Background In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear. Objective The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy. Methods This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a “Normal” and a “Delayed” group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups. Results A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, P = 0.004, and OR = 4.33, P = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, P = 0.006, and AOR = 8.11, P = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment. Conclusions and Relevance Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.

When undergoing 90 Y-ibritumomab tiuxetan (90Y-IT) treatment, patients are discharged from hospital soon after initiation of treatment and followed up as outpatients. Thus it is important to apprise patients of the safety information regarding 90Y-IT treatment. However, studies investigating the safety of 90Y-IT in real-world clinical practice are lacking. We sought to investigate the adverse events arising from 90Y-IT administration to patients in our hospital. Patients who received 90Y-IT treatment at Hiroshima University Hospital from April 2010 to December 2014 were eligible for this study. The medical records of the patients were reviewed retrospectively. Eleven patients (median age, 65 years) were enrolled. Patients were classiˆed into 3 groups according to the number of prior regimens: 1, 2 3, or ＞ 3, consisting of 5, 4, and 2 patients, respectively. The number of patients with induced grade 3 and 4 hematotoxicity, respectively, was 5 and 0 for leukocytopenia, 3 and 2 for neutropenia, and 3 and 2 for thrombocytopenia. The median nadir time was 37 d for leukocytopenia, 37 d for neutropenia, 36 d for thrombocytopenia, and 43 d for anemia. Patients with 2 or more prior regimens tended to experience grade 3 or 4 hematotoxicity more frequently than those with 1 prior regimen. In conclusion, we showed that hematotoxicity is a major adverse event of 90Y-IT treatment and that the nadir time is later than that with conventional anticancer agents. Medical staŠ, including pharmacists, should direct attention to the initial symptoms of hematotoxicity, especially in those patients who have received several prior regimens.

Background: Instillation of sterile graded talc in the pleural space is performed to prevent reaccumulation of malignant pleural effusion after drainage. Talc is thought to encourage pleural adhesions as part of the repair process by provoking inflammation, suggesting that adhesions are less likely to form in patients taking corticosteroids or other drugs with anti-inflammatory effects. However, the relationship between steroid therapy and pleurodesis efficacy remains unclear. Case presentation: We report the outcomes of six patients who underwent pleurodesis at Hiroshima University Hospital while being treated with systemic steroid therapy for non-cancer-related illnesses. Talc pleurodesis was successful at the first attempt in five of the six patients. The five successful cases were receiving low-dose oral prednisolone or methyl prednisolone (range, 1-20 mg/day) at the time of pleurodesis and had serum albumin levels ranging from 2.2 to 3.0 g/dL. In contrast, the patient in whom pleurodesis was unsuccessful was receiving a higher dose of prednisolone (40 mg/day) intravenously and had a relatively low serum album level (1.7 g/dL). Conclusions: The outcome of pleurodesis may be affected by the dose and/or route of systemic steroid therapy. Further analysis with more patients will be necessary to clarify the relationship between steroid dosage and talc pleurodesis success rate.

Ward-based pharmacy interventions are effective for proper medical management. In Hiroshima University Hospital, clinical pharmacists participate in almost all inpatient cases. In addition to the regular clinical pharmacists for the 4 wards, a supervising pharmacist was allocated additionally to overview and to help them as a trial. The supervising pharmacist reviewed the prescriptions and assignments of physicians, and ordered authorized prescriptions. As a result, the number of drug-related incident reports for two months decreased from 17.3 to 3.0, compared to the number of reports of the past three years. The revision of prescriptions by a supervising pharmacist assembly might reduce the inspection workload and number of inquiries by the central pharmacy. On the questionnaire, 94％ of physicians expressed a decreased burden during this trial. Also a decreasing trend of overtime work of nursing staff was reported. Therefore, the allocation of a supervising pharmacist may contribute to medical safety and efficient work management of medical staff who are concerned with drug therapy.

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