Background Factors Associated with the Development of Neutropenia in Breast Cancer Patients Taking Abemaciclib / 日本農村医学会雑誌

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.

Impact of Expanding Pharmacist Duties in Wards on Nursing Duties / 日本農村医学会雑誌

Engaru-Kosei General Hospital expanded its pharmacist duties in hospital wards in April 2018 following the nationwide switch to out-of-hospital prescriptions. The purpose of this study was to examine the effect of pharmacists’ ward duties on nursing duties. Pharmacists expanded their duties to cover drug distribution management, infusions of total parenteral nutrition (TPN) mixed with drugs, and aseptic preparation of 24-h infusions (including peripheral parenteral nutrition). The effects were compared between April 2018 before the expansion of duties and May-September 2018 after the expansion, and we compared the number of meetings set up to discuss nurses’ overtime hours and patient problems. In addition, interviews were conducted about the changes experienced on site. Drug distribution management averaged 3,150 cases/month. The number of TPN mixed infusions was 25 cases/month before expansion and this increased to 88 cases/month after expansion. The number of mixed injections of 24-h infusions was 296/month. Nurses' overtime hours did not decrease significantly, but the number of meetings increased from 47/month to 79.4/month. In the interviews, positive responses were obtained about, for example, the increased number of meetings held and more time for patient care. The pharmacist and the nurse collaborated to improve work by using their expertise, we think that the results obtained from work improvement contributed to the improvement of medical quality and medical safety.

UGT1A1 Gene Polymorphism in FOLFIRI±αTherapy:Initial Dose, Relative Dose Intensity, and Side Effects Observed / 日本農村医学会雑誌

Indices for dose regulation for irinotecan (CPT-11) toxicity are diarrhea, reduction in neutrophil (NEUT) count, and level of UDP-glucuronyltransferase (UGT), which is involved in conjugation of the active metabolite SN-38. An association with the glucuronosyltransferase (UGT) 1A1 gene polymorphism has been reported. Therefore, we investigated UGT1A1 gene polymorphism and the incidence of side effects in patients who received FOLFIRI±αat our institution from November 2008 to March 2017. UGT1A1 genetic testing was performed, and 25 cases treated with FOLFIRI±αwere included. Age, sex, height, weight, and body surface area (BSA)were analyzed. UGT1A1 genotype was determined as follows:*1/*6 heterozygous (*6 he genotype), *1/*28 heterozygous (*28 he genotype), homozygous, and compound heterozygous (compound genotype). We also investigated the combination drugs (classified as he genotype) and wild type. In addition, the initial dose of CPT-11/5-FU bolus, initial relative dose intensity (RDI) (％), and blood toxicity in the first course were investigated. Mean age was 70.4±8.6 years, UGT1A1 genotype was*28 he in 5 cases, *6 he in 6 cases, and wild type in 14 cases. There were no cases of compound he or homo type. There was no significant difference between the initial dose and the initial RDI. Reduction in leukocyte count was seen in 2 cases with Grade(G)3*6 he and in 2 cases with G4*28 he. Platelet count was reduced in 2 cases with G4*28 he, 2 cases with G4*2 he, 2 cases with G4*28 he, and in 2 cases with*6 he. In this study, there was no significant difference in the initial dose and initial RDI for*6 he, *28 he, and wild type. However, *28 he and *6 he showed hematologic toxicity of G3 or more. Also, the frequency of the he genotype tended to be higher than that of wild type. Thus, it is necessary to clarify the significance of weight loss in the he type in future.

Assessments of the Effectiveness of Sodium Glucose Co-Transporter 2 Inhibitor and Secondary Effect / 日本農村医学会雑誌

Sodium glucose co-transporter 2 (SGLT2) inhibitors typically have various secondary effects in addition to the hypoglycemic effect. Therefore, we examined their effectiveness and other secondary effects. We targeted 86 patients with type 2 diabetes treated with SGLT2 inhibitors for the first time from June 2014 to the end of March 2017 at our hospital. Mean body mass index (BMI) was 28.69±4.91kg/m2. Body weight, BMI, and levels of hemoglobin A1c (HbA1c), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), estimated glomerular filtration rate (eGFR), triglyceride (TG) and uric acid (UA) were significantly lower,while hematocrit (HCT), blood urea nitrogen (BUN), creatinine (Cre), and high-density lipoprotein cholesterol were significantly higher 2 months after than before administration of SGLT2 inhibitors. A significant negative correlation was observed between HbA1c, body weight, AST, ALT, γ-GTP, BUN, low-density lipoprotein cholesterol (LDL-C), and change in UA before and 2 months after administration of SGLT2 inhibitors. HbA1c was lower in patients with high HbA1c before treatment, and weight loss was noted in patients with increased body weight before treatment. These results suggest that SGLT2 inhibitors may be highly effective in patients with type 2 diabetes with uncontrolled obesity. In addition, potential risk factors for cardiovascular events and deranged liver function test values were identified, and there was a possibility that long-term SGLT2 inhibitor use could induce cardiovascular events, but with possible improvement of fatty liver. However, because it was observed that HCT was elevated and renal function was impaired, it may be necessary to administer rehydration therapy in the initial stages of treatment and to continuously monitor renal function.