Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Querying clinical database.
Статті в журналах з теми "Querying clinical database"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "Querying clinical database".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Nigrin, D. J., and I. S. Kohane. "Temporal Expressiveness in Querying a Time-stamp--based Clinical Database." Journal of the American Medical Informatics Association 7, no. 2 (March 1, 2000): 152–63. http://dx.doi.org/10.1136/jamia.2000.0070152.
Повний текст джерела
2
Giardine, Belinda M., Philippe Joly, Serge Pissard, Henri Wajcman, David H. K. Chui, Ross C. Hardison, and George P. Patrinos. "Clinically relevant updates of the HbVar database of human hemoglobin variants and thalassemia mutations." Nucleic Acids Research 49, no. D1 (October 30, 2020): D1192—D1196. http://dx.doi.org/10.1093/nar/gkaa959.
Повний текст джерелаАнотація:
Abstract HbVar (http://globin.bx.psu.edu/hbvar) is a widely-used locus-specific database (LSDB) launched 20 years ago by a multi-center academic effort to provide timely information on the numerous genomic variants leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Here, we report several advances for the database. We made clinically relevant updates of HbVar, implemented as additional querying options in the HbVar query page, allowing the user to explore the clinical phenotype of compound heterozygous patients. We also made significant improvements to the HbVar front page, making comparative data querying, analysis and output more user-friendly. We continued to expand and enrich the regular data content, involving 1820 variants, 230 of which are new entries. We also increased the querying potential and expanded the usefulness of HbVar database in the clinical setting. These several additions, expansions and updates should improve the utility of HbVar both for the globin research community and in a clinical setting.
3
Tradigo, G., P. Veltri, and S. Greco. "Geomedica: managing and querying clinical data distributions on geographical database systems." Procedia Computer Science 1, no. 1 (May 2010): 979–86. http://dx.doi.org/10.1016/j.procs.2010.04.108.
Повний текст джерела
4
d’Acierno, Antonio, Angelo Facchiano, and Anna Marabotti. "GALT Protein Database: Querying Structural and Functional Features of GALT Enzyme." Human Mutation 35, no. 9 (July 23, 2014): 1060–67. http://dx.doi.org/10.1002/humu.22613.
Повний текст джерела
5
Hurdle, J. F., S. C. Haroldsen, A. Hammer, C. Spigle, A. M. Fraser, G. P. Mineau, and S. J. Courdy. "Identifying clinical/translational research cohorts: ascertainment via querying an integrated multi-source database." Journal of the American Medical Informatics Association 20, no. 1 (January 1, 2013): 164–71. http://dx.doi.org/10.1136/amiajnl-2012-001050.
Повний текст джерела
6
Mudaranthakam, Dinesh Pal, Jeffrey Thompson, Jinxiang Hu, Dong Pei, Shanthan Reddy Chintala, Michele Park, Brooke L. Fridley, Byron Gajewski, Devin C. Koestler, and Matthew S. Mayo. "A Curated Cancer Clinical Outcomes Database (C3OD) for accelerating patient recruitment in cancer clinical trials." JAMIA Open 1, no. 2 (July 10, 2018): 166–71. http://dx.doi.org/10.1093/jamiaopen/ooy023.
Повний текст джерелаАнотація:
Abstract Data used to determine patient eligibility for cancer clinical trials often come from disparate sources that are typically maintained by different groups within an institution, use differing technologies, and are stored in different formats. Collecting data and resolving inconsistencies across sources increase the time it takes to screen eligible patients, potentially delaying study completion. To address these challenges, the Biostatistics and Informatics Shared Resource at The University of Kansas Cancer Center developed the Curated Cancer Clinical Outcomes Database (C3OD). C3OD merges data from the electronic medical record, tumor registry, bio-specimen and data registry, and allows querying through a single unified platform. By centralizing access and maintaining appropriate controls, C3OD allows researchers to more rapidly obtain detailed information about each patient in order to accelerate eligibility screening. This case report describes the design of this informatics platform as well as initial assessments of its reliability and usability.
7
Schwabe-Fry, Kristen, Mark Bollenbeck, Merilee Teylan, Duane Beekly, George Thomas, Janene Hubbard, Mary Jacka, Joylee Wu, Lilah M. Besser, and Walter A. Kukull. "THE NATIONAL ALZHEIMER'S COORDINATING CENTER: QUERYING THE DATABASE AND REQUESTING DATA." Alzheimer's & Dementia 13, no. 7 (July 2017): P158. http://dx.doi.org/10.1016/j.jalz.2017.06.2599.
Повний текст джерела
8
Bollenbeck, Mark, Kristen Schwabe-Fry, Merilee Teylan, Duane Beekly, George Thomas, Janene Hubbard, Mary Jacka, Joylee Wu, Lilah M. Besser, and Walter A. Kukull. "[P1-555]: THE NATIONAL ALZHEIMER'S COORDINATING CENTER: QUERYING THE DATABASE AND REQUESTING DATA." Alzheimer's & Dementia 13, no. 7S_Part_10 (July 2017): P507. http://dx.doi.org/10.1016/j.jalz.2017.06.571.
Повний текст джерела
9
Nagarakshitha, B. R., K. S. Lohith, K. P. Aarthy, Arjun Gopkumar, and Uma Satya Ranjan. "Application of NoSQL Technology to Facilitate Storing and Retrieval of Clinical Data Using IndexedDb in Offline Conditions." Journal of Computational and Theoretical Nanoscience 17, no. 9 (July 1, 2020): 4012–15. http://dx.doi.org/10.1166/jctn.2020.9010.
Повний текст джерелаАнотація:
Data collection is a very important aspect of any research, especially while dealing with the collection of clinical data. This paper presents a way to collect and manage clinical data using a web application with offline functionality. The whole application is an end-to-end PWA providing an interface to collect the data, store, and query. The available data is very huge and it is unstructured. To store it, a NoSQL database such as Cassandra is most suitable. The data will mostly be used for an OLAP system for querying the data, cleaning and performing analysis on it. In the process of collection of data, the application has to work under low or no bandwidth conditions for which a NoSQL system provided by most web browsers called IndexedDB, can be used to locally store data under offline conditions.
10
Dong, Qun, Feng Li, Yanjun Xu, Jing Xiao, Yingqi Xu, Desi Shang, Chunlong Zhang, et al. "RNAactDrug: a comprehensive database of RNAs associated with drug sensitivity from multi-omics data." Briefings in Bioinformatics 21, no. 6 (December 3, 2019): 2167–74. http://dx.doi.org/10.1093/bib/bbz142.
Повний текст джерелаАнотація:
Abstract Drug sensitivity has always been at the core of individualized cancer chemotherapy. However, we have been overwhelmed by large-scale pharmacogenomic data in the era of next-generation sequencing technology, which makes it increasingly challenging for researchers, especially those without bioinformatic experience, to perform data integration, exploration and analysis. To bridge this gap, we developed RNAactDrug, a comprehensive database of RNAs associated with drug sensitivity from multi-omics data, which allows users to explore drug sensitivity and RNA molecule associations directly. It provides association data between drug sensitivity and RNA molecules including mRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) at four molecular levels (expression, copy number variation, mutation and methylation) from integrated analysis of three large-scale pharmacogenomic databases (GDSC, CellMiner and CCLE). RNAactDrug currently stores more than 4 924 200 associations of RNA molecules and drug sensitivity at four molecular levels covering more than 19 770 mRNAs, 11 119 lncRNAs, 438 miRNAs and 4155 drugs. A user-friendly interface enriched with various browsing sections augmented with advance search facility for querying the database is offered for users retrieving. RNAactDrug provides a comprehensive resource for RNA molecules acting in drug sensitivity, and it could be used to prioritize drug sensitivity–related RNA molecules, further promoting the identification of clinically actionable biomarkers in drug sensitivity and drug development more cost-efficiently by making this knowledge accessible to both basic researchers and clinical practitioners. Database URL: http://bio-bigdata.hrbmu.edu.cn/RNAactDrug.
11
Rolston, John D., Seunggu J. Han, Catherine Y. Lau, Mitchel S. Berger, and Andrew T. Parsa. "Frequency and predictors of complications in neurological surgery: national trends from 2006 to 2011." Journal of Neurosurgery 120, no. 3 (March 2014): 736–45. http://dx.doi.org/10.3171/2013.10.jns122419.
Повний текст джерелаАнотація:
Object Surgical complications increase the cost of health care worldwide and directly contribute to patient morbidity and mortality. In an effort to mitigate morbidity and incentivize best practices, stakeholders such as health insurers and the US government are linking reimbursement to patient outcomes. In this study the authors analyzed a national database to determine basic metrics of how comorbidities specifically affect the subspecialty of neurosurgery. Methods Data on 1,777,035 patients for the years 2006–2011 were acquired from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as “neurological surgery.” Univariate statistics were calculated using the chi-square test, and 95% confidence intervals were determined for the resultant risk ratios. A multivariate model was constructed using significant variables from the univariate analysis (p < 0.05) with binary logistic regression. Results Over 38,000 neurosurgical cases were analyzed, with complications occurring in 14.3%. Cranial cases were 2.6 times more likely to have complications than spine cases, and African Americans and Asians/Pacific Islanders were also at higher risk. The most frequent complications were bleeding requiring transfusion (4.5% of patients) and reoperation within 30 days of the initial operation (4.3% of patients), followed by failure to wean from mechanical ventilation postoperatively (2.5%). Significant predictors of complications included preoperative stroke, sepsis, blood transfusion, and chronic steroid use. Conclusions Understanding the landscape of neurosurgical complications will allow better targeting of the most costly and harmful complications of preventive measures. Data from the ACS NSQIP database provide a starting point for developing paradigms of improved care of neurosurgical patients.
12
Chrimes, Dillon, and Hamid Zamani. "Using Distributed Data over HBase in Big Data Analytics Platform for Clinical Services." Computational and Mathematical Methods in Medicine 2017 (2017): 1–16. http://dx.doi.org/10.1155/2017/6120820.
Повний текст джерелаАнотація:
Big data analytics (BDA) is important to reduce healthcare costs. However, there are many challenges of data aggregation, maintenance, integration, translation, analysis, and security/privacy. The study objective to establish an interactive BDA platform with simulated patient data using open-source software technologies was achieved by construction of a platform framework with Hadoop Distributed File System (HDFS) using HBase (key-value NoSQL database). Distributed data structures were generated from benchmarked hospital-specific metadata of nine billion patient records. At optimized iteration, HDFS ingestion of HFiles to HBase store files revealed sustained availability over hundreds of iterations; however, to complete MapReduce to HBase required a week (for 10 TB) and a month for three billion (30 TB) indexed patient records, respectively. Found inconsistencies of MapReduce limited the capacity to generate and replicate data efficiently. Apache Spark and Drill showed high performance with high usability for technical support but poor usability for clinical services. Hospital system based on patient-centric data was challenging in using HBase, whereby not all data profiles were fully integrated with the complex patient-to-hospital relationships. However, we recommend using HBase to achieve secured patient data while querying entire hospital volumes in a simplified clinical event model across clinical services.
13
Kopanitsa, Georgy. "Integration of Hospital Information and Clinical Decision Support Systems to Enable the Reuse of Electronic Health Record Data." Methods of Information in Medicine 56, no. 03 (2017): 238–47. http://dx.doi.org/10.3414/me16-01-0057.
Повний текст джерелаАнотація:
SummaryBackground: The efficiency and acceptance of clinical decision support systems (CDSS) can increase if they reuse medical data captured during health care delivery. High heterogeneity of the existing legacy data formats has become the main barrier for the reuse of data. Thus, we need to apply data modeling mechanisms that provide standardization, transformation, accumulation and querying medical data to allow its reuse.Objectives: In this paper, we focus on the interoperability issues of the hospital information systems (HIS) and CDSS data integration.Materials and Methods: Our study is based on the approach proposed by Marcos et al. where archetypes are used as a standardized mechanism for the interaction of a CDSS with an electronic health record (EHR). We build an integration tool to enable CDSSs collect data from various institutions without a need for modifications in the implementation. The approach implies development of a conceptual level as a set of archetypes representing concepts required by a CDSS.Results: Treatment case data from Regional Clinical Hospital in Tomsk, Russia was extracted, transformed and loaded to the archetype database of a clinical decision support system. Test records’ normalization has been performed by defining transformation and aggregation rules between the EHR data and the archetypes. These mapping rules were used to automatically generate openEHR compliant data. After the transformation, archetype data instances were loaded into the CDSS archetype based data storage. The performance times showed acceptable performance for the extraction stage with a mean of 17.428 s per year (3436 case records). The transformation times were also acceptable with 136.954 s per year (0.039 s per one instance). The accuracy evaluation showed the correctness and applicability of the method for the wide range of HISes. These operations were performed without interrupting the HIS workflow to prevent the HISes from disturbing the service provision to the users.Conclusions: The project results have proven that archetype based technologies are mature enough to be applied in routine operations that require extraction, transformation, loading and querying medical data from heterogeneous EHR systems. Inference models in clinical research and CDSS can benefit from this by defining queries to a valid data set with known structure and constraints. The standard based nature of the archetype approach allows an easy integration of CDSSs with existing EHR systems.
14
Lopez, Gianluca, Giulia Lazzeri, Alessandra Rappa, Giuseppe Isimbaldi, Fulvia Milena Cribiù, Elena Guerini-Rocco, Stefano Ferrero, Valentina Vaira, and Alessio Di Fonzo. "Comprehensive Genomic Analysis Reveals the Prognostic Role of LRRK2 Copy-Number Variations in Human Malignancies." Genes 11, no. 8 (July 24, 2020): 846. http://dx.doi.org/10.3390/genes11080846.
Повний текст джерелаАнотація:
Genetic alterations of leucine-rich repeat kinase 2 (LRRK2), one of the most important contributors to familial Parkinson’s disease (PD), have been hypothesized to play a role in cancer development due to demographical and preclinical data. Here, we sought to define the prevalence and prognostic significance of LRRK2 somatic mutations across all types of human malignancies by querying the publicly available online genomic database cBioPortal. Ninety-six different studies with 14,041 cases were included in the analysis, and 761/14,041 (5.4%) showed genetic alterations in LRRK2. Among these, 585 (76.9%) were point mutations, indels or fusions, 168 (22.1%) were copy number variations (CNVs), and 8 (1.0%) showed both types of alterations. One case showed the somatic mutation R1441C. A significant difference in terms of overall survival (OS) was noted between cases harboring somatic LRRK2 whole deletions, amplifications, and CNV-unaltered cases (median OS: 20.09, 57.40, and 106.57 months, respectively; p = 0.0008). These results suggest that both LRRK2 amplifications and whole gene deletions could play a role in cancer development, paving the way for future research in terms of potential treatment with LRRK2 small molecule inhibitors for LRRK2-amplified cases.
15
Noorbakhsh, Cameron, Yang Liu, Frederick Lang, John DeGroot, Kadir Akdemir, Kristin Alfaro-Munoz, Brittany Parker-Kerrigan, et al. "EPCO-19. SYSTEMS BIOLOGY APPROACH ON MGMT-METHYLATED, IDH WILD-TYPE SHORT-TERM SURVIVORS REVEALS MUTATIONS IN THE BRCA1-MEDIATED DNA REPAIR SIGNALING PATHWAY." Neuro-Oncology 23, Supplement_6 (November 2, 2021): vi5—vi6. http://dx.doi.org/10.1093/neuonc/noab196.018.
Повний текст джерелаАнотація:
Abstract Numerous multi-omic studies have revealed the vast molecular complexity of glioblastoma; however, these studies have failed to identify actionable drivers for definitive therapy. Unlike conventional relational data analysis methods used to examine such data, systems biology approaches using graph databases have emerged as powerful tools with flexibility and scalability needed to reveal specific vulnerabilities. Here we demonstrate the utility of a patient-centric graph database in identifying novel factors associated with poor outcome (survival < 8 months) in patients with MGMT promoter methylated glioblastoma. Using a cohort of 112 patients from the TCGA database, we integrated high-impact mutations with MGMT methylation status. Network analysis revealed three subnetworks, consisting of (a) methylated patients, the M-network, (b) methylated and unmethylated patients, the MU-network, and (c) unmethylated patients, the U-network. In addition, querying the genes in the M-network revealed three key molecules in the DNA repair pathway, namely, FANC-A, FANC-E, and MYUTH, mutated in five patients (q-value < 2.3E-02). Moreover, we observed that BRCA1 mediates other critical signaling molecules in the MU-network. Interestingly, in intermediate (8-24 months) or long-term ( >24 months) survivors networks, this pathway is not implicated. In light of recent studies implicating BRCA1 modulating temozolomide resistance in GBM sphere-forming cells and BRCA1’s protein expression predicting survival in patients, this result suggests that mutations in BRCA1-mediated DNA repair pathways hinder response to chemotherapy despite methylated MGMT, reducing the survival in patients. Besides this novel result explaining low survival in MGMT methylated patients through a synthesis of epigenetic and genetic data, our framework provides a novel and compelling paradigm for data integration at various scales from molecular events in a single patient’s tumor to integrating the molecular profile (or genotype) with phenotypic characteristics at the population level. We will present additional insights derived from this analysis at the SNO annual meeting.
16
Jamjoom, Aimun A. B., Angus B. Gane, and Andreas K. Demetriades. "Randomized controlled trials in neurosurgery: an observational analysis of trial discontinuation and publication outcome." Journal of Neurosurgery 127, no. 4 (October 2017): 857–66. http://dx.doi.org/10.3171/2016.8.jns16765.
Повний текст джерелаАнотація:
OBJECTIVEThis study aimed to determine the trial discontinuation and publication rate of randomized controlled trials (RCTs) in neurosurgery.METHODSTrials registered from 2000 to 2012 were identified on the website clinicaltrials.gov using a range of key words related to neurosurgery. Any trials that were actively recruiting or had unknown status were excluded. Included trials were assessed for whether they were discontinued early on the clinicaltrials.gov database; this included trials identified as withdrawn, suspended, or terminated in the database. For included trials, a range of parameters was identified including the subspecialty, primary country, study start date, type of intervention, number of centers, and funding status. Subsequently, a systematic search for published peer-reviewed articles was undertaken. For trials that were discontinued early or were found to be unpublished, principal investigators were sent a querying email.RESULTSSixty-four neurosurgical trials fulfilled our inclusion criteria. Of these 64, 26.6% were discontinued early, with slow or insufficient recruitment cited as the major reason (57%). Of the 47 completed trials, 14 (30%) remained unpublished. Discontinued trials showed a statistically significant higher chance of remaining unpublished (88%) compared with completed trials (p = 0.0002). Industry-funded trials had a higher discontinuation rate (31%) compared with non–industry-funded trials (23%), but this result did not reach significance (p = 0.57). Reporting of primary outcome measures was complete in 20 (61%) of 33 trials. For secondary outcome measures, complete reporting occurred in only 11 (33.3%) of 33.CONCLUSIONSMore than a fifth (26.6%) of neurosurgical RCTs are discontinued early and almost a third of those that are completed remain unpublished. This result highlights significant waste of financial resources and clinical data.
17
Hong, Zongchao, Xueyun Duan, Songtao Wu, Yang Yanfang, and Hezhen Wu. "Network Pharmacology Integrated Molecular Docking Reveals the Anti-COVID-19 Mechanism of Qing-Fei-Da-Yuan Granules." Natural Product Communications 15, no. 6 (June 1, 2020): 1934578X2093421. http://dx.doi.org/10.1177/1934578x20934219.
Повний текст джерелаАнотація:
Coronavirus disease (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly infectious viral disease. Clinical observations have shown that Qing-Fei-Da-Yuan (QFDY) granules have good anti-COVID-19 effects, but the underlying molecular mechanisms are unclear. In this study, we explored the potential mechanism of QFDY with regard to its anti-COVID-19 effect. We first screened the active chemical constituents of QFDY based on the pharmacodynamic activity parameters, followed by screening with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The Uniprot database was used for querying the corresponding genes of the target, and Cyoscape 3.6.1 software was used to construct the network of herb-compound-target. Protein interaction analysis, target gene function enrichment analysis, and signal pathway analysis were performed via STRING database, Database for Annotation, Visualization, and Integrated Discovery, and KEGG Pathway database. Molecular docking was used to predict the binding capacity of the core compound with COVID-19 hydrolase 3CL and angiotensin converting enzyme 2 (ACE2). The results showed that a network of herb-compound-target was successfully constructed, with key targets involving PTGS2, HSP90AA1, CAMKK2, NCOA2, and ESR1. Major metabolic pathways affected were those in cancer, procancer, nonsmall cell lung cancer, and apoptosis. The core compounds, such as quercetin, luteolin, and naringenin, showed a strong binding ability with COVID-19 3CL hydrolase; compounds such as anemasaponin C and medicocarpin showed a strong binding ability with ACE2. Thus, it is predicted that QFDY has the characteristics for multicomponent, multitarget, and multichannel overall control. The mechanism of action of QFDY in the treatment of COVID-19 may be associated with the regulation of genes co-expressed with ACE2, the regulation of inflammation and immune-related signaling pathways, and the influence of COVID-19 3CL hydrolase and ACE2 binding ability.
18
Kalanithi, Paul, Ryan D. Schubert, Shivanand P. Lad, Odette A. Harris, and Maxwell Boakye. "Hospital costs, incidence, and inhospital mortality rates of traumatic subdural hematoma in the United States." Journal of Neurosurgery 115, no. 5 (November 2011): 1013–18. http://dx.doi.org/10.3171/2011.6.jns101989.
Повний текст джерелаАнотація:
Object This study provides the first US national data regarding frequency, cost, and mortality rate of traumatic subdural hematoma (SDH), and identifies demographic factors affecting morbidity and death in patients with traumatic SDH undergoing surgical drainage. Methods A retrospective analysis was conducted by querying the Nationwide Inpatient Sample, the largest all-payer database of nonfederal community hospitals. All cases of traumatic SDH were identified using ICD-9 codes. The study consisted of 2 parts: 1) trends data, which were abstracted from the years 1993–2006, and 2) univariate analysis and multivariate logistic regression of demographic variables on inhospital complications and deaths for the years 1993–2002. Results Admissions for traumatic SDH increased 154% from 17,328 in 1993 to 43,996 in 2006. Inhospital deaths decreased from 16.4% to 11.6% for traumatic SDH. Average costs increased 67% to $47,315 per admission. For the multivariate regression analysis, between 1993 and 2002, 67,864 patients with traumatic SDH underwent operative treatment. The inhospital mortality rate was 14.9% for traumatic SDH drainage, with an 18% inhospital complication rate. Factors affecting inhospital deaths included presence of coma (OR = 2.45) and more than 2 comorbidities (OR = 1.60). Increased age did not worsen the inhospital mortality rate. Conclusions Nationally, frequency and cost of traumatic SDH cases are increasing rapidly.
19
Gutman, I. M., and S. R. Gilbert. "Trends in slipped capital femoral epiphysis: is the rate declining?" Journal of Children's Orthopaedics 12, no. 5 (October 2018): 428–33. http://dx.doi.org/10.1302/1863-2548.12.180081.
Повний текст джерелаАнотація:
Purpose Slipped capital femoral epiphysis (SCFE) is an adolescent hip condition with a high risk of complication. The purpose of this study was to evaluate trends in treatment using a prospectively collected paediatric nationally representative database. Methods A total of 9034 patients undergoing treatment for idiopathic SCFE were selected by querying the Healthcare Cost and Utilization Project’s Kids’ Inpatient Database for the years 1997, 2000, 2003, 2006, 2009 and 2012. The selected patients were separated based on operative approach and these cohorts were analyzed based on temporal and categorical differences in operative approach, patient demographics and clinical characteristics. Univariate and multivariate analyses were used when appropriate and the Mantel-Haenszel test for trend was used in temporal analysis. Results Overall SCFE procedures have decreased 27.5% (p < 0.001). Closed procedures have decreased 28.5% (p < 0.001), while open procedures have decreased 44.8% (p < 0.001). Bilateral closed procedures have increased 7.2% (p < 0.001). The ratio of open to closed procedures decreased in patients aged nine to 12 years and increased in patients aged 13 to 16 years (p < 0.001). Conclusion Here we report age stratified trends in treatment for idiopathic SCFE using nationally representative data and show an overall decrease in admissions and procedures over time. Level of Evidence Level III, retrospective comparison study
20
Du, Jingcheng, Qing Wang, Jingqi Wang, Prerana Ramesh, Yang Xiang, Xiaoqian Jiang, and Cui Tao. "COVID-19 trial graph: a linked graph for COVID-19 clinical trials." Journal of the American Medical Informatics Association 28, no. 9 (April 24, 2021): 1964–69. http://dx.doi.org/10.1093/jamia/ocab078.
Повний текст джерелаАнотація:
Abstract Objective Clinical trials are an essential part of the effort to find safe and effective prevention and treatment for COVID-19. Given the rapid growth of COVID-19 clinical trials, there is an urgent need for a better clinical trial information retrieval tool that supports searching by specifying criteria, including both eligibility criteria and structured trial information. Materials and Methods We built a linked graph for registered COVID-19 clinical trials: the COVID-19 Trial Graph, to facilitate retrieval of clinical trials. Natural language processing tools were leveraged to extract and normalize the clinical trial information from both their eligibility criteria free texts and structured information from ClinicalTrials.gov. We linked the extracted data using the COVID-19 Trial Graph and imported it to a graph database, which supports both querying and visualization. We evaluated trial graph using case queries and graph embedding. Results The graph currently (as of October 5, 2020) contains 3392 registered COVID-19 clinical trials, with 17 480 nodes and 65 236 relationships. Manual evaluation of case queries found high precision and recall scores on retrieving relevant clinical trials searching from both eligibility criteria and trial-structured information. We observed clustering in clinical trials via graph embedding, which also showed superiority over the baseline (0.870 vs 0.820) in evaluating whether a trial can complete its recruitment successfully. Conclusions The COVID-19 Trial Graph is a novel representation of clinical trials that allows diverse search queries and provides a graph-based visualization of COVID-19 clinical trials. High-dimensional vectors mapped by graph embedding for clinical trials would be potentially beneficial for many downstream applications, such as trial end recruitment status prediction and trial similarity comparison. Our methodology also is generalizable to other clinical trials.
21
Klann, Jeffrey G., Aaron Abend, Vijay A. Raghavan, Kenneth D. Mandl, and Shawn N. Murphy. "Data interchange using i2b2." Journal of the American Medical Informatics Association 23, no. 5 (February 5, 2016): 909–15. http://dx.doi.org/10.1093/jamia/ocv188.
Повний текст джерелаАнотація:
Abstract Objective Reinventing data extraction from electronic health records (EHRs) to meet new analytical needs is slow and expensive. However, each new data research network that wishes to support its own analytics tends to develop its own data model. Joining these different networks without new data extraction, transform, and load (ETL) processes can reduce the time and expense needed to participate. The Informatics for Integrating Biology and the Bedside (i2b2) project supports data network interoperability through an ontology-driven approach. We use i2b2 as a hub, to rapidly reconfigure data to meet new analytical requirements without new ETL programming. Materials and Methods Our 12-site National Patient-Centered Clinical Research Network (PCORnet) Clinical Data Research Network (CDRN) uses i2b2 to query data. We developed a process to generate a PCORnet Common Data Model (CDM) physical database directly from existing i2b2 systems, thereby supporting PCORnet analytic queries without new ETL programming. This involved: a formalized process for representing i2b2 information models (the specification of data types and formats); an information model that represents CDM Version 1.0; and a program that generates CDM tables, driven by this information model. This approach is generalizable to any logical information model. Results Eight PCORnet CDRN sites have implemented this approach and generated a CDM database without a new ETL process from the EHR. This enables federated querying within the CDRN and compatibility with the national PCORnet Distributed Research Network. Discussion We have established a way to adapt i2b2 to new information models without requiring changes to the underlying data. Eight Scalable Collaborative Infrastructure for a Learning Health System sites vetted this methodology, resulting in a network that, at present, supports research on 10 million patients’ data. Conclusion New analytical requirements can be quickly and cost-effectively supported by i2b2 without creating new data extraction processes from the EHR.
22
Srinivasan, Visish M., Gouthami Chintalapani, Edward A. M. Duckworth, and Peter Kan. "Advanced cone-beam CT venous angiographic imaging." Journal of Neurosurgery 129, no. 1 (July 2018): 114–20. http://dx.doi.org/10.3171/2017.2.jns162997.
Повний текст джерелаАнотація:
OBJECTIVEThe evaluation of the venous neurovasculature, especially the dural venous sinuses, is most often performed using MR or CT venography. For further assessment, diagnostic cerebral angiography may be performed. Three-dimensional rotational angiography (3D-RA) can be applied to the venous system, producing 3D rotational venography (3D-RV) and cross-sectional reconstructions, which function as an adjunct to traditional 2D digital subtraction angiography.METHODSAfter querying the database of Baylor St. Luke’s Medical Center in Houston, Texas, the authors reviewed the radiological and clinical data of patients who underwent 3D-RV. This modality was performed based on standard techniques for 3D-RA, with the catheter placed in the internal carotid artery and a longer x-ray delay calculated based on time difference between the early arterial phase and the venous phase.RESULTSOf the 12 cases reviewed, 5 patients had neoplasms invading a venous sinus, 4 patients with idiopathic intracranial hypertension required evaluation of venous sinus stenosis, 2 patients had venous diverticula, and 1 patient had a posterior fossa arachnoid cyst. The x-ray delay ranged from 7 to 10 seconds. The 3D-RV was used both for diagnosis and in treatment planning.CONCLUSIONSThree-dimensional RV and associated cross-sectional reconstructions can be used to assess the cerebral venous vasculature in a manner distinct from established modalities. Three-dimensional RV can be performed with relative ease on widely available biplane equipment, and data can be processed using standard software packages. The authors present the protocol and technique used along with potential applications to venous sinus stenosis, venous diverticula, and tumors invading the venous sinuses.
23
Rolston, John D., Seunggu J. Han, Orin Bloch, and Andrew T. Parsa. "What clinical factors predict the incidence of deep venous thrombosis and pulmonary embolism in neurosurgical patients?" Journal of Neurosurgery 121, no. 4 (October 2014): 908–18. http://dx.doi.org/10.3171/2014.6.jns131419.
Повний текст джерелаАнотація:
Object Venous thromboembolisms (VTEs) occur frequently in surgical patients and can manifest as pulmonary emboli (PEs) or deep venous thromboses (DVTs). While many medical therapies have been shown to prevent VTEs, neurosurgeons are concerned about the use of anticoagulants in the postoperative setting. To better understand the prevalence of and the patient-level risk factors for VTE, the authors analyzed data from the National Surgical Quality Improvement Program (NSQIP). Methods Retrospective data on 1,777,035 patients for the years from 2006 to 2011 were acquired from the American College of Surgeons NSQIP database. Neurosurgical cases were extracted by querying the data for which the surgical specialty was listed as “neurological surgery.” Univariate statistics were calculated using the chi-square test, with 95% confidence intervals used for the resultant risk ratios. Multivariate models were constructed using binary logistic regression with a maximum number of 20 iterations. Results Venous thromboembolisms were found in 1.7% of neurosurgical patients, with DVTs roughly twice as common as PEs (1.3% vs 0.6%, respectively). Significant independent predictors included ventilator dependence, immobility (that is, quadriparesis, hemiparesis, or paraparesis), chronic steroid use, and sepsis. The risk of VTE was significantly higher in patients who had undergone cranial procedures (3.4%) than in those who had undergone spinal procedures (1.1%). Conclusions Venous thromboembolism is a common complication in neurosurgical patients, and the frequency has not changed appreciably over the past several years. Many factors were identified as independently predictive of VTEs in this population: ventilator dependence, immobility, and malignancy. Less anticipated predictors included chronic steroid use and sepsis. Venous thromboembolisms appear significantly more likely to occur in patients undergoing cranial procedures than in those undergoing spinal procedures. A better appreciation of the prevalence of and the risk factors for VTEs in neurosurgical patients will allow targeting of interventions and a better understanding of which patients are most at risk.
24
Dookeran, Keith A., James M. Groh, David G. Ritacco, Lydia R. Marcus, Yang Wang, and Janine Y. Khan. "An assessment of prevalence and expenditure associated with discharge brain MRI in preterm infants." PLOS ONE 16, no. 3 (March 5, 2021): e0247857. http://dx.doi.org/10.1371/journal.pone.0247857.
Повний текст джерелаАнотація:
To assess national expenditure associated with preterm-infant brain MRI and potential impact of reduction per Choosing Wisely campaign 2015 recommendation to “avoid routine screening term-equivalent or discharge brain MRIs in preterm-infants”. Cross-sectional U.S. trend data from the Agency for Healthcare Research and Quality (AHRQ), Healthcare Cost and Utilization Project (HCUP) Kids’ Inpatient Database (KID) database (2006, 2009, 2012, 2016) was used to estimate overall national expenditure associated with brain MRI among infants with gestational age (GA) ≤36 weeks, and also when classified as ‘not indicated’ (NI-MRI) i.e., equivalent to routine use without clinical indications and regarded as low-value service (LVS). Associated cost was determined by querying CMS-database for physician-fee-schedules to find the highest global procedure-cost per cycle, then adjusting for inflation. Sensitivity-analyses were conducted to account for additional clinical charges associated with NI-MRI. 3,768 (0.26%) of 1,472,236 preterm-infants had brain MRI across all cycles (inflation-adjusted total $3,690,088). Overall proportion of brain MRIs increased across 2006–2012 from 0.25%-0.33% but decreased in 2016 to 0.16% (P<0.001). Inflation-adjusted overall expenditure by cycle was: 2006, $1,299,130 (95% CI: $987,505, $1,610,755); 2009, $1,194,208 (95% CI: $873,487, $1,516,154); 2012, $931,836 (95% CI: $666,114, $1,197,156); and 2016, $264,648 (95% CI: $172,061, $357,280). Prevalence for NI-MRI in 2006, 2009, 2012 and 2016 was 86% (n = 809), 88% (n = 940), 89% (n = 1028) and 50% (n = 299), respectively; and 70% were in infants 35–36 weeks GA. NI-MRI prevalence was not different over time by payer-type (Medicaid, private), sex or race/ethnicity (white, black, Hispanic); larger hospital size was significantly associated across 2006–2012 but this declined for all sizes in 2016, with most decline in larger hospitals (P for interaction <0.05). NI-MRI expenditure sensitivity-analysis with addition of cycle median total-admission-charge to inflation-adjusted CMS-fee was $1,190,919/$518,343, for 2012/2016 cycles respectively. National MRI prevalence in preterm infants (both overall and LVS) and associated expenditure decreased substantially post recommendation; however, annual savings are modest and unlikely to be >$1.2 million.
25
Loen, Harry Van, Mary Thiongo, and Yven Van Herrewege. "PO 8495 DATA SHARING IS PART OF DATA MANAGEMENT: THE NEED FOR A HOLISTIC AND COHERENT VIEW ON RESEARCH DATA MANAGEMENT." BMJ Global Health 4, Suppl 3 (April 2019): A46.1—A46. http://dx.doi.org/10.1136/bmjgh-2019-edc.120.
Повний текст джерелаАнотація:
BackgroundAwareness of data management (DM) is often restricted to ‘the cost of computers’ or ‘the need for a database’. Recently, ‘data sharing’ can be added to this shortlist. Indeed, in recent years data sharing became often required or so strongly promoted that the importance of all other aspects related to DM or data handling in clinical tended still to be overlooked. However, the development of data sharing guidelines and associated privacy regulations (e.g. the EU General Data Protection Regulation) created a new momentum for highlighting the importance of qualitative data management.MethodsAn overview of DM processes is given, within the framework and challenges of conducting non-commercial clinical trials in North-South partnerships.ResultsThe DM workflow of a clinical trial is presented, highlighting essential DM tasks, deliverables and milestones. Pre-study tasks and deliverables are addressed: SOPs, a data management plan, the implementation of a GCP-compliant validated data management system and compliance to data quality, privacy, security and standards (e.g. MedDRA, CDISC). Subsequent study-specific processes including the collection, entry, querying and cleaning of the data are discussed. In addition, DM metrics important to guide quality, productivity and timelines are reviewed while considering their impact on post-study activities such as data sharing.ConclusionData sharing is only one of many DM tasks, at the end of the DM workflow. Focusing too much on data sharing while neglecting other DM aspects might lead to underestimating the workload, resources, quality assurance and time needed for data management and by and large for the trial itself. Integrating data sharing into a holistic vision on data management is paramount for clinical research.
26
Combi, Carlo, Giuseppe Pozzi, and Rosalba Rossato. "Querying temporal clinical databases on granular trends." Journal of Biomedical Informatics 45, no. 2 (April 2012): 273–91. http://dx.doi.org/10.1016/j.jbi.2011.11.005.
Повний текст джерела
27
Gabetta, M., G. Milani, M. Bucalo, F. Mulas, A. Nuzzo, V. Favalli, E. Arbustini, R. Bellazzi, and C. Larizza. "Supporting Translational Research on Inherited Cardiomyopathies through Information Technology." Methods of Information in Medicine 52, no. 02 (2013): 137–47. http://dx.doi.org/10.3414/me12-01-0046.
Повний текст джерелаАнотація:
SummaryObjectives: The INHERITANCE project, funded by the European Commission, is aimed at studying genetic or inherited Dilated cardiomyopathies (DCM) and at understanding the impact and management of the disease within families that suffer from heart conditions that are caused by DCMs. The biomedical informatics research activity of the project aims at implementing information technology solutions to support the project team in the different phases of their research, in particular in genes screening prioritization and new gene-disease association discovery.Methods: In order to manage the huge quantity of scientific, clinical and patient data generated by the project several advanced biomedical informatics tools have been developed. The paper describes a layer of software instruments to support translation of the results of the project in clinical practice as well as to support the scientific discovery process. This layer includes data warehousing, intelligent querying of the phenotype data, integrated search of biological data and knowledge repositories, text mining of the relevant literature, and case based reasoning.Results: At the moment, a set of 1,394 patients and 9,784 observations has been stored into the INHERITANCE data warehouse. The literature database contains more than 1,100,000 articles retrieved from the Pubmed and generically related to cardiac diseases, already analyzed for extracting medical concepts and genes.Conclusions: After two years of project the data warehouse has been completely set up and the text mining tools for automatic literature analysis have been implemented and tested. A first prototype of the decision support tool for knowledge discovery and gene prioritization is available, but a more complete release is still under development.
28
Scherschinski, Lea, Joshua S. Catapano, Katherine Karahalios, Stefan W. Koester, Dimitri Benner, Ethan A. Winkler, Christopher S. Graffeo, et al. "Electroencephalography for detection of vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: a retrospective analysis and systematic review." Neurosurgical Focus 52, no. 3 (March 2022): E3. http://dx.doi.org/10.3171/2021.12.focus21656.
Повний текст джерелаАнотація:
OBJECTIVE Good functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH) are often dependent on early detection and treatment of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI). There is growing evidence that continuous monitoring with cranial electroencephalography (cEEG) can predict CVS and DCI. Therefore, the authors sought to assess the value of continuous cEEG monitoring for the detection of CVS and DCI in aSAH. METHODS The cerebrovascular database of a quaternary center was reviewed for patients with aSAH and cEEG monitoring between January 1, 2017, and July 31, 2019. Demographic data, cardiovascular risk factors, Glasgow Coma Scale score at admission, aneurysm characteristics, and outcomes were abstracted from the medical record. Patient data were retrospectively analyzed for DCI and angiographically assessed CVS. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and odds ratio for cEEG, transcranial Doppler ultrasonography (TCDS), CTA, and DSA in detecting DCI and angiographic CVS were calculated. A systematic literature review was conducted in accordance with PRISMA guidelines querying the PubMed, Cochrane Controlled Trials Register, Web of Science, and Embase databases. RESULTS A total of 77 patients (mean age 60 years [SD 15 years]; female sex, n = 54) were included in the study. Continuous cEEG monitoring detected DCI and angiographically assessed CVS with specificities of 82.9% (95% CI 66.4%–93.4%) and 94.4% (95% CI 72.7%–99.9%), respectively. The sensitivities were 11.1% (95% CI 3.1%–26.1%) for DCI (n = 71) and 18.8% (95% CI 7.2%–36.4%) for angiographically assessed CVS (n = 50). Furthermore, TCDS detected angiographically determined CVS with a sensitivity of 87.5% (95% CI 71.0%–96.5%) and specificity of 25.0% (95% CI 7.3%–52.4%). In patients with DCI, TCDS detected vasospasm with a sensitivity of 85.7% (95% CI 69.7%–95.2%) and a specificity of 18.8% (95% CI 7.2%–36.4%). DSA detected vasospasm with a sensitivity of 73.9% (95% CI 51.6%–89.8%) and a specificity of 47.8% (95% CI 26.8%–69.4%). CONCLUSIONS The study results suggest that continuous cEEG monitoring is highly specific in detecting DCI as well as angiographically assessed CVS. More prospective studies with predetermined thresholds and endpoints are needed to assess the predictive role of cEEG in aSAH.
29
Ragg, Susanne, Marc B. Rosenman, Eve M. Doucette, Zhong Yan, Julie C. Haydon, Jada H. Paine, Nadine D. Lee, Terry Vik, Ketan Mane, and Katy Borner. "Data Visualization of Multiparameter Information in Acute Lymphoblastic Leukemia Expands the Ability To Explore Prognostic Factors." Blood 106, no. 11 (November 16, 2005): 862. http://dx.doi.org/10.1182/blood.v106.11.862.862.
Повний текст джерелаАнотація:
Abstract In clinical studies and for patient care, data collections have become more and more complex. Clinical studies often include millions of data points, and even data collections about individual patients can include several thousand data points. To enable searches for meaningful relationships and patterns, and to gain understanding and knowledge of the data, state-of-the-art visualization approaches have to be adapted to the needs of clinicians and clinical researchers, in order to best reveal relevant patterns in the data. However, despite the progress that has been made in the field of information visualization, none of the currently available high dimensional visualization tools are used in clinical research or practice. The goal of this research was to develop visualization tools that allow clinical researchers to explore multidimensional datasets, as well as temporal clinical datasets. The dataset used for this presentation involves 300 pediatric patients with acute lymphoblastic leukemia diagnosed at Indiana University between 1992 and 2000. Clinical and laboratory data were extracted electronically from the Regenstrief Medical Records System. The dosages of all medications during the treatment period were extracted from the patients’ charts. This information was supplemented, for a subset of 78 patients for whom Indiana Medicaid claims data were available, with actual fill dates and quantities dispensed. Cytogenetic data were extracted from the clinical genetic database, and immunophenotype data were extracted from the pathology database at Indiana University. Temporal patient data, such as laboratory data, prescription fill dates, and medication dosage, are visualized through custom-designed multiple layer graphics. The visualization tools developed allow the user to interactively visualize and query the data. For exploratory analysis, the application offers an overview of the data through visual representations such as parallel coordinates and matrix methods. The user can interact with the data set in diverse ways, e.g, the order in which the variables are visualized can be changed; interactivity augments the insight that can be gained from visually exploring such data. The visualizations are dynamically linked, so that the user can obtain coordinate views of the data. Dynamic querying interactively filters data in all views. In addition, the user can highlight or select a subset of data elements in one view and thereby highlight data for the same subset in other views. For example, we show that patient data with a specific pattern in the parallel coordinate view can be selected, and then clinical, laboratory, and prescription data for the entire treatment period can be viewed through multiple layer graphics. In summary, the adaptation of temporal and multidimensional visualization tools to clinical data allows clinicians or clinical researchers to better explore these datasets. These tools improve understanding of the complex prognostic features of acute lymphoblastic leukemia, including type of leukemia, initial risk factors, therapy, adherence to therapy, and host factors that affect tolerance of therapy.
30
Safari, Leila, and Jon D. Patrick. "Restricted natural language based querying of clinical databases." Journal of Biomedical Informatics 52 (December 2014): 338–53. http://dx.doi.org/10.1016/j.jbi.2014.07.012.
Повний текст джерела
31
Pressl, Christina, Caroline Jiang, Joel Correa da Rosa, Maximilian Friedrich, Winrich Freiwald, and Jonathan Tobin. "2093." Journal of Clinical and Translational Science 1, S1 (September 2017): 23. http://dx.doi.org/10.1017/cts.2017.93.
Повний текст джерелаАнотація:
OBJECTIVES/SPECIFIC AIMS: We aim to examine the epidemiological characteristics of prosopagnosia by querying and analyzing a large deidentified clinical data set from 12 New York City-based hospitals and Federally Qualified Health Centers (FQHCs). The PCORI-funded New York City Clinical Data Research Network (NYC-CDRN) contains ~4.5 million deidentified ICD-coded electronic health records (EHRs) with comprehensive longitudinal information on demographics, patient visits, clinical conditions/diagnoses, laboratory and radiology results, medications, and clinical procedures. The NYC-CDRN will be expanded to include other data sources, including insurance claims, social determinant of health, patient reported outcomes, and patient generated data. The central hypothesis was that systematic mining of this database would reveal new epidemiological information about prosopagnosia. We developed a computable phenotype for prosopagnosia, using the International Classification of Diseases version 9 (ICD-9). The computable phenotype consisted of the diagnostic code for the condition under study, prosopagnosia (ICD-9 code 368.16), as well as the codes for known surrogate diagnoses. We expected to identify cases of acquired prosopagnosia, where the condition occurs only after brain damage, due to stroke, trauma, or meningitis for example, and cases of developmental prosopagnosia, where the condition is present from an early age, with no history of brain damage. The goals of this project were to provide new information about the condition’s prevalence rate in the New York City area, which could be furthermore translated into wider geographical areas and to yield novel details about its antecedents and comorbid conditions. METHODS/STUDY POPULATION: To determine the presence of the diagnosis of interest, prosopagnosia, and common co-occurring conditions among a New York City-based study population, we investigated a large database in collaboration with the NYC-CDRN. At the time the large database was mined it contained ~4 million ICD-9 coded EHRs. We first created a search paradigm; applicable for screening the database that consists of ICD-9 coded EHRs. We generated a list of ICD-9 codes indicative for the patients’ difficulties with the perception of faces (368.16), which indicates the presence of the condition as part of the psychophysical visual disturbances complex, and this code identified 871 patients. Furthermore, we collected codes that indicate the presence of conditions that are known to be surrogate diagnoses of prosopagnosia. ICD-9 codes for surrogate diagnoses included for example, 854.* (coding for personal history of traumatic brain injury, n=1,409), 434.01, 434.11, and 434.91 (coding for cerebral thrombosis, embolus and artery occlusion unspecified with cerebral infarction, n=19,409), and 191.2 (coding for malignant neoplasm of the temporal lobe, n=566). In October 2015, coding was changed to the new ICD-10 coding system. No additional patients were revealed from the data set when the cohort was searched for the presence of corresponding ICD-10 codes, as institutions are currently in transition from ICD-9 to ICD-10. Using this search query with the large database, we extracted novel information about the epidemiological and demographical distribution of prosopagnosia and furthermore, gained new knowledge about commonly associated diseases. The fact that it must be presumed that the majority of diagnoses of prosopagnosia have been made on the basis of patients’ self-reports and clinicians’ judgments represents a limiting factor in this study. We are currently exploring machine-learning strategies to identify potential false-negative cases among the patients with surrogate diagnoses. RESULTS/ANTICIPATED RESULTS: Investigations and application of our search query revealed a total number of n=129,549 patients carrying either the diagnosis code for prosopagnosia or the codes for the known surrogate diagnoses. There were 871 patients who carried the ICD-9 code 368.16, indicating the potential presence of prosopagnosia among other visual disturbances. Remaining patients (n=128,678) carried codes for known surrogate diagnoses, contained in the search query. Statistical analyses revealed elevated odds ratios for men (OR=1.55, 95% CI: 1.36, 1.77, p<0.0001), and for Black/African Americans Versus White individuals (OR=2.09, 95% CI: 1.74, 2.51, p<0.0001). DISCUSSION/SIGNIFICANCE OF IMPACT: Currently, the prevalence of prosopagnosia remains unknown. Face blind individuals are struggling to recognize their social contacts by their face only in every day life and are therefore prone to experience reduced quality of life. We searched the large NYC-based clinical database, containing more than 4.5 million deidentified ICD-coded health records, for cases of prosopagnosia to shed light into its prevalence and epidemiological characteristics. We furthermore, mined the database for cases carrying known surrogate diagnoses to explore the magnitude and characteristics of individuals potentially under increased risk. Our efforts address a great healthcare need, as they revealed new epidemiological knowledge of a vulnerable and understudied population. The results of this project reveal new insights into the epidemiological characteristics of prosopagnosia and its surrogate diagnoses, and demonstrate the feasibility of mining large clinical databases to identify rare clinical populations. Our results suggest the need for a more targeted diagnostic assessment of face perception abilities in populations under increased risk.
32
Kirby, Chaim, Peter F. Ambros, David Billiter, Wendy B. London, Eneida Mendonca, Tom Monclair, Andrew DJ Pearson, Susan Lerner Cohn, and Samuel Louis Volchenboum. "Development of an open-source, flexible framework for interinstitutional data sharing and collaboration." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 9583. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.9583.
Повний текст джерелаАнотація:
9583 Background: Clinical information, “-omic” datasets, and tissue samples are becoming more difficult to harmonize and manage for advanced data mining. We believe that clinical research data can be centralized and provide direct access to sample availability and associated data from a variety of information stores. Methods: We obtained a standardized set of anonymized patient data from the International Neuroblastoma Risk Group. The cohort consists of more than 11,000 children diagnosed worldwide between 1974 and 2002. The data consist of 34 metrics, such as age at diagnosis, stage of tumor, and other clinical and biological markers. We instantiated the dataset into a Postgres database, and using the Django web framework, created a data model for rapid development of tools and views and built a front-end interface for generating complex queries. To test the feasibility of accessing information on disparate and geographically distinct data samples, we have a formal agreement with the Children's Oncology Group Tumor Bank at The Research Institute at Nationwide Children's Hospital. Based on query results, we consume the Tumor Bank tissue inventory data through a web-facing application programming interface. The end-user is presented only with the number of patients who match their query search terms and for whom tissue samples are available. Results: We have completed our initial implementation and have agreements for collaboration with other international consortium groups. We have created a paradigm for statisticians to securely update and add data, and a verification system checks for internal validity and provides a report of the transaction. Our system can initiate queries and accept results in a variety of standards-compliant formats, and will be available in demonstration form by May 2012. Conclusions: Querying patient data while interrogating external sources allows researchers to observe which ancillary data and samples are available and to quickly download data or request any samples. While designed around a neuroblastoma dataset, our system can be applied to a variety of clinical scenarios and will be made available through an open-source license.
33
Soualmia, L. F., and T. Lecroq. "From Genome Sequencing to Bedside." Yearbook of Medical Informatics 22, no. 01 (August 2013): 175–77. http://dx.doi.org/10.1055/s-0038-1638852.
Повний текст джерелаАнотація:
Summary Objectives: To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and evidence-based medicine. Method: We provide a synopsis of the articles selected for the IMIA Yearbook 2013, from which we attempt to derive a synthetic overview of current and future activities in the field. Three steps of selection were performed by querying PubMed and Web of Science. A first set of 5,549 articles was refined into a second set of 1,272 articles from which 15 articles were retained for peer-review. Results: The selection and evaluation process of this Yearbook's section on Bioinformatics and Translational Informatics yielded four excellent articles regarding the Human Genome and Medicine. Exploiting genomic data depends on having the appropriate reference annotation available. In the first article, the goal of the GENCODE Consortium is to produce and publish The GENCODE human reference gene set. As a result it is composed by merged manual and automatic annotations, which are frequently updated from public experimental databases. The quality of genome sequencing is platform-dependant. In the second article, a generic database independent from the sequencing technologies, Huvariome, can help to identify errors and inconsistencies in sequencing. To understand complex diseases of patients it will be of great importance to detect rare gene variants. This is the aim of the third study. Finally, in the last article, the plasma's DNA of healthy individual and patients suffering from cancer is compared. Conclusions: The current research activities attest to the continuous convergence of Bioinformatics and Medical Informatics for clinical practice. For instance, a direct use of high throughput sequencing technologies for patients could aid the diagnosis of complex diseases (such as cancer) without invasive surgery (such as biopsy) but only with blood analysis. However, ongoing genomic tests will generate massive amounts of data and will imply new trends in the near future: “Big Data” and smart health management.
34
Lubarsky, David A., Peter S. A. Glass, Brian Ginsberg, Guy L. de Dear, Mark E. Dentz, Tong J. Gan, Iain C. Sanderson, et al. "The Successful Implementation of Pharmaceutical Practice Guidelines." Anesthesiology 86, no. 5 (May 1, 1997): 1145–60. http://dx.doi.org/10.1097/00000542-199705000-00019.
Повний текст джерелаАнотація:
Background Although approximately 2,000 medical practice guidelines have been proposed, few have been successfully implemented and sustained. We hypothesized that we could develop and institute practice guidelines to promote more appropriate use of costly anesthetics, to generate and sustain widespread compliance from a large physician group, and to decrease costs without adversely affecting clinical outcomes. Methods A prospective before and after comparison study was performed at a tertiary care medical center. Clinical outcomes data and times indicative of perioperative patient flow were collected on the first of two sets of patients 1 month before discussion of practice guidelines. Practice guidelines were developed by the physicians and their associated care team for the intraoperative use of anesthetic drugs. A drug distribution process was developed to aid compliance. Clinical outcomes data and times indicative of perioperative patient flow were collected on the second set of patients 1 month after institution of practice guidelines. Hospital drug costs and adherence to guidelines were noted throughout the study period and for each of the following 9 months by querying the database of an automated anesthesia record keeper. Results A total of 1,744 patients were studied. Drug costs decreased from 56 dollars per case to 32 dollars per case as a result of adherence to practice guidelines. Perioperative patient flow was minimally affected. Time (mean +/- SD) from end of surgery to arrival in the post-anesthesia care unit (PACU) increased from 11 +/- 7 min before the authors instituted practice guidelines to 14 +/- 8 min after practice guidelines (P < 0.0001). Admission of inpatients to the PACU receiving monitored anesthesia care increased from 6.5 to 12.9% (P < 0.02). Perioperative patient flow and clinical outcomes were not otherwise adversely affected. Compliance and cost savings have been sustained. Conclusions This study is an example of a successful physician-directed program to promote more appropriate utilization of health care resources. Cost savings were obtained without any substantial changes in clinical outcomes. Institution of similar practice guidelines should result in pharmaceutical savings in the range of 50% at tertiary care centers around the country, with a slightly smaller degree of savings expected at institutions with more ambulatory surgery.
35
Haston, Julia C., Christina A. Rostad, Robert C. Jerris, Sarah S. Milla, Courtney McCracken, Catherine Pratt, Michael Wiley, et al. "Prospective Cohort Study of Next-Generation Sequencing as a Diagnostic Modality for Unexplained Encephalitis in Children." Journal of the Pediatric Infectious Diseases Society 9, no. 3 (May 20, 2019): 326–33. http://dx.doi.org/10.1093/jpids/piz032.
Повний текст джерелаАнотація:
Abstract Background Encephalitis is an inflammatory condition of the brain associated with long-term neurologic sequelae and even death in children. Although viruses are often implicated, an etiology is not identified in the majority of cases. Metagenomics-based next-generation sequencing (mNGS) is a high-throughput sequencing technique that can enhance the detection of novel or low-frequency pathogens. Methods Hospitalized immunocompetent children aged 6 months to 18 years with encephalitis of unidentified etiology were eligible for enrollment. Demographic, historical, and clinical information was obtained, and residual blood and cerebrospinal fluid (CSF) samples were subjected to mNGS. Pathogens were identified by querying the sequence data against the NCBI GenBank database. Results Twenty children were enrolled prospectively between 2013 and 2017. mNGS of CSF identified 7 nonhuman nucleic acid sequences of significant frequency in 6 patients, including that of Mycoplasma bovis, parvovirus B19, Neisseria meningitidis, and Balamuthia mandrillaris. mNGS also detected Cladophialophora species, tobacco mosaic virus, and human bocavirus, which were presumed to be contaminants or nonpathogenic organisms. One patient was found to have positive serology results for California encephalitis virus, but mNGS did not detect it. Patients for whom mNGS identified a diagnosis had a significantly higher CSF white blood cell count, a higher CSF protein concentration, and a lower CSF glucose level than patients for whom mNGS did not identify a diagnosis. Conclusion We describe here the results of a prospective cohort analysis to evaluate mNGS as a diagnostic tool for children with unexplained encephalitis. Although mNGS detected multiple nonpathogenic organisms, it also identified multiple pathogens successfully and was most useful in patients with a CSF abnormality.
36
Calero, Christopher, Shauna Usiak, Anoshé Aslam, Margaret A. Palazzolo, Tracy McMillen, Esther Babady, Rebecca Guest, Anabella Lucca Bianchi, Elizabeth Robilotti, and Mini Kamboj. "553. Outbreak of Methicillin-Resistant Staphylococcus aureus Associated with Hepatic Artery Infusion Pumps." Open Forum Infectious Diseases 6, Supplement_2 (October 2019): S263. http://dx.doi.org/10.1093/ofid/ofz360.622.
Повний текст джерелаАнотація:
Abstract Background Device-related infections account for a fourth of all HAIs. Hepatic artery infusion pump (HAIP) devices are used to deliver chemotherapy directly into the hepatic artery. This device is used primarily in patients with colorectal cancer for the management of unresectable hepatic metastases. We describe the infection rates and outbreak management of MRSA-related infections in newly placed HAIPs. Methods In December 2018, a cluster of 3 MRSA cases was identified within 15–26 days of HAIP insertion. From January 1, 2017 to December 31, 2018, patients with culture proven SSIs within 30 days of HAIP placement were identified through the infection control database to establish baseline rates. Procedural denominator data were found by querying CPT procedure codes. EMR was reviewed to extract clinical characteristics. In response to the cluster, healthcare personnel (HCP) were screened for MRSA by PCR and environmental cultures performed. PFGE and whole-genome sequencing (WGS) was performed to compare isolates recovered in culture and SNP analysis performed using the BioNumerics software v7.6. Results IIn December 2018, 3/15 patients with HAIP procedures developed MRSA infections within 30 days of the procedures (post-op days: 15,16,26). The baseline 30 day SSI rate for HAIP in 2017 was 1.3% (2/160). No infections, prior to the cluster, in 2017–18 were MRSA related. All patients were male, with a median age of 49 years (range: 45–54). Sixty HCP who provided direct care during the peri and early post-operative period for the 3 cases were screened for MRSA carriage; 2/60 (3.3%) were positive. All 56 environmental cultures were negative for MRSA. WGS of the 3 patient samples showed 2/3 samples were identical (1 SNP difference); confirming common source transmission. Only one HCP isolate was available for WGS and shown to be unrelated to the two patient isolates. Both employees underwent decolonization. Review of HAIP handling did not reveal obvious lapses, but mask use and strict hand hygiene were enforced with HCPs. No further infections have been identified in the 76 procedures since the cluster. Conclusion WGS confirmed common source transmission between two newly placed HAIP although the definitive source could not be identified. Surveillance and prevention efforts should extend to all types of vascular access devices. Disclosures All authors: No reported disclosures.
37
Dasari, S., A. Chiu, J. Theis, J. A. Vrana, P. J. Kurtin, K. L. Rech, L. N. Dao, et al. "Bone marrow involvement by ATTR amyloid is common in cardiac amyloidosis patients and may signal advanced-stage disease." American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S94. http://dx.doi.org/10.1093/ajcp/aqab191.200.
Повний текст джерелаАнотація:
Abstract Introduction/Objective Amyloidosis encompasses a heterogeneous group of disorders characterized by abnormal deposition of misfolded proteins leading to progressive organ failure. Accurate amyloid typing is essential for proper patient management, as treatment regimens vary dramatically across different types. Bone marrow (BM) biopsy, in conjunction with fat pad aspiration/biopsy, is often the first step in patients with suspected amyloidosis. Although BM involvement by AL amyloid has been previously characterized, little is known about the incidence, morphology and clinical phenotype of non-AL amyloid in BM. Methods/Case Report We retrospectively identified 1469 BM biopsies by querying our reference laboratory database of 19,298 specimens from myriad anatomic sites typed by mass spectrometry-based proteomics (LC-MS/MS). These were reviewed for frequency of amyloid types (N=1469), distribution of amyloid deposits (N=139), and clinical phenotypes (N=345), with particular emphases on cardiac involvement. Results (if a Case Study enter NA) We identified the following amyloid types: AL (N=1172; 79.8%), ATTR (transthyretin) (N=240; 16.3%), AH (immunoglobulin heavy chain) (N=38; 2.6%), AA (serum amyloid A) (N=17; 1.2%), and Aβ2M (β2-microglobulin) (N=2; 0.1%). ATTR deposits showed striking predilection for periosteal soft tissue and/or periosteal vessels, and rarely involved BM stroma and/or interstitial vessels, while AL variably involved these compartments. AA primarily involved interstitial vessels. Both AL and ATTR cases commonly had a monoclonal gammopathy (AL: 92.9%; ATTR: 62.5%) with concomitant cardiac amyloidosis (AL: 91.6%; ATTR: 100%). Compared to AL, ATTR patients had higher stage cardiac amyloidosis and lower overall survival. Conclusion ATTR is common in BM, constituting16.3% of cases in our cohort. Rarer amyloid types, such as AA, AH and AB2M can also occur in BM. ATTR was frequently identified in patients with concomitant monoclonal gammopathy, in whom AL may have been suspected. Although ATTR deposits have distinctive morphologic distribution, primarily involving periosteal soft tissue and/or periosteal vessels and rarely involving BM stroma and/or interstitial vessels, there is considerable morphologic overlap with AL. Therefore, it is imperative to type BM amyloidosis, preferably by LC-MS/MS, to ensure proper patient management. Furthermore, BM involvement by ATTR may be a marker for advanced stage of disease.
38
Baglivo, Sara, Fortunato Bianconi, Francesca Romana Tofanetti, Biagio Ricciuti, Lorenza Pistola, Annamaria Siggillino, Maria Sole Reda, et al. "Immune gene expression and bayesian network analysis in advanced non small cell lung cancer (NSCLC) patients treated with immunotherapy." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e20693-e20693. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e20693.
Повний текст джерелаАнотація:
e20693 Background: Immune checkpoint inhibitors (ICIs) have revoluzionized the therapeutic paradigm for different types of cancer including NSCLC. Clinical benefit, however, is limited to a minority of patients. The only adopted predictive biomarker, PD-L1 IHC testing, suffers from some limitations. A better understanding of biomarkers associated with response to ICIs is needed. Here, we studied immune gene expression profile and association with clinical response to immunotherapy in advanced NSCLC patients (pts) treated with ICI. Methods: A total of 37 Formalin-fixed, paraffin-embedded (FFPE) samples from advanced NSCLCs were analyzed by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) (ThermoFisher Scientific) to measure the expression level of 395 genes associated with 36 functional groups including checkpoint pathways, lymphocyte regulation and cytokine interactions, using the Ion Chef and Ion Torrent PGM. Gene level differential expression analysis were performed with the Torrent Suite and Transcriptome Analysis Console (TAC) 4.0 Software. Gene network analysis based on Bayesian algorithm was performed by GeneMANIA database querying with the genes selected through mRNA expression analysis. Results: Among 37 FFPE samples only 18 showed more than 300 OIRRA detectable target genes. In this subgroup, gene expression analysis revealed 7 genes (CCR2, CRTAM, FASLG, SELL, TIGIT, TNFRSF4, and TP63) up-regulated and one gene (CXCL8) down-regulated (p-value < 0.05) in ICI-responders compare to ICI-no responders. Bayesian enrichment computational analysis of the eight gene expression signature showed a more complex network which involves other 10 genes (SIRPG, GZMK, XCL2, CD8A, CD2, IFNG, SIT1, TAGAP, PTPRC and GZMH), correlated with different functional groups. Three main immune-pathways were identified (p < 0.01) (T cell activation, leucocyte activation and migration) involving TIGIT, TNFRSF4, CCR2 and CXCL8 genes among the gene expression signature identified. Conclusions: Our results revealed an immune response gene expression signature of 8 genes differentially expressed between ICI and ICI-no responders. Cancer systems biology analysis approach strengthen our findings identifying an immune molecular network and confirm the correlation of the gene expression signature with relevant immune regulatory functions. If validated, our results may have an important role for the development of a robust test to select patients properly and predict immune response to enable precision immunotherapy.
39
Pardanani, Animesh, Christos Vaklavas, Joseph Butterfield, Rhett Ketterling, Srdan Verstovsek, Hagop Kantarjian, and Ayalew Tefferi. "’Idiopathic’ Eosinophilia with an Occult T-Cell Clone: Prevalence, FIP1L1-PDGFRA Status, and Clinical Course." Blood 108, no. 11 (November 16, 2006): 2701. http://dx.doi.org/10.1182/blood.v108.11.2701.2701.
Повний текст джерелаАнотація:
Abstract Background: Blood eosinophilia results either from autonomous expansion of a myeloid stem/progenitor cell, or as a response to cytokines that promote growth and differentiation of eosinophil progenitors. A subset of patients with hypereosinophilic syndrome/idiopathic eosinophilia (HES/IE) display abnormal T-cell immunophenotype and/or clonal rearrangements of the T-cell receptor (TCR), operationally assigned the term “lymphocyte variant” HES/IE. Information on the prevalence, FIP1L1-PDGFRA status, and clinical course of such patients is limited. Methods: Consecutive patients with eosinophilia were identified by querying our institutional electronic database from 1995 to 2004. Clonal rearrangements of the γchain of the TCR were identified by polymerase chain reaction followed by gel electrophoresis in all cases, and confirmed by Southern Blot analysis of the gene coding for the β chain of the TCR, using standard methods. FIP1L1-PDGFRA was screened by fluorescence in situ hybridization. Results: We studied a total of 205 consecutive patients with eosinophilia defined as an absolute eosinophil count (AEC) of > 600/μL, who also had a bone marrow study performed. Of these, TCR gene rearrangements studies were performed in 99 patients (AEC range of 650 to 38,000/μL) including 3 children and 96 adults (age range 18 to 88 years; 58 males). Among these 99 patients, 14 (~14%) had a demonstrable T-cell clone in peripheral blood, bone marrow aspirate, lymph node, and/or skin. Six of the 14 patients with a demonstrable T-cell clone were found to have a concurrent T-cell malignancy at the time of evaluation including T-cell large granular lymphocytic (T-LGL) leukemia - 1 case and peripheral T-cell lymphoma - 5 cases. The other 8 (~8%) patients otherwise fulfilled the working diagnosis of “lymphocyte variant” HES/IE (median AEC=2045/μL, range 720/μL to 9600/μL). The median duration of eosinophilic prodrome, prior to identification of the occult T-cell clone was 5 years (range 3 months to 11 years), and virtually all had dominant skin involvement presenting as dermatitis (5 cases) or episodic angioedema with eosinophilia (EAE) (2 cases). Five of 7 patients tested had an elevated serum IgE level, and a similar proportion displayed an abnormal T-cell immunophenotype (most commonly, aberrant CD5 and/or CD7 expression). Six of the 8 patients with an occult T-cell clone were evaluated for FIP1L1-PDGFRA and tested negative. Two patients were effectively treated with low-dose oral cyclophosphamide or methotrexate (follow-up duration of 3+ and 6+ years, respectively) whereas imatinib treatment was ineffective in another 2 patients. Two patients (25%) transformed into cutaneous T-cell lymphoma after 3 to 8 years of eosinophilic prodrome. Conclusion: The current study suggests that the presence of a T-cell clone in idiopathic eosinophilia is a marker/harbinger of a primarily skin-based peripheral T-cell lymphoma that responds to T cell-directed therapy but not imatinib therapy, which is consistent with the absence of FIP1L1-PDGFRA in such cases.
40
Padua, Tiago Costa de, Greta Malena, Marco Moschini, Alberto Martini, Laura Marandino, Daniele Raggi, Alberto Briganti, Francesco Montorsi, and Andrea Necchi. "Efficacy and toxicity of antibody-drug conjugates (ADCs) in the treatment of metastatic urothelial cancer (mUC): A systematic review." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16536-e16536. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16536.
Повний текст джерелаАнотація:
e16536 Background: mUC is an aggressive disease with limited overall survival. Recently, immunotherapy with checkpoint inhibitors (ICI) has dramatically improved outcomes but with limited response rates and overall survival. ADC were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to mAbs and have emerged as a new option of treatment with promising results. We aimed to realize a systematic review of efficacy, treatment-related AEs (trAEs) and impact on quality of life of ADC in mUC. Methods: A systematic review of the literature has been performed in January 2022 using Pubmed and Embase database according to the Preferred Reported Items for Systematic Reviews and Meta-analyses (PRISMA) statement. After excluding review, duplicate and non-relevant articles, 10 clinical trials were included in the analysis. The search method involved querying for the terms bladder carcinoma or urothelial carcinoma with any of the following: enfortumab vedotin (EV), sacituzumab govitecan (SG), antibody-drug conjugate. Only prospective clinical trials were included. Results: The systematic review yielded 1103 records using MEDLINE (741 records) and EMBASE (362 records). Ultimately, 9 phase 1, 2 or 3 clinical trials with 1355 patients were selected for inclusion and 4 drugs were identified: Enfortumab vedotin (EV), sacituzumab govitecan (SG), an anti-HER2 compound (RC48-ADC), and an anti- SLITRK6 drug (ASG-15ME). Efficacy outcomes are presented in table 1. Phase 2 trials have reported promising response rates in mUC and one randomized phase 3 trial showed the superiority of EV vedotin over CT after failure to platinum-based CT and ICI with improvement in overall survival. TRAEs of any grade occurred in more than 90% of patients in phase 2 or 3 trials, with high rates of discontinuation (table 2). TRAEs of special interest related to EV were rash, neuropathy, and hyperglycemia. SG is associated with diarrhea and hematologic toxicity. Data from phase 2 and 3 trials of EV suggest no impact on quality of life and an improvement in some parameters. Conclusions: ACDs represent a very promising new option for the treatment of mUC. A phase 3 trial confirmed the superiority of EV over CT after platinum and IO failure. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Practitioners’ oncologists should be aware of potential adverse events and optimal management. Quality of life is preserved during the treatment with EV.
41
Padua, Tiago Costa de, Greta Malena, Marco Moschini, Alberto Martini, Laura Marandino, Daniele Raggi, Alberto Briganti, Francesco Montorsi, and Andrea Necchi. "Efficacy and toxicity of antibody-drug conjugates (ADCs) in the treatment of metastatic urothelial cancer (mUC): A systematic review." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16536-e16536. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16536.
Повний текст джерелаАнотація:
e16536 Background: mUC is an aggressive disease with limited overall survival. Recently, immunotherapy with checkpoint inhibitors (ICI) has dramatically improved outcomes but with limited response rates and overall survival. ADC were designed with the intent to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells by linking cytotoxins to mAbs and have emerged as a new option of treatment with promising results. We aimed to realize a systematic review of efficacy, treatment-related AEs (trAEs) and impact on quality of life of ADC in mUC. Methods: A systematic review of the literature has been performed in January 2022 using Pubmed and Embase database according to the Preferred Reported Items for Systematic Reviews and Meta-analyses (PRISMA) statement. After excluding review, duplicate and non-relevant articles, 10 clinical trials were included in the analysis. The search method involved querying for the terms bladder carcinoma or urothelial carcinoma with any of the following: enfortumab vedotin (EV), sacituzumab govitecan (SG), antibody-drug conjugate. Only prospective clinical trials were included. Results: The systematic review yielded 1103 records using MEDLINE (741 records) and EMBASE (362 records). Ultimately, 9 phase 1, 2 or 3 clinical trials with 1355 patients were selected for inclusion and 4 drugs were identified: Enfortumab vedotin (EV), sacituzumab govitecan (SG), an anti-HER2 compound (RC48-ADC), and an anti- SLITRK6 drug (ASG-15ME). Efficacy outcomes are presented in table 1. Phase 2 trials have reported promising response rates in mUC and one randomized phase 3 trial showed the superiority of EV vedotin over CT after failure to platinum-based CT and ICI with improvement in overall survival. TRAEs of any grade occurred in more than 90% of patients in phase 2 or 3 trials, with high rates of discontinuation (table 2). TRAEs of special interest related to EV were rash, neuropathy, and hyperglycemia. SG is associated with diarrhea and hematologic toxicity. Data from phase 2 and 3 trials of EV suggest no impact on quality of life and an improvement in some parameters. Conclusions: ACDs represent a very promising new option for the treatment of mUC. A phase 3 trial confirmed the superiority of EV over CT after platinum and IO failure. A high incidence of potential adverse events was observed in phase 2 and 3 trials, including rash, neutropenia, hematologic toxicity, and neuropathy. Practitioners’ oncologists should be aware of potential adverse events and optimal management. Quality of life is preserved during the treatment with EV.
42
Gao, Li, Yu-Yan Pang, Xian-Yu Guo, Jing-Jing Zeng, Zhong-Qing Tang, Dan-Dan Xiong, Xia Yang, et al. "Polo like kinase 1 expression in cervical cancer tissues generated from multiple detection methods." PeerJ 8 (December 8, 2020): e10458. http://dx.doi.org/10.7717/peerj.10458.
Повний текст джерелаАнотація:
Background Existing studies of PLK1 in cervical cancer had several flaws. The methods adopted by those studies of detecting PLK1 expression in cervical cancer were single and there lacks comprehensive evaluation of the clinico-pathological significance of PLK1 in cervical cancer. Methods A total of 303 cervical tissue samples were collected for in-house tissue microarrays. Immunohistochemistry was performed for evaluating PLK1 expression between cervical cancer (including cervical squamous cell carcinoma (CESC) and cervical adenocarcinoma) and non-cancer samples. The Expression Atlas database was searched for querying PLK1 expression in different cervical cancer cell lines and different tissues in the context of pan-cancer. Standard mean difference (SMD) was calculated and the summarized receiver’s operating characteristics (SROC) curves were plotted for integrated tissue microarrays, exterior high-throughput microarrays and RNA sequencing data as further verification. The effect of PLK1 expression on the overall survival, disease-free survival and event-free survival of cervical cancer patients was analyzed through Kaplan Meier survival curves for cervical cancer patients from RNA-seq and GSE44001 datasets. The gene mutation and alteration status of PLK1 in cervical cancer was inspected in COSMIC and cBioPortal databases. Functional enrichment analysis was performed for genes correlated with PLK1 from aggregated RNA-seq and microarrays. Results A total of 963 cervical cancer samples and 178 non-cancer samples were collected from in-house tissue microarrays and exterior microarrays and RNA-seq datasets. The combined expression analysis supported overexpression of PLK1 in CESC, cervical adenocarcinoma and all types of cervical cancer (SMD = 1.59, 95%CI [0.56–2.63]; SMD = 2.99, 95%CI [0.75–5.24]; SMD = 1.57, 95% CI [0.85–2.29]) and the significant power of PLK1 expression in distinguishing CESC or all types of cervical cancer samples from non-cancer samples (AUC = 0.94, AUC = 0.92). Kaplan-Meier survival curves showed that the event-free survival rate of cervical cancer patients with higher expression of PLK1 was shorter than that of patients with lower PLK1 (HR = 2.020, P = 0.0197). Genetic alteration of PLK1 including missense mutation and mRNA low occurred in 6% of cervical cancer samples profiled in mRNA expression. Genes positively or negatively correlated with PLK1 were mainly assembled in pathways such as DNA replication, cell cycle, mismatch repair, Ras signaling pathway, melanoma, EGFR tyrosine kinase inhibitor resistance and homologous recombination (P < 0.05). Conclusions Here, we provided sufficient evidence of PLK1 overexpression in cervical cancer. The overexpression of PLK1 in cervical cancer and the contributory effect of it on clinical progression indicated the hopeful prospect of PLK1 as a biomarker for cervical cancer.
43
Sidana, Surbhi, Lisa Rybicki, Frederic J. Reu, and Thomas Daly. "High Serum Free Kappa Chains Are Frequently Missed By Serum Immunofixation." Blood 124, no. 21 (December 6, 2014): 5708. http://dx.doi.org/10.1182/blood.v124.21.5708.5708.
Повний текст джерелаАнотація:
Abstract Background: Serum free light chains (sFLC) and immunofixation (IFE) analysis are used to detect monoclonal proteins. We noticed that some multiple myeloma (MM) patients (pts) had negative IFE results despite very high sFLC levels. This analysis was done to determine the frequency of this finding in a large cohort. Methods: Following IRB approval, samples with simultaneous sIFE and sFLCs ordered from 1/2013 to 9/2013 were identified by querying our lab electronic database. Freelite (R) Human Kappa & Lambda Free kit (The Binding Site, Birmingham, UK) was used for sFLC and SPIFE® ImmunoFix-15 gels (Helena Laboratories, Beaumont, TX) for IFE. Clinical review was performed for a subset of patients with discrepant results between the two assays. Results: 4404 samples from 2200 pts were identified with simultaneous sFLC and sIFE results. Overall 348 of 4404 (7.9%) samples had an abnormal sFLC ratio but a negative sIFE. Of 205 pts (457 samples) with involved serum free kappa above the expected IFE threshold (200 mg/L), 42 pts (103 samples) had negative sIFEs (20.5% pts; 22.5% samples) despite median free kappa of 556.6 mg/L (range 208.1 to 4954.4). This was much less common for involved free lambda. Only 4 of 107 pts with free lambda above 200mg/L had negative sIFEs (3.7%). Information of the nature of the plasma cell disorder was available on 40 of the 42 patients with free kappa > 200mg/L and negative IFE. In this group, 62.5% (n=25) had symptomatic MM, 12.5% (n=5) had asymptomatic MM, 5% (n=2) had light chain amyloidosis, 5% (n=2) had both amyloidosis and MM, and 15% (n=6) had MGUS or a not yet fully worked up plasma cell disorder. Conclusions: Serum IFE, with a commonly used kit, missed about 20% of patients with free kappa above the expected IFE threshold, while free lambda was detected more reliably. Results suggest current criteria for complete remission which rely on immunofixation and bone marrow plasma cell infiltration may need to be revised for kappa light chain myeloma. Disclosures No relevant conflicts of interest to declare.
44
Baxter, Sally L., Adam R. Klie, Bharanidharan Radha Saseendrakumar, Gordon Y. Ye, and Michael Hogarth. "Text Processing for Detection of Fungal Ocular Involvement in Critical Care Patients: Cross-Sectional Study." Journal of Medical Internet Research 22, no. 8 (August 14, 2020): e18855. http://dx.doi.org/10.2196/18855.
Повний текст джерелаАнотація:
Background Fungal ocular involvement can develop in patients with fungal bloodstream infections and can be vision-threatening. Ocular involvement has become less common in the current era of improved antifungal therapies. Retrospectively determining the prevalence of fungal ocular involvement is important for informing clinical guidelines, such as the need for routine ophthalmologic consultations. However, manual retrospective record review to detect cases is time-consuming. Objective This study aimed to determine the prevalence of fungal ocular involvement in a critical care database using both structured and unstructured electronic health record (EHR) data. Methods We queried microbiology data from 46,467 critical care patients over 12 years (2000-2012) from the Medical Information Mart for Intensive Care III (MIMIC-III) to identify 265 patients with culture-proven fungemia. For each fungemic patient, demographic data, fungal species present in blood culture, and risk factors for fungemia (eg, presence of indwelling catheters, recent major surgery, diabetes, immunosuppressed status) were ascertained. All structured diagnosis codes and free-text narrative notes associated with each patient’s hospitalization were also extracted. Screening for fungal endophthalmitis was performed using two approaches: (1) by querying a wide array of eye- and vision-related diagnosis codes, and (2) by utilizing a custom regular expression pipeline to identify and collate relevant text matches pertaining to fungal ocular involvement. Both approaches were validated using manual record review. The main outcome measure was the documentation of any fungal ocular involvement. Results In total, 265 patients had culture-proven fungemia, with Candida albicans (n=114, 43%) and Candida glabrata (n=74, 28%) being the most common fungal species in blood culture. The in-hospital mortality rate was 121 (46%). In total, 7 patients were identified as having eye- or vision-related diagnosis codes, none of whom had fungal endophthalmitis based on record review. There were 26,830 free-text narrative notes associated with these 265 patients. A regular expression pipeline based on relevant terms yielded possible matches in 683 notes from 108 patients. Subsequent manual record review again demonstrated that no patients had fungal ocular involvement. Therefore, the prevalence of fungal ocular involvement in this cohort was 0%. Conclusions MIMIC-III contained no cases of ocular involvement among fungemic patients, consistent with prior studies reporting low rates of ocular involvement in fungemia. This study demonstrates an application of natural language processing to expedite the review of narrative notes. This approach is highly relevant for ophthalmology, where diagnoses are often based on physical examination findings that are documented within clinical notes.
45
Joseph, Amanda L., Helen Monkman, Andre Kushniruk, and Yuri Quintana. "Exploring Patient Journey Mapping and the Learning Health System: Scoping Review." JMIR Human Factors 10 (February 27, 2023): e43966. http://dx.doi.org/10.2196/43966.
Повний текст джерелаАнотація:
Background Journey maps are visualization tools that can facilitate the diagrammatical representation of stakeholder groups by interest or function for comparative visual analysis. Therefore, journey maps can illustrate intersections and relationships between organizations and consumers using products or services. We propose that some synergies may exist between journey maps and the concept of a learning health system (LHS). The overarching goal of an LHS is to use health care data to inform clinical practice and improve service delivery processes and patient outcomes. Objective The purpose of this review was to assess the literature and establish a relationship between journey mapping techniques and LHSs. Specifically, in this study, we explored the current state of the literature to answer the following research questions: (1) Is there a relationship between journey mapping techniques and an LHS in the literature? (2) Is there a way to integrate the data from journey mapping activities into an LHS? (3) How can the data gleaned from journey map activities be used to inform an LHS? Methods A scoping review was conducted by querying the following electronic databases: Cochrane Database of Systematic Reviews (Ovid), IEEE Xplore, PubMed, Web of Science, Academic Search Complete (EBSCOhost), APA PsycInfo (EBSCOhost), CINAHL (EBSCOhost), and MEDLINE (EBSCOhost). Two researchers applied the inclusion criteria and assessed all articles by title and abstract in the first screen, using Covidence. Following this, a full-text review of included articles was done, with relevant data extracted, tabulated, and assessed thematically. Results The initial search yielded 694 studies. Of those, 179 duplicates were removed. Following this, 515 articles were assessed during the first screening phase, and 412 were excluded, as they did not meet the inclusion criteria. Next, 103 articles were read in full, and 95 were excluded, resulting in a final sample of 8 articles that satisfied the inclusion criteria. The article sample can be subsumed into 2 overarching themes: (1) the need to evolve service delivery models in health care, and (2) the potential value of using patient journey data in an LHS. Conclusions This scoping review demonstrated the gap in knowledge regarding integrating the data from journey mapping activities into an LHS. Our findings highlighted the importance of using the data from patient experiences to enrich an LHS and provide holistic care. To satisfy this gap, the authors intend to continue this investigation to establish the relationship between journey mapping and the concept of LHSs. This scoping review will serve as phase 1 of an investigative series. Phase 2 will entail the creation of a holistic framework to guide and streamline data integration from journey mapping activities into an LHS. Lastly, phase 3 will provide a proof of concept to demonstrate how patient journey mapping activities could be integrated into an LHS.
46
Dobbins, Nicholas J., Clifford H. Spital, Robert A. Black, Jason M. Morrison, Bas de Veer, Elizabeth Zampino, Robert D. Harrington, et al. "Leaf: an open-source, model-agnostic, data-driven web application for cohort discovery and translational biomedical research." Journal of the American Medical Informatics Association 27, no. 1 (October 8, 2019): 109–18. http://dx.doi.org/10.1093/jamia/ocz165.
Повний текст джерелаАнотація:
Abstract Objective Academic medical centers and health systems are increasingly challenged with supporting appropriate secondary use of clinical data. Enterprise data warehouses have emerged as central resources for these data, but often require an informatician to extract meaningful information, limiting direct access by end users. To overcome this challenge, we have developed Leaf, a lightweight self-service web application for querying clinical data from heterogeneous data models and sources. Materials and Methods Leaf utilizes a flexible biomedical concept system to define hierarchical concepts and ontologies. Each Leaf concept contains both textual representations and SQL query building blocks, exposed by a simple drag-and-drop user interface. Leaf generates abstract syntax trees which are compiled into dynamic SQL queries. Results Leaf is a successful production-supported tool at the University of Washington, which hosts a central Leaf instance querying an enterprise data warehouse with over 300 active users. Through the support of UW Medicine (https://uwmedicine.org), the Institute of Translational Health Sciences (https://www.iths.org), and the National Center for Data to Health (https://ctsa.ncats.nih.gov/cd2h/), Leaf source code has been released into the public domain at https://github.com/uwrit/leaf. Discussion Leaf allows the querying of single or multiple clinical databases simultaneously, even those of different data models. This enables fast installation without costly extraction or duplication. Conclusions Leaf differs from existing cohort discovery tools because it does not specify a required data model and is designed to seamlessly leverage existing user authentication systems and clinical databases in situ. We believe Leaf to be useful for health system analytics, clinical research data warehouses, precision medicine biobanks, and clinical studies involving large patient cohorts.
47
Janne, Pasi A., Jessica Kim Lee, Russell Madison, Jeffrey Michael Venstrom, Alexa Betzig Schrock, and Geoffrey R. Oxnard. "Incidence and heterogeneity of C797S and other EGFR resistance mutations on routine comprehensive genomic profiling (CGP)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 9101. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.9101.
Повний текст джерелаАнотація:
9101 Background: The emergence of osimertinib (osi) as standard of care therapy for EGFR-mutant NSCLC has led to investigations into understanding and overcoming drug resistance. There are now a number of therapeutic approaches aimed at overcoming EGFR resistance mutations (muts). We sought to understand the biology of EGFR C797S and other EGFR resistance muts through querying our clinico-genomic database (CGDB). Methods: CGP results from tissue (n = 60,889) or circulating tumor DNA (ctDNA; [n = 9,922]) samples from 70,811 NSCLC patients (pts) were queried for known osi resistance muts in EGFR (C797, L792, G796, L718, G724). Clinical outcomes were evaluated for a cohort of NSCLC pts with osi resistance from the Flatiron Health-Foundation Medicine CGDB, a nationwide de-identified EHR-derived database linked to CGP data. Results: Between 12/2014 and 11/2020, 261 osi resistance mutations in EGFR were detected in 228 samples. The most common were C797S (66%), L718X (14%), G724S (11%), and others (9%). 173 C797S muts were detected in 155 samples (123 ex19del, 30 L858R, 2 other EGFR muts); 100 tissue, 55 ctDNA (median VAF = 7.6%). EGFR T790M co-occurred with C797S muts (96% cis, 3.7% trans) in 118 (76%) samples and decreased over time, occurring in 92% (24/26) of C797S samples tested in 2017 vs 56% (20/36) of samples tested in 2020 (p = 0.002). In 19/155 (12%) samples with C797S (14 ctDNA), multiple changes resulting in EGFR resistance muts were present: 16 samples had > 1 nucleotide changes resulting in C797S (100% trans), 3 samples had other resistance muts (L718Q/V, L792H, L792F) and 3 samples had multiple C797S changes with other resistance muts (C797G, L792H/F + G796S, L718Q + G796S+C797G). 29 pts (14 ctDNA) had C797S with potential off-target resistance (17 PIK3CA muts, 4 BRAF muts, 3 CCDC6- RET fusions, 3 KRAS muts, 2 ERBB2 amplifications (amps), 1 ERBB2 ex16 del, 1 STRN- ALK fusion, 1 FGFR3- TACC3 fusion). In the CGDB, 527 EGFR-mut NSCLC pts had documented receipt of osi. Pre and post osi-treated specimens were available for 19 of these pts (12 ex19del, 6 L858R, 1 G719A/S768I). Heterogeneous acquired resistance mechanisms were observed in the post-osi specimen, including 2 CCDC6- RET fusions, 2 MET amps, 2 BRAF fusions, BRAF V600E, and secondary EGFR muts (C797S, L704F, L718V). 161/527 pts had a documented line of therapy after osi discontinuation and most frequently received platinum doublet + immunotherapy (27%) or platinum doublet alone (23%); 17 (11%) pts received another EGFR tyrosine kinase inhibitor. 214/527 had documented osi progression and median post-progression survival was 11.8 months. Conclusions: Osi resistance in EGFR-mutant NSCLC is a poor prognosis condition. EGFR C797S is a recurring resistance mut which, in a minority of cases, can co-occur with alternate on and off target resistance muts detected with tissue and liquid biopsy.
48
Piedra, Katrina M., Hani Hassoun, Larry W. Buie, Sean M. Devlin, Jessica Flynn, Malin Hultcrantz, Alexander M. Lesokhin, et al. "VTE Rates and Safety Analysis of Newly Diagnosed Multiple Myeloma Patients Receiving Carfilzomib-Lenalidomide-Dexamethasone (KRD) with or without Rivaroxaban Prophylaxis." Blood 134, Supplement_1 (November 13, 2019): 1835. http://dx.doi.org/10.1182/blood-2019-124403.
Повний текст джерелаАнотація:
Introduction Immunomodulatory agents (IMiD's) are associated with an increased risk of venous thromboembolism (VTE), particularly when combined with high dose steroids. Studies evaluating the use of lenalidomide-bortezomib-dexamethasone (RVD) and carfilzomib-lenalidomide-dexamethasone (KRD) in the frontline setting for multiple myeloma (MM) have reported a 6% and 24% incidence of thrombosis, respectively, despite primary thrombotic prophylaxis with aspirin (ASA) (Richardson, et al. Blood. 2010; Korde, et al. JAMA Oncol 2015). Recent data, including the Hokusai VTE Cancer Trial, have suggested that safety and efficacy of direct oral anticoagulants (DOACs) are preserved in the setting of treatment of solid malignancy-associated thrombosis (Raskob, et al. N Engl J Med. 2018; Mantha, et al. J Thromb Thrombolysis. 2017). Despite this data, there is limited experience and use of DOACs in prevention of thromboses in the setting of hematologic malignancies, specifically MM. After careful review of literature, since early 2018, we changed our clinical practice and routinely placed newly diagnosed MM (NDMM) patients receiving KRD at Memorial Sloan Kettering Cancer Center (MSKCC) on concomitant rivaroxaban 10 mg once daily, regardless of VTE risk stratification. In the following abstract, we present VTE rates and safety data for newly diagnosed MM patients receiving RVD with ASA vs. KRD with ASA vs. KRD with rivaroxaban prophylaxis. Methods This was an IRB-approved, single-center, retrospective chart review study. All untreated patients with newly diagnosed MM, receiving at least one cycle of RVD or KRD between January 2015 and October 2018 were included. The period of observation included the time between the first day of therapy until 90 days after completion of induction therapy. Patients were identified by querying the pharmacy database for carfilzomib or bortezomib administration and outpatient medication review of thromboprophylaxis with rivaroxaban or ASA. VTE diagnoses were confirmed by ICD-10 codes and appropriate imaging studies (computed tomography and ultrasound). Descriptive statistics were performed. Results During the observation period, 241 patients were identified to have received RVD or KRD in the frontline (99 RVD with ASA; 97 KRD with ASA; 45 KRD with rivaroxaban). Baseline characteristics were well distributed among the three arms, with a median age of 60 (30-94) in the RVD ASA arm, 62 (33-77) in the KRD ASA arm, and 60 (24-79) in the KRD rivaroxaban arm. Patients had International Staging System (ISS) stage 3 disease in 13% (N=13), 9.3% (N=9), and 11% (N=5) of the RVD ASA, KRD ASA, and KRD rivaroxaban arms, respectively. Median weekly doses of dexamethasone were higher in both KRD arms, 40 mg (20-40) vs. 20 mg (10-40) in the RVD ASA arm. The average initial doses of lenalidomide were 22 mg in the RVD ASA arm compared to 25 mg in both the KRD ASA and KRD rivaroxaban arms. After querying the pharmacy database, no patients were identified to have a history or concomitant use of erythropoietin stimulating agent (ESA) use. Treatment-related VTE's occurred in 4 patients (4.0%) in the RVD ASA arm, 16 patients (16.5%) in the KRD ASA arm, and in 1 patient (2.2%) in the KRD rivaroxaban arm. Average time to VTE was 6.15 months (Range 5.42, 9.73) after treatment initiation in the RVD ASA group, while it was 2.61 months (Range 0.43, 5.06) in the KRD ASA group and 1.35 months in the KRD rivaroxaban group. Minor, grade 1 bleeding events per the Common Terminology Criteria for Adverse Events (CTCAE) were identified in 1 (1.1%) patient in the RVD ASA arm, 5 (5.2%) patients in the KRD ASA arm, and 1 (2.2%) patient in the KRD rivaroxaban arm. Conclusion More efficacious MM combination therapies have been found to increase the risk of VTE when using ASA prophylaxis, indicating better thromboprophylaxis is needed. We found patients receiving ASA prophylaxis with KRD were more likely to experience a VTE and these events occurred earlier compared to patients receiving ASA prophylaxis with RVD. Importantly, the rate of VTE was reduced to the same level as ASA prophylaxis with RVD when low-dose rivaroxaban 10 mg daily was used with KRD, and without necessarily increasing bleeding risk. Our retrospective data support the development of prospective clinical trials further investigating DOAC use in thromboprophylaxis for NDMM patients receiving carfilzomib-based treatments. Figure Disclosures Hassoun: Novartis: Consultancy; Janssen: Research Funding; Celgene: Research Funding. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Research Funding; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Genentech: Research Funding; Juno: Consultancy, Honoraria. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Landgren:Theradex: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Other: IDMC; Sanofi: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Off-label use of rivaroxaban for outpatient prophylaxis of venous thromboembolism (VTE) will be explicitly disclosed to the audience.
49
Combi, C., G. Cucchi, and F. Pinciroli. "Applying object-oriented technologies in modeling and querying temporally oriented clinical databases dealing with temporal granularity and indeterminacy." IEEE Transactions on Information Technology in Biomedicine 1, no. 2 (June 1997): 100–127. http://dx.doi.org/10.1109/4233.640654.
Повний текст джерела
50
Leonti, Amanda R., Makia Manselle, Jenny L. Smith, Rhonda E. Ries, Anders E. Kolb, and Soheil Meshinchi. "Target-Informed Repurposing of Immunotherapies in AML - a Transcriptome Based Approach for Identifying Immediately Available Therapeutics." Blood 136, Supplement 1 (November 5, 2020): 5–6. http://dx.doi.org/10.1182/blood-2020-138566.
Повний текст джерелаАнотація:
Acute Myeloid Leukemia (AML) is an aggressive hematopoietic malignancy with limited therapeutic options and a great need for innovative treatment. However, the identification of novel molecular biomarkers remains challenging, and significant lag time from target discovery to clinical development impedes timely implementation of novel therapies. We previously demonstrated aberrant expression of non-hematopoetic (NH) antigens on leukemic cells in AML; one such antigen, mesothelin (MSLN), has recently begun AML clinical development, providing evidence for the use of NH directed therapeutics in AML. Given this observation, we questioned whether we could build a computational platform to identify misregulated genes in AML that are targeted by currently available immunotherapies in other malignancies. Early phase trial data for these targets will provide vital safety and tolerability information, thereby supporting a rapid path to AML clinical development. To this end, we curated a knowledgebase of antibody-drug conjugate (ADC) and chimeric antigen receptor T-cell (CAR T) therapies by querying all cancer immunotherapy trials registered in the U.S. National Library of Medicine clinical trials database (https://clinicaltrials.gov) and the Journal of Antibody-Drug Conjugates (https://adcreview.com) in November of 2019. In total, our knowledgebase contained 893 clinical trials assessing 141 prospective gene targets. We interrogated transcriptome expression of these targets using ribodepleted RNA-seq data from the TARGET AML and TpAML initiatives (N = 1,394, age <0 to 30 years) and the TCGA LAML cohort (N = 173, age 18 - 88 years). We selected for therapeutic targets expressed in AML by employing a minimum transcript expression threshold of 5 TPM in >50% of our AML cases. This led to the identification of 35 targets of interest for further analysis (Figure 1A). A total of 131 immunotherapies (70 ADCs and 61 CAR Ts) directed against these targets are in various stages of clinical development (Figure 1B). These included 62 AML-directed therapies targeting a total of 13 antigens; among these, CD33, CD123, FLT3, CD117, and CLEC12A have been well described in the context of AML. The remaining 69 therapies (43 ADCs and 26 CAR-Ts) target 30 NH antigens. Nine (30%) of these NH antigens, including CD74, BSG, TFRC, CXCR4, and CD44, all possesed a median of >90 TPM in our AML cohort and were subjects of therapies in Phase I or later. Additionally, these genes were universally expressed across major fusion groups (Figure 1C), suggesting potential as therapeutic targets regardless of age or genetic abnormality. A table of NH targets with high expression in AML is provided in Figure 1D. Conversely, we also identified targets for which expression was uniquely restricted to rare, high-risk, and therapeutically challenging AML variants. Upregulated genes in these variants were identified via differential expression analysis of CBFA2T3-GLIS2, NUP98-NSD1, and NUP98-KDM5A fusions. Genes were filtered using a log fold-change (logFC) threshold of 1 and FDR-adjusted p < 0.05, then cross-referenced with the full knowledgebase to identify 37 rare-variant enriched targets. The top 5 most highly enriched targets (ranked by logFC) were FOLR1, NCAM1, MMP14, TNF, and DLK1. The association of NCAM1 with CBFA2T3-GLIS2 has been previously described. However, FOLR1, a member of the folate receptor family that is overexpressed in epithelial-derived tumors, is a novel target in the context of AML. Like NCAM1, FOLR1 expression in our AML population is almost entirely limited to the CBFA2T3-GLIS2 fusion: 36/43 FOLR1-expressing patients possessed a CBFA2T3-GLIS2 fusion, comprising 94.74% of all CBFA2T3-GLIS2 fusions in our cohort. We screened transcriptome data from a large AML cohort for expression of immunotherapeutic targets with potential utility in AML. This enabled the identification of both broadly expressed and subtype-restricted putative targets. Future expansion of this methodology into other cellular therapies (CAR NK or BiTE) and the examination of new data sources could reveal additional targets with robust expression in AML. Demonstration of cell surface expression of these targets, and appropriate preclinical evidence of efficacy, could lay the groundwork for quickly moving these therapies to clinical trials in AML. Figure Disclosures No relevant conflicts of interest to declare.