Evaluation of the lifetime brain/central nervous system cancer risk associated with childhood head CT scanning in Japan.

The use of computed tomography (CT) scanning has increased worldwide over the decades, and Japan is one of the leading countries in annual frequency of diagnostic CT. Although benefits of CT scan are undisputable, concerns have been raised about potential health effects of ionizing radiation exposure from CT, particularly among children who are likely more susceptible to radiation than adults. Our study aims to evaluate the cumulated lifetime risk of the brain/central nervous system (CNS) cancer due to head CT examinations performed on Japanese children at age 0 to 10 years in 2012, 2015 and 2018. The frequency and dose distribution of head CT examinations were estimated based on information from recent national statistics and nationwide surveys. The lifetime risk attributable to exposure was calculated by applying risk models based on the study of Japanese atomic-bomb survivors. In contrast to the overall increasing trend, the frequency of childhood CT, especially at age < 5, was decreasing, reflecting a growing awareness for efforts to reduce childhood CT exposure over the past decade. In 2018, 138 532 head CT examinations were performed at age 0 to 10, which would consequently induce a lifetime excess of 22 cases (1 per 6300 scans) of brain/CNS cancers, accounting for 5% of the total cases. More excess cases were estimated among men than among women, and excess cases could emerge at relatively young ages. These results would have useful implications as scientific basis for future large-scale epidemiological studies and also as quantitative evidence to justify the benefits of CT vs risks in Japan.

Shadow pitching deviates ball release position: kinematic analysis in high school baseball pitchers.

BACKGROUND: Although shadow pitching, commonly called "towel drill," is recommended to improve the throwing motion for the rehabilitation of pitching disorders before the initiation of a throwing program aimed at returning to throwing using a ball, the motion differs from that of normal throwing. Learning improper motion during ball release (BR) may increase shoulder joint forces. Abnormal throwing biomechanics leads to injures. However, there has been no study of shadow pitching focusing on the BR position. The purpose of the present study was to evaluate the BR position and kinematic differences between shadow pitching and normal throwing. In addition, the effect of setting a target guide for BR position on throwing motion was examined in shadow pitching. METHODS: The participants included in this study were 20 healthy male students who were overhand right-handed pitchers with no pain induced by a throwing motion. Participants performed normal throwing (task 1), shadow pitching using a hand towel (task 2), and shadow pitching by setting a target of the BR position (task 3). A motion capture system was used to evaluate kinematic differences in throwing motions, respectively. Examination items comprised joint angles and the differences in BR position. RESULTS: BR position of task 2 shifted significantly toward the anterior, leftward, and downward directions compared with task 1. The distance of BR position between tasks 1 and 2 was 24 ± 10%. However, task 3 had decreased BR deviation compared with task 2 (the distance between 3 and 1 was 14 ± 7%). Kinematic differences were observed among groups at BR. For shoulder joint, task 2 showed the highest value in abduction and horizontal adduction among groups. In spine flexion, left rotation and thorax flexion, task 2 was significantly higher than task 1. Task 3 showed small differences compared with task 1. CONCLUSIONS: The BR position of shadow pitching deviated significantly in the anterior, leftward, and downward directions compared with normal throwing. Furthermore, we demonstrated that the setting of BR target reduces this deviation. Thus, the target of BR position should be set accurately during shadow pitching exercises in the process of rehabilitation.

How was cognitive behavioural therapy for mood disorder implemented in Japan? A retrospective observational study using the nationwide claims database from FY2010 to FY2015.

OBJECTIVES: To clarify the dissemination status of cognitive behavioural therapy (CBT) in Japan under the national health insurance scheme. DESIGN: Retrospective observational study. SETTING: National Database of Health Insurance Claims and Specific Health Checkups of Japan. PARTICIPANTS: Patients who received CBT under the national health insurance scheme from fiscal years (FY) 2010 to 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the change rate and the standardised claim ratio (SCR) for the number of patients receiving CBT and analysed the association between the CBT status and several regional factors. RESULTS: We found that (a) a total of 60 304 patients received CBT during the study period; (b) the number of patients receiving CBT was highest in the first year (-1.8% from FY2010 to FY2015); (c) the number of patients who received CBT per 100 000 population decreased (or remained at zero) in most prefectures (32 out of 47); (d) there was a maximum 424.7-fold difference between prefectures in the standardised claim ratio for CBT and (e) the number of registered CBT institutions was significantly associated with the number of patients who received CBT. CONCLUSIONS: The provision of CBT did not increase in the first 6 years (FY2010-2015) after its coverage in Japan's national health insurance scheme. Further studies including a questionnaire survey of registered CBT institutions are required to get more detailed information on the dissemination of CBT in Japan.

Expression levels of human P-glycoprotein in in vitro cell lines: correlation between mRNA and protein levels for P-glycoprotein expressed in cells.

The purpose of this study was to investigate the correlation between mRNA and protein levels for P-glycoprotein (P-gp) expressed in various cell lines to validate the estimation of P-gp activity from its mRNA levels. P-gp expression levels in various cell monolayers, normal, P-gp-induced, P-gp-highly induced, (multidrug resistance, MDR) MDR1-knockdown (A2-2) and MDR1-knockdown (B2-2) Caco-2 cells and MDCKII/MDR1 cells, were quantified by real-time quantitative polymerase chain reaction (PCR) and western blot analysis. Both mRNA and protein levels of P-gp were lowest in the MDR1-knockdown (B2-2) Caco-2 cells, followed by the MDR1-knockdown (A2-2) Caco-2, normal Caco-2, P-gp-induced Caco-2 and P-gp-highly induced Caco-2 cells, and highest in the MDCKII/MDR1 cells. Except for the MDCKII/MDR1 cells, the protein levels of P-gp in all Caco-2 cell lines showed a linear correlation with its mRNA levels; however, although the MDR1 mRNA level in MDCKII/MDR1 cells was much higher than in the P-gp-highly induced Caco-2 cells, the protein levels were almost the same in both cells. From these findings, it was suggested that P-gp activity in MDCKII/MDR1 cells could not be estimated from its mRNA levels.

Phase I and pharmacokinetic study of tegafur-uracil/leucovorin combined with 5-fluorouracil/leucovorin and irinotecan in patients with advanced colorectal cancer.

OBJECTIVES: FOLFIRI is one of the current standard first-line regimens for advanced colorectal cancer, but its administration is onerous. Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation. METHODS: Treatment consisted of infusional irinotecan (100 mg/m)/l-LV (15 mg/m) and a bolus injection of 5-FU (500 mg/m) on day 1, and oral UFT (300 mg as tegafur/m/d)/LV (75 mg/d) on days 1-5 (level 1), days 1-7 (level 2), or days 1-10 (level 3). Cycles were repeated every 14 days. After determination of the recommended UFT/LV administration period, irinotecan was dose-escalated (level 4: 125 mg/m; level 5: 150 mg/m). RESULTS: Nineteen patients were enrolled. One dose-limiting toxicity (DLT), grade 4 neutropenia lasting for > or =4 days was observed at level 2. At level 3, one DLT of treatment delay of > or =8 days occurred due to prolonged neutropenia, and 2 patients refused to continue the treatment because of prolonged grade 2 anorexia. Therefore, a 7-day administration of UFT/LV was recommended. No DLT was observed at levels 4 and 5. Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination. CONCLUSIONS: The recommended administration period was 7 days for oral UFT/LV, and the recommended dose of irinotecan was 150 mg/m. A phase II study is ongoing to validate the clinical outcome.

Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese.

OBJECTIVES: This study was performed to find the genetic factors predictive of clinical outcome to a 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Thirty-one patients with stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions (PVIs) of 5-FU (400 mg/m2/24 hours for days 1-5 and 8-12), CDDP (40 mg/m2/3 hours on days 1 and 8) and radiation (2 Gy/d on days 1-5, 8-12, and 15-19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1), multidrug resistant transporter MDR1/P-glycoprotein, and intercellular adhesion molecule-1, and in a circadian rhythm-relating gene, CLOCK. RESULTS: The CR rate depended on stage (P = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (P = 0.061). For stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5'-TSER, a 6 bp of 3'-TSUTR, and GSTP1-Ile105Val resulted in an extensively longer survival (P = 0.020), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinicopathologic characteristics. CONCLUSIONS: The prognostic index may allow predictions of the clinical outcome of a 5-FU/CDDP-based CRT in stage II/III ESCC patients.