We present the case of a 76-year-old man who underwent preoperative endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for obstructive jaundice caused by pancreatic head cancer. The patient had obstructive jaundice and cholangitis during neoadjuvant chemotherapy. Transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography was attempted; however, it was unsuccessful because of duodenal tumor invasion. Therefore, EUS-HGS was performed. Jaundice and cholangitis improved promptly after EUS-HGS, and stent obstruction and migration were not observed before surgery. The stent was safely removed during surgery, and no postoperative complications occurred. Most studies of EUS-HGS for preoperative biliary drainage have been small and retrospective, and few have examined the safety of intraoperative stent removal. The fistula in our patient was promptly identified and the stent was safely removed despite the relatively limited field of view during robot-assisted laparoscopy.The promising findings of our case report can be used to inform EUS-based surgical strategies for biliary drainage with obstructive jaundice.

We present the case of a 76-year-old man who underwent preoperative endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for obstructive jaundice caused by pancreatic head cancer. The patient had obstructive jaundice and cholangitis during neoadjuvant chemotherapy. Transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography was attempted; however, it was unsuccessful because of duodenal tumor invasion. Therefore, EUS-HGS was performed. Jaundice and cholangitis improved promptly after EUS-HGS, and stent obstruction and migration were not observed before surgery. The stent was safely removed during surgery, and no postoperative complications occurred. Most studies of EUS-HGS for preoperative biliary drainage have been small and retrospective, and few have examined the safety of intraoperative stent removal. The fistula in our patient was promptly identified and the stent was safely removed despite the relatively limited field of view during robot-assisted laparoscopy.The promising findings of our case report can be used to inform EUS-based surgical strategies for biliary drainage with obstructive jaundice.

We present the case of a 76-year-old man who underwent preoperative endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for obstructive jaundice caused by pancreatic head cancer. The patient had obstructive jaundice and cholangitis during neoadjuvant chemotherapy. Transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography was attempted; however, it was unsuccessful because of duodenal tumor invasion. Therefore, EUS-HGS was performed. Jaundice and cholangitis improved promptly after EUS-HGS, and stent obstruction and migration were not observed before surgery. The stent was safely removed during surgery, and no postoperative complications occurred. Most studies of EUS-HGS for preoperative biliary drainage have been small and retrospective, and few have examined the safety of intraoperative stent removal. The fistula in our patient was promptly identified and the stent was safely removed despite the relatively limited field of view during robot-assisted laparoscopy.The promising findings of our case report can be used to inform EUS-based surgical strategies for biliary drainage with obstructive jaundice.

This document reports the results of a questionnaire survey conducted among pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association as part of a collaborative research project within the AMED Research on Regulatory Science of Pharmaceuticals and Medical Devices ‘Research for the promotion of the utilization of real-world evidence in the pharmaceutical regulatory system and the harmonization of international regulations, and for the proposal of an ideal system in Japan’ (Principal Investigator： Harumasa Nakamura, National Center of Neurology and Psychiatry). This survey is the first domestic attempt to clarify the current state of development and utilization of data for companion applications (CPs) in pharmaceuticals. It is expected that the widespread development and use of pharmaceutical CPs will enhance the collection of patient-reported outcomes (PROs), which in turn will foster the utilization of real-world data (RWD) under pharmaceutical regulations. In anticipation that the results of this survey will contribute to this promotion, we are publishing the entire questionnaire results in this report.

This document reports the results of a questionnaire survey conducted among pharmaceutical companies that are members of the Japan Pharmaceutical Manufacturers Association as part of a collaborative research project within the AMED Research on Regulatory Science of Pharmaceuticals and Medical Devices ‘Research for the promotion of the utilization of real-world evidence in the pharmaceutical regulatory system and the harmonization of international regulations, and for the proposal of an ideal system in Japan’ (Principal Investigator： Harumasa Nakamura, National Center of Neurology and Psychiatry). This survey is the first domestic attempt to clarify the current state of development and utilization of data for companion applications (CPs) in pharmaceuticals. It is expected that the widespread development and use of pharmaceutical CPs will enhance the collection of patient-reported outcomes (PROs), which in turn will foster the utilization of real-world data (RWD) under pharmaceutical regulations. In anticipation that the results of this survey will contribute to this promotion, we are publishing the entire questionnaire results in this report.

Left ventricle to right atrial communication is a rare cardiac pathology, and it is either congenital or acquired. Recently, case reports of acquired left ventricle to right atrial communication have been increasing because of the increased numbers of cardiovascular procedures and improved cardiac diagnostic techniques. We report a case of acquired left ventricle to right atrial communication in a patient with native aortic valve infective endocarditis. A 52-year-old man with worsening dyspnea on exertion and lower leg edema was admitted to a hospital. Blood examination revealed elevated inflammatory marker levels, and transthoracic echocardiography (TTE) showed an aortic valve vegetation. The patient was subsequently transferred to our hospital for infective endocarditis with congestive heart failure. Medical treatment with antibiotics and diuretics was initiated. Cardiac computed tomography (CT) demonstrated left ventricle to right atrial communication. An urgent operation was performed wherein the defect was closed with autologous pericardial patches from both the right atrium and left ventricle. Aortic valve replacement was performed with a mechanical valve. The postoperative course was uneventful, and TTE showed no residual shunt. In our case, cardiac CT was useful for accurately diagnosing left ventricle to right atrial communication.

BACKGROUND: Studies on the adverse effects of Asian dust (AD) on respiratory function in children are scarce. The objective of this study was to examine the association between AD and respiratory function by measuring peak expiratory flow rates (PEFRs) in asthmatic children. METHODS: The study was carried out from March to May from 2014 through 2016. One hundred ten children with bronchial asthma were recruited from four hospitals in the Goto Islands and south Nagasaki area in Nagasaki prefecture. The parents were asked to record their children's PEFRs every morning/evening and clinical symptoms in an asthma diary. AD was assessed from light detection and ranging data, and a linear mixed-effects model was used to estimate the effects of AD on daily PEFR. Time-stratified case-crossover analyses were performed to examine the association between AD and asthma attacks defined by reduction levels in PEFR. RESULTS: AD was detected on 11 days in the Goto Islands, and on 23 days in the south Nagasaki area. After adjusting for age, sex, temperature, and daily oxidants, we found a consistent association between AD and a 1.1% to 1.7% decrease in PEFR in the mornings and a 0.7% to 1.3% decrease in the evenings at a lag of 0 to 5 days. AD was not associated with the number of asthma attacks, respiratory symptoms, or other symptoms at any lag days examined. CONCLUSIONS Exposure to AD was associated with reduced PEFR, although the effects were not large enough to induce clinically apparent symptoms, in clinically well-controlled asthmatic children.

We have previously reported on a predictive model for deficiency-excess pattern diagnosis that was unable to predict the medium pattern. In this study, we aimed to develop predictive models for deficiency, medium,and excess pattern diagnosis, and to confirm whether cutoff values for diagnosis differed between the clinics. We collected data from patients' first visit to one of six Kampo clinics in Japan from January 2012 to February 2015. Exclusion criteria included unwillingness to participate in the study, missing data, duplicate data, under 20 years old, 20 or less subjective symptoms, and irrelevant patterns. In total, 1,068 participants were included. Participants were surveyed using a 153-item questionnaire. We constructed a predictive model for deficiency, medium, and excess pattern diagnosis using a random forest algorithm from training data, and extracted the most important items. We calculated predictive values for each participant by applying their data to the predictive model, and created receiver operating characteristic (ROC) curves with excess-medium and medium-deficiency patterns. Furthermore, we calculated the cutoff value for these patterns in each clinic using ROC curves, and compared them. Body mass index and blood pressure were the most important items. In all clinics, the cutoff values for diagnosis of excess-medium and medium-deficiency patterns was > 0.5 and < 0.5, respectively. We created a predictive model for deficiency, medium, and excess pattern diagnosis from the data of six Kampo clinics in Japan. The cutoff values for these patterns fell within a narrow range in the six clinics.

Pharmaceutical regulatory schemes concerned with real world data have been changing remarkably in terms of both drug development and post-marketing.As for drug development, ICH proposed “GCP Renovation” , which includes modernization of E8 Guideline (General Consideration for Clinical Trials) and subsequent renovation of E6 Guideline (Good Clinical Practice). It covers pragmatic clinical trials, randomized controlled trials using patient registry data, and even observational studies using real world data. In the US, “The 21st Century Cures Act” refers to the proposal concerning speeding up the approval review by making clinical trials more efficient. In fact, there are some cases where real world data was used in the approval review of expanding the application. Also, in Japan, Clinical Innovation Network (CIN) plan was announced, and utilizing the natural history data like patient registry as the control group of clinical trials for the approval review is now under consideration.As regards post-marketing surveillance, “Conditional & Accelerated Approval” (October 20, 2017, Yakuseiyakushinhatsu 1020 No. 1) stated that post-marketing confirmation of validity of efficacy and safety using real world data, such as Medical Information Database Network (MID-NET) project and patients registries in CIN plan, is required to get the early approval. Moreover, “The Ordinance on Good Post-Marketing Practice” (October 26, 2017, MHLW Ordinance No. 116) newly provided “Post-marketing Database Study” , which is conducted by use of medical information database like MID-NET, and utilizing real world data for post-marketing safety monitoring began.