Background : The safety of newly approved drugs must be assessed using postmarketing surveillance data. One of the difficulties in assessing the hazard rates of adverse events induced by the anti-cancer drug TS-1 was that the time to event was not exactly identified due to the interval censoring. Most patients were outpatients who underwent clinical laboratory tests almost periodically at 1- or 2-week intervals and therefore, the occurrence of an adverse event was confirmed at the time of testing days after the event occurrence.
Objective : The purpose of this study was to propose a new model of hazard functions for each of 4 items of adverse event induced by TS-1 using post-marketing surveillance data considering the interval censoring.
Methods : The data obtained from 3, 294 patients with gastric cancer who received an initial 4-week course of therapy with TS-1 administered orally twice a day, followed by a 4-week second course with a 2-week no-treatment period after the initial course, were used to estimate hazard functions. Four items of adverse event--hemoglobin level (HB), white blood cell (WBC), neutrophil (NEUT) and platelet counts (PLT) --were graded, respectively, using the criteria established by the Japan Society of Clinical Oncology. Slip-mixed log-logistic and slip-mixed Weibull models were proposed as candidate models for estimating hazard functions. The goodness of fit of the two candidate models was evaluated by applying them to the above-mentioned data. The hazard functions for each of 4 items were assessed using the model with the better fit.
Results : The initial occurrence of adverse event was shown to follow the slip-mixed log-logistic model for each of 4 items. Although most events occurred early on in the initial course of therapy, a small peak in HB was also observed in the second course, while no such peak appeared for the other items.

In April 2014, a Letter of Rapid Safety Communication was issued, because 21 fatalities following administration of paliperidone palmitate (PP) were reported over a 5-month period since its launch in November, 2013. At the Department of Pharmacy of Hakodate Watanabe Hospital (our hospital), we established criteria for the use of long-acting antipsychotic injections (LAIs) when we began to prescribe LAIs at our hospital and shared information on the use of LAIs with pharmacists at community pharmacies by placing seals in medication notebooks. In March 2014, we conducted a questionnaire survey of pharmacists at 223 community pharmacies in Southern Hokkaido to compared the investigation items by the percentage of prescriptions filled in by the department of psychiatry among all the prescriptions dispensed by the pharmacies. The pharmacists who answered that injectable drug use information and seals for medication notebooks were necessary accounted for 75.8% and 74.2% of the responders, respectively. On the other hand, the percentages comprising the acquisition rates of information on injectable drug use and information on the injectable drugs used were low with 12.1% and 7.6% respectively. Also, a significant difference was seen in the recognition of LAI use in the comparison by the percentage of prescriptions filled in by the department of psychiatry among all of the prescriptions dispensed by the pharmacies (p＝0.001). Our results show that collaboration between hospital pharmacists and community pharmacists is necessary to ensure the safe use of LAI.

The purpose of the present study was to examine the importance of the agonist muscle activity of the post-impact 30 ms phase during drop jump (DJ) for effective rebound performance by comparing those of sprint runners and swimmers. The eight sprint runners (SPRINT) and twelve swimmers (SWIM) were participated in this study. They performed DJ from a 0.3-m height box with maximal rebound efforts. Electromyograms (EMG) of the lower leg muscles (medial gastrocnemius [MG], soleus [SOL] and tibialis anterior [TA]), and vertical ground reaction force together with kinematic data were measured simultaneously during DJ. In addition, the onsets of fascicle stretching of the MG and SOL muscles were measured by using high-speed ultrasonography (521Hz) during DJ. The onsets of the fascicle stretching of SOL during DJ were not significantly different between SPRINT and SWIM (15 ± 7 ms and 16 ± 6 ms, respectively). During DJ, SPRINT showed onset of the SOL EMG before the ground contact (-26 ± 19 ms). Meanwhile, SWIM showed the onset of the SOL EMG after the ground contact of DJ (16 ± 19 ms). These results suggest that the SOL muscles for SWIM cannot be fully-activated during the braking phase. Consequently, the rate of force development during the braking phase of DJ and subsequently rebound height could be reduced in SWIM.

Objective : The incidence rate is used frequently in drug safety assessment. The incidence rate of adverse events is defined as the number of patients experiencing a certain adverse event divided by the number of patients administered a drug in spite of duration of administration (observation). In post-marketing surveillance, the duration of administration (observation) typically differs by patient and most of the analyses fail to take into account the differences in duration of administration (observation). Therefore, we investigated the usefulness of hazard functions in a drug safety assessment using the interim results from Clinical Experience Investigation of the oral anticancer drug, TS-1.
Methods : About three thousand patients with gastric cancer were enrolled in this Clinical Experience Investigation. TS-1 was administrated orally twice daily. One course consisted of consecutive administration for 28 days and 14 days rest. Administration was repeated in two courses. Hematological measurements, stomatitis, anorexia, nausea/vomiting, diarrhea, malaise were analyzed. Adverse events were evaluated in accordance with the criteria of the Japan Society for Cancer Therapy, which were established based on criteria established by the WHO. Time to occurrence of an adverse event was calculated from the first day of administration until the adverse event was first observed. Hazard functions were estimated by smoothing methods using kernel functions.
Results : The occurrence of adverse events using smoothed hazard functions had one peak around 10 days in the first course and decreased by administration rest. With the resumption of administration, the occurrence increased again. The occurrence in the second course were less than that of the first course.
Conclusion : The occurrence peaks of adverse events were estimated graphically by smoothed hazard functions. We conclude that hazard functions are useful as an analytical tool in drug safety assessment.

The purpose of the present study was to examine characteristics of muscle anatomical cross-sectional area (CSA) for different regions from proximal to distal parts of each muscle of the hamstring muscles in high-level sprinters, and to examine the relationship with those and the sprint performance. The CSA of the semitendinosus (ST), semimembranosus (SM), biceps femoris long head (BFL) and biceps femoris short head (BFS) at the four different region of hamstring muscles for twenty sprinters (SPRINT) and twenty healthy male control subjects (CTRL) were measured by using B-mode ultrasonography. The measured regions were divided into four parts from proximal to distal parts (PRO1, PRO2, DIS2, DIS1). The results clearly showed that absolute CSA values in distal parts for all muscles together with PRO2 in ST were greater in SPRINT than in CTRL. When relative CSA values to the entire hamstrings muscles in each region were compared, only relative CSA at PRO1 in ST was greater in SPRINT than in CTRL, conversely, that at proximal regions in BFL and distal regions in BFS were smaller in SPRINT. In the relationships with sprint performance, the CSAs at PRO1 and PRO2 in ST and at PRO1 in SM were only related negatively. These results suggest that distal parts of hamstring muscles for SPRINT may be characteristics for sprint runners. However, the movements related to the specific hypertrophy (PRO1 and PRO2 in ST, PRO1in SM) may play important roles of the improvement of their sprint performance.