PMDA, the Japanese regulatory agency, has worked for reinforcing and enhancing its post-marketing safety measures as stated in the second mid-term (FY 2009-2013) plan. MIHARI Project-Medical Information for Risk Assessment Initiative was started in FY 2009 to develop a new safety assessment system for post-marketing drugs using Japanese electronic healthcare data in PMDA. In the second mid-term, we examined characteristics of some electronic healthcare data available in Japan including, claims data, hospital information system data and Diagnosis Procedure Combination (DPC) data in order to make efficient use of those databases for the purpose of drug safety assessment. In addition, some pilot pharmacoepidemiological studies for risk assessment and drug utilization were conducted by use of these electronic healthcare data. Based on the accumulated findings, knowledge, and experiences from the pilot studies, we established the framework by FY 2013 to implement pharmacoepidemiology-based safety assessment in PMDA. In the third mid-term (FY 2014-2018), one of the important mission is to apply this framework into the current risk management process of drug safety. For that purpose, cooperation with other divisions of PMDA such as Office of Safety and Office of New Drug is a key. Simultaneously, we will work to establish an access to another database and novel pharmacoepidemiological methods using electronic healthcare data. A large-scale electronic health record database (MID-NET) as well as national claims database are expected to be an important database in the future activities of MIHARI Project. Furthermore, in April 2015, PMDA established new office focusing on Medical Informatics and Epidemiology for further promotion of electronic healthcare data utilization in Japan. In this article, we describe history and past activities of MIHARI Project followed by future challenges.

A man in his seventies sustained continuous bleeding from local recurrence at the residual rectal stump after Hartmann's surgery for rectal cancer. This patient declined chemotherapy and radiation therapy and conventional local anti-hemorrhagic treatments had not been effective. To assess the risk of Mohs' paste application to the rectal recurrence area, we checked the anatomical structures surrounding the application site by a CT study. In addition, two reasons we evaluated this Mohs' paste treatment to the rectal recurrence would be very safe were as follows: 1. A small amount of Mohs' paste was needed for the small rectal bleeding site. 2. Mohs' paste would not be applied to the rectum used for stoma. To avoid applying Mohs' paste to the neighbouring normal structures, a gauze coated with Mohs' paste was inserted into the rectum and placed only on the local recurrence site. Petroleum jelly was applied to the surface of normal rectal mucosa to prevent fixation. Bleeding and malodorous effusion decreased significantly without side effects such as pain, bleeding, or ulceration. Thereafter, additional fixation was not necessary. When all the other antihemorrhagic modalities are not available, Mohs' paste could be used for bleeding or an effusion from non-superficial tumors after a thorough risk assessment on this treatment.

The three‐dimensional digital substraction angiography (3D‐DSA) significantly elevated detection rate of intracranial small vessel aneurysms in recent years .It has become the novel gold standard diagnosing antracranial small vessel aneurysms .The present article made a review on 3D‐DSA value for diagnosis ,treatment and prognostic assessment of intracranial small vessel aneurysms .

A number of studies have shown that sleep disordered breathing (SDB) has a strong relation with obesity. The purpose of this study was to examine the effect of a short-term weight-loss program in obese men with SDB. In our 14-week weight-loss program, forty-one obese men (mean±SD, age ; 49.6±10.8 yr, body mass index ; 27.9±2.5 kg/m²) were assigned to 2 subgroups : diet only (DO ; n=19) and diet plus aerobic exercise (DE ; n=22). 2%, 3%, and 4% oxygen desaturation index (ODI) were measured by pulse oximetry before and after the weight-loss program. Weight and %fat significantly (p<0.05) decreased in the total subject pool consisting of DO plus DE (weight ; -8.4±3.5 kg, %fat ; -7.5±3.5%). 2%, 3%, and 4% ODI significantly decreased by -3.46±5.01 event/hour, -2.37±3.57 event/hour, and -1.99±2.84 event/hour, respectively. Significant correlations were found between 2%, 3%, and 4% ODI at baseline and changes of 2%, 3%, and 4% ODI during the weight-loss program (2% ODI ; r=0.48, 3% ODI ; r=0.51, 4% ODI ; r=0.67). Weight loss and %fat loss did not differ significantly between DO and DE (DO : -7.6±3.2 kg, -6.8±3.2%, DE : -9.2±3.7 kg, -8.1±3.7%). The increase in maximal oxygen uptake was slightly larger for DE (4.7±4.6 ml/kg/min) compared to DO (2.5±3.3 ml/kg/min), but there was no significant interaction. Changes of 2%, 3%, and 4% ODI did not differ significantly between groups. These results suggest that for obese men with SDB, the weight-loss program is an effective method, leading to improvement in SDB, although the combination of aerobic exercise to diet may not produce additional effects to SDB, compared with the diet only.

Objective : Serum albumin is important marker in all aspects of stroke care including rehabilitation. We examined the serum albumin level of stroke patients, and investigated the relation between their serum albumin level and their prognosis. Methods : The serum albumin levels of 295 patients enrolled from 2008 to 2014 were sequentially checked in our hospital and in subsequent rehabilitation hospitals. Functional outcome was measured by functional independence measure (FIM) at the time of discharge from the rehabilitation hospital. Results : In all types (cerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage (SAH)) of apoplexy, serum albumin levels were the highest at the time of admission, temporarily declined after admission, and almost recovered at the time of discharge. In SAH, the serum albumin levels deteriorated at a greater rate than in other types of stroke. In cerebral infarction and cerebral hemorrhage, the lowest serum albumin level was positively correlated with FIM at the time of discharge from the rehabilitation hospital (p<0.001). But, in SAH, there was no significant correlation between the lowest serum albumin level and FIM at the time of discharge (p=0.844). Conclusion : Our data suggest that serum albumin level is associated with the outcome of stroke patients, except for SAH patients. Serum albumin level should be one of the prognostic factors used in stroke patients, but we should consider that SAH patients are exceptional because of other neurological complications.

　　The impact of health guidance is recently becoming higher quality health services, and the next task is finding ways to establish a system that delivers higher quality services. Institutions that provide health guidance need to improve their services by analyzing the lifestyle habits and health examination results (e.g., BMI and blood pressure) of their clients. This study conducted simultaneous health and dietary habit checkups so that key elements for guidance (e.g., individual dietary habits, population characteristics, and main tasks) could be shared among guidance providers and be utilized for follow-up guidance. Most subjects were in their sixties or seventies, many of whom were diagnosed with obesity and/or dyslipidemia based on health examination results. Dietary habit evaluations revealed high intake of a main dish among both men and women. Intake of a main dish and a sweet snack was particularly high among men. Many subjects who excessively take in both a main dish and sweet snack were obese with a high percentage of saturated fatty acid-derived energy, indicating that this subgroup needs to be prioritized to receive guidance. Those with an appropriate intake of both a main dish and sweet snack might have consumed inadvisable levels of other dietary components, including luxury food items. However, an individual approach is also required to address the risk associated with intake of a low percentage of protein-derived energy. Similar studies in other populations and other communities are needed to assess whether the characteristics revealed in this study are specific to this particular population.

　　Muscle training is effective for improving motor function, although withdrawal within 3-6 months has been reported in many cases. Thus, we aimed to establish locomotion training recommended by the Japanese Orthopaedic Association and our own locomotive syndrome prevention training (herein after collectively referred to as “locomotive training”) as a daily routine. Subjects were 30 participants of a training course held in 2014. Nine sessions (including 1 follow-up session) were organized to repetitively teach the importance of locomotive training; participants were instructed to record daily training activities during the course. Duration of oneleg standing balance with eyes open was measured each session so that participants were aware of the effects of the training. At the time of the last session of the course and at the follow-up session, 90% and 83% of participants completed home training twice or three times a week, respectively. Participants reported physical changes such as amelioration of knee pain and ability to put on a Wellington boot while standing on one leg. Also, physical fitness tests performed before and after the course showed significant improvement on the Timed Up and Go test, 30-s chair stand test, and one-leg standing with eyes open after the training course. Furthermore, the locomotive syndrome test resulted in a decrease in the number of participants who were judged to have a possibility to suffer from locomotive syndrome. Taken together, introducing a cycle comprising the three components of motivation-building through lectures, increasing awareness by recording performance, and awareness of the training effect by measuring duration of one-leg standing balance contributed to training continuity and consequent improvement in motor function.

Objective: Atopic dermatitis (AD) is one of the known risk factors for Staphylococcus aureus infection. The authors report the case of a patient with cervical spondylosis and AD who developed delayed surgical site infection after posterior cervical instrumented surgery.Patient: A 39-year-old male presented to our hospital with paralysis of the left upper extremity without any cause or prior injury. He had a history of severe AD. We performed C3–C7 posterior decompression and instrumented fusion based on the diagnosis of cervical spondylotic amyotrophy. One year after surgery, his deltoid and bicep muscle strength were fully recovered. Nevertheless, his neck pain worsened 2 years after surgery following worsening of AD. One month after that, he developed severe myelopathy and was admitted to our hospital. Radiographic findings showed that all the screws had loosened and the retropharyngeal space had expanded. Magnetic resonance imaging and computed tomography showed severe abscess formation and destruction of the C7/T1 vertebrae.Result: We diagnosed him with delayed surgical site infection. Methicillin-resistant Staphylococcus aureus was identified on abscess culture. The patient responded adequately to treatment with antibiotic therapy and two debridements and the infection subsided.Conclusion: We should consider the possibility of delayed surgical site infection when conducting instrumented spinal surgery in patients with severe AD.