Early Detection of Adverse Drug Reaction Signals by Association Rule Mining Using Large-Scale Administrative Claims Data

INTRODUCTION: Adverse drug reactions (ADRs) are a leading cause of mortality worldwide and should be detected promptly to reduce health risks to patients. A data-mining approach using large-scale medical records might be a useful method for the early detection of ADRs. Many studies have analyzed medical records to detect ADRs; however, most of them have focused on a narrow range of ADRs, limiting their usefulness. OBJECTIVE: This study aimed to identify methods for the early detection of a wide range of ADR signals. METHODS: First, to evaluate the performance in signal detection of ADRs by data-mining, we attempted to create a gold standard based on clinical evidence. Second, association rule mining (ARM) was applied to patient symptoms and medications registered in claims data, followed by evaluating ADR signal detection performance. RESULTS: We created a new gold standard consisting of 92 positive and 88 negative controls. In the assessment of ARM using claims data, the areas under the receiver-operating characteristic curve and the precision-recall curve were 0.80 and 0.83, respectively. If the detection criteria were defined as lift > 1, conviction > 1, and p-value < 0.05, ARM could identify 156 signals, of which 90 were true positive controls (sensitivity: 0.98, specificity: 0.25). Evaluation of the capability of ARM with short periods of data revealed that ARM could detect a greater number of positive controls than the conventional analysis method. CONCLUSIONS: ARM of claims data may be effective in the early detection of a wide range of ADR signals

Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia

ジスキネジア新治療法の発見 --副作用を減らす併用薬から新しい創薬標的へ--. 京都大学プレスリリース. 2021-04-16.Antipsychotics often cause tardive dyskinesia, an adverse symptom of involuntary hyperkinetic movements. Analysis of the U.S. Food and Drug Administration Adverse Event Reporting System and JMDC insurance claims revealed that acetaminophen prevents the dyskinesia induced by dopamine D₂ receptor antagonists. In vivo experiments further showed that a 21-day treatment with haloperidol increased the number of vacuous chewing movements (VCMs) in rats, an effect that was inhibited by oral acetaminophen treatment or intracerebroventricular injection of N-(4-hydroxyphenyl)-arachidonylamide (AM404), an acetaminophen metabolite that acts as an activator of the transient receptor potential vanilloid 1 (TRPV1). In mice, haloperidol-induced VCMs were also mitigated by treatment with AM404 applied to the dorsal striatum, but not in TRPV1-deficient mice. Acetaminophen prevented the haloperidol-induced decrease in the number of c-Fos⁺/preproenkephalin⁺ striatal neurons in wild-type mice but not in TRPV1-deficient mice. Finally, chemogenetic stimulation of indirect-pathway medium spiny neurons in the dorsal striatum decreased haloperidol-induced VCMs. These results suggest that acetaminophen activates the indirect pathway neurons by activating TRPV1 channels via AM404