Since the reexamination system of new drugs has been in place for about thirty years, it is necessary to reconsider its management. The time from the reexamination application of new drugs until issuance of the results takes several years recently. General drugs are applied during the reexamination application and are approved before reconfirmation of the efficacy and safety of new drugs. Therefore, the reexamination system is not effectively operated. Although the informations for proper use collected from post-marketing investigations and clinical trials, and spontaneous adverse reaction reports of new drugs, etc. during the reexamination period are utilized for its safety measures, the plan for effective use is not systematically managed. We propose an improved plan for a future reexamination system. Further, we propose the introduction of a risk management plan in Japan; the current one of which lags behind EU and US.

The problems of breath-by-breath measurement of respiratory gas exchange to analyze the transient responses during complex load work are described and treated. With review for the experimental systems developed by other investigators, our signal transducers and data processing were improved. We found the computer-processed data were in good agreement with those obtained from simultaneous Douglas bag gas collection.
1) Errors in the measurement of volume arose from errors in the flow signals such as nonlinearity, base-line drift, noise, and frequency response, as well as composition and temperature of gas, water vapor condensation, quantization errors, and breathing valve leakage. ±1.74% error in the flow integration reproducibility resulted from the modification of the upstream geometry of the pneumotachometer and the pressure tubing as well as a compensation for base-line drift and filter smoothing.
2) Errors in the gas concentration signals were attributed to inaccuracy, drift, noise, and water vapor concentration. The transport delay of gas concentration signals was overestimated in order to cancel the underestimation in Vco₂and Vo₂·Other compensation methods for the response time were discussed.
3) Error magnitudes below±0.97% in the A/D amplitude quantization were found by means of signal simulation.
4) The optimal compromises between breath recognition threshold and the fluctuation in flow signal were examined to permit identification of irregular breath.
5) Since the breathing valve dead space was modified to tidal volume dependent, errors in the gas exchange variables were reduced.
6) To validate the accuracy of the equipment operation and the gas exchange algorithm, problems in signal simulation and the model lung were described.

Thirty-four patients with congenital cardiac disease were studied to evaluated the role of ultrafiltration after cardiopulmonary bypass without homologous blood transfusion. We used either polypropylene microporous hollow fiber hemoconcentrator (HC-30M or 100M) or polyacrylonitrile microporous hollow fiber hemoconcentrator (PHC-500). Ultrafiltration was useful in the reduction of fluid overloading after cardiopulmonary bypass with extreme hemodilution. Thirty-two patients tolerated the procedure uneventfully without donor blood transfusion and were discharged from the hospital. The values of hematocrit, serum protein and free hemoglobin increased significantly after ultrafiltration with either type of hemoconcentrator. However the degree of concentration of blood components was significantly higher with polyacrylonitrile hemoconcentrator than those with polypropylene hemoconcentrator. These results indicated that ultrafiltration was useful for maintaining water balance after cardiopulmonary bypass without homologous blood transfusion in pediatric cardiac surgery and that polyacrylonitrile microporous hollow fiber hemoconcentrator should be employed in patients with shorter bypass time and less hemolysis.

Transcatheter embolization of 25 aortopulmonary collateral arteries (7 bronchial arteries and 18 intercostal arteries) was attempted prior to intracardiac repair in 7 patients. The underlying disease was tetralogy of Fallot in 3 patients, pulmonary atresia with ventricular septal defect in 2, double-outlet right ventricle with ventricular septal defect and pulmonary stenosis in 1 and tricuspid stenosis with pulmonary atresia in 1. The intervals between embolization and intracardiac repair ranged from 0 to 17 days (mean 4.5 days). Embolization resulted in total occlusion in 7 bronchial arteries and 17 intercostal arteries, with an overall success rate of 96%. Complications included a coil dislodgement from a collateral artery into the aorta in one patient, necessitating surgical removal of the dislodged coil from the femoral artery, an exacerbation of cyanosis and dyspnea on exercise in 5, and slight fever in 2. In one patient with tetralogy of Fallot, who had 5 collateral vessels, transcatheter embolization caused hypoxemia, bradycardia and hypotension and therefore intracardiac repair was performed immediately after embolization. Aortopulmonary collateral arteries in patients with congenital heart disease can be effectively treated by transcatheter embolization. Embolization should be performed just before intracardiac repair because an excessive decrease in arterial oxygen saturation after embolization may require an emergency operation.

Objective: Instructions contained in over-the-counter medicine package inserts can be hard to read because of the limited printing space.  Pictograms are one means of helping users to understand important information.  However, few pictogram systems have been reliably and validly evaluated.  Therefore, a new method was developed to improve the clarity of each illustration and the legitimacy as a pictogram for conveying information important.
Methods: Four creators developed 69 illustrations, each of which expressed one of 24 instructions in the package insert of an H2 blocker.  In a survey, participants (449 university undergraduate and graduate students and 103 pharmacy users) were asked to describe the possible meaning of each illustration and to provide their personal suggestions for improvement.  To evaluate comprehension of information, each instruction was broken into two or three different parts.  Comprehension level was calculated by: (number of people who answered correctly) × 100 / (total number of respondents).  Existing pictograms were included to compare comprehension levels for the same instructions.
Results: Using 67% as the minimum standard for comprehension, we classified each illustration into one of three categories: “no need for improvement,” “need for partial improvement,” and “need for total improvement.”  The students and pharmacy users tended to accurately interpret the possible meanings of illustrations that were familiar to them.
Conclusion: Breaking one instruction of the package insert into a few important pieces of information was useful for determining the level of improvement needed for each illustration.  Evaluating how well each illustration conveys important information in the instructions through two steps was also beneficial, which are to improve the illustration’s clarity with students and its legitimacy among pharmacy users for fulfilling the intended functions of a pictogram.

In 2006 26 first-year residents at St.Luke's International Hospital underwent training with a highly sophisticated simulator to learn how to treat patients with cardiopulmonary arrest or anaphylactic shock.We evaluated the effects of simulation training for first-year residents.
1) After training, we analyzed the residents' performance in the 2 scenarios and the residents' satisfaction with simulation training.
2) According to the resident's performance dataduring simulation training, first-year residents have sufficient skill to treat patients in cardiopulmonary arrest but not patients with anaphylactic shock.
3) Twenty-five of the 26 residents (96.2%) were highly satisfied with simulation training.

In order to study respiratory transients during exercise, we examined breath-by-breath differences between gas exchange kinetics measured at the mouth and those estimated at the alveolar level. The gas exchange data at the mouth were obtained by measurement of expired gases only (expiratory flow method) . Correction for breath-by-breath changes in lung gas stores was applied to the total gas exchange, which was obtained by subtracting expired from inspired gas volume (alveolar gas exchange method) . Constant work loads (150, 200, 250 W) and a ramp work load (30 W/min) preceded and followed by a 50 W load were generated by a computerized cycle ergometer. Best-fit first- or second-order model values for gas exchange kinetic parameters were found by the non-linear least-squares method.
1. Regardless of work intensity and forcing function, the breath-by-breath variation in gas exchange measured at the mouth was larger than the gas exchange estimated at the alveolar level, in both a non-steady state and a steady state. The variation was caused by the invalidity of assuming zero N₂ exchange at the mouth, which was attributed to changes in lung volume.
2. Vo₂ kinetics at the alveolar level were faster than those at the mouth, while the converse held for Vco₂ at the onset of constant load work, due to the effects of fluctuations in lung gas stores on the kinetics of gas exchange at the mouth. During ramp load work, Vo₂ and Vco₂ kinetics at the alveolar level were faster than those at the mouth.
3. Steady state gas exchange values at the alveolar level and at the mouth were the same during constant load work, since the lung gas stores corrections added up to small fractions of the total gas exchange when summed over the long term.
4. Consideration of both the proper end-expiratory lung volume and ventilationperfusion inhomogeneity was required in order to estimate the true alveolar gas exchange.

OBJECTIVES: It is not unusual for a cochlear implantation (CI) candidate to have some type of ear malformation, in particular an abnormal course of the facial nerve (FN). In this study, we attempted to reconstruct a three-dimensional (3D) image of temporal bone structures with malformation using computed tomography (CT) imaging and examined its usefulness in the surgical planning of CI in a malformed ear. METHODS: We prepared 3D images for 6 separate CI cases before surgery. First, we manually colored preoperative CT images using Photoshop CS Extended. We then converted the colored CT images to 3D images using Delta Viewer, free-ware for Macintosh. Before surgery, we discussed any problems anticipated based on the 3D images and plans for surgery with those who would be performing the CI. RESULTS: Case 1: The subject was a 3-year-old boy with malformed ossicles, semicircular canal (SC) hypoplasia, internal auditory canal stenosis, and an abnormal course of the FN. 3D image indicated that the stapes were absent, and the FN was more anteriorly displaced, so that it was difficult to perform cochleostomy. The surgical findings were similar to those depicted on the 3D image, so we could insert an electrode based on the preoperative image simulation without complications. Case 2: The subject was a 7-year-old boy with malformed stapes, atresia of the round window, cochlear and SC aplasia, and an abnormal course of the FN with bifurcation. CI was performed with no problems, in the same manner as in Case 1. CONCLUSION: We were able to successfully depict the structures of the inner ear, ossicles, and FN as 3D images, which are very easy to understand visually and intuitively. These 3D images of the malformed ear are useful in preoperative image simulation and in surgical planning for those performing a CI procedure.
Child ; Cochlear Implantation ; Cochlear Implants ; Constriction, Pathologic ; Ear ; Ear, Inner ; Electrodes ; Facial Nerve ; Humans ; Imaging, Three-Dimensional ; Preschool Child ; Round Window, Ear ; Semicircular Canals ; Stapes ; Temporal Bone

BACKGROUND: Use of complementary and alternative medicine (CAM) has become popular in Japan.
OBJECTIVE: To investigate associations of symptom-related CAM use with sociodemographic factors in Japan.
DESIGN AND SETTING: A prospective cohort study of a nationally representative sample of households in Japan.
PARTICIPANTS: Community-dwelling adults who developed at least one symptom during a 31-day period.
MAIN OUTCOME MEASURES: Self-reported, symptom-related use of CAM, either physical CAM or oral CAM.
RESULTS: Of 2, 453 adults, 2, 103 participants (86%) developed at least one symptom. Of these symptomatic adults, 156 (7.4% ; 95% CI: 6.3-8.5%) used physical CAM therapy. The likelihood of using physical CAM was not significantly influenced by annual household income, employment, or education. Participants living in large cities had an increased likelihood of using physical CAM with an odds ratio (OR) of 2.6 (95% CI: 1.2-5.8), compared to those living in rural areas. Oral CAM therapy was used by 480 participants (22.8%; 95% CI: 21.0-24.6%) among the symptomatic adults. An age of 60 years old and older (OR 2.0; 95% CI: 1.2-3.3) and female gender (OR 1.8; 95% CI: 1.3-2.6) were significantly associated with an increased use of oral CAM. The unemployed participants had a lower likelihood of using oral CAM, with an OR of 0.6 (95% CI: 0.4-0.9), compared to the employed.
CONCLUSIONS: Oral CAM use is common among Japanese patients and is associated with older age, female gender, and employed status, while physical CAM use is less common and is associated with living in a large city.

OBJECTIVES: The number of patients with bilateral cochlear implant (CI) has gradually increased as patients and/or parents recognize its effectiveness. The purpose of this report is to evaluate the efficacy of 29 bilateral CI out of 169 pediatric CI users, who received auditory-verbal/oral habilitation at our hearing center. METHODS: We evaluated the audiological abilities 29 Japanese children with bilateral CIs including wearing threshold, word recognition score, speech discrimination score at 1 m from front speaker (SP), 1 m from second CI side SP, speech discrimination score under the noise (S/N ratio=80 dB sound pressure level [SPL]/70 dB SPL, 10 dB) at 1 m from front SP, word recognition score under the noise (S/N ratio=80 dB SPL/70 dB SPL, 10 dB) at 1 m from front SP. RESULTS: Binaural hearing using bilateral CI is better than first CI in all speech understanding tests. Especially, there were significant differences between the results of first CI and bilateral CI on SDS at 70 dB SPL (P=0.02), SDS at 1 m from second CI side SP at 60 dB SPL (P=0.02), word recognition score (WRS) at 1 m from second CI side SP at 60 dB SPL (P=0.02), speech discrimination score (SDS) at 1 m from front SP under the noise (S/N=80/70; P=0.01) and WRS at 1 m from front SP under the noise (S/N=80/70; P=0.002). At every age, a second CI is very effective. However, the results of under 9 years old were better than of over 9 years old on the mean SDS under the noise (S/N=80/70) on second CI (P=0.04). About use of a hearing aid (HA) in their opposite side of first CI, on the WRS and SDS under the noise, there were significant differences between the group of over 3 years and the group of under 10 months of HA non user before second CI. CONCLUSION: These results may show important binaural effectiveness such as binaural summation and head shadow effect. Bilateral CI is very useful medical intervention for many children with severe-to-profound hearing loss in Japan as well as elsewhere.
Asian Continental Ancestry Group ; Child ; Cochlear Implantation ; Cochlear Implants ; Head ; Hearing ; Hearing Aids ; Hearing Loss ; Humans ; Japan ; Noise ; Parents ; Speech Perception