Toward a unified understanding of drug-drug interactions: mapping Japanese drug codes to RxNorm concepts.

OBJECTIVES: Linking information on Japanese pharmaceutical products to global knowledge bases (KBs) would enhance international collaborative research and yield valuable insights. However, public access to mappings of Japanese pharmaceutical products that use international controlled vocabularies remains limited. This study mapped YJ codes to RxNorm ingredient classes, providing new insights by comparing Japanese and international drug-drug interaction (DDI) information using a case study methodology. MATERIALS AND METHODS: Tables linking YJ codes to RxNorm concepts were created using the application programming interfaces of the Kyoto Encyclopedia of Genes and Genomes and the National Library of Medicine. A comparative analysis of Japanese and international DDI information was thus performed by linking to an international DDI KB. RESULTS: There was limited agreement between the Japanese and international DDI severity classifications. Cross-tabulation of Japanese and international DDIs by severity showed that 213 combinations classified as serious DDIs by an international KB were missing from the Japanese DDI information. DISCUSSION: It is desirable that efforts be undertaken to standardize international criteria for DDIs to ensure consistency in the classification of their severity. CONCLUSION: The classification of DDI severity remains highly variable. It is imperative to augment the repository of critical DDI information, which would revalidate the utility of fostering collaborations with global KBs.

Prospective Multicenter Registry-Based Study on Thyroid Storm: The Guidelines for the Management from Japan are Useful.

CONTEXT: The mortality rate in thyroid storm (TS) has been reported to be higher than 10%. OBJECTIVE: We aimed to evaluate the effectiveness of the 2016 guidelines for the management of TS proposed by the Japan Thyroid Association and Japan Endocrine Society. DESIGN: Prospective registry-based study through a secure web platform. SETTING: Prospective multicenter registry. PATIENTS AND MEASUREMENTS: Patients with new-onset TS were registered in the Research Electronic Data Capture (REDCap). On day 30 after admission, clinical information and prognosis of each patient were added to the platform. On day 180, the prognosis was described. RESULTS: This study included 110 patients with TS. The median of Acute Physiology and Chronic Health Evaluation (APACHE) II score was 13, higher than the score in the previous nationwide epidemiological study, 10 (p = 0.001). Nonetheless, the mortality rate at day 30 was 5.5%, approximately half compared with 10.7% in the previous nationwide survey. Lower body mass index, shock and lower left ventricular ejection fraction were positively associated with poor prognosis at day 30, while the lack of fever ≥ 38℃ was related to the outcome. The mortality rate in patients with an APACHE II score ≥12 for whom the guidelines were not followed was significantly higher than the rate in patients for whom the guidelines were followed (50% vs. 4.7%) (p = 0.01). CONCLUSIONS: Prognosis seemed better than in the previous nationwide survey, even though disease severity was higher. The mortality rate was lower when the guidelines were followed. Thus, the guidelines are useful for managing TS.

Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Smoking and secondhand smoke exposure and carotid intima-media thickness: Baseline data from the Aidai Cohort Study in Japan.

INTRODUCTION: Epidemiological evidence regarding the relationship between smoking and secondhand smoke (SHS) exposure and carotid intima-media thickness (CIMT) has been limited in Asian populations. Employing baseline data from the Aidai Cohort Study, Japan, we evaluated the evidence in this cross-sectional study. METHODS: Study subjects were 727 men aged 35-88 years and 1297 women aged 34-85 years. Information on smoking, SHS exposure, and confounders was obtained through a self-administered questionnaire. An automated carotid ultrasonography device was used to measure the right and left CIMT. The greatest CIMT measurement in the left or right common carotid artery was considered the maximum CIMT, and a maximum CIMT >1.0 mm was indicative of carotid wall thickening. Age, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, and education level were adjusted at one time. RESULTS: The prevalence of carotid wall thickening was 13.0%. The prevalence of never smoking was 30.5% in men and 90.1% in women. Among those who had never smoked, the prevalence of never SHS exposure at home and work was 74.3% and 48.2% in men and 38.3% and 56.3% in women, respectively. Active smoking and pack-years of smoking were independently positively related to carotid wall thickening regardless of sex, although the association with current smoking in women was not significant. Independent positive relationships were shown between former smoking and pack-years of smoking and maximum CIMT in men but not in women. No significant relationships were found between SHS exposure at home and work and carotid wall thickening or maximum CIMT in either men or women. CONCLUSIONS: Active smoking, especially pack-years of smoking, was positively associated with carotid wall thickening in both sexes. Such positive associations with maximum CIMT were found only in men; however, interactions between smoking and sex were not significant.

Feasibility of Bone Mineral Density and Bone Microarchitecture Assessment Using Deep Learning With a Convolutional Neural Network.

OBJECTIVES: We evaluated the feasibility of using deep learning with a convolutional neural network for predicting bone mineral density (BMD) and bone microarchitecture from conventional computed tomography (CT) images acquired by multivendor scanners. METHODS: We enrolled 402 patients who underwent noncontrast CT examinations, including L1-L4 vertebrae, and dual-energy x-ray absorptiometry (DXA) examination. Among these, 280 patients (3360 sagittal vertebral images), 70 patients (280 sagittal vertebral images), and 52 patients (208 sagittal vertebral images) were assigned to the training data set for deep learning model development, the validation, and the test data set, respectively. Bone mineral density and the trabecular bone score (TBS), an index of bone microarchitecture, were assessed by DXA. BMDDL and TBSDL were predicted by deep learning with a convolutional neural network (ResNet50). Pearson correlation tests assessed the correlation between BMDDL and BMD, and TBSDL and TBS. The diagnostic performance of BMDDL for osteopenia/osteoporosis and that of TBSDL for bone microarchitecture impairment were evaluated using receiver operating characteristic curve analysis. RESULTS: BMDDL and BMD correlated strongly (r = 0.81, P < 0.01), whereas TBSDL and TBS correlated moderately (r = 0.54, P < 0.01). The sensitivity and specificity of BMDDL for identifying osteopenia or osteoporosis were 93% and 90%, and 100% and 94%, respectively. The sensitivity and specificity of TBSDL for identifying patients with bone microarchitecture impairment were 73% for all values. CONCLUSIONS: The BMDDL and TBSDL derived from conventional CT images could identify patients who should undergo DXA, which could be a gatekeeper tool for detecting latent osteoporosis/osteopenia or bone microarchitecture impairment.

Fish and Polyunsaturated Fatty Acid Intake and Carotid Intima-Media Thickness in Japan: the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan.

AIM: Epidemiological evidence regarding the relationship between fish and fatty acid intake and carotid intima-media thickness (CIMT) has been limited and inconsistent. The current cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study. METHODS: Study subjects were 2024 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value ＞1.0 mm. RESULTS: The prevalence of carotid wall thickening was 13.0%. In men, intake of n-3 polyunsaturated fatty acids (PUFA) was independently positively related to the prevalence of carotid wall thickening, while no associations were found between intake of fish and the other fatty acids and carotid wall thickening or maximum CIMT. In women, intake levels of fish, n-3 PUFA, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were independently inversely associated with carotid wall thickening and intake levels of fish, n-3 PUFA, α-linolenic acid, n-6 PUFA, and linoleic acid were independently inversely associated with the maximum CIMT. No significant relationships were found between intake of total fat, saturated fatty acids, or monounsaturated fatty acids and carotid wall thickening or maximum CIMT regardless of sex. CONCLUSIONS: In women, higher intake of fish and n-3 and n-6 PUFA may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT.

Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan.

OBJECTIVES: The relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single-nucleotide polymorphisms (SNPs) and diabetes mellitus (DM) has not been investigated. Therefore, we performed a case-control study to examine this relationship. METHODS: The study subjects included 2,390 Japanese men and women aged 34 to 88 years. In total, 190 cases were defined as having a fasting plasma glucose level ≥126 mg/dL, having a glycated hemoglobin ≥6.5% or currently using diabetic medication. The 2,200 remaining participants served as control subjects. RESULTS: Compared with study subjects with the CC genotype of AGXT2 SNP rs37369, those with the TT, but not CT, genotype had a significantly increased risk of DM: the adjusted odds ratio (OR) for the TT genotype was 1.83 (95% confidence interval [CI], 1.04 to 3.47). AGXT2 SNPs rs37370 and rs180749 were not significantly associated with the risk of DM. The CTA haplotype of rs37370, rs37369 and rs180749 was significantly positively associated with the risk of DM (crude OR, 1.25; 95% CI, 1.01 to 1.56), whereas the CCA haplotype was significantly inversely related to DM (crude OR, 0.53; 95% CI, 0.27 to 0.95). The multiplicative interaction between AGXT2 SNP rs37369 and smoking status with regard to the risk of DM was not significant (p=0.32 for interaction). CONCLUSIONS: This is the first study to show significant associations between AGXT2 SNP rs37369, the CTA haplotype, and the CCA haplotype and DM. No interaction with regard to the risk of DM was observed between rs37369 and smoking.

Education and household income and carotid intima-media thickness in Japan: baseline data from the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan.

BACKGROUND: Epidemiological evidence for the relationship between education and income and carotid intima-media thickness (CIMT) has been limited and inconsistent. The present cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study. METHODS: Study subjects were 2012 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value > 1.0 mm. RESULTS: The prevalence of carotid wall thickening was 13.0%. In participants under 60 years of age (n = 703) and in those aged 60 to 69 years (n = 837), neither education nor household income was associated with carotid wall thickening or with maximum CIMT. Among those aged 70 years or older (n = 472), however, higher educational level, but not household income, was independently related to a lower prevalence of carotid wall thickening: the multivariate-adjusted odds ratio for high vs. low educational level was 0.43 (95% confidence interval 0.21-0.83, p for trend = 0.01). A significant inverse association was observed between education, but not household income, and maximum CIMT (p for trend = 0.006). CONCLUSIONS: Higher educational level may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT only in participants aged 70 years or older.

Hypertension and dyslipidemia are risk factors for herpes zoster in patients with rheumatoid arthritis: a retrospective analysis using a medical information database.

This study used data from a large-scale multicenter medical information database in Japan to estimate the incidence rate of herpes zoster (HZ) and to examine the relationship between hypertension, dyslipidemia, and diabetes mellitus (DM), and the risk of HZ among patients with rheumatoid arthritis (RA). The research dataset consisted of 221,196 records of potential target patients with RA extracted between April 1, 2008 and August 31, 2017 from the Medical Data Vision database. To assess the association between hypertension, dyslipidemia, and DM and the risk of HZ, a case-control study was set up. Records of 101,498 study subjects met the inclusion criteria. During the observation period, 2566 patients developed HZ and the overall incidence rate was 5.2 (95% confidence interval: 5.0-5.4 per 1000 patient-years). Hypertension, dyslipidemia, and DM were significantly associated with an increased risk of HZ after adjustment for sex, age, hospital size, and use of anti-rheumatic drugs. When mutual adjustment was made for hypertension, dyslipidemia, and DM, the positive associations between hypertension and dyslipidemia and the risk of HZ remained significant; however, the positive association with DM completely disappeared. RA patients with hypertension or dyslipidemia may be at higher risk of HZ.

Prediction of the service life of surgical instruments from the surgical instrument management system log using radio frequency identification.

BACKGROUND: Bar code- or radio frequency identification (RFID)-based medical instrument management systems have gradually been introduced in the field of surgical medicine for the individual management and identification of instruments. We hypothesized that individual management of instruments using RFID tags can provide previously unavailable information, particularly the precise service life of an instrument. Such information can be used to prevent medical accidents caused by surgical instrument failure. This study aimed to predict the precise service life of instruments by analyzing the data available in instrument management systems. METHODS: We evaluated the repair history of instruments and the usage count until failure and then analyzed the data by the following three methods: the distribution of the instrument usage count was determined, an instrument failure probability model was generated through logistic regression analysis, and survival analysis was performed to predict instrument failure. RESULTS: The usage count followed a normal distribution. Analysis showed that instruments were not used uniformly during surgery. In addition, the Kaplan-Meier curves plotted for five types of instruments showed significant differences in the cumulative survival rate of different instruments. CONCLUSIONS: The usage history of instruments obtained with RFID tags or bar codes can be used to predict the probability of instrument failure. This prediction is significant for determining the service life of an instrument. Implementation of the developed model in instrument management systems can help prevent accidents due to instrument failure. Knowledge of the instrument service life will also help in developing a purchase plan for instruments to minimize wastage.

Development of a Common Data Model Facilitating Clinical Decision-Making and Analyses.

Currently, the Common Data Model (CDM) for primary use (as distinct from models designed for secondary use) poorly supports clinical decision-making and medical process analyses. We designed a CDM featuring a search flow that identifies facts after defining the clinical process, and we make the data definition language of the CDM employed freely available as open source.

The Survey for Determining Knowledge-Related Problems in the Dissemination of ICD-11.

Changes in the 11th revision of the International Classification of Diseases (ICD-11) from ICD-10 may significantly impact coding quality. We conducted a field trial in 2017 to evaluate the line coding quality of 19 cases coded using the coding method of the World Health Organization. The cases with low agreement between the accuracy rates of ICD-10 and ICD-11 were cases that required the extension code. We should prepare effective educational content about how to use the extension code for proper coding in ICD-11.

Quality Requirements for Electronic Health Record Systems*. A Japanese-German Information Management Perspective.

BACKGROUND: For more than 30 years, there has been close cooperation between Japanese and German scientists with regard to information systems in health care. Collaboration has been formalized by an agreement between the respective scientific associations. Following this agreement, two joint workshops took place to explore the similarities and differences of electronic health record systems (EHRS) against the background of the two national healthcare systems that share many commonalities. OBJECTIVES: To establish a framework and requirements for the quality of EHRS that may also serve as a basis for comparing different EHRS. METHODS: Donabedian's three dimensions of quality of medical care were adapted to the outcome, process, and structural quality of EHRS and their management. These quality dimensions were proposed before the first workshop of EHRS experts and enriched during the discussions. RESULTS: The Quality Requirements Framework of EHRS (QRF-EHRS) was defined and complemented by requirements for high quality EHRS. The framework integrates three quality dimensions (outcome, process, and structural quality), three layers of information systems (processes and data, applications, and physical tools) and three dimensions of information management (strategic, tactical, and operational information management). CONCLUSIONS: Describing and comparing the quality of EHRS is in fact a multidimensional problem as given by the QRF-EHRS framework. This framework will be utilized to compare Japanese and German EHRS, notably those that were presented at the second workshop.

Evaluation of the Anonymity and Utility of De-Identified Clinical Data Based on Japanese Anonymization Criteria.

We analyze the deterioration of clinical data quality due to anonymization. The result shows that data quality remained high with micro-aggregation and also verify the availability of noise addition to prevent illegal re-identification by matching another personal data.

Evaluation of Secure Computation in a Distributed Healthcare Setting.

Issues related to ensuring patient privacy and data ownership in clinical repositories prevent the growth of translational research. Previous studies have used an aggregator agent to obscure clinical repositories from the data user, and to ensure the privacy of output using statistical disclosure control. However, there remain several issues that must be considered. One such issue is that a data breach may occur when multiple nodes conspire. Another is that the agent may eavesdrop on or leak a user's queries and their results. We have implemented a secure computing method so that the data used by each party can be kept confidential even if all of the other parties conspire to crack the data. We deployed our implementation at three geographically distributed nodes connected to a high-speed layer two network. The performance of our method, with respect to processing times, suggests suitability for practical use.

Evaluation of Efficiency Improvement in Vital Documentation Using RFID Devices.

We introduced medical devices with RFID tags and the terminal with RFID reader in our hospital. Time study was conducted in two phases. In phase I, nurses round as usual, and in phase II, the nurse round the ward with a terminal installed on a cart. This study concluded that RFID system shortens the time for vital sign documentation. However, deploying the terminals at every bedside did not contribute the more time reduction.

Internal domain-specific language based on Arden Syntax and FHIR.

We demonstrate the concept of Arden Syntax, which is like Domain Specific Language (DSL), for describing decision support rules that take advantage of modern programming language concepts. Using object relational mapper and meta programming enables the conceptualization of FHIR resources from various data sources, and reduces the complexity of knowledge retrieval in decision rules.

Virtual file system on NoSQL for processing high volumes of HL7 messages.

The Standardized Structured Medical Information Exchange (SS-MIX) is intended to be the standard repository for HL7 messages that depend on a local file system. However, its scalability is limited. We implemented a virtual file system using NoSQL to incorporate modern computing technology into SS-MIX and allow the system to integrate local patient IDs from different healthcare systems into a universal system. We discuss its implementation using the database MongoDB and describe its performance in a case study.

HTML5 microdata as a semantic container for medical information exchange.

Achieving interoperability between clinical electronic medical records (EMR) systems and cloud computing systems is challenging because of the lack of a universal reference method as a standard for information exchange with a secure connection. Here we describe an information exchange scheme using HTML5 microdata, where the standard semantic container is an HTML document. We embed HL7 messages describing laboratory test results in the microdata. We also annotate items in the clinical research report with the microdata. We mapped the laboratory test result data into the clinical research report using an HL7 selector specified in the microdata. This scheme can provide secure cooperation between the cloud-based service and the EMR system.