Objective: To investigate quantitatively the risk factors of hyperkalaemia or increased blood potassium associated with ACE-inhibitor therapy
Design: Nested case-control study
Methods: We used the antihypertensive drug database(72,379 subjects)developed by the RAD-AR Council, Japan and the Institute of Statistical Mathematics based on the post-marketing surveillance(PMS) data of pharmaceutical companies. Of 37,372 subjects taking ACE-inhibitors, the case group was composed of 64 patients who experienced hyperkalaemia or blood potassium increase while taking ACE-inhibitors, and the control group was composed of 1,280 patients(20 patients per case)randomly selected from patients who did not experience hyperkalaemia or blood potassium increase while taking ACE-inhibitors. The relevant factors that can be extracted from the database were the followings: age, WHO classification of hypertension, complications, antihypertensive drugs used before the PMS survey, and concomitant drugs.
Results: Among the subjects taking antihypertensive agents, 65 patients experienced hyperkalaemia orincreased blood potassium, 64(98.5%)of whom were taking ACE-inhibitors. The factors that were significantly different between two groups(p<0.05)by univariate analysis were WHO classification of hypertension(p=0.005), complications of nephritis/nephrosis(p<0.001), other disorder of urinary system(p<0.001), unclear symptom or diagnosis(p=0.005), taking diuretics as antihypertensive drugs before study(p=0.032), and concomitant treatment with diuretics(p=0.004), vasodilators(p<0.001), and antigout agents(p=0.001). Conditional multivariate logistic analysis of these factors yielded adjusted odds ratio of 21.31 for complications of nephritis/nephrosis(p<0.001), 6.83 for other disorder of urinary system(p<0.001), and 2.30 for concomitant therapy with diuretics(p=0.049).
Conclusion: The risk factors of hyperkalaemia or blood potassium increase associated with taking ACE-inhibitors were nephritis/nephrosis, other disorder of urinary system and concomitant therapy with diuretics.

Objective: Databases, such as the Medicaid recipient database in the USA and the General Practice Research Database (GPRD) in the UK, take on an important role as resources for balancing the benefits and risks of medicines in Europe and the United States.
Their record sizes are several ten million and a few million each. They are actually used for epidemiological studies. However, in Japan, a database that can be used for such studies is insufficient. We attempted to create a database of pre-marketing clinical trial data for antihypertensive drugs. These data have been managed by a Controller Committee.
(Design : not applicable )
Methods: The database is made from the data and the documents, including electronic and paper media. The creation process was as follows : computerizing documents, item-name identification, defining the integrated database, protocol review, batch processing, and logical/validation checking.
Results: The database has 13 datasets and consists of 56 trials and 12,389 subjects. Overall, 15 trials involved beta-blockers which is the largest drugs as the investigational drug, and 43 trials compared the same group of antihypertensive drugs.
Conclusion: A database that can be used for quantitative evaluation of various hypotheses has been built. It is possible to completely analyze all of the data in this large-scale database to conduct, for example, individual patient data (IPD) meta-analyses.

Objective: The mechanism underlying the development of neuropsychiatric symptoms such as unconsciousness, abnormal behavior, delirium, hallucinations, and convulsions in influenza has not been thoroughly investigated. The relationship between drug administration and neuropsychiatric symptoms during influenza is also poorly understood. This study is the first pharmacoepidemiologic study focused on investigating the relationship between drug administration and neuropsychiatric symptoms.
Design: Cohort study
Methods: Study subjects were patients under 18 years old who had influenza during the 2006/07 season. We prepared two kinds of questionnaires for doctor and for patient's family, and carried out the survey between January and March, 2007. Using data from 9,389 patients, we analyzed the relationship between neuropsychiatric symptoms, such as delirium, unconsciousness and convulsion, and drug administration of acetaminophen and oseltamivir.
Results: Analysis of the relationship between delirium and drug administration provided hazard ratios of 1.55(p=0.061)for acetaminophen and 1.51(p=0.084)for oseltamivir. These hazard ratios, which were adjusted for risk factors by multivariate analysis of the proportional hazard model, showed an increasing tendency of delirium after administration of each drug. In patients who received oseltamivir, a high incidence of delirium was observed between 6 and 12 hours after onset of fever. Furthermore, delirium was found to develop in a shorter time following oseltamivir use than it did after acetaminophen use. There was no relationship between unconsciousness and acetaminophen administration, as demonstrated by a hazard ratio of 1.06(p=0.839). The incidence of unconsciousness increased significantly with oseltamivir use with a hazard ratio of 1.79(p=0.0389), and unconsciousness was found to occur in a short time after oseltamivir use.
Conclusion: The results obtained from this study suggest that there are increased risks of delirium and unconsciousness with drug administration. Further pharmacoepidemiologic studies for hypothesis testing are required to study the relationship between abnormal behavior and drug administration.

We examined the relationship between the timing of habitual physical activities and sleep quality in older adults. The subjects were Japanese community-dwelling older adults (n=49, average age 70.1±3.5 years; men: 36.7%). We measured habitual physical activity using a 3-axis accelerometer (HJA-350 IT, Omron) for a week. Timing of physical activity was classified into the following three periods: (1) morning: waking to 11:59, (2) afternoon: 12:00 to 17:59, and (3) night: 18:00 to bedtime. We also categorized the intensity of habitual physical activity during 2 sessions as either (1) low (1.6-2.9 METs) or (2) moderate-to-vigorous (≧3.0 METs) intensity. The subjective sleep parameters were assessed using the Pittsburgh Sleep Quality Index (PSQI). We used a forced-entry multiple regression analysis to investigate the relationships between subjective sleep parameters and the timing of physical activities. Forced-entry multiple regression analysis revealed that sleep latency and PSQI global score were positively correlated with low-intensity physical activity at night. However, there was no significant correlation with moderate-to-vigorous activity. These results suggest that low-intensity habitual physical activity at night would be one useful and modifiable factor to improve sleep quality in the elderly.

This study investigated the effects of exercise intervention with a 12-week slightly-weighted shoe on lower-limb skeletal muscle and gait patterns in the elderly. A total of 29 healthy elderly Japanese who had irregular walking habits were randomly assigned to either slightly-weighted-shoe (WS group, n = 14; Age, 70.6 ± 5.7 years; WS, 493 g) or normal-shoe (NS group, n = 15; Age, 69.3 ± 6.9 years; NS, 293 g) intervention groups. The participants were instructed to maintain their normal daily physical activity (PA) during the intervention period. Segmental intracellular water (ICW) and muscle thickness (MT) were measured as an index of skeletal muscle mass in the lower limb, and kinematic gait data were acquired by motion analysis. Walking stability was assessed as a standard deviation of the vertical fluctuation in whole-body center of mass (COM fluctuation). The daily PA was monitored using an accelerometer and an activity record. ICW in the upper leg and MT of rectus femoris increased significantly in the WS group compared with the NS group (ICW: 13.8% vs. 2.2%, MT: 12.1% vs. 1.3%), while COM fluctuation was significantly reduced in the WS group (p<0.05) during normal walking. The present study demonstrated that interventions with a slightly-weighted-shoe may be able to increase muscle volume in the upper leg and change gait patterns in the healthy elderly.

BACKGROUND/AIMS: This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascular invasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance. METHODS: In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUS image findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion, types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors and evaluated vessels. RESULTS: The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in the veins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings were significantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0–742] µm vs. 2,833 [1,076–5,694] µm, p=0.012) and arteries (623 [0–854] µm vs. 3,097 [1,396–6,000] µm, p=0.0061). All cases with a distance of ≥1,000 µm between the tumors and main vessels were correctly diagnosed. CONCLUSIONS: Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.
Arteries ; Diagnosis ; Endosonography ; Humans ; Pancreatic Neoplasms ; Retrospective Studies ; Sensitivity and Specificity ; Veins

Methods: A total of 224 consecutive patients with OVFs aged ≥65 years who received treatment within 2 weeks after the occurrence of injury were enrolled. The patients were followed up for 6 months thereafter. The criteria for evaluating the degree of independence were applied to evaluate ADLs. Multivariable analysis with a logistic regression model was performed to evaluate the risk factors for ADL decline. Results: In total, 49/224 patients (21.9%) showed a decline in ADLs. Of these, 23/116 patients (19.8%) in the rest group and 26/108 patients (24.1%) in the no-rest group experienced a decline in ADLs. In the logistic regression analyses, a diffuse low signal on T2- weighted magnetic resonance imaging (MRI) (odds ratio, 5.78; 95% confidence interval, 2.09–16.0; p=0.0007) and vertebral instability (odds ratio, 3.89; 95% confidence interval, 1.32–11.4; p=0.0135) were identified as independent factors in the rest and no-rest groups, respectively. Conclusions In patients with acute OVFs, a diffuse low signal on T2-weighted MRI and severe vertebral instability were independently associated with ADL decline in patients treated with and without initial bed rest, respectively.

Methods: A total of 224 consecutive patients with OVFs aged ≥65 years who received treatment within 2 weeks after the occurrence of injury were enrolled. The patients were followed up for 6 months thereafter. The criteria for evaluating the degree of independence were applied to evaluate ADLs. Multivariable analysis with a logistic regression model was performed to evaluate the risk factors for ADL decline. Results: In total, 49/224 patients (21.9%) showed a decline in ADLs. Of these, 23/116 patients (19.8%) in the rest group and 26/108 patients (24.1%) in the no-rest group experienced a decline in ADLs. In the logistic regression analyses, a diffuse low signal on T2- weighted magnetic resonance imaging (MRI) (odds ratio, 5.78; 95% confidence interval, 2.09–16.0; p=0.0007) and vertebral instability (odds ratio, 3.89; 95% confidence interval, 1.32–11.4; p=0.0135) were identified as independent factors in the rest and no-rest groups, respectively. Conclusions In patients with acute OVFs, a diffuse low signal on T2-weighted MRI and severe vertebral instability were independently associated with ADL decline in patients treated with and without initial bed rest, respectively.

Methods: A total of 224 consecutive patients with OVFs aged ≥65 years who received treatment within 2 weeks after the occurrence of injury were enrolled. The patients were followed up for 6 months thereafter. The criteria for evaluating the degree of independence were applied to evaluate ADLs. Multivariable analysis with a logistic regression model was performed to evaluate the risk factors for ADL decline. Results: In total, 49/224 patients (21.9%) showed a decline in ADLs. Of these, 23/116 patients (19.8%) in the rest group and 26/108 patients (24.1%) in the no-rest group experienced a decline in ADLs. In the logistic regression analyses, a diffuse low signal on T2- weighted magnetic resonance imaging (MRI) (odds ratio, 5.78; 95% confidence interval, 2.09–16.0; p=0.0007) and vertebral instability (odds ratio, 3.89; 95% confidence interval, 1.32–11.4; p=0.0135) were identified as independent factors in the rest and no-rest groups, respectively. Conclusions In patients with acute OVFs, a diffuse low signal on T2-weighted MRI and severe vertebral instability were independently associated with ADL decline in patients treated with and without initial bed rest, respectively.

Methods: A total of 224 consecutive patients with OVFs aged ≥65 years who received treatment within 2 weeks after the occurrence of injury were enrolled. The patients were followed up for 6 months thereafter. The criteria for evaluating the degree of independence were applied to evaluate ADLs. Multivariable analysis with a logistic regression model was performed to evaluate the risk factors for ADL decline. Results: In total, 49/224 patients (21.9%) showed a decline in ADLs. Of these, 23/116 patients (19.8%) in the rest group and 26/108 patients (24.1%) in the no-rest group experienced a decline in ADLs. In the logistic regression analyses, a diffuse low signal on T2- weighted magnetic resonance imaging (MRI) (odds ratio, 5.78; 95% confidence interval, 2.09–16.0; p=0.0007) and vertebral instability (odds ratio, 3.89; 95% confidence interval, 1.32–11.4; p=0.0135) were identified as independent factors in the rest and no-rest groups, respectively. Conclusions In patients with acute OVFs, a diffuse low signal on T2-weighted MRI and severe vertebral instability were independently associated with ADL decline in patients treated with and without initial bed rest, respectively.