decision variable of response caution (thresholds), the amount of evidence required for a decision to be made, in the SAT. Previous imaging has associated frontal regions, notably the left prefrontal cortex and the presupplementary motor area (pre-SMA), with the setting of such caution levels. In addition, causal brain stimulation studies, using transcranial direct current stimulation (tDCS), have indicated that while both of these regions are involved in the SAT, their role appears to be dissociable. tDCS efficacy to impact decision-making processes has previously been linked with neurochemical concentrations and cortical thickness of stimulated regions. However, to date, it is unknown whether these neurophysiological measures predict individual differences in the SAT, and brain stimulation effects on the SAT. Using ultra-high field (7T) imaging, here we report that instruction-based adjustments in caution are associated with both neurochemical excitability (the balance between GABA+ and glutamate) and cortical thickness across a range of frontal regions in both sexes. In addition, cortical thickness, but not neurochemical concentrations, was associated with the efficacy of left prefrontal and superior medial frontal cortex (SMFC) stimulation to modulate performance. Overall, our findings elucidate key neurophysiological predictors, frontal neural excitation, of individual differences in latent psychological processes and the efficacy of stimulation to modulate these.
The speed-accuracy trade-off (SAT), faster decisions increase the likelihood of an error, reflects a cognitive strategy humans must engage in during most daily tasks. The SAT is often investigated by explicitly instructing participants to prioritize speed or accuracy when responding to stimuli. Using ultra-high field (7T) magnetic resonance imaging (MRI), we found that individual differences in the extent to which participants adjust their decision strategies with instruction related to neurochemical excitability (ratio of GABA+ to glutamate) and cortical thickness in the frontal cortex. Moreover, brain stimulation to the left prefrontal cortex and the superior medial frontal cortex (SMFC) modulated performance, with the efficacy specifically related to cortical thickness. This work sheds new light on the neurophysiological basis of decision strategies and brain stimulation.
Hypoxia-inducible factor 1α (HIF-1α), a major mediator of tumor physiology, is activated during tumor progression, and its abundance is correlated with therapeutic resistance in a broad range of ...solid tumors. The accumulation of HIF-1α is mainly caused by hypoxia or through the mutated succinate dehydrogenase A (SDHA) or fumarate hydratase (FH) expression to inhibit its degradation. However, its activation under normoxic conditions, termed pseudohypoxia, in cells without mutated SDHA or FH is not well documented. Here, we show that dimethyl-2-ketoglutarate (DKG), a cell membrane-permeable precursor of a key metabolic intermediate, α-ketoglutarate (α-KG), known for its ability to rescue glutamine deficiency, transiently stabilized HIF-1α by inhibiting activity of the HIF prolyl hydroxylase domain-containing protein, PHD2. Consequently, prolonged DKG-treatment under normoxia elevated HIF-1α abundance and up-regulated the expression of its downstream target genes, thereby inducing a pseudohypoxic condition. This HIF-1α stabilization phenotype is similar to that from treatment of cells with desferrioxamine (DFO), an iron chelator, or dimethyloxalyglycine (DMOG), an established PHD inhibitor, but was not recapitulated with other α-KG analogues, such as Octyl-2KG, MPTOM001 and MPTOM002. Our study is the first example of an α-KG precursor to increase HIF-1α abundance and activity. We propose that DKG acts as a potent HIF-1α activator, highlighting the potential use of DKG to investigate the contribution of PHD2-HIF-1α pathway to tumor biology.
JCO
The purpose of this update was to determine differences in patient-reported chronic toxicity and disease outcomes with intensity-modulated radiation therapy (IMRT) compared with conventional ...pelvic radiation. Patients with cervical and endometrial cancers who received postoperative pelvic radiation were randomly assigned to conventional radiation therapy (CRT) or IMRT. Toxicity and quality of life were assessed using Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, Expanded Prostate Cancer Index Composite (EPIC) bowel and urinary domains, and Functional Assessment of Cancer Therapy-General. Between 2012 and 2015, 279 eligible patients were enrolled to the study with a median follow-up of 37.8 months. There were no differences in overall survival (
= .53), disease-free survival (
= .21), or locoregional failure (
= .81). One year after RT, patients in the CRT arm experienced more high-level diarrhea frequency (5.8% IMRT
15.1% CRT,
= .042) and a greater number had to take antidiarrheal medication two or more times a day (1.2% IMRT
8.6% CRT,
= .036). At 3 years, women in the CRT arm reported a decline in urinary function, whereas the IMRT arm continued to improve (mean change in EPIC urinary score = 0.5, standard deviation = 13.0, IMRT
-6.0, standard deviation = 14.3, CRT,
= .005). In conclusion, IMRT reduces patient-reported chronic GI and urinary toxicity with no difference in treatment efficacy at 3 years.
PDF
