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.

PURPOSE: Furcation involvement in the molars is difficult to treat, and has been recognized as a risk factor for tooth loss. Although periodontal regenerative therapies, including guided tissue regeneration and various types of bone grafts, have been applied to furcation defects, the effects of these treatments are limited, especially in large class III furcation defects. The purpose of this pilot study was to investigate the effect of reciprocal autologous root transplantation on periodontal wound healing and regeneration in class III furcation defects in dogs. METHODS: Furcation defects (7 mm wide and 6 mm high) were surgically created after root separation of the unilateral third and fourth premolars in 4 dogs. Eight furcation defects were randomized to receive either reciprocal autologous root transplantation (test) or no further treatment (control). In the test group, the mesial and distal roots were transplanted into the distal and mesial extraction sockets, respectively. The animals were sacrificed 10 weeks after surgery for histologic evaluation. RESULTS: The healing pattern in the control group was characterized by extensive collapse of the flap and limited periodontal regeneration. New bone formation in the test group (3.56±0.57 mm) was significantly greater than in the control group (0.62±0.21 mm). Dense collagen fibers inserting into the residual cementum on the transplanted root surfaces were observed in the test group. Slight ankylosis was observed in 2 of the 4 specimens in the test group on the mesiodistal sides where the root-planed surfaces faced the existing bone. Root resorption (RR) was detected in both the control and test groups. CONCLUSIONS: Within the limits of this study, it can be concluded that reciprocal autologous root transplantation was effective for bone regeneration in class III furcation defects in dogs. However, further studies are required to standardize the approach in order to prevent unwanted RR prior to clinical application.
Animals ; Ankylosis ; Bicuspid ; Bone Regeneration ; Collagen ; Dental Cementum ; Dogs ; Furcation Defects* ; Guided Tissue Regeneration ; Models, Animal ; Molar ; Osteogenesis ; Periodontal Diseases ; Periodontal Ligament ; Pilot Projects ; Regeneration ; Risk Factors ; Root Resorption ; Tooth Loss ; Transplants ; Wound Healing* ; Wounds and Injuries*

Methods: In total, 76 patients participated in this case-control study (neurologically symptomatic adjacent canal stenosis, n=33; neurologically asymptomatic cases at follow-up, n=43). Their risk factors during surgery and magnetic resonance (MR) images before the surgery and at follow-up were evaluated. Data from the two groups (n=25 each) were matched using propensity scores for age, sex, time to MR imaging at follow-up, surgical procedure, and LF hypertrophy in adjacent segments before the surgery and analyzed. Results: Compared with the asymptomatic group, the symptomatic adjacent canal stenosis group had a significantly larger LF area/spinal canal area in the spondylolisthetic segments before the surgery. During the follow-up periods (in months), they had a larger LF area/ spinal canal area in the adjacent segments: the two values were significantly correlated. The sensitivity, specificity, and positive and negative predictive values for determining symptomatic adjacent canal stenosis were high compared with on the cutoff value for the LF area/spinal canal area at the spondylolisthetic segments before the surgery. These results were the same after matching. Conclusions Symptomatic adjacent canal stenosis is mainly caused by LF hypertrophy. Ligamentous stenosis at the spondylolisthetic segments before fusion surgery might be strongly associated with symptomatic adjacent canal stenosis at follow-up.

Methods: The study enrolled a total of 237 older female patients: 50 and 187 patients had prevalent morphometric VFs (VF [+] group) and nonprevalent morphometric VFs (VF [−] group), respectively. The time to subsequent clinical VFs after fusion surgery was compared between the two groups using the Kaplan-Meier method. Moreover, 40 and 80 patients in the VF (+) and VF (−) groups, respectively, were analyzed and matched by propensity scores for age, follow-up duration, surgical procedure, number of fused segments, body mass index, and number of patients treated for osteoporosis. Results: Kaplan-Meier analysis indicated that the VF (+) group had a higher incidence of subsequent clinical VFs than the VF (−) group, and Cox regression analysis showed that the presence of prevalent morphometric VFs was an independent risk factor for subsequent clinical VFs before matching. Kaplan-Meier analysis demonstrated comparable results after matching. Conclusions The presence of prevalent morphometric VFs may be a risk factor for subsequent clinical VFs in older women with degenerative spondylolisthesis who underwent short-fusion surgery.

Objective: Avoiding injection incompatibilities is important. At our hospital, pharmacists are present at the intensive care unit (ICU),where they manage drip lines and use a lookup table for injection incompatibilities. We assessed the risk of injection incompatibilities in the ICU and the contribution of pharmacists toward their avoidance.Methods: We investigated the number of injections and main drip lines used for outpatients admitted to the general ward and ICU from an emergency setting. We further investigated inappropriate drip line conditions, subsequent interventions by pharmacists, and the actual number of injection incompatibilities. The investigation period lasted 1 year from April 2016 onward.Results: The number of injections and drip lines used in the ICU was significantly higher than that used in the general ward (p<0.001). Patients in the ICU received multiple continuous intravenous injections from one drip line despite the number of main drip lines being high. Even using the lookup table, 78.3% inquiries made by nurses were related to injection incompatibilities. Fourteen inappropriate drip lines selected by nurses were associated with a risk of injection incompatibility; these occurred during the absence of pharmacists and involved a combination of continuous intravenous injections to be administered from a side line. Subsequently,pharmacists intervened and avoided injection incompatibilities. There was no report of injection incompatibilities in the ICU.Conclusion: At ICU, the risk of injection incompatibilities is high and it is necessary to focus on the combination of injections to be administered from main drip lines and side lines as well as incompatibilities of multiple continuous intravenous injections to be administered from side lines. A lookup table is insufficient to avoid injection incompatibilities. Therefore, pharmacists can contribute to avoiding injection incompatibilities by maintaining constant presence in the ICU, designing drip line layouts, and proposing line selections.