Automated clinical trial eligibility prescreening: increasing the efficiency of patient identification for clinical trials in the emergency department

Objectives (1) To develop an automated eligibility screening (ES) approach for clinical trials in an urban tertiary care pediatric emergency department (ED); (2) to assess the effectiveness of natural language processing (NLP), information extraction (IE), and machine learning (ML) techniques on real-world clinical data and trials.Data and methods We collected eligibility criteria for 13 randomly selected, disease-specific clinical trials actively enrolling patients between January 1, 2010 and August 31, 2012. In parallel, we retrospectively selected data fields including demographics, laboratory data, and clinical notes from the electronic health record (EHR) to represent profiles of all 202795 patients visiting the ED during the same period. Leveraging NLP, IE, and ML technologies, the automated ES algorithms identified patients whose profiles matched the trial criteria to reduce the pool of candidates for staff screening. The performance was validated on both a physician-generated gold standard of trial–patient matches and a reference standard of historical trial–patient enrollment decisions, where workload, mean average precision (MAP), and recall were assessed.Results Compared with the case without automation, the workload with automated ES was reduced by 92% on the gold standard set, with a MAP of 62.9%. The automated ES achieved a 450% increase in trial screening efficiency. The findings on the gold standard set were confirmed by large-scale evaluation on the reference set of trial–patient matches.Discussion and conclusion By exploiting the text of trial criteria and the content of EHRs, we demonstrated that NLP-, IE-, and ML-based automated ES could successfully identify patients for clinical trials.     

Branching out: a molecular fingerprint of endothelial differentiation into tube-like structures generated by Affymetrix oligonucleotide arrays

The process of endothelial differentiation into a network of tube-like structures with patent lumens requires an integrated program of gene expression. To identify genes upregulated in endothelial cells during the process of tube formation, RNA was prepared from several different time points (0, 4, 8, 24, 40, and 48 hours) and from three different experimental models of human endothelial tube formation: in collagen gels and fibrin gels driven by the combination of PMA (80), bFGF (40 ng/ml) and bFGF (40 ng/ml) or in collagen gels driven by the combination of HGF (40 ng/ml) and VEGF (40 ng/ml). Gene expression was evaluated using Affymetrix Gene Chip oligonucleotide arrays. Over 1000 common genes were upregulated greater than twofold over baseline at one or more time points in the three different models. In the present study, we discuss the identified genes that could be assigned to major functional classes: apoptosis, cytoskeleton, proteases, matrix, and matrix turnover, pumps and transporters, membrane lipid turnover, and junctional molecules or adhesion proteins.     

Continuous positive airway pressure therapy in sleep apnoea

Sleep apnoea is associated with increased mortality and morbidity. The treatment goal is to reduce the neurocognitive and cardiovascular sequelae. CPAP therapy in sleep apnoea is discussed in two parts in the article. The first part will consider CPAP therapy in the more common form of sleep apnoea (i.e. obstructive or mixed sleep apnoea) and the second part will consider CPAP therapy in central sleep apnoea. Alternative positive airway pressure modalities are discussed. CPAP therapy has been extensively studied and it remains the mainstay of treatment in obstructive sleep apnoea, as it is still the most consistently efficacious and safe option. However, its major disadvantage is that it does not confer a cure to this disorder and hence therapy is generally life long with its usual treatment compliance problems. As such, there are continuous improvement strategies. The role of CPAP therapy in central sleep apnoea is more limited. There has been increasing data on the beneficial effect of CPAP on central sleep apnoea/Cheyne-Stokes respiration in congestive heart failure. Evidence for CPAP therapy in sleep apnoea has evolved significantly over the last decade. However, more research and publication of large-scale long-term randomized trials of treatment in sleep apnoea to assess patient-orientated outcomes and preferences are necessary.     

Stability of local brain levels of insulin-like growth factor-I in two well-characterized models of decreased plasma IGF-I

Insulin-like growth factor-I (IGF-I), a functionally important neurotrophic factor, impacts tissues throughout the body including the central nervous system. In addition to the significant proportion of IGF-I that is synthesized in the liver and released into the plasma, IGF-I is expressed locally in tissues. The present study investigated the relationship between plasma and local brain levels of IGF-I in two well-characterized models of decreased IGF-I. The first is an adult-onset growth hormone deficiency (AOGHD) model, and the second is a caloric restriction (CR) model. In the first cohort of animals from both models, the hippocampus was removed from the brain immediately following decapitation, and in the second cohort, the animals were perfused transcardially with phosphate buffered saline to remove cerebral blood prior to harvesting the hippocampus. Our results demonstrated that although the plasma IGF-I levels were decreased in the CR and AOGHD rats compared to controls, the hippocampal IGF-I levels did not differ among the groups. These data suggest that local brain IGF-I levels are regulated in a different manner than plasma IGF-I levels.     

CD4+ T cells regulate glucose homeostasis independent of adipose tissue dysfunction in mice

Obesity is frequently associated with a chronic low-grade inflammation in the adipose tissue (AT) and impaired glucose homeostasis. Adipose tissue macrophages (ATMs) have been shown to accumulate in the inflamed AT either by means of recruitment from the blood or local proliferation. ATM proliferation and activation can be stimulated by TH2 cytokines, such as IL-4 and IL-13, suggesting involvement of CD4-positive T cells in ATM proliferation and activation. Furthermore, several studies have associated T cells to alterations in glucose metabolism. Therefore, we sought to examine a direct impact of CD4-positive T cells on ATM activation, ATM proliferation and glucose homeostasis using an in vivo depletion model. Surprisingly, CD4 depletion did not affect ATM activation, ATM proliferation, or insulin sensitivity. However, CD4 depletion led to a significant improvement of glucose tolerance. In line with this, we found moderate disturbances in pancreatic endocrine function following CD4 depletion. Hence, our data suggest that the effect on glucose metabolism observed after CD4 depletion might be mediated by organs other than AT and independent of AT inflammation.     

The relative locations of the supraorbital,infraorbital, and mental foramina: A cadaveric study

The purpose of this study is to investigate the applicability of the current surgical guideline stating that the main facial foramina that transmit cutaneous nerves to the face (supraorbital notch/foramen, infraorbital foramen, and mental foramen) are equidistant from the midline in European and Hispanic populations. Previous studies suggest this surgical guideline is not applicable for all ethnicities; however, to our knowledge, no data have been published regarding the accuracy of this guideline pertaining to the Hispanic population. An experimental study was performed on 67 cadavers donated to the Human Anatomy Program at UT Health San Antonio. The supraorbital, infraorbital, and mental foramina were dissected and midline structures including the crista galli, internasal suture, anterior nasal spine, and mandibular symphysis were identified. The distance from each foramen to midline was recorded using a digital caliper. For all cadavers/ethnicities studied, the supraorbital, infraorbital, and mental foramina were 25.32 mm, 29.57 mm, and 25.55 mm to the midline, respectively. Thus, the infraorbital foramen is located significantly more lateral compared to the supraorbital (p < 0.0001) and mental foramina (p < 0.0001). After dividing the sample based on ethnicity, this relationship was also true for the European sample and tended to be true for the Hispanic sample. Significant anatomical variations exist in the current surgical guideline stating that the supraorbital foramen, infraorbital foramen, and mental foramen are equidistant from the midline. Clinicians may need to adjust their methodology during surgical procedures of the face in order to optimize patient care.     

Cognitive screening for adult psychiatric outpatients: Comparison of the Cognivue® to the Montreal Cognitive Assessment

In this editorial we comment on the article by Cahn-Hidalgo D published in a recent issue of the World Journal of Psychiatry 2020; 10(1); 1-11. We focus on the importance of utilizing psychometrically valid cognitive screening tools when assessing for cognitive decline in older adults in a psychiatric outpatient setting. We compared the use of Cognivue^® to use of the montreal cognitive assessment (MoCA) as a cognitive screening tool. A total of 58 patients aged 55 and over participated in this comparison study. Patients completed cognitive screening on Cognivue^®, a new Food and Drug Administration-cleared computer screening device, and the MoCA. The results of patient performance using these two instruments were analyzed. Sixteen (28%) patients screened negative for cognitive impairment on both assessments. Forty-two (72%) patients screened positive on one or both of the assessments. There was 43% agreement between Cognivue^® and the MoCA in identifying patients with cognitive impairment, and individual subtests were weakly correlated. The MoCA was determined to be the preferred instrument due to its high sensitivity and specificity (100% and 87%, respectively) when screening for cognitive impairment. We propose that the use of Cognivue^® cognitive screening tool be closely reviewed until more research proves that the test meets the standards for reliability and validity. It is important for clinicians to remember that screeners should not be used to diagnosis patients with neurocognitive disorders; instead, they should be used to determine whether further evaluation is warranted. Additionally, misdiagnosing of neurocognitive disorders can pose unnecessary psychological and emotional harm to patients and their families and also lead to incorrect treatment and undue healthcare costs.     

Analysis of gene expression in wild‐type and Notch1 mutant retinal cells by single cell profiling

Results: To examine the molecular underpinnings of this observation, microarray analysis of single retinal cells from wild‐type or Notch1 conditional knockout retinas was performed. In situ hybridization was carried out to validate some of the findings. 相似文献