ABSTRACT
Drug therapy is necessary to treat metastatic and recurrent breast cancer. In Japan, two types of cyclin-dependent kinases (i.e., CDK4/6 inhibitors) are covered under the national healthinsurance system: palbociclib (since December 2017) and abemaciclib (since November 2018). Although there are many reports on the use and side effects of palbociclib in clinical practice, there are few such reports on abemaciclib. Therefore, we investigated the rate of neutropenia and associated background factors in patients taking abemaciclib. Of the 39 patients taking abemaciclib recruited for the study, 22 satisfied the inclusion criteria. Of these, 7 developed Grade 3 or higher neutropenia and had a significantly lower body weight and body mass index (BMI). Furthermore, the white blood cell and neutrophil counts before administration were significantly lower in the expression group compared with the non-expressing group. To predict the development of Grade 3 or higher neutropenia, the receiver operating characteristic (ROC) curve was used to calculate a BMI cut-off value of 23.9 (specificity 85.7%, sensitivity 73.3%, area under the ROC curve 0.80). Based on this cut-off value, BMI was divided into two groups (<23.9 and ≥23.9) and Fisher's exact test was performed. Patients with a low body mass index were more likely to develop Grade 3 or higher neutropenia as a result of increased dosage per kilogram body weight, while among patients with BMI < 25, those with BMI < 23.9 were at high risk of developing Grade 3 or higher neutropenia. Accordingly, caution is required in the treatment of such patients.
ABSTRACT
In recent years, the problem of antimicrobial resistance (AMR) from inappropriate use of antimicrobial drugs has emerged, and a plan to counter AMR has been formulated. From October 2017, our hospital started interventions to guide prescribing physicians in the proper use of intravenous antibiotics for patients requiring said treatment for more than 15 days. In the present study, we investigated the status of treatment with intravenous antibiotics and considered the effects of intervention. This study targeted a total of 2627 patients, 1971 of whom were hospitalized, who started using intravenous antibiotics from June 2017 to January 2018. We assigned those who started between June and September 2017 to the pre-intervention group and those who started between October 2017 and January 2018 to the post-intervention group. The number of patients using long-term intravenous antibiotics, total number of days of treatment, antimicrobial use density (AUD), day of therapy (DOT), and rate of use by lineage of antibiotics were compared. The number of patients using long-term intravenous antibiotics decreased to 40 in the pre-intervention group and 31 in the post-intervention group. There was no significant difference in the total number of treatment days, which was 5.1 ± 5.5 days before and 4.8 ± 4 9 days after, in the intervention group. The AUD of penicillin antibiotics increased and that of aminoglycosides decreased. Furthermore, the DOT of third-generation cephems and lincomycin decreased. Penicillin had an increased lineage use ratio, while that for thirdgeneration cephems, carbapenems, and lincomycin decreased. The number of patients using long-term intravenous antibiotics as well third-generation cephem and carbapenem antibiotics, which are broad spectrum antibiotics, decreased; the overall use of penicillin, a narrow-spectrum antimicrobial, increased. This suggested that the intervention resulted in the promotion of proper use of antimicrobial drugs.
ABSTRACT
Direct-acting oral anticoagulants (DOAC) were approved for the prevention of cardiogenic embolism in non-valvular atrial fibrillation in recent years. However, the dosage of DOAC has to be reduced in patients with bleeding tendencies where the risk of hemorrhage is high, and dose reduction strategies differ depending on the type of DOAC. Therefore, we examined the dosage regimens of 4 DOACs (dabigatran, rivaroxaban, apixaban, edoxaban). Among 129 patients treated with DOACs, 85 received the standard dosage and 44 received non-standard dosage regimens. Among the non-standard dosage patients, 6 were taking a high dose (dose reduction was desirable) and 38 patients were taking a low dose (low dose is usually desirable). The low dosage group were significantly older and had a significantly lower CHADS2 score than that of the high dosage group. Hemorrhagic events occurred in 2 patients in the standard dosage group and in 3 patients in the low dosage group. Also, a thrombotic event occurred in only 1 patient in the standard dosage group. About 30% of the patients were on low dosage versus standard dosage. In practice, attending physicians tend to reduce the dose to avoid a hemorrhagic event particularly in elderly persons. However, a hemorrhagic event also occurred with low dosage in this survey. The validity and safety of dosages outside the limits of standard dosage have not been reported even though this dosage method is commonly used in clinical practice. Thus, more data should be accumulated from a large-scale cohort study to clarify this.
ABSTRACT
The World Health Organization (WHO) recommends antimicrobial use density (AUD) as an indicator for evaluating the amount of antimicrobials used, an index that is now widely employed in many facilities. Defined daily doses (DDD) set by WHO are used for calculating AUD. However, discrepancies have been noted between other countries and Japan in the standard dosage of antimicrobials, which may cause a problem evaluating antimicrobial use with the DDD. Therefore, in this study, we calculated AUD (modified antimicrobial use density: mAUD) with the DDD (modified defined daily dose: mDDD) of our hospital for the carbapenem antimicrobial meropenem (MEPM), mAUD, and resistance rate of Pseudomonas aeruginosa. From 2010 through fiscal year 2016 (ending in March), AUD was 5.9±1.4, 7.0±2.9, 8.2±2.3, 6.8±2.1, 7.3±2.2, 7.0±2.1, and 8.0±3.0 and mAUD was 11.7±2.7, 12.0±4.9, 11.3±3.1, 11.0± 3.4, 11.4±3.5, 11.5±3.5, and 11.2±4.2, respectively. The corresponding resistance rate of P. aeruginosa was 35.1%, 37.9%, 10.0%, 6.0%, 22.6%, 10.6%, and 10.0%. A significant positive correlation was found between mAUD and the resistance rate of Pseudomonas aeruginosa (P < 0.01, r = 0.88). Our results confirm that the mAUD is an effective index for controlling resistance of P. aeruginosa.