Use of Diagnosis Codes to Find Blood Transfusion Adverse Events in Electronic Health Records.

OBJECTIVE: Electronic health records (EHRs) and big data tools offer the opportunity for surveillance of adverse events (patient harm associated with medical care). We used International Classification of Diseases, Ninth Revision, codes in electronic records to identify known, and potentially novel, adverse reactions to blood transfusion. METHODS: We used 49,331 adult admissions involving critical care at a major teaching hospital, 2001-2012, in the Medical Information Mart for Intensive Care III EHRs database. We formed a T (defined as packed red blood cells, platelets, or plasma) group of 21,443 admissions versus 25,468 comparison (C) admissions. The International Classification of Diseases, Ninth Revision, Clinical Modification , diagnosis codes were compared for T versus C, described, and tested with statistical tools. RESULTS: Transfusion adverse events (TAEs) such as transfusion-associated circulatory overload (TACO; 12 T cases; rate ratio [RR], 15.61; 95% confidence interval [CI], 2.49-98) were found. There were also potential TAEs similar to TAEs, such as fluid overload disorder (361 T admissions; RR, 2.24; 95% CI, 1.88-2.65), similar to TACO. Some diagnoses could have been sequelae of TAEs, including nontraumatic compartment syndrome of abdomen (52 T cases; RR, 6.76; 95% CI, 3.40-14.9) possibly being a consequence of TACO. CONCLUSIONS: Surveillance for diagnosis codes that could be TAE sequelae or unrecognized TAE might be useful supplements to existing medical product adverse event programs.

Finding Potential Adverse Events in the Unstructured Text of Electronic Health Care Records: Development of the Shakespeare Method.

BACKGROUND: Big data tools provide opportunities to monitor adverse events (patient harm associated with medical care) (AEs) in the unstructured text of electronic health care records (EHRs). Writers may explicitly state an apparent association between treatment and adverse outcome ("attributed") or state the simple treatment and outcome without an association ("unattributed"). Many methods for finding AEs in text rely on predefining possible AEs before searching for prespecified words and phrases or manual labeling (standardization) by investigators. We developed a method to identify possible AEs, even if unknown or unattributed, without any prespecifications or standardization of notes. Our method was inspired by word-frequency analysis methods used to uncover the true authorship of disputed works credited to William Shakespeare. We chose two use cases, "transfusion" and "time-based." Transfusion was chosen because new transfusion AE types were becoming recognized during the study data period; therefore, we anticipated an opportunity to find unattributed potential AEs (PAEs) in the notes. With the time-based case, we wanted to simulate near real-time surveillance. We chose time periods in the hope of detecting PAEs due to contaminated heparin from mid-2007 to mid-2008 that were announced in early 2008. We hypothesized that the prevalence of contaminated heparin may have been widespread enough to manifest in EHRs through symptoms related to heparin AEs, independent of clinicians' documentation of attributed AEs. OBJECTIVE: We aimed to develop a new method to identify attributed and unattributed PAEs using the unstructured text of EHRs. METHODS: We used EHRs for adult critical care admissions at a major teaching hospital (2001-2012). For each case, we formed a group of interest and a comparison group. We concatenated the text notes for each admission into one document sorted by date, and deleted replicate sentences and lists. We identified statistically significant words in the group of interest versus the comparison group. Documents in the group of interest were filtered to those words, followed by topic modeling on the filtered documents to produce topics. For each topic, the three documents with the maximum topic scores were manually reviewed to identify PAEs. RESULTS: Topics centered around medical conditions that were unique to or more common in the group of interest, including PAEs. In each use case, most PAEs were unattributed in the notes. Among the transfusion PAEs was unattributed evidence of transfusion-associated cardiac overload and transfusion-related acute lung injury. Some of the PAEs from mid-2007 to mid-2008 were increased unattributed events consistent with AEs related to heparin contamination. CONCLUSIONS: The Shakespeare method could be a useful supplement to AE reporting and surveillance of structured EHR data. Future improvements should include automation of the manual review process.

Presumed Choline Chloride Toxicosis in Cats With Positive Ethylene Glycol Tests After Consuming a Recalled Cat Food.

Four previously healthy adult domestic shorthair cats (2 male, 2 female) from one household developed acute vomiting and ataxia less than 12 hours after consuming a commercial canned cat food. Blood work abnormalities included mild hyperglycemia with increased alanine aminotransferase (n = 1) and decreased blood urea nitrogen (n = 2). The veterinarian conducted whole blood ethylene glycol (EG) tests, which were positive for all cats. There were no known EG exposures. All cats were treated for suspected EG toxicosis and fully recovered after 48 hours. Separately from the cats' case, the same food was voluntarily recalled by the manufacturer 5 days later due to a higher-than-formulated amount of choline chloride added to the food. The 4 cats' canned cat food was tested for choline, choline chloride, EG, diethylene glycol, and propylene glycol to look for causes of the positive whole blood EG test. The cat food contained an average of 165,300 ppm (165,300 mg/kg) choline and 221,600 ppm (221,600 mg/kg) choline chloride on a dry matter basis, which is at least 65 times the recommended choline amount for adult cats. No glycols were detected. This case documents suspected choline toxicosis in cats after consuming a commercial canned cat food with a higher-than-formulated amount of choline chloride, and it suggests that choline toxicosis may cause a positive result on some EG whole blood tests. Choline toxicosis could be a possible differential diagnosis when a cat has a positive EG test and no known exposure to antifreeze.

Pet Food-Associated Dietary Exogenous Thyrotoxicosis: Retrospective Study (2016-2018) and Clinical Considerations.

Dietary exogenous thyrotoxicosis is infrequently observed in pet food. A retrospective evaluation of pet food investigations (PFI) was conducted for 17 dogs, including review of medical records, dietary and environmental exposure interviews, food testing, and regulatory action. Five PFIs occurring between 2016 and 2018 involved 7 food products including 2 food types, jerky treats or canned food, made from beef or bison. The dogs' serum thyroid hormone concentrations were evaluated before and after diet change. The foods were tested for active thyroid hormones and hormone precursors using high performance liquid chromatography with inductively coupled plasma mass spectrometry detection. The foods were also examined microscopically. Serum thyroid hormone concentrations of thyroxine (T4) varied depending on the food type consumed. Dogs that consumed dried jerky containing greater T4 concentrations often had increased serum T4 concentrations, whereas dogs that consumed canned products containing greater and 3,4,5- and 3,5,3'-triiodothyronine (T3) concentrations often had decreased serum T4 concentrations. After the diets were changed, serum T4 and T3 concentrations normalized at 1 month. Seven foods containing beef or bison had iodine concentrations greater than 11 mg/kg, and iodine speciation identified variable concentrations of iodide, T4, T3, monoiodotyrosine (MIT), and di-iodotyrosine (DIT). Thyroid gland was found in microscopic sections from one finished food and one ingredient, gullet. FDA performed Health Hazard Evaluations to categorize the exposure risk, and 5 foods were recalled for which the product packaging had not been discarded. Dietary exogenous thyrotoxicosis should be considered in dogs exhibiting clinical signs compatible with hyperthyroidism, especially if consuming beef-based food. A thyroid panel that includes serum iodine, coupled with a thorough feeding history can aid in diagnosis. Thyrotoxicosis is typically reversible after removing the contaminated food from the diet.

Use of data mining at the Food and Drug Administration.

OBJECTIVES: This article summarizes past and current data mining activities at the United States Food and Drug Administration (FDA). TARGET AUDIENCE: We address data miners in all sectors, anyone interested in the safety of products regulated by the FDA (predominantly medical products, food, veterinary products and nutrition, and tobacco products), and those interested in FDA activities. SCOPE: Topics include routine and developmental data mining activities, short descriptions of mined FDA data, advantages and challenges of data mining at the FDA, and future directions of data mining at the FDA.