Data-driven discovery of seasonally linked diseases from an Electronic Health Records system

BackgroundPatterns of disease incidence can identify new risk factors for the disease or provide insight into the etiology. For example, allergies and infectious diseases have been shown to follow periodic temporal patterns due to seasonal changes in environmental or infectious agents. Previous work searching for seasonal or other temporal patterns in disease diagnosis rates has been limited both in the scope of the diseases examined and in the ability to distinguish unexpected seasonal patterns. Electronic Health Records (EHR) compile extensive longitudinal clinical information, constituting a unique source for discovery of trends in occurrence of disease. However, the data suffer from inherent biases that preclude an identification of temporal trends.MethodsMotivated by observation of the biases in this data source, we developed a method (Lomb-Scargle periodograms in detrended data, LSP-detrend) to find periodic patterns by adjusting the temporal information for broad trends in incidence, as well as seasonal changes in total hospitalizations. LSP-detrend can sensitively uncover periodic temporal patterns in the corrected data and identify the significance of the trend. We apply LSP-detrend to a compilation of records from 1.5 million patients encoded by ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification), including 2,805 disorders with more than 500 occurrences across a 12 year period, recorded from 1.5 million patients.Results and conclusionsAlthough EHR data, and ICD-9 coded records in particular, were not created with the intention of aggregated use for research, these data can in fact be mined for periodic patterns in incidence of disease, if confounders are properly removed. Of all diagnoses, around 10% are identified as seasonal by LSP-detrend, including many known phenomena. We robustly reproduce previous findings, even for relatively rare diseases. For instance, Kawasaki disease, a rare childhood disease that has been associated with weather patterns, is detected as strongly linked with winter months. Among the novel results, we find a bi-annual increase in exacerbations of myasthenia gravis, a potentially life threatening complication of an autoimmune disease. We dissect the causes of this seasonal incidence and propose that factors predisposing patients to this event vary through the year.

[1]  B. Penninx,et al.  Serum BDNF Concentrations Show Strong Seasonal Variation and Correlations with the Amount of Ambient Sunlight , 2012, PloS one.

[2]  Charles F. Bearden,et al.  A Nondegenerate Code of Deleterious Variants in Mendelian Loci Contributes to Complex Disease Risk , 2013, Cell.

[3]  Xavier Rodó,et al.  Association of Kawasaki disease with tropospheric wind patterns , 2011, Scientific reports.

[4]  E. Fadel,et al.  Implication of double‐stranded RNA signaling in the etiology of autoimmune myasthenia gravis , 2013, Annals of neurology.

[5]  D. Cayan,et al.  Seasonality and Temporal Clustering of Kawasaki Syndrome , 2005, Epidemiology.

[6]  Muhammad Mamdani,et al.  Simplicity within complexity: Seasonality and predictability of hospital admissions in the province of Ontario 1988–2001, a population-based analysis , 2005, BMC health services research.

[7]  Samir S. Shah,et al.  Accuracy of Administrative Billing Codes to Detect Urinary Tract Infection Hospitalizations , 2011, Pediatrics.

[8]  Ravina Kullar,et al.  Use of electronic health record data to identify skin and soft tissue infections in primary care settings: a validation study , 2013, BMC Infectious Diseases.

[9]  F. A. Seiler,et al.  Numerical Recipes in C: The Art of Scientific Computing , 1989 .

[10]  M. Lambe,et al.  Seasonal variation in the diagnosis of cancer: a study based on national cancer registration in Sweden , 2003, British Journal of Cancer.

[11]  M. Esler,et al.  Effect of sunlight and season on serotonin turnover in the brain , 2002, The Lancet.

[12]  R. Manfredini,et al.  Seasonal Variation in Heart Failure Hospitalization , 2011, Clinical cardiology.

[13]  J. Anderson Seasonality of symptomatic bacterial urinary infections in women. , 1983, Journal of epidemiology and community health.

[14]  B. Penninx,et al.  Seasonality in depressive and anxiety symptoms among primary care patients and in patients with depressive and anxiety disorders; results from the Netherlands Study of Depression and Anxiety , 2011, BMC psychiatry.

[15]  Melissa A. Basford,et al.  The Electronic Medical Records and Genomics (eMERGE) Network: past, present, and future , 2013, Genetics in Medicine.

[16]  William H. Press,et al.  The Art of Scientific Computing Second Edition , 1998 .

[17]  Michelle Shardell,et al.  Seasonal and Temperature-Associated Increases in Gram-Negative Bacterial Bloodstream Infections among Hospitalized Patients , 2011, PloS one.

[18]  I. Illa,et al.  Myasthenia gravis and the neuromuscular junction , 2013, Current opinion in neurology.

[19]  Ralph Gonzales,et al.  Trends and characteristics of US emergency department visits, 1997-2007. , 2010, JAMA.

[20]  J. Scargle Studies in astronomical time series analysis. II - Statistical aspects of spectral analysis of unevenly spaced data , 1982 .

[21]  Richard D. Deveaux,et al.  Applied Smoothing Techniques for Data Analysis , 1999, Technometrics.

[22]  D. Matthaiou,et al.  Effect of meteorological variables on the incidence of lower urinary tract infections , 2009, European Journal of Clinical Microbiology & Infectious Diseases.

[23]  Jessina C. McGregor,et al.  Summer Peaks in the Incidences of Gram-Negative Bacterial Infection Among Hospitalized Patients , 2008, Infection Control & Hospital Epidemiology.

[24]  J. Birkmeyer,et al.  Trends in hospital volume and operative mortality for high-risk surgery. , 2011, The New England journal of medicine.

[25]  M. Bobák,et al.  The seasonality of live birth is strongly influenced by socio-demographic factors. , 2001, Human reproduction.

[26]  D. Lauderdale,et al.  The validity of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for identifying patients hospitalized for COPD exacerbations. , 2012, Chest.

[27]  M. Simka Seasonal variations in the onset and healing rates of venous leg ulcers , 2010, Phlebology.

[28]  R. Rabadán,et al.  Signs of the 2009 Influenza Pandemic in the New York-Presbyterian Hospital Electronic Health Records , 2010, PloS one.

[29]  Martijn J Schuemie,et al.  Identification of acute myocardial infarction from electronic healthcare records using different disease coding systems: a validation study in three European countries , 2013, BMJ Open.

[30]  G. Chowell,et al.  A Population Based Study of Seasonality of Skin and Soft Tissue Infections: Implications for the Spread of CA-MRSA , 2013, PloS one.

[31]  N. Lomb Least-squares frequency analysis of unequally spaced data , 1976 .

[32]  Gabriel Bekö,et al.  Seasonal Variations of Indoor Microbial Exposures and Their Relation to Temperature, Relative Humidity, and Air Exchange Rate , 2012, Applied and Environmental Microbiology.

[33]  R. Rabadán,et al.  Discovering Disease Associations by Integrating Electronic Clinical Data and Medical Literature , 2011, PloS one.