Extended-spectrum ß-lactamase-producing Enterobacteriaceae in children: old foe, emerging threat.

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae present an ever-growing burden in the hospital and community settings, across all ages and demographics. Infections due to ESBL-containing pathogens continue to be associated with significant morbidity and mortality worldwide. With widespread empiric broad-spectrum ß-lactam use creating selective pressure, and the resultant emergence of stable, rapidly proliferating ESBL-producing clones with continued horizontal gene transfer across genera, addressing this issue remains imperative. Although well characterized in adults, the epidemiology, risk factors, outcomes, therapies, and control measures for ESBL-producing bacteria are less appreciated in children. This analysis provides a brief summary of ESBL-producing Enterobacteriaceae in children, with a focus on recent clinical and molecular data regarding colonization and infection in nonoutbreak settings.

NFKBIA deletion in glioblastomas.

BACKGROUND: Amplification and activating mutations of the epidermal growth factor receptor (EGFR) oncogene are molecular hallmarks of glioblastomas. We hypothesized that deletion of NFKBIA (encoding nuclear factor of κ-light polypeptide gene enhancer in B-cells inhibitor-α), an inhibitor of the EGFR-signaling pathway, promotes tumorigenesis in glioblastomas that do not have alterations of EGFR. METHODS: We analyzed 790 human glioblastomas for deletions, mutations, or expression of NFKBIA and EGFR. We studied the tumor-suppressor activity of NFKBIA in tumor-cell culture. We compared the molecular results with the outcome of glioblastoma in 570 affected persons. RESULTS: NFKBIA is often deleted but not mutated in glioblastomas; most deletions occur in nonclassical subtypes of the disease. Deletion of NFKBIA and amplification of EGFR show a pattern of mutual exclusivity. Restoration of the expression of NFKBIA attenuated the malignant phenotype and increased the vulnerability to chemotherapy of cells cultured from tumors with NFKBIA deletion; it also reduced the viability of cells with EGFR amplification but not of cells with normal gene dosages of both NFKBIA and EGFR. Deletion and low expression of NFKBIA were associated with unfavorable outcomes. Patients who had tumors with NFKBIA deletion had outcomes that were similar to those in patients with tumors harboring EGFR amplification. These outcomes were poor as compared with the outcomes in patients with tumors that had normal gene dosages of NFKBIA and EGFR. A two-gene model that was based on expression of NFKBIA and O(6)-methylguanine DNA methyltransferase was strongly associated with the clinical course of the disease. CONCLUSIONS: Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival.

The Application of Dental Fluoride Varnish in Children: A Low Cost, High-Value Implementation Aided by Passive Clinical Decision Support.

BACKGROUND: Fluoride is vital in the prevention of dental caries in children. In 2014, the U.S. Preventive Services Task Force deemed fluoride varnish a recommended preventive service (grade B). Electronic health record-based clinical decision support (CDS) tools have shown variable ability to alter physicians' ordering behaviors. OBJECTIVES: This study aimed to increase the application of fluoride varnish in children while analyzing the effect of two passive CDS tools-an order set and a note template. METHODS: Data on outpatient pediatric visits over an 18-month period before and after CDS implementation (October 15, 2020-April 15, 2022) were queried, while trends in application rate of fluoride were examined. We constructed a multiple logistic regression model with a primary outcome of whether a patient received fluoride at his/her visit. The primary predictor was a "phase" variable representing the CDS implemented. Physician interaction with CDS as well as the financial effects of the resulting service use were also examined. RESULTS: There were 3,049 well-child visits of children aged 12 months to 5 years. The addition of a fluoride order to a "Well Child Check" order set led to a 10.6% increase in ordering over physician education alone (25.4 vs. 14.8%, p = 0.001), while the insertion of fluoride-specific text to drop-down lists in clinical notes led to a 6.2% increase (31.5 vs. 25.4%, p = 0.005). Whether a patient received topical fluoride was positively associated with order set implementation (odds ratio [OR] = 5.87, 95% confidence interval [CI]: 4.20-8.21) and fluoride-specific drop-down lists (OR = 7.81, 95% CI: 5.41-11.28). Female providers were more likely to use order sets when ordering fluoride (56.2 vs. 40.9% for males, p ≤ 0.0001). Added revenue totaled $15,084. CONCLUSION: The targeted use of order sets and note templates was positively associated with the ordering of topical fluoride by physicians.

Evaluating the predictive ability of natural language processing in identifying tertiary/quaternary cases in prioritization workflows for interhospital transfer.

Objectives: Tertiary and quaternary (TQ) care refers to complex cases requiring highly specialized health services. Our study aimed to compare the ability of a natural language processing (NLP) model to an existing human workflow in predictively identifying TQ cases for transfer requests to an academic health center. Materials and methods: Data on interhospital transfers were queried from the electronic health record for the 6-month period from July 1, 2020 to December 31, 2020. The NLP model was allowed to generate predictions on the same cases as the human predictive workflow during the study period. These predictions were then retrospectively compared to the true TQ outcomes. Results: There were 1895 transfer cases labeled by both the human predictive workflow and the NLP model, all of which had retrospective confirmation of the true TQ label. The NLP model receiver operating characteristic curve had an area under the curve of 0.91. Using a model probability threshold of ≥0.3 to be considered TQ positive, accuracy was 81.5% for the NLP model versus 80.3% for the human predictions (P = .198) while sensitivity was 83.6% versus 67.7% (P<.001). Discussion: The NLP model was as accurate as the human workflow but significantly more sensitive. This translated to 15.9% more TQ cases identified by the NLP model. Conclusion: Integrating an NLP model into existing workflows as automated decision support could translate to more TQ cases identified at the onset of the transfer process.

Gene-protein correlation in single cells.

We present a novel methodology combining traditional fluorescent in situ hybridization with an in situ protein detection technology called proximity ligation assay. This method has potential to perform a detailed analysis of the relationship between gene status and corresponding protein expression in cells and tissues. We demonstrate that the fluorescent in situ gene protein assay methodology is capable of resolving gene and protein patterns simultaneously on a cell-by-cell basis.