Plerixafor is an expensive medicine priced at approximately JPY580,000/24 mg bottle. Hence, from a medical and economic viewpoint, it is essential that plerixafor is administered at the appropriate timing to patients who require it. In this study, we conducted cost-effectiveness analysis, with a focus on situations in which plerixafor was administered from day four after starting administration of the G-CSF preparation or in which plerixafor administration was determined based on the CD34⁺ cell count.

We retrospectively reviewed the medical records of patients with malignant lymphoma or multiple myeloma, who underwent autologous peripheral blood stem cell collection in this hospital between March 2017 and April 2018. Decision tree algorithms were used to analyze cost-effectiveness.

The expected cost of collecting CD34⁺ cells (2 × 10⁶ cells/kg) within two days of apheresis was approximately JPY1.2 million, when plerixafor was administered from day four regardless of the CD34⁺ cell count. However, the expected cost of that was approximately JPY1 million, when plerixafor administration was determined based on the CD34⁺ cell count. Furthermore, even when the parameters affecting the expected cost, such as the drug price of plerixafor, were changed, the expected cost of collecting the CD34⁺ cells when plerixafor administration was determined based on the CD34⁺ cell count was lower than that when plerixafor was administered regardless of the CD34⁺ cell count.

Percutaneous coronary intervention (PCI) sometimes causes ischemic heart disease (IHD). Statins have a recovery effect on vascular endothelial cell function, and it is suggested that statin administration during PCI may help prevent IHD. However, this has not been validated by a large-scale clinical study. Therefore, we evaluated the relationship between statin administration during PCI and cardiovascular events by analyzing the national claims database, which covers most residents in Japan. We analyzed patients who underwent PCI, who were diagnosed with angina or myocardial infarction, and had been continuously administered statin. Among these patients, we assigned patients who were administered statins for 7 days before the procedure to the exposure group and those who were not to the non-exposure group. After matching patients’ backgrounds using two statistical methods, we compared the incidence of IHD, atrial fibrillation, bleeding, and mortality after the procedure. The results indicated lower incident risks of IHD and atrial fibrillation after the procedure in angina patients in the exposure group and lower mortality after the procedure in myocardial infarction patients in the exposure group. These results suggest that perioperative treatment with statin during PCI could improve PCI prognosis.

Albumin-bound paclitaxel (Abraxane^®) is a lyophilized preparation that takes time to dissolve. Previously, we used a metal needle for dissolving Abraxane^®. We then transitioned to a side hole-type plastic needle to prevent accidental needle-stick injuries. There is no literature regarding the ideal needle type, according to the material it is made of, for dissolving Abraxane^®, and the effect on the characteristics of Abraxane^® after dissolving with each needle is unknown. Therefore, we investigated the efficacy of the plastic needle for dissolving Abraxane^®. The formulation was dissolved in three ways: by injecting saline for 30 s with a metal needle (M30s), injecting saline for 15 s with a plastic needle (P15s), and injecting saline for 30 s with a plastic needle (P30s). Each group was kept at rest for 5 min after saline infusion, and then the dissolution time was estimated. The median dissolution time was 82.5 (15 - 210) s for M30s, 75 (30 - 135) s for P15s, and 45 (15 - 120) s for P30s. P30s had a significantly shorter dissolution time than M30s (P < 0.01) and P15s (P < 0.05). There was no significant difference in the dissolution time between M30s and P15s; however, P15s tended to have a shorter dissolution time than M30s. We measured the diameter of Abraxane^® particles after dissolving with each needle and found that the diameter was almost the same. Therefore, a side hole-type plastic needle might reduce the dissolution time compared with a metal needle without affecting the characteristics of Abraxane®.

Warfarin suppresses the formation of coagulation factors by inhibiting vitamin K. This action is enhanced by the antibiotics on the intestinal flora. The intestinal flora of children matures as they grow and the effects of antibiotics on warfarin anticoagulation may change with the growth of children. In this study, an alteration of prothrombin time-international normalized ratio (PT-INR) before and after antibiotic treatment in children younger than 4 years old receiving warfarin was reviewed retrospectively using medical charts of patients from January 2013 to March 2019. Records for 12 patients (median age; 2 years and 3 months) receiving 14 therapeutic courses of antibiotics under warfarin treatment were included for analysis. All of the 12 cases showed PT-INR prolongation after antibiotic administration, and the median (range) rate of change in PT-INR was 1.25 (1.04 to 2.25). Four patients reduced their warfarin dosage due to antibiotic administration. The incident of PT-INR prolongation tended to be higher in younger patients. Other patient backgrounds such as the types of antibiotics, delivery methods and the status of nutrition, which impact on the intestinal flora, were not associated with the PT-INR prolongation by antibiotic treatment. This study was a small case series and further investigation is required to clarify the factors of the change in PT-INR and optimize the warfarin dosage for children during antibiotic treatment.

In the administration of vancomycin (VCM) for emergency and critically ill patients, insufficient VCM trough concentrations were occasionally observed. We performed this study to identify independent risk factors related to VCM low trough concentrations (< 10 µg/mL) for emergency and critically ill patients. Forty-six patients treated with VCM based on therapeutic drug monitoring guidelines between January 2013 and December 2015 were enrolled. Risk factors associated with VCM low trough concentrations were examined by comparing various factors of patients. Multiple regression analysis showed that the initial trough concentrations of VCM were related to age, body weight, estimated glomerular filtration ratio (eGFR (mL/min/1.73m²)), presence of trauma, average urine volume, and daily dose of VCM. Additionally logistic regression analysis identified eGFR (adjusted odds ratio = 1.044, 95％ confidence interval = 1.005 - 1.085, P = 0.028), average urine volume (adjusted odds ratio = 1.066, 95％ confidence interval = 1.018 - 1.116, P = 0.007), and daily dose of VCM (adjusted odds ratio = 0.873, 95％ confidence interval = 0.764 - 0.998, P = 0.046) as being an independent risk factor associated with VCM low trough concentrations. Therefore, determining the daily dose of VCM in consideration of the eGFR and the average urine volume may prevent VCM low trough concentrations. Also, it is important to actively monitor since two factors change over time.

Several studies have described factors such as augmented renal clearance that lead to low trough levels of vancomycin (VCM) in patients in the intensive care unit (ICU). In contrast, few studies have examined such factors in patients admitted to general wards. Therefore, the purpose of this study was to clarify factors associated with low VCM trough levels in general ward inpatients. We conducted this retrospective study on patients who had been monitored for changes in VCM blood levels at Gunma University Hospital for a 5-year period from January 1, 2014. Children under 18 years of age, pregnant women, and patients receiving renal replacement therapy were excluded; in total, 217 patients were examined. Subjects were divided into two groups: a low-level group comprising 88 patients with an initial trough concentration of less than 10 µg/mL and an optimal group comprising 129 patients with a trough concentration of 10 - 20 µg/mL. Of the 177 general ward patients other than ICU, 74 were in the low-level group and 103 were in the optimal group. Multivariate logistic regression analysis revealed that low fluid volume, febrile neutropenia (FN), and non-sepsis were mainly independent risk factors for reduced trough levels. We believe that FN is one of the important risk factors for low trough levels, especially in general ward patients rather than ICU.

High-dose melphalan is one of the most active agents for the treatment of multiple myeloma but is associated with numerous toxicities, including myelosuppression, mucositis, diarrhea, nausea, and vomiting. This study aimed to retrospectively examine the relationship between melphalan exposure and adverse events in 19 Japanese patients with multiple myeloma receiving high-dose melphalan. The area under the curve (AUC) using the population pharmacokinetic model derived parameters was estimated. The mean (SD) estimated total and unbound melphalan AUC were 10.7 (1.6) mg･h/L and 2.3 (0.3) mg･h/L, respectively. The total AUC and unbound AUC were significantly higher in patients with severe diarrhea (≥ grade 3). Thus, high-dose melphalan exposure is associated with the risk of toxicity in Japanese patients with multiple myeloma. The estimated AUC may be able to predict serious toxicities among patients treated with high dose melphalan.