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In the high-dose methotrexate (HD-MTX) treatment of patients with osteosarcoma, a dose-adjustment method using individual pharmacokinetic parameters (PK method) to optimize the concentration was developed in 2010. However, to the best of our knowledge, the clinical usefulness of the PK method has not been verified until now. In the present retrospective study, to assess the usefulness of the PK method, the achievement rate of an effective and safe concentration range was evaluated. A total of 43 patients with osteosarcoma who were administered HD-MTX therapy (43 first courses and 200 subsequent courses) were enrolled. The MTX dose in the first course was determined using a common method based on body surface area (BSA method); a total of 8–12 g/m2 was administered as an initial dose for 1 h and a maintenance dose for 5 h. In the subsequent courses, loading and maintenance doses were calculated by the PK method based on the serum MTX concentration profile of the previous course. The effective target concentration during 1–6 h after the start of MTX administration was 700–1,000 µmol/l, whereas the target safe MTX level was less than 10, 1 and 0.1 µmol/l at 24, 48 and 72 h, respectively. Notably, the rate of achieving the effective target concentration was significantly higher when using the PK method as compared to that when using the BSA method. The achievement rate of the safe target concentration at 24, 48 and 72 h when using the PK method was significantly higher. Additionally, the incidence of abnormal laboratory values of aspartate aminotransferase and alanine aminotransferase was significantly lower when using the PK method. Therefore, the PK method was suggested to be very useful in HD-MTX therapy for patients with osteosarcoma. [ABSTRACT FROM AUTHOR]

Objectives: To compare the genetic and clinical factors that cause large interpatient variability and ethnic differences in warfarin efficacy, we investigated variations of the VKORC1, CYP2C9, and CYP2C19 genes in Japanese subjects. Furthermore, we evaluated the genetic variations and clinical data as contributors of variation in warfarin maintenance dose.Methods: Gene variations of VKORC1, CYP2C9, and CYP2C19 in 125 patients treated with warfarin and 114 healthy subjects were analyzed. The daily dose of warfarin, concentrations of S- and R-warfarin in plasma, and prothrombin time expressed as the international normalized ratio were used as the pharmacokinetic and pharmacodynamic indices. Data were evaluated by a multivariate analysis method.Results: Three missense mutations (47 G>C, 113 A>C, and 1338 A>G) in VKORC1 were newly identified in the Japanese population. The 113 A>C (Asp38Ser) variant decreased the warfarin dose requirement from 3.33 ± 1.54 mg/d (n = 122) to 1.5 mg/d (n = 1). The variants −1639 G>A in the 5′-upstream region, 1173 C>T in intron 1, and 1542 G>C in intron 2 were in complete linkage disequilibrium, and the frequency of the −1639 G>A variation was only 0.8%, which contrasts with the frequency (39.8%-45.8%) reported previously for white persons. The dose of warfarin was larger in the VKORC1 −1639 GA genotype group (4.55 ± 1.75 mg/d, P < .001) than in the −1639 AA group (2.94 ± 1.15 mg/d). The mean daily dose of warfarin was lower in subjects with CYP2C9*1/*3 (1.86 ± 0.80 mg/d, P = .007) than in subjects with CYP2C9*1/*1 (3.36 ± 1.43 mg/d). When the relative contributions of the VKORC1 variants, CYP2C9*2, CYP2C9*3, CYP2C19*2, and CYP2C19*3, as well as the clinical characteristics of the patients, diagnoses, and concurrent medications, were compared, the VKORC1 −1639 GA genotype group accounted for 16.5% and CYP2C9 variants accounted for 13.4% of variation in warfarin dose.Conclusion: The ethnic difference in warfarin maintenance dose was mainly dependent on the linked VKORC1 variants. Genotyping of −1639 G>A of the VKORC1 gene could be clinically important for predicting individual variability in anticoagulant responses to warfarin.Clinical Pharmacology & Therapeutics (2006) 80, 169–178; doi: 10.1016/j.clpt.2006.04.010 [ABSTRACT FROM AUTHOR]

The modified Attitudes Toward Health Care Teams Scale (mATHCTS) is a self-administered questionnaire with 14 items to assess participants’ perceptions of the impact of interprofessional collaboration. Its validity and reliability have been widely evaluated. The effect of interprofessional education (IPE) has been evaluated using changes in mATHCTS factor scores. However, several aspects of the scale require clarification: the difficulty of correctly answering each item; how well each item discriminates between respondents’ abilities; and whether the mATHCTS is better at identifying those with higher/lower abilities. We investigated the mATHCTS’s item characteristics such as difficulty, discrimination, and measurement accuracy using item-response theory (IRT) analysis. Health and welfare university students were administered a questionnaire prior to starting IPE in 2021. The results for 180 participants were analyzed based on IRT. The test-response (TRF) and test-information (TIF) functions, discrimination, and difficulty were estimated. All items’ discrimination and difficulty were adequate. The TRF, which shows the relationship between scores and ability, increased monotonically. The TIF, which shows the relationship between ability and measurement accuracy, decreased as the total score increased. The mATHCTS effectively assessed participants’ attitudes toward health care teams as a one-dimensional ability. The mATHCTS performed well in identifying participants with relatively low scores. [ABSTRACT FROM AUTHOR]

The presence of EGFR mutations is correlated with a positive therapeutic response to tyrosine kinase inhibitors; therefore, the accurate detection of EGFR mutations is crucial when deciding appropriate therapeutic strategies. Recently, the rapid and sensitive assay smart amplification process version 2 (SmartAmp2) was developed. However, this method can only detect one type of mutation in EGFR exon 19; therefore, we applied the PNA technology to the SmartAmp2 assay to develop PNA-clamp SmartAmp2 for the detection of many types of deletions in EGFR exon 19, in a single reaction. This new assay was evaluated using 172 clinical samples. Thirty-nine (22.7%) samples were found to have deletions by PNA-clamp SmartAmp2; whereas 30 (17.4%) and 38 (22.1%) tumors were found to have deletions by direct sequencing and PNA-enriched sequencing, respectively. Three cases, in which we detected mutations with PNA-clamp SmartAmp2, but not with direct sequencing, were treated with gefitinib, and all cases showed a partial therapeutic response. Using clinical samples, we demonstrated that PNA-clamp SmartAmp2 can detect various types of mutations in EGFR exon 19 in a relatively short time and with high sensitivity. This method detected small amounts of mutant DNA and identified patients for whom clinical information was previously unavailable from other tests. This test may contribute to the administration of efficient therapeutic strategies.

Gemcitabine(GEM)is the standard therapy for advanced pancreatic cancer. GEM-oxaliplatin (GEMOX) combination treatment has been reported to be superior to GEM alone in terms of clinical progression-free survival, but it is not the therapy of choice for pancreatic cancer. We report a case of advanced mucinous cystic neoplasm (MCN) of the pancreas with multiple hepatic metastases in a 39-year-old female. She was treated with 16 courses of GEMOX (GEM 1,500 mg/day at a rate of 10 mg/m2/min on the first day and oxaliplatin 150 mg/day at 100 mg/m2 on the second day, every 3 weeks). The pharmacist helped her to avoid severe side effects. When the hepatic metastases disappeared after 13 courses, the primary MCN was removed surgically after 16 courses of GEMOX treatment. No recurrence has been observed 22 months postoperatively. GEMOX might be effective for the treatment of MCN of the pancreas.

We have developed a patient case database at Gunma University Hospital. The transmission of the data contained in this database via the Internet is protected by SSH encryption technology. The database may also function as an education tool for medical and pharmaceutical students who can access this system through the Internet using a special browser system that we have also developed. In a survey questionnaire relating to our system conducted among graduate students, most responded positively to its usefulness as an opportunity for exposure to actual clinical practice. Because this system can introduce students to realistic and daily practices at hospitals, it might have a great impact on Japanese pharmaceutical education in universities or pharmaceutical colleges where early exposure to actual hospital practices is not appropriately included in the curriculum. In addition, our system will function to establish a mutual feedback system between hospitals and basic research institutions such as pharmaceutical universities.