No abstract available.
Adrenal Cortex Hormones*

PMDA started MIHARI project in FY2009 to enhance drug safety assessment by developing ways to utilize electronic medical information as additional data sources to spontaneous adverse drug reaction reports. The project has been established according to PMDA's second midterm plan. In this article, we will introduce latest two studies (pilot studies No. 4 and 5) using data of standardized electronic medical record(EMR) called SS-MIX (standardized structured medical record information exchange) data out of our several pilot studies. SS-MIX is a standard specification published by the Ministry of Health, Labour and Welfare. In these studies, anonymized SS-MIX data were provided by six collaborative hospitals respectively. In pilot study No. 4, we explored approaches for evaluating the impact of regulatory action which instructed relevant manufacturers to revise package inserts of sitagliptin phosphate hydrate (sitagliptin) to call physician's attention. The revision was about reducing dose of sulfonylurea (SU) to avoid serious hypoglycemia when it is prescribed concomitantly with sitagliptin. As indicators of the impact, we evaluated changes in proportion of concomitant use and average SU dose before and after the action and estimated the risk of hypoglycemia in concomitant users compared to SU alone users before and after the action. In conclusion, evaluating impact of the regulatory action using SS-MIX data was technically feasible; however, it was difficult to analyze with adequate accuracy due to limited size of the data. In pilot study No. 5, we examined validity of outcome definitions for hyperthyroidism which were applied to combinations of some data elements of SS-MIX data to identify the patients. Three types of outcome definitions were prepared; 1) definitive diagnosis of hyperthyroidism, 2) prescription of medication for hyperthyroidism, 3) prescription of medication for hyperthyroidism in or after the month in which definitive diagnosis of hyperthyroidism was given. Criteria for case ascertainment were determined according to relevant clinical guidelines. After the cases were ascertained, positive predictives values were calculated. The results suggested that using information on prescription of medication improves validity of definition of outcome. The findings from pilot studies in MIHARI project have been utilized in another project which PMDA is carrying forward now (EMR network project). The findings would be also helpful when we use data from this network. (Jpn J Pharmacoepidemiol 2013；18(1)：23-29)

The Committee for the Meridian Point (Chairman, Kansho Yamada) focused on the significance of “the Meridian denial theory” which Hirohisa Yoneyama announced in 1952. Pros and cons emerged, and the so-called “Meridian controversy” raged for about two years. Documents relating to this controversy along with basic research on the meridian and the meridian point during the period were collected, arranged, examined, and presented at Workshop i of the 51st Annual Meeting of the Japan Society of Acupuncture and Moxibustion which was held in Tsukuba in June 2002. This is a condensed version of the reports.

The relationships between physical activity and childhood body size, low physical fitness epidemic are still unclear. The purpose of this study was to examine the relationship between energy expenditure estimated by doubly labeled water (DLW) method and body fatness, physical fitness in children, and the relationship between physical activity levels and percent time spent in activities. 30 healthy Japanese children (20 boys and 10 girls) participated in this study. The total energy expenditure (TEE) and % body fat were measured by the DLW method over a 6-day period. The physical activity-related energy expenditure (PAEE) was calculated as (TEE × 0.90) – basal metabolic rate (BMR). The physical activity level (PAL) was also calculated as TEE/BMR. The physical fitness tests (8 items) were applied to evaluate fitness, and scores of each test were calculated as overall physical fitness score. The TEE was 2009.8 ± 272.6 kcal/day, the PAEE was 558.4 ± 206.1 kcal/day and the PAL was 1.61 ± 0.18. TEE per weight and PAEE per weight (PAEE/wt) was significantly negatively correlated with % body fat (r = - 0.626; r = - 0.400, respectively). These results suggest that increasing energy expenditure is important for achieving adequate body size. The PAEE/wt was most strongly correlated with physical fitness score (r = 0.680). The PAL was associated with percent time spent of inactivity ( r = -0.506), light-moderate activity ( r = 0.450) and vigorous activity ( r = 0.545). It was suggested that physically active lifestyle would be necessary for childhood health.

The purpose of this study was to examine the relationships between patterns of daily physical activities measured by accelerometer and physical activity level (PAL) in children. Firstly, activity intensities during incremental exercise were measured using a tri-axial accelerometer (HJA-350IT) in twenty one children aged 10.6 ± 0.9 years. As a result of receiver-operating characteristic curve analysis, the cut-off value for discrimination between walking and running activity was set at 7.2 METs of HJA-350IT. Secondly, total energy expenditure (TEE) in daily life was measured by doubly labeled water method, and durations of lifestyle, walking, and running activities were measured by the accelerometer in 6^th grade elementary school children (11 boys and 10 girls). TEE and physical activity level (PAL) were 2,021 ± 343 kcal/day and 1.56 ± 0.17, respectively. The average durations of lifestyle, walking and running activities were 188 ± 30 min/day (50.6 ± 6.0 %), 171±28 min/day (45.9 ± 5.0 %) and 13.3 ± 7.6 min/day (3.5 ± 1.8 %), respectively. The proportion of the duration of running activity was positively correlated with PAL (r = 0.615, p < 0.01), and the proportion of the duration of lifestyle activity was negatively correlated with PAL (r = -0.439, p < 0.05). There was no relationship between the proportion of the duration of walking activity and PAL (r = 0.300, n.s.). These results suggest that running activity is important to increase PAL more than ever in primary school children.

Introduction : To promote disease management in the community, general physicians should refer their patients to specialists in a timely and appropriate manner. In this study, we propose an indicator for evaluation of such referrals.
Methods : We analyzed all referrals in an urban clinic from September 1, 2011 to August 31, 2012. Symptoms and diagnoses documented by general physicians were collected from medical records, and the final diagnoses by specialists were collected from their reports. The symptoms and diagnoses were classified using the International Classification of Primary Care second edition (ICPC-2). Referral rates, hospitalization rates, and place of referral were analyzed.
Results : The average number of encounters in the candidate clinic was 1402 per month, and the mean number of referrals was 23 (1.6% of encounters). Of patients who received a referral, 6.75 (29.1%) were admitted to hospitals. The symptoms and diagnoses of the referred patients were distributed across all chapters (A to Z) of ICPC-2. Diagnoses of admitted patients included pneumonia (R81) (24%), urinary tract infection (U70 and U71) (9%), and acute gastroenteritis with dehydration (D73 with T11) (9%).
Conclusion : We identified the referral rates, hospitalization rates, and distribution of referral patients as indicators of the triage function of primary care physicians. These should be evaluated further as potential indicators of “the quality of medical care.”

　　Although axillary lymph node dissection (ALND) is conventionally indicated for metastasis in the sentinel lymph node (SLN), the omission of ALND is being discussed more often in recent years. However, because of the lack of specific guidelines, it is unclear which cases should be treated without ALND. In this study, we performed one-step nucleic acid amplification of the SLN with metastasis to determine the total tumor load (TTL), that is, the number of cytokeratin (CK) 19 mRNA copies. After ultrasonography (US) of ALN, the ultrasonographic findings were combined with TTL to rate SLN metastasis. In the rating, a total score was obtained by assigning 1 point each for (a) TTL of ≥15000 copies/μL, (b) US findings of a long-to-short LN diameter ratio of ≤2, and (c) US findings of no echogenic hilus. We then investigated the association between the total score and metastasis in the non-SLN. Results showed that while 87.5% (5/6) of patients with positive non-SLN scored ≥2 points, only 3.1% (1/34) of patients with negative non-SLN did so, suggesting that a total copy number of CK19 mRNA, US findings of a long-to-short LN diameter ratio, and the presence/absence of echogenic hilus are important predictors for non-SLN metastasis. This novel scoring system is expected to help determine which patients need ALND or what postoperative therapy is necessary.

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.

The Research Committee for the Meridian Point held its third workshop at the 57th Annual Meeting of the Japan Society Acupuncture and Moxibustion in Kyoto. Evaluations and reports were presented on two topics.

The first topic:Study of PSC in Japan and China.
1) Literature search on PSC in China (Wang):A literature search on major studies on PSC in China since 1979 was conducted. The report introduces the definition, characteristics and the mechanism of PSC development together with meridian phenomena.

2) PSC in reference to the ryodoraku (Morikawa):Development of the reactive ryodo point in patients under hemodialysis or those who have had a total gastrectomy and the cases in which reactive ryodo points or needle sensation developed when specific regions were stimulated were reported. The relationship between reactive ryodo points and PSC was examined.

3) The mechanism by which PSC develops (Yamada):Neurotransmitter substances are released from sensory nerve endings during acupuncture stimulation. Absorbed by lymphatic vessels, these substances stimulate the smooth muscle of these vessels, thus causing the PSC. Based on factors such as transmission velocity and inhibitory factors, the mechanism by which PSC develops was investigated.

The second topic:Specific locations of meridian points and clinical effects of the meridian point.
1) Anatomical regions for GB 30 huantiao (Ozaki and Matsuoka):In establishing the international standard for the meridian points under the guidance of WHO, both Chinese and Japanese proposals were listed for GB 30. The clinical effects-presumably emanating from the subcutaneous structure when acupuncture stimuli are applied to these points in a direction perpendicular to the body surface-were comparatively evaluated.

2) Transition in the regions and main effects of GB 30 (Sakaguchi):As stated above, both Japanese and Chinese definitions were cited in establishing the international standard for GB 30 under the guidance of WHO. By quoting the classic literature from China and Japan, changes in the regions and main effects of GB 30 were comparatively evaluated.