Automated detection of medication administration errors in neonatal intensive care

AbstractObjectiveTo improve neonatal patient safety through automated detection of medication administration errors (MAEs) in high alert medications including narcotics, vasoactive medication, intravenous fluids, parenteral nutrition, and insulin using the electronic health record (EHR); to evaluate rates of MAEs in neonatal care; and to compare the performance of computerized algorithms to traditional incident reporting for error detection.MethodsWe developed novel computerized algorithms to identify MAEs within the EHR of all neonatal patients treated in a level four neonatal intensive care unit (NICU) in 2011 and 2012. We evaluated the rates and types of MAEs identified by the automated algorithms and compared their performance to incident reporting. Performance was evaluated by physician chart review.ResultsIn the combined 2011 and 2012 NICU data sets, the automated algorithms identified MAEs at the following rates: fentanyl, 0.4% (4 errors/1005 fentanyl administration records); morphine, 0.3% (11/4009); dobutamine, 0 (0/10); and milrinone, 0.3% (5/1925). We found higher MAE rates for other vasoactive medications including: dopamine, 11.6% (5/43); epinephrine, 10.0% (289/2890); and vasopressin, 12.8% (54/421). Fluid administration error rates were similar: intravenous fluids, 3.2% (273/8567); parenteral nutrition, 3.2% (649/20124); and lipid administration, 1.3% (203/15227). We also found 13 insulin administration errors with a resulting rate of 2.9% (13/456). MAE rates were higher for medications that were adjusted frequently and fluids administered concurrently. The algorithms identified many previously unidentified errors, demonstrating significantly better sensitivity (82% vs. 5%) and precision (70% vs. 50%) than incident reporting for error recognition.ConclusionsAutomated detection of medication administration errors through the EHR is feasible and performs better than currently used incident reporting systems. Automated algorithms may be useful for real-time error identification and mitigation

Developing and evaluating a machine learning based algorithm to predict the need of pediatric intensive care unit transfer for newly hospitalized children

AbstractBackgroundEarly warning scores (EWS) are designed to identify early clinical deterioration by combining physiologic and/or laboratory measures to generate a quantified score. Current EWS leverage only a small fraction of Electronic Health Record (EHR) content. The planned widespread implementation of EHRs brings the promise of abundant data resources for prediction purposes. The three specific aims of our research are: (1) to develop an EHR-based automated algorithm to predict the need for Pediatric Intensive Care Unit (PICU) transfer in the first 24h of admission; (2) to evaluate the performance of the new algorithm on a held-out test data set; and (3) to compare the effectiveness of the new algorithm's with those of two published Pediatric Early Warning Scores (PEWS).MethodsThe cases were comprised of 526 encounters with 24-h Pediatric Intensive Care Unit (PICU) transfer. In addition to the cases, we randomly selected 6772 control encounters from 62516 inpatient admissions that were never transferred to the PICU. We used 29 variables in a logistic regression and compared our algorithm against two published PEWS on a held-out test data set.ResultsThe logistic regression algorithm achieved 0.849 (95% CI 0.753–0.945) sensitivity, 0.859 (95% CI 0.850–0.868) specificity and 0.912 (95% CI 0.905–0.919) area under the curve (AUC) in the test set. Our algorithm's AUC was significantly higher, by 11.8 and 22.6% in the test set, than two published PEWS.ConclusionThe novel algorithm achieved higher sensitivity, specificity, and AUC than the two PEWS reported in the literature

Large-scale evaluation of automated clinical note de-identification and its impact on information extraction

Objective: (1) To evaluate a state-of-the-art natural language processing (NLP)-based approach to automatically de-identify a large set of diverse clinical notes. (2) To measure the impact of de-identification on the performance of information extraction algorithms on the de-identified documents. Material and methods A cross-sectional study that included 3503 stratified, randomly selected clinical notes (over 22 note types) from five million documents produced at one of the largest US pediatric hospitals. Sensitivity, precision, F value of two automated de-identification systems for removing all 18 HIPAA-defined protected health information elements were computed. Performance was assessed against a manually generated ‘gold standard’. Statistical significance was tested. The automated de-identification performance was also compared with that of two humans on a 10% subsample of the gold standard. The effect of de-identification on the performance of subsequent medication extraction was measured. Results: The gold standard included 30 815 protected health information elements and more than one million tokens. The most accurate NLP method had 91.92% sensitivity (R) and 95.08% precision (P) overall. The performance of the system was indistinguishable from that of human annotators (annotators' performance was 92.15%(R)/93.95%(P) and 94.55%(R)/88.45%(P) overall while the best system obtained 92.91%(R)/95.73%(P) on same text). The impact of automated de-identification was minimal on the utility of the narrative notes for subsequent information extraction as measured by the sensitivity and precision of medication name extraction. Discussion and conclusion NLP-based de-identification shows excellent performance that rivals the performance of human annotators. Furthermore, unlike manual de-identification, the automated approach scales up to millions of documents quickly and inexpensively

EMR-linked GWAS study: investigation of variation landscape of loci for body mass index in children

Common variations at the loci harboring the fat mass and obesity gene (FTO), MC4R, and TMEM18 are consistently reported as being associated with obesity and body mass index (BMI) especially in adult population. In order to confirm this effect in pediatric population five European ancestry cohorts from pediatric eMERGE-II network (CCHMC-BCH) were evaluated. Method: Data on 5049 samples of European ancestry were obtained from the Electronic Medical Records (EMRs) of two large academic centers in five different genotyped cohorts. For all available samples, gender, age, height, and weight were collected and BMI was calculated. To account for age and sex differences in BMI, BMI z-scores were generated using 2000 Centers of Disease Control and Prevention (CDC) growth charts. A Genome-wide association study (GWAS) was performed with BMI z-score. After removing missing data and outliers based on principal components (PC) analyses, 2860 samples were used for the GWAS study. The association between each single nucleotide polymorphism (SNP) and BMI was tested using linear regression adjusting for age, gender, and PC by cohort. The effects of SNPs were modeled assuming additive, recessive, and dominant effects of the minor allele. Meta-analysis was conducted using a weighted z-score approach. Results: The mean age of subjects was 9.8 years (range 2–19). The proportion of male subjects was 56%. In these cohorts, 14% of samples had a BMI ≥95 and 28 ≥ 85%. Meta analyses produced a signal at 16q12 genomic region with the best result of p = 1.43 × 10-7 [p(rec) = 7.34 × 10-8) for the SNP rs8050136 at the first intron of FTO gene (z = 5.26) and with no heterogeneity between cohorts (p = 0.77). Under a recessive model, another published SNP at this locus, rs1421085, generates the best result [z = 5.782, p(rec) = 8.21 × 10-9]. Imputation in this region using dense 1000-Genome and Hapmap CEU samples revealed 71 SNPs with p < 10-6, all at the first intron of FTO locus. When hetero-geneity was permitted between cohorts, signals were also obtained in other previously identified loci, including MC4R (rs12964056, p = 6.87 × 10-7, z = -4.98), cholecystokinin CCK (rs8192472, p = 1.33 × 10-6, z = -4.85), Interleukin 15 (rs2099884, p = 1.27 × 10-5, z = 4.34), low density lipoprotein receptor-related protein 1B [LRP1B (rs7583748, p = 0.00013, z = -3.81)] and near transmembrane protein 18 (TMEM18) (rs7561317, p = 0.001, z = -3.17). We also detected a novel locus at chromosome 3 at COL6A5 [best SNP = rs1542829, minor allele frequency (MAF) of 5% p = 4.35 × 10-9, z = 5.89]. Conclusion: An EMR linked cohort study demonstrates that the BMI-Z measurements can be successfully extracted and linked to genomic data with meaningful confirmatory results. We verified the high prevalence of childhood rate of overweight and obesity in our cohort (28%). In addition, our data indicate that genetic variants in the first intron of FTO, a known adult genetic risk factor for BMI, are also robustly associated with BMI in pediatric population

Proboscis Morphology and Its Relationship to Feeding Habits in Noctuid Moths

This study describes proboscis morphology and identifies morphometric differences among five species of noctuid moths with different feeding habits (fruit versus nectar-feeding). Morphological and morphometric parameters were analyzed using scanning electron microscopy and light microscopy. Measurements included: galea height in ten sites from base to tip, total proboscis length, and length of the distal region that contains large sensilla styloconica and / or tearing hooks and erectible barbs. Both morphometric and morphological differences were identified among species within and between feeding guilds, and these results are discussed in light of the feeding habits of each species

Phenome-wide association study (PheWAS) in EMR-linked pediatric cohorts, genetically links PLCL1 to speech language development and IL5-IL13 to Eosinophilic Esophagitis

Objective: We report the first pediatric specific Phenome-Wide Association Study (PheWAS) using electronic medical records (EMRs). Given the early success of PheWAS in adult populations, we investigated the feasibility of this approach in pediatric cohorts in which associations between a previously known genetic variant and a wide range of clinical or physiological traits were evaluated. Although computationally intensive, this approach has potential to reveal disease mechanistic relationships between a variant and a network of phenotypes. Method: Data on 5049 samples of European ancestry were obtained from the EMRs of two large academic centers in five different genotyped cohorts. Recently, these samples have undergone whole genome imputation. After standard quality controls, removing missing data and outliers based on principal components analyses (PCA), 4268 samples were used for the PheWAS study. We scanned for associations between 2476 single-nucleotide polymorphisms (SNP) with available genotyping data from previously published GWAS studies and 539 EMR-derived phenotypes. The false discovery rate was calculated and, for any new PheWAS findings, a permutation approach (with up to 1,000,000 trials) was implemented. Results: This PheWAS found a variety of common variants (MAF > 10%) with prior GWAS associations in our pediatric cohorts including Juvenile Rheumatoid Arthritis (JRA), Asthma, Autism and Pervasive Developmental Disorder (PDD) and Type 1 Diabetes with a false discovery rate < 0.05 and power of study above 80%. In addition, several new PheWAS findings were identified including a cluster of association near the NDFIP1 gene for mental retardation (best SNP rs10057309, p = 4.33 × 10−7, OR = 1.70, 95%CI = 1.38 − 2.09); association near PLCL1 gene for developmental delays and speech disorder [best SNP rs1595825, p = 1.13 × 10−8, OR = 0.65(0.57 − 0.76)]; a cluster of associations in the IL5-IL13 region with Eosinophilic Esophagitis (EoE) [best at rs12653750, p = 3.03 × 10−9, OR = 1.73 95%CI = (1.44 − 2.07)], previously implicated in asthma, allergy, and eosinophilia; and association of variants in GCKR and JAZF1 with allergic rhinitis in our pediatric cohorts [best SNP rs780093, p = 2.18 × 10−5, OR = 1.39, 95%CI = (1.19 − 1.61)], previously demonstrated in metabolic disease and diabetes in adults. Conclusion: The PheWAS approach with re-mapping ICD-9 structured codes for our European-origin pediatric cohorts, as with the previous adult studies, finds many previously reported associations as well as presents the discovery of associations with potentially important clinical implications

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Abstract Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe