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

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An Autopsy Case of Disseminated Cytomegalovirus Infection in a Classic Hemophiliac A with Acquired Immunodeficiency Syndrome

This is a case report of disseminated cytomegalovirus infection which occured in 23-year-old male hemophiliac with AIDS. He has been receiving Factor VIII concentrate. Postmortem examination revealed generalized CMV infection in the lungs, the adrenal glands and the large intestine resulting in multiple organ system failure. These observations suggest that when Factor VIII concentrate used, careful evaluation of the pathogens such as ATL and HIV is essential

Lectin Immunohistochemistry in Human Non-Malignant and Malignant Gallbladder Tissuses

Changes in the lectin binding pattern in non-malignant and malignant gallbladder tissues were examined using the following eight types of carbohydrate binding lectins : Ulex europaeus-1 (UEA-1), Arachis hypogaea (PNA), Griffonia simplicifolia (GS-1), Glycine maximum (SBA), Bauhinia purpurea (BPA), Dolichos biflorus (DBA), Canavalia ensiformis (Con-A), and Triticum vulgare (WGA). We used a total of 109 tissues including 31 normal tissues, 25 metaplasias, and 53 carcinomas. Lectin staining pattern was evaluated using the Hamada\u27s crieria of the following four types : apical type, cytoplasmic type with polarity, cytoplasmic type without polarity, and stromal type. Normal cases showed apical type and cytoplasmic type with polarity, while carcinoma cases revealed cytoplasmic type with or without polarity. In carcinoma cases, GS-I and DBA lectins showed higher immunohistochemical positive rate and more frequent cytoplasmic type with polarity pattern of immunohistochemical localization than the other types of lectins. These results suggest that the GS-I and DBA are the most reliable lectin marker for malignant transformation of the gallbladder tissues. Key words : Lectin, immunohistochemistry, gallbladder carcinoma

CLASSIFICATION OF BIPOLAR DISORDER, MAJOR DEPRESSIVE DISORDER, AND HEALTHY STATE USING VOICE

Objective: In this study, we propose a voice index to identify healthy individuals, patients with bipolar disorder, and patients with major depressive disorder using polytomous logistic regression analysis.Methods: Voice features were extracted from voices of healthy individuals and patients with mental disease. Polytomous logistic regression analysis was performed for some voice features.Results: With the prediction model obtained using the analysis, we identified subject groups and were able to classify subjects into three groups with 90.79% accuracy.Conclusion: These results show that the proposed index may be used as a new evaluation index to identify depression

Enhancement of Murine Tumor Cell Lysability by Interleukin-2 Activated Killer Cells After Treatment with Mitomycin C

The cytotoxicity of interleukin-2 activated killer cells with antitumor drug, mitomycin C (MMC) against murine tumor cell lines with acquired drug resis-tance was evaluated in vitro by a 51Cr release cytotoxicity assay. Tumor cell lines, a mouse fibrosarcoma cells (MCA-F) and its individual metastatic lung clones (MCA-F-M1, 2, 3, and 4) have been established in vitro. Furthermore, using a soft agar cloning technique, MMC resistant clones (MCA-F-M2-1, 2, 4, 8, and 10) and sensitive clones (MCA-F-M1-3, MCA-F-M3-8, 9, MCA-F-M4-9, and 10) were established and their lysability was examined with or without MMC against lymphokine-activated killer (LAK) cells, demonstrating that LAK cells showed high % cytotoxicity against 2 resistant clones (MCA-F-M2-1 and 8) by the 7 day-exposure of 1.0 pg/ml MMC concentration in culture but with a low % cytotoxicity in the case of only 3 day-MMC exposure. The other resis-tant clones showed high % cytotoxicity at 3 day-MMC exposure. On the other hand, all the sensitive clones showed high % cytotoxicity against LAK cells with the only 1 day-exposure of MMC. Thus, the combination of LAK cells and MMC treatment had a synergistic effect on MMC resistant clones as well as sensitive clones and these results suggested that the lysability of MMC resistant clones might be due to the altered susceptibility to LAK cells by use of MMC time-dependently

Detection of p53 Gene Mutations and Their Protein Overexpression in Fine-needle Biopsy Specimens with False-negative Diagnoses in Breast Cancer

To achieve a more accurate diagnosis in the first aspiration biopsy from breast tumor, p53 gene mutations were detected by PCR-SSCP analysis in aspira-tion biopsy specimens taken from 26 patients with breast tumors. Of 26 aspirat-ed cell specimens from breast tumors that were all initially diagnosed as being cytologically benign, 2 point mutations of the p53 gene were detected and were subsequently proved to be cancer cells. Further, the p53 protein expression was also examined in the initial aspirated specimens and in the resected tumors that were rediagnosed as being malignant as a result of the second biopsy. Conse-quently, these p53 gene mutations did not appear to correlate with their protein overexpression in the aspiration biopsy specimens (all cases were negative), how-ever, the specimens from 2 resected tumors that showed p53 gene mutations were positive. In addition, a positive ER level and DNA aneuploidy status were also found only in these two p53 gene mutation cases. Therefore, detection of p53 mutations in aspiration biopsy specimens may prove to be a useful method for detecting breast cancers