Diagnostic and predictive performance and standardized threshold of traditional biomarkers for drug‐induced liver injury in rats

Traditional biomarkers such as alanine and aspartate aminotransferase (ALT, AST) and total bilirubin (TBIL) have been widely used for detecting drug‐induced liver injury (DILI). Although the Food and Drug Administration (FDA) proposed standardized thresholds for human as Hy's law, those for animals have not been determined, and predictability of these biomarkers for future onset of hepatic lesions remains unclear. In this study, we investigated these diagnostic and predictive performance of 10 traditional biomarkers for liver injury by receiver‐operating characteristic (ROC) curve, using a free‐access database where 142 hepatotoxic or non‐hepatotoxic compounds were administrated to male rats (n = 5253). Standardization of each biomarker value was achieved by calculating the ratio to control mean value, and the thresholds were determined under the condition of permitting 5% false positive. Of these 10 biomarkers, AST showed the best diagnostic performance. Furthermore, ALT and TBIL also showed high performance under the situation of hepatocellular necrosis and bile duct injury, respectively. Additionally, the availability of the diagnostic thresholds in difference testing facility was confirmed by the application of these thresholds to in‐house prepared dataset. Meanwhile, incorrect diagnosis by the thresholds was also observed. Regarding prediction, all 10 biomarkers showed insufficient performance for future onset of hepatic lesions. In conclusion, the standardized diagnostic thresholds enable consistent evaluation of traditional biomarkers among different facilities, whereas it was suggested that novel biomarker is required for more accurate diagnosis and prediction of DILI. Copyright © 2014 John Wiley & Sons, Ltd.     

Input–output analysis on the economic impact of medical care in Japan

Objectives

Since the Cabinet’s decision concerning the Basic Policies 2005, the Japanese government has implemented specific measures to suppress increases in national medical care expenditure. However, we believe that the economic significance of medical care should be quantified in terms of its economic impact on national medical care expenditure. No one has examined the economic impact of all medical institutions in Japan using data from a statement of profits and losses. We used an input–output analysis to quantitatively estimate economic impact of medical care and examined its estimation range with a probabilistic sensitivity analysis.

Methods

To estimate the economic impact and economic impact multipliers of all medical institutions in Japan, an input–output analysis model was developed using an input–output table, statement of profits and losses, margin rates, employee income rates, consumption propensity and an equilibrium output model. Probabilistic sensitivity analysis was conducted using a Monte Carlo simulation.

Results

Economic impact of medical care in all medical institutions was ¥72,107.4 billion ($661.5 billion). This impact yielded a 2.78-fold return of medical care expenditure with a 95 % confidence interval ranging from 2.74 to 2.90.

Conclusion

Economic impact of medical care in Japan was two to three times the medical care expenditure (per unit). Production inducement of medical care is comparable to other industrial sectors that are highly influential toward the economy. The contribution to medical care should be evaluated more explicitly in national medical care expenditure policies.     

Association between the sense of coherence 13-item version scale score of pregnant women in the second trimester of pregnancy and threatened premature birth

Objectives

The purpose of this study is to determine whether the score of the sense of coherence 13-item version (SOC-13) scale in the second trimester of pregnancy is associated with threatened premature birth.

Methods

All the subjects gave their informed written consent before their participation in the study. A self-reported questionnaire survey was conducted on the pregnant women at approximately 18 weeks of pregnancy. The questionnaire consisted of items on demographic characteristics, perinatal abnormalities, stress perception scale (SPS), and SOC-13 scale. Approximately 30 weeks of pregnancy after the first survey, we surveyed whether any treatment had been provided for threatened premature birth during the course of the current pregnancy. The study period was from December 2007 to February 2010. One hundred and seventy-seven pregnant women participated in the study, but only the data from 151 pregnant women were analyzed.

Results

Forty-three (28.5 %) pregnant women had threatened premature birth and received some treatment. Logistic regression analysis was carried out with threatened premature birth as the dependent variable and age, childbirth history, smoking habit, history of miscarriage or premature birth in previous pregnancies, SPS score, and SOC-13 scale score as the independent variables. It was shown that SOC-13 scale score affected threatened premature birth (p < 0.001) and that a low SOC-13 scale score was associated with threatened premature birth.

Conclusions

This study suggests that the SOC-13 scale score in the second trimester of pregnancy could be of great value in clinical health care of pregnant women with a risk of threatened premature birth in the subsequent course of pregnancy.     

Imido-substituted triazines as dehydrative condensing reagents for the chemoselective formation of amides in the presence of free hydroxy groups

In this paper, we discuss the synthesis of imido-substituted chlorotriazines and demonstrate their use in dehydrative condensation reactions. Chemoselective amide-forming reactions of amino alcohols using succinimido-substituted chlorotriazine (2A) proceeded smoothly. Occasionally, nonselectivity was problematic during the synthesis of hydroxy-substituted amides. Moreover, it was noteworthy that this method was applicable to hydroxy-substituted carboxylic acids that could have formed a lactone or an ester during the carboxylic acid activation step. The imido-substituted chlorotriazine (2A) was superior to the amido-substituted chlorotriazine and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) in terms of reaction rates and yields.

In this paper, we discuss the synthesis of imido-substituted chlorotriazines and demonstrate their use in dehydrative condensation reactions.     

Trends of hepatitis B virus genotype distribution in chronic hepatitis B patients in Japan

Journal of Gastroenterology - Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of...     

The impact of sarcopenia on short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer

Journal of Gastroenterology - Sarcopenia prevalence has increased in proportion to the aging population in Japan. We aimed to investigate the association between sarcopenia and clinical outcomes...     

Type 1 Autoimmune Pancreatitis Extending along the Main Pancreatic Duct: IgG4-related Pancreatic Periductitis

We herein report a unique form of autoimmune pancreatitis (AIP) spreading along the main pancreatic duct (MPD). A 70-year-old man was referred for a small lesion at the pancreatic neck, accompanying an adjacent cyst and dilated upstream MPD. Four years earlier, health checkup images had shown a pancreatic cyst but no mass lesion. Endoscopic ultrasonography showed a contrast-enhanced, tumorous lesion, mainly occupying the MPD. With a preoperative diagnosis of ductal neoplasms mainly spreading in the MPD, Whipple''s resection was performed. The resected specimens showed MPD periductitis with IgG4-related pathology, indicating type 1 AIP. Clinicians should practice caution concerning the various AIP forms.