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.

Safety of antibiotic drugs in food animals: comparison of findings from preapproval studies and postapproval experience in the United States with safety information in published literature.

Antibiotics are among the most widely prescribed drugs and are generally considered safe for the target species. However, their use has been associated with various adverse toxic effects in target animals, such as allergic reactions, gastrointestinal signs, cardiovascular effects, hypoglycemia, hepatic/renal toxicity, thrombocytopenia, and anaphylaxis. This article provides a qualitative summary of the adverse events observed in target animals during the evaluation of antibiotics by the Food and Drug Administration during both preapproval and postapproval periods. As there is a marked scarcity of published data on safety of antibiotics in food animals, more research is needed in this area.

Treatment of animal toxicoses: a regulatory perspective.

This article focuses on the regulatory issues to consider when veterinarians are called upon to treat animal toxicoses, in particular those involving food-producing animals. The lack of Food and Drug Administration-approved drugs to treat animal toxicoses has been a long-standing problem. This article reviews extralabel drug use regulations, and the responsibilities of the treating veterinarian. It discusses the legal implications of compounding and the use of unapproved drugs to treat animal toxicoses. Efforts should be made to increase the availability of life-saving antidotal therapies.