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.

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.

From 1998 to 2001, using questionnaires, we surveyed the use of travel vaccines among Japanese expatriates in developing countries. The percentage of those using more than one type of travel vaccine before departure increased significantly (45.6% in 1998 to 53.4% in 2001 (p<0.001)). In regions such as tropical Africa and South Asia, vaccination rates were high. But the increase was most noticeable in East Asia, the Middle East, and Latin America. Vaccinations against hepatitis A, hepatitis B, and tetanus were high throughout the developing countries. Vaccinations against yellow fever and Japanese encephalitis were high in endemic regions. Vaccination rates were slightly higher for typhoid fever in South Asia and tropical Africa than that in other areas. Vaccination rates for cholera, however, showed yearly declines. These trends seem to reflect a growing awareness among expatriates of the benefits of travel vaccines. Even so, nearly half of those living the countries have not received sufficient vaccination, indicating a need for further education.

Psoriasis vulgaris is a chronic disease in which demarcated erythema and rashes with silvery-white scales occur at various sites, and it is sometimes intractable. We report that Kampo medicines are effective in the treatment of psoriasis vulgaris. An 83-year-old woman suffered from erythema with pruritus and strong redness on the trunk and upper limbs and she visited the dermatology department. She was diagnosed with psoriasis vulgaris and started treatment with betamethasone ointment. However, her symptoms did not improved, and she requested Kampo medicine treatment. After the administration of maorenshoshakushozuto, erythema gradually improved. Maorenshoshakushozuto is effective for the dermatological diseases with pruritus and strong redness like psoriasis vulgaris.

Background: Recent animal studies have suggested the role of GABA type A (GABA- A ) receptors in salivation, showing that GABA- A receptor agonists inhibit salivary secretion. This study aimed to evaluate the effects of propofol (a GABA- A agonist) on salivary secretions from the submandibular, sublingual, and labial glands during intravenous sedation in healthy volunteers. Methods: Twenty healthy male volunteers participated in the study. They received a loading dose of propofol 6 mg/kg/h for 10 min, followed by 3 mg/kg/h for 15 min. Salivary flow rates in the submandibular, sublingual, and labial glands were measured before, during, and after propofol infusion, and amylase activity was measured in the saliva from the submandibular and sublingual glands. Results: We found that the salivary flow rates in the submandibular, sublingual, and labial glands significantly decreased during intravenous sedation with propofol (P < 0.01). Similarly, amylase activity in the saliva from the submandibular and sublingual glands was significantly decreased (P < 0.01). Conclusion It can be concluded that intravenous sedation with propofol decreases salivary secretion in the submandibular, sublingual, and labial glands via the GABA- A receptor. These results may be useful for dental treatment when desalivation is necessary.

Objective: This study aimed to clarify the details of inpatient cancer rehabilitation interventions provided by designated cancer hospitals in Japan. Methods: This questionnaire-based survey asked specialists regarding the outline of their facilities’ inpatient cancer rehabilitation, Dietz classification, disease, and intervention details. Results: Restorative interventions were the most common, and the most common cancer was lung cancer followed by colorectal cancer; hematologic malignancy; gastric cancer; and liver, gallbladder, and pancreatic cancer. Intervention proportions for colorectal and gastric cancer were significantly higher in general hospitals than in university hospitals and cancer centers; in contrast, those for hematological malignancy were significantly higher in university hospitals than in general hospitals. For bone and soft tissue sarcomas, intervention proportions in cancer centers were significantly higher than those in university and general hospitals; and for oral, pharyngeal, and laryngeal cancers, they were significantly higher in university hospitals and cancer centers than in general hospitals. The most common intervention was walking training, followed by resistance training, basic motor training, activities of daily living training, and respiratory rehabilitation. Respiratory rehabilitation was performed significantly more frequently in university and general hospitals than in cancer centers.Conclusion: The diseases had differed according to the characteristics of the facilities, and the interventions were considered accordingly. In future, it will be necessary to verify the effectiveness of inpatient cancer rehabilitation according to facility characteristics and to disseminate information on inpatient cancer rehabilitation.

In accordance with the new model-core-curriculum for medical education, the current status of education about the science of radiation health was surveyed in all medical schools in Japan. Among the four learning points related to the “Biological effects of radiation and radiation hazards” , about half of the schools covered issues on “radiation and human body” and the “effect of medical radiation exposure” in one, or less than one, 60-minutes class, but did not touch on “radiation risk communication” and “radiological disaster medicine” . A significant deviation of human resources was also observed between schools. Learning tools such as presentation files and video content were preferred as education support materials. Therefore, development and distribution of the learning tools, especially in “radiation risk communication” and “radiological disaster medicine” , may be a first step to promoting high-quality education on the science of radiation health risk in each school’s curriculum.