Temporal phenome analysis of a large electronic health record cohort enables identification of hospital-acquired complications.

OBJECTIVE To develop methods for visual analysis of temporal phenotype data available through electronic health records (EHR). MATERIALS AND METHODS 24 580 adults from the multiparameter intelligent monitoring in intensive care V.6 (MIMIC II) EHR database of critically ill patients were analyzed, with significant temporal associations visualized as a map of associations between hospital length of stay (LOS) and ICD-9-CM codes. An expanded phenotype, using ICD-9-CM, microbiology, and computerized physician order entry data, was defined for hospital-acquired Clostridium difficile (HA-CDI). LOS, estimated costs, 30-day post-discharge mortality, and antecedent medication provider order entry were evaluated for HA-CDI cases compared to randomly selected controls. RESULTS Temporal phenome analysis revealed 191 significant codes (p value, adjusted for false discovery rate, ≤0.05). HA-CDI was identified in 414 cases, and was associated with longer median LOS, 20 versus 9 days, and adjusted HR 0.33 (95% CI 0.28 to 0.39). This prolongation carries an estimated annual incremental cost increase of US$1.2-2.0 billion in the USA alone. DISCUSSION Comprehensive EHR data have made large-scale phenome-based analysis feasible. Time-dependent pathological disease states have dynamic phenomic evolution, which may be captured through visual analytical approaches. Although MIMIC II is a single institutional retrospective database, our approach should be portable to other EHR data sources, including prospective 'learning healthcare systems'. For example, interventions to prevent HA-CDI could be dynamically evaluated using the same techniques. CONCLUSIONS The new visual analytical method described in this paper led directly to the identification of numerous hospital-acquired conditions, which could be further explored through an expanded phenotype definition.

[1]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[2]  Ben Shneiderman,et al.  LifeLines: using visualization to enhance navigation and analysis of patient records , 1998, AMIA.

[3]  C. Steiner,et al.  Comorbidity measures for use with administrative data. , 1998, Medical care.

[4]  L. Cooper,et al.  Medicare intensive care unit use: Analysis of incidence, cost, and payment* , 2004, Critical care medicine.

[5]  A. Butte,et al.  Creation and implications of a phenome-genome network , 2006, Nature Biotechnology.

[6]  Victoria J. Fraser,et al.  ICD-9 Codes and Surveillance for Clostridium difficile–associated Disease , 2006, Emerging infectious diseases.

[7]  G. Clermont,et al.  Growth of intensive care unit resource use and its estimated cost in Medicare* , 2008, Critical care medicine.

[8]  I. Kohane,et al.  Instrumenting the health care enterprise for discovery research in the genomic era. , 2009, Genome research.

[9]  Richard F. Averill,et al.  Estimating the Costs of Potentially Preventable Hospital Acquired Complications , 2009, Health care financing review.

[10]  D R Lairson,et al.  Economic healthcare costs of Clostridium difficile infection: a systematic review. , 2010, The Journal of hospital infection.

[11]  Yuval Shahar,et al.  Intelligent visualization and exploration of time-oriented data of multiple patients , 2010, Artif. Intell. Medicine.

[12]  Marylyn D. Ritchie,et al.  PheWAS: demonstrating the feasibility of a phenome-wide scan to discover gene–disease associations , 2010, Bioinform..

[13]  S. Omholt,et al.  Phenomics: the next challenge , 2010, Nature Reviews Genetics.

[14]  B. Hota,et al.  Multicenter Study of Surveillance for Hospital-Onset Clostridium difficile Infection by the Use of ICD-9-CM Diagnosis Codes , 2010, Infection Control & Hospital Epidemiology.

[15]  Griffin M. Weber,et al.  Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2) , 2010, J. Am. Medical Informatics Assoc..

[16]  D. Blumenthal,et al.  Achieving a Nationwide Learning Health System , 2010, Science Translational Medicine.

[17]  N. Halpern,et al.  Critical care medicine in the United States 2000–2005: An analysis of bed numbers, occupancy rates, payer mix, and costs* , 2010, Critical care medicine.

[18]  T. H. Kyaw,et al.  Multiparameter Intelligent Monitoring in Intensive Care II: A public-access intensive care unit database* , 2011, Critical care medicine.

[19]  Ben Shneiderman,et al.  Extracting Insights from Electronic Health Records: Case Studies, a Visual Analytics Process Model, and Design Recommendations , 2011, Journal of Medical Systems.

[20]  C Kooperberg,et al.  The use of phenome‐wide association studies (PheWAS) for exploration of novel genotype‐phenotype relationships and pleiotropy discovery , 2011, Genetic epidemiology.

[21]  Monica Chan,et al.  Surveillance for Clostridium difficile Infection: ICD-9 Coding Has Poor Sensitivity Compared to Laboratory Diagnosis in Hospital Patients, Singapore , 2011, PloS one.

[22]  Lucila Ohno-Machado,et al.  Realizing the full potential of electronic health records: the role of natural language processing , 2011, J. Am. Medical Informatics Assoc..

[23]  John Boyle,et al.  Methods for visual mining of genomic and proteomic data atlases , 2012, BMC Bioinformatics.

[24]  E. Naumova,et al.  Visual Analytics for Epidemiologists: Understanding the Interactions Between Age, Time, and Disease with Multi-Panel Graphs , 2011, PloS one.

[25]  S. Haque Ethics approval This study was conducted with the approval of the East London and City Health Authority Ethic Committee. Provenance and peer review Not commissioned; externally peer reviewed. , 2011 .

[26]  Hua Xu,et al.  Data from clinical notes: a perspective on the tension between structure and flexible documentation , 2011, J. Am. Medical Informatics Assoc..

[27]  Melissa A. Basford,et al.  Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: using electronic medical records for genome- and phenome-wide studies. , 2011, American journal of human genetics.

[28]  C. Chute,et al.  Electronic Medical Records for Genetic Research: Results of the eMERGE Consortium , 2011, Science Translational Medicine.

[29]  Steven H. Brown,et al.  Automated identification of postoperative complications within an electronic medical record using natural language processing. , 2011, JAMA.

[30]  I. Kohane Using electronic health records to drive discovery in disease genomics , 2011, Nature Reviews Genetics.

[31]  Gil Alterovitz,et al.  Phenome-Based Analysis as a Means for Discovering Context-Dependent Clinical Reference Ranges , 2012, AMIA.

[32]  Hua Xu,et al.  Portability of an algorithm to identify rheumatoid arthritis in electronic health records , 2012, J. Am. Medical Informatics Assoc..

[33]  D. Nathwani,et al.  Clinical and economic burden of Clostridium difficile infection in Europe: a systematic review of healthcare-facility-acquired infection. , 2012, The Journal of hospital infection.

[34]  Melissa A. Basford,et al.  Validation of electronic medical record-based phenotyping algorithms: results and lessons learned from the eMERGE network. , 2013, Journal of the American Medical Informatics Association : JAMIA.