The spontaneous reporting system for adverse drug reactions(ADRs), through which information is collected on patients who experience ADRs, can lead to hypotheses on causal relationships between drugs and ADRs; however, lack of information on patient characteristics or patients who have not experienced ADRs makes quantitative, relative comparison of risks difficult. From the viewpoint of adapting pharmacoepidemiology to supplement spontaneous reporting of ADRs, RAD-AR Council Japan(RCJ) has been promoting development of a database assembling drug use-results surveillance(DURS) data under the re-examination system for secondary use. RCJ received observational DURS data on antihypertensive drug users from pharmaceutical companies and integrated to develop a database of over 100,000 patients and 19 antihypertensives in 2003. RCJ maintains the database, expanding it to 143,509 patients and 21 antihypertensives in 2007, and also developed a database of antihyperlipidemics with approximately 34,000 patients in 2011. Researchers study these databases through an application and protocol review process stipulated by RCJ, and their results have been presented at conferences and published in articles. This report summarizes DURS data collection and its underpinning regulated systems in terms of data assembly and database maintenance at RCJ. The report also introduces the example for constructing the antihyperlipidemics DURS database and summarizes its patient characteristics. The database is characterized by ADR information and treatment-related laboratory values in addition to patient backgrounds and drug use information. However, it is too small to study rare ADRs and has limited longitudinal observational data. Therefore, RCJ worked to expand the antihypertensives DURS database in 2012 by adding data that include long-term surveillance results. (Jpn J Pharmacoepidemiol 2012; 17(2): 87-97)

The purpose of this study was to investigate the prognostic value of change in heart rate (HR) response to oxygen uptake (VO₂) during exercise in patients with coronary heart disease (CHD).We retrospectively studied 204 patients with CHD who were sent to our exercise testing laboratory between August 1983 and February 1985. The following equation was used to determine the relation between VO₂ and HR during a graded treadmill exercise test: HR= A・exp ^B･VO2, where the constant b was defined as the inclination of the exponential curve-fitting model for oxygen uptake and heart rate during graded treadmill exercise (I-ECOH). Data on mortality were determined in May 2006 by examining medical records from the outpatient clinic and/or conducting telephone interviews with the patients or their families. Among the 204 study subjects, there were 54 cardiac deaths during the entire 20-year follow-up period. Kaplan-Meier survival curves for 20 years of follow-up demonstrated a survival rate of 81.3% for patients with a lower I-ECOH (＜35) and 56.0% for those with a higher I-ECOH (≧35), showing a significant difference in survival (p＜0.001). Multivariate Cox proportional hazards analysis revealed left ventricular ejection fraction (LVEF), peak oxygen uptake (VO₂ peak) and I-ECOH as independent predictors of survival. In this analysis, the prognostic power of minutes ventilation/carbon dioxide output (VE/VCO₂)slope was insignificant. The patients were divided into two groups with (＜45%) and without (≧60%) LV dysfunction using LVEF for more detailed analysis. The VO₂ peak and VE/VCO₂ slope were significant independent predictors of survival in patients with LV dysfunction. However, the I-ECOH was a significant independent predictor of survival in patients with and without LV dysfunction. Our data indicate that I-ECOH provides independent prognostic information on CHD patients with and without LV dysfunction.

A study was conducted to clarify the validity and availability of inclination of exponential curve-fitting model for oxygen uptake (VO₂) and heart rate (HR) during incremental exercise (IECOH) as an index of cardio-pulmonary functional reserve in healthy subjects. A treadmill exercise test was used to measure the VO₂ (L/kg/min) and HR (beat /min) during incremental exercise of all subjects. The IECOH was derived from the following equation : HR=A⋅exp^B·VO₂. The constant “B” represents the IECOH. The following three identifications were made : 1) the relationship between maximal oxygen uptake (VO₂max) and IECOH in 82 healthy males ; 2) the relationship between IECOH and age in 428 healthy males and females ; 3) the effect of physical training in 8 healthy males.
There was inverse correlation between IECOH and VO₂max (r= -0.824) . And also, there were inverse correlations between IECOH detected from submaximal tests and VO₂max (above r=-0.6) . There were no differences in the IECOH detected from maximal and submaximal tests. In Bland-Altman plot method, accuracy of measurment in the IECOH detected from submaximal exercise test was precise. There was a significant relationship between IECOH and age in male and female subjects (r=0.499 and r=0.310, respectively) . Physical training increased VO₂max and decreased IECOH significantly. The VO₂max before and after physical training correlated inversely with the IECOH before and after physical training (r=-0.514) .
In conclusion, these results suggest that IECOH is adequate and useful as an index of cardio-pulmonary functional reserve which can be measured by the submaximal exercise test in healthy subjects.

We report 2 patients with unilateral pulmonary edema after heart surgery who were successfully treated using venovenous extracorporeal membrane oxygenation (VV ECMO). Case 1 : A 35-year-old woman presented with dyspnea. Echocardiography showed severe mitral regurgitation (MR) and tricuspid regurgitation (TR) and therefore, mitral valve plasty (MVP) and tricuspid annular plasty (TAP) were performed via right thoracotomy. After weaning from cardiopulmonary bypass, respiratory failure occurred with expectoration of foamy sputum and it was difficult to maintain oxygenation. Therefore, we performed VV ECMO to maintain oxygenation. A chest X-ray film after surgery showed ipsilateral pulmonary edema. After weaning from VV ECMO, deep venous thrombosis occurred and therefore we inserted an IVC filter. Case 2 : A 67-year-old man, who had previously received aortic valve replacement experienced dyspnea and visited our hospital. Echocardiography showed an aortic root abscess, and therefore Bentall operation was performed. After weaning from cardiopulmonary bypass, oxygenation was difficult to maintain, and therefore we performed VV ECMO. A chest X-ray film post operatively showed right ipsilateral pulmonary edema. The patient was weaned from VV ECMO 5 days post operatively and was discharged 60 days post operatively. We believe that VV ECMO can be beneficial for patients with respiratory failure after heart surgery, but complications related to this approach such as DVT should also be considered.

This study examined the effects of physical training on exercise hyperpnea (EH) in patients on hemodialysis (HD) . In baseline, 17 (trained group) and 12 (control group) patients on HD performed symptom limited exercise test using a treadmill. Trained group, but not control group, exercised 2 to 3 times weekly on non-dialysis days under medical supervision. Exercise testing was repeated 20 weeks after the baseline. Ventilatory response to exercise was evaluated using the regression slope relating minute ventilation (VE) to carbon dioxide output (VCO₂ ) during incremental exercise (VE/VCO₂ slope) below the point of respiratory compensation. In trained group, VE, oxygen uptake ( VO₂) and VCO₂ at peak exercise increased and VE/VO₂ and VE/VCO₂ decreased after physical training, respectively. No change was observed in control group. VO₂ at the anaerobic threshold increased in trained group, but not in control group. The post training VE/VCO₂ slope (33.9±5.0) was significantly (p<0.05) lower than the pre-training slope (38.0± 4.8) and remained constant in control group. In trained group, changes in the VE/VCO₂ slope correlated with those in peak VO₂ (p<0.05) . These results suggest that physical training decreases EH in patients on HD and that it correlates with changes in exercise tolerance.

A 2-month-old girl had been urgently seen on postnatal day 10 due to poor weight gain and tachypnea. Echocardiography showed congenital valvular aortic stenosis (AS), ventricular septal defect (VSD), atrial septal defect (ASD), and aortic valve dysplasia, but no cyst image was seen at the aortic valve level. Aortography revealed a dysplastic aortic valve along with coarctation of aorta (CoA) and patent ductus arterious (PDA). Balloon aortic valvotomy (BAV) was performed on day 53. Ballooning was satisfactory, but there was no change in gradient. Operation was performed on day 70 under a diagnosis of congenital AS and CoA complex. After cardiopulmonary bypass was established, the ascending aorta was transected. The blood cyst originated from the center of the anterior leaflet and was resected. The pressure gradient at the aortic valve decreased to 22.5mmHg. The patient was discharged 25 days after surgery.

Objective: To examine the association between the mobilization level during intensive care unit (ICU) admission and independence in activity of daily living (ADL), defined as Barthel Index (BI)≥70. Methods: This was a post-hoc analysis of the EMPICS study involving nine hospitals. Consecutive patients who spend >48 hours in the ICU were eligible for inclusion. Mobilization was performed at each hospital according to the shared protocol and the highest ICU mobility score (IMS) during the ICU stay, baseline characteristics, and BI at hospital discharge. Multiple logistic regression analysis, adjusted for baseline characteristics, was used to deter-mine the association between the highest IMS (using the receiver operating characteristic [ROC]) and ADL. Results: Of the 203 patients, 143 were assigned to the ADL independence group and 60 to the ADL dependence group. The highest IMS score was significantly higher in the ADL independence group than in the dependence group and was a predictor of ADL independence at hospital discharge (odds ratio, 1.22; 95% confidence interval, 1.07–1.38; adjusted p=0.002). The ROC cutoff value for the highest IMS was 6 (specificity, 0.67; sensitivity, 0.70; area under the curve, 0.69). Conclusion These results indicate that, in patients who were in the ICU for more than 48 hours, that patients with good function in the ICU also exhibit good function upon discharge. However, prospective, multicenter trials are needed to confirm this conclusion.

In C1–C2 posterior fixation, the C1 lateral mass and C2 pedicle/translaminar screw insertion under spine navigation have been used frequently. To avoid the risk of neurovascular damage in atlantoaxial stabilization, we assessed the safety and effectiveness of a preoperative computed tomography (CT) image-based navigation system with intraoperative independent C1 and C2 vertebral registration. It is ideal when a reference frame can be linked directly to the C1 posterior arch for C1-direct-captured navigation, but there is a mechanical challenge. A new spine clamp-tracker system was implemented recently, which allows reliable C1- and C2- direct-captured navigation in nine patients with traumatic C2 fractures. In this way, there was no misalignment of C1–C2 screws. C1 lateral mass screws were used except for one case, and translaminar screws were primarily used as an anchor for C2. The C1 lateral mass screw locations, which are 19 mm laterally from the C1 posterior arch’s center, are taken to be constant. However, there is one unusual circumstance in which using a C1 laminar hook instead of a C1 lateral mass screw appears to be a beneficial substitute. The increase of surgical accuracy for posterior C1–C2 screw fixation without cost constraints is significantly facilitated by intraoperative C1- and C2-direct-captured navigation with preoperative computed CT images.

BACKGROUND/OBJECTIVES: Alzheimer's disease is a neurodegenerative disease that induces symptoms such as a decrease in motor function and cognitive impairment. Increases in the aggregation and deposition of amyloid beta protein (Aβ) in the brain may be closely correlated with the development of Alzheimer's disease. In this study, the effects of an adzuki bean extract on the aggregation of Aβ were examined; moreover, the anti-Alzheimer's activity of the adzuki extract was examined. MATERIALS/METHODS: First, we undertook thioflavin T (ThT) fluorescence analysis and transmission electron microscopy (TEM) to evaluate the effect of an adzuki bean extract on Aβ42 aggregation. To evaluate the effects of the adzuki extract on the symptoms of Alzheimer's disease in vivo, Aβ42-overexpressing Drosophila were used. In these flies, overexpression of Aβ42 induced the formation of Aβ42 aggregates in the brain, decreased motor function, and resulted in cognitive impairment. RESULTS: Based on the results obtained by ThT fluorescence assays and TEM, the adzuki bean extract inhibited the formation of Aβ42 aggregates in a concentration-dependent manner. When Aβ42-overexpressing flies were fed regular medium containing adzuki extract, the Aβ42 level in the brain was significantly lower than that in the group fed regular medium only. Furthermore, suppression of the decrease in motor function, suppression of cognitive impairment, and improvement in lifespan were observed in Aβ42-overexpressing flies fed regular medium with adzuki extract. CONCLUSIONS: The results reveal the delaying effects of an adzuki bean extract on the progression of Alzheimer's disease and provide useful information for identifying novel prevention treatments for Alzheimer's disease.
Alzheimer Disease ; Amyloid beta-Peptides ; Brain ; Cognition Disorders ; Diptera ; Drosophila ; Fluorescence ; Microscopy, Electron, Transmission ; Neurodegenerative Diseases