Prior data have suggested that suboptimal antibiotic prescribing in the emergency department (ED) is common for uncomplicated lower respiratory tract infections (LRTI), urinary tract infections ...(UTI), and acute bacterial skin and skin structure infections (ABSSSI). The objective of this study was to measure the effect of indication-based antibiotic order sentences (AOS) on optimal antibiotic prescribing in the ED.
This was an IRB-approved quasi-experiment of adults prescribed antibiotics in EDs for uncomplicated LRTI, UTI, or ABSSSI from January to June 2019 (pre-implementation) and September to December 2021 (post-implementation). AOS implementation occurred in July 2021. AOS are lean process, electronic discharge prescriptions retrievable by name or indication within the discharge order field. The primary outcome was optimal prescribing, defined as correct antibiotic selection, dose, and duration per local and national guidelines. Descriptive and bivariate statistics were performed; multivariable logistic regression was used to determine variables associated with optimal prescribing.
A total of 294 patients were included: 147 pre-group and 147 post-group. Overall optimal prescribing improved from 12 (8%) to 34 (23%) (P < 0.001). Individual components of optimal prescribing were optimal selection at 90 (61%) vs 117 (80%) (P < 0.001), optimal dose at 99 (67%) vs 115 (78%) (P = 0.036), and optimal duration at 38 (26%) vs 50 (34%) (P = 0.13) for pre- and post-group, respectively. AOS was independently associated with optimal prescribing after multivariable logistic regression analysis (adjOR, 3.6; 95%CI,1.7–7.2). A post-hoc analysis showed low uptake of AOS by ED prescribers.
AOS are an efficient and promising strategy to enhance antimicrobial stewardship in the ED.
Objective
Body mass index (BMI) is the most commonly used predictor of weight‐related comorbidities and outcomes. However, the presumed relationship between height and weight intrinsic to BMI may ...introduce bias with respect to prediction of clinical outcomes. A series of analyses comparing the performance of models representing weight and height as separate interacting variables to models using BMI were performed using Vanderbilt University Medical Center's deidentified electronic health records and landmark methodology.
Methods
Use of BMI or height‐weight interaction in prediction models for established weight‐related cardiometabolic traits and metabolic syndrome was evaluated. Specifically, prediction models for hypertension, diabetes mellitus, low high‐density lipoprotein, and elevated triglycerides, atrial fibrillation, coronary artery disease, heart failure, and peripheral artery disease were developed. Model performance was evaluated using likelihood ratio, R2, and Somers' Dxy rank correlation. Differences in model predictions were visualized using heat maps.
Results
Compared to BMI, the maximally flexible height‐weight interaction model demonstrated improved prediction, higher likelihood ratio, R2, and Somers' Dxy rank correlation, for event‐free probability for all outcomes. The degree of improvement to the prediction model differed based on the outcome and across the height and weight range.
Conclusions
Because alternative measures of body composition such as waist‐to‐hip ratio are not routinely collected in the clinic clinical risk models quantifying risk based on height and weight measurements alone are essential to improve practice. Compared to BMI, modeling height and weight as independent, interacting variables results in less bias and improved predictive accuracy for all tested traits. Considering an individual's height and weight opposed to BMI is a better method for quantifying individual disease risk.
Students may do well answering exam questions that are similar to examples presented in class. Yet, some of these students perform poorly on exam questions that require applying instructed concepts ...to a new problem whereas others fare better on such questions. Our hypothesis is that these performance differences reflect, in part, individual differences in learners' tendencies to focus on acquiring the particular exemplars and responses associated with the training exemplars (exemplar learners) versus attempting to abstract underlying regularities reflected in particular exemplars (abstraction learners). Using a web-based learning task developed in previous laboratory research, we differentiated students on this dimension, and then tracked their final exam performances in introductory chemistry courses. Abstraction learners demonstrated advantages over exemplar learners for transfer questions but not for retention questions. The results converge on the idea that individual differences displayed in how learners acquire and represent concepts persist from laboratory concept learning to learning complex concepts in science courses.
General Audience Summary
Instructors sometimes note that though students do well answering exam questions that are similar to examples (or problems) presented in class, a sizeable proportion of students flounder on exam questions that require applying instructed concepts to a new context (or problem). Yet, other students perform satisfactorily on these exam questions requiring transfer to a new context. To understand this difference, we suggest that some students orient toward learning an underlying abstraction of a concept, whereas other students focus on memorizing the set of problems (e.g., chemistry problems) or examples that illustrate the concept. In our study, we indexed students in a college chemistry course as either exemplar learners (memorizers) or abstractors, using a laboratory concept-building task (outside of the classroom). We found that learners identified as exemplar learners performed more poorly than learners identified as abstraction learners on chemistry exam problems requiring extrapolation (transfer) but not on exam problems that were very similar to class or homework problems. The present findings offer tantalizing evidence of an individual difference not yet identified in the academic-achievement literature that may have significant implications for students' learning outcomes in authentic educational situations.
Prior coronary artery bypass grafting (CABG) has been a contraindication to lung transplantation (LTx) because of disease severity and technical considerations. Although patients increasingly are ...being referred for and receiving LTx, whether it should remain a contraindication is unknown. We sought to define the prevalence of LTx after CABG and determine the effect on outcomes.
The United Network for Organ Sharing Standard Transplant Analysis and Research data set was queried during the period 2004-2013 for adult LTx patients, as prior CABG became a mandatory reporting field in 2004. The primary end-points were 30-day and 1-, 3-, and 5-year survivals.
The study cohort included 14,791 patients, of whom 292 patients had previously undergone CABG (single left, n = 68; single right, n = 181; bilateral, n = 43), representing 2% of all transplants. For the entire cohort, 30-day survival was 97%, and survival at 1, 3, and 5 years was 88%, 79%, and 74%. CABG was a predictor of mortality at all time points, with hazard ratios ranging from 1.97 (confidence interval, 1.23-3.16; p < 0.01) at 30 days to 1.38 (confidence interval, 1.12-1.69; p < 0.01) at 5 years. When stratified by type of transplant, CABG strongly predicted mortality at all time points for patients receiving bilateral, but not single, transplants.
Although LTx after CABG is uncommon, it is increasingly performed in the current era. Single right LTx is the most common procedure performed in patients with prior CABG. CABG before LTx is an independent predictor of mortality at all time points and is driven by increased mortality in patients receiving bilateral LTx.
The genus Flavivirus contains many mosquito-borne human pathogens of global epidemiological importance such as dengue virus, West Nile virus, and Zika virus, which has recently emerged at epidemic ...levels. Infections with these viruses result in divergent clinical outcomes ranging from asymptomatic to fatal. Myriad factors influence infection severity including exposure, immune status and pathogen/host genetics. Furthermore, pre-existing infection may skew immune pathways or divert immune resources. We profiled immune cells from dengue virus-infected individuals by multiparameter mass cytometry (CyTOF) to define functional status. Elevations in IFNβ were noted in acute patients across the majority of cell types and were statistically elevated in 31 of 36 cell subsets. We quantified response to in vitro (re)infection with dengue or Zika viruses and detected a striking pattern of upregulation of responses to Zika infection by innate cell types which was not noted in response to dengue virus. Significance was discovered by statistical analysis as well as a neural network-based clustering approach which identified unusual cell subsets overlooked by conventional manual gating. Of public health importance, patient cells showed significant enrichment of innate cell responses to Zika virus indicating an intact and robust anti-Zika response despite the concurrent dengue infection.
Brain metastases from lung adenocarcinoma (BM-LUAD) frequently cause patient mortality. To identify genomic alterations that promote brain metastases, we performed whole-exome sequencing of 73 ...BM-LUAD cases. Using case-control analyses, we discovered candidate drivers of brain metastasis by identifying genes with more frequent copy-number aberrations in BM-LUAD compared to 503 primary LUADs. We identified three regions with significantly higher amplification frequencies in BM-LUAD, including MYC (12 versus 6%), YAP1 (7 versus 0.8%) and MMP13 (10 versus 0.6%), and significantly more frequent deletions in CDKN2A/B (27 versus 13%). We confirmed that the amplification frequencies of MYC, YAP1 and MMP13 were elevated in an independent cohort of 105 patients with BM-LUAD. Functional assessment in patient-derived xenograft mouse models validated the notion that MYC, YAP1 or MMP13 overexpression increased the incidence of brain metastasis. These results demonstrate that somatic alterations contribute to brain metastases and that genomic sequencing of a sufficient number of metastatic tumors can reveal previously unknown metastatic drivers.
Objective:
The aim of this study was to evaluate if somatosensory retraining programmes assist people to improve somatosensory discrimination skills and arm functioning after stroke.
Data sources:
...Nine databases were systematically searched: Medline, Cumulative Index to Nursing and Allied Health Literature, PsychInfo, Embase, Amed, Web of Science, Physiotherapy Evidence Database, OT seeker, and Cochrane Library.
Review methods:
Studies were included for review if they involved (1) adult participants who had somatosensory impairment in the arm after stroke, (2) a programme targeted at retraining somatosensation, (3) a primary measure of somatosensory discrimination skills in the arm, and (4) an intervention study design (e.g. randomized or non-randomized control designs).
Results:
A total of 6779 articles were screened. Five group trials and five single case experimental designs were included (N = 199 stroke survivors). Six studies focused exclusively on retraining somatosensation and four studies focused on somatosensation and motor retraining. Standardized somatosensory measures were typically used for tactile, proprioception, and haptic object recognition modalities. Sensory intervention effect sizes ranged from 0.3 to 2.2, with an average effect size of 0.85 across somatosensory modalities. A majority of effect sizes for proprioception and tactile somatosensory domains were greater than 0.5, and all but one of the intervention effect sizes were larger than the control effect sizes, at least as point estimates. Six studies measured motor and/or functional arm outcomes (n = 89 participants), with narrative analysis suggesting a trend towards improvement in arm use after somatosensory retraining.
Conclusion:
Somatosensory retraining may assist people to regain somatosensory discrimination skills in the arm after stroke.
OBJECTIVE Meningiomas located in the skull base are surgically challenging. Recent genomic research has identified oncogenic SMO and AKT1 mutations in a small subset of meningiomas. METHODS The ...authors performed targeted sequencing in a large cohort of patients with anterior skull base meningiomas (n = 62) to better define the frequency of SMO and AKT1 mutations in these tumors. RESULTS The authors found SMO mutations in 7 of 62 (11%) and AKT1 mutations in 12 of 62 (19%) of their cohort. Of the 7 meningiomas with SMO mutations, 6 (86%) occurred in the olfactory groove. Meningiomas with an SMO mutation presented with significantly larger tumor volume (70.6 ± 36.3 cm
) compared with AKT1-mutated (18.2 ± 26.8 cm
) and wild-type (22.7 ± 23.9 cm
) meningiomas, respectively. CONCLUSIONS Combined, these data demonstrate clinically actionable mutations in 30% of anterior skull base meningiomas and suggest an association between SMO mutation status and tumor volume. Genotyping of SMO and AKT1 is likely to be high yield in anterior skull base meningiomas with available surgical tissue.
Asthma, type 2 diabetes (T2D), and anthropometric measures are correlated complex traits that all have a major genetic component.
To investigate the overlap in genetic variants associated with these ...complex traits.
Using United Kingdom Biobank data, we performed univariate association analysis, fine-mapping, and mediation analysis to identify and dissect shared genomic regions associated with asthma, T2D, height, weight, body mass index (BMI), and waist circumference (WC).
We found several genome-wide significant variants in and around the
gene that are associated with asthma, T2D, or height with two of these variants shared by the three phenotypes. We also observed an association in this region with WC when adjusted for BMI. However, there was no association with WC when it was not adjusted for BMI or weight. Additionally, only suggestive associations between variants in this region and BMI were observed. Fine-mapping analyses suggested that within
there are non-overlapping regions harboring causal susceptibility variants for asthma, T2D, and height. Mediation analyses supported the conclusion that these are independent associations.
Our findings indicate that variants in the
are associated with asthma, T2D, and height, but the associated causal variant(s) are different for each of the three phenotypes.
The genetic alterations that define primary central nervous system lymphoma (PCNSL) are incompletely elucidated, and the genomic evolution from diagnosis to relapse is poorly understood. We performed ...whole-exome sequencing (WES) on 36 PCNSL patients and targeted MYD88 sequencing on a validation cohort of 27 PCNSL patients. We also performed WES and phylogenetic analysis of 3 matched newly diagnosed and relapsed tumor specimens and 1 synchronous intracranial and extracranial relapse. Immunohistochemistry (IHC) for programmed death-1 ligand (PD-L1) was performed on 43 patient specimens. Combined WES and targeted sequencing identified MYD88 mutation in 67% (42 of 63) of patients, CDKN2A biallelic loss in 44% (16 of 36), and CD79b mutation in 61% (22 of 36). Copy-number analysis demonstrated frequent regions of copy loss (ie, CDKN2A), with few areas of amplification. CD79b mutations were associated with improved progression-free and overall survival. We did not identify amplification at the PD-1/PD-L1 loci. IHC for PD-L1 revealed membranous expression in 30% (13 of 43) of specimens. Phylogenetic analysis of paired primary and relapsed specimens identified MYD88 mutation and CDKN2A loss as early clonal events. PCNSL is characterized by frequent mutations within the B-cell receptor and NF-κB pathways. The lack of PD-L1 amplifications, along with membranous PD-L1 expression in 30% of our cohort, suggests that PD-1/PD-L1 inhibitors may be useful in a subset of PCNSL. WES of PCNSL provides insight into the genomic landscape and evolution of this rare lymphoma subtype and potentially informs more rational treatment decisions.
Display omitted
PDF
