One of the priority issues in the oncology setting is to improve the efficacy and safety of cancer chemotherapy. Therefore, side effects that do not directly affect prognosis are frequently overlooked by healthcare professionals or investigators. The development of management methods for those side effects tends to take a backseat to priority issues, resulting in reduction of QOL in patients. We resolved those side effects focusing on olfactory impairment, phlebitis, vascular pain and through the conduct of detection, assessment, development of prophylactic methods in the clinical setting. This review summarizes our findings:

1. Investigation of actual conditions of olfactory impairment in patients receiving cancer chemotherapy

2. Assessment for olfactory impairment using objective evaluation method in patients receiving cancer chemotherapy

3. Improvement of epirubicin-induced phlebitis by switching from liquid preparation to lyophilized formulation

4. Protective effect for epirubicin-induced phlebitis by reduced infusion time and flashing after the infusion

5. Explore risk factors of gemcitabine-induced vascular pain and involvement of prostaglandin E2 to the vascular pain

These findings provide useful information for the prevention of side effects induced by cancer chemotherapy.

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When hospitalized patients develop infections, it extends their hospital stay and can increase their risk of death. Preventing the onset of infection reduces the burden on patients as well as on the hospital. Controlling the amount of antibiotics used can also help to suppress drug-resistant bacteria. When the flow rate of long chain triglyceride lipid emulsion in nutritional supplementation is fast, it has been reported that it could inhibit reticuloendothelial function because artificial triglycerides accumulate in the blood. However, accumulation of artificial triglycerides can be avoided when the flow rate is less than 0.10 g/kg/hr. We examined the relationship between the presence/lack of infections and the flow rate of lipid emulsion, by studying 23 patients with body weights under 40 kg who were administered lipid emulsion intravenously for a period of 14 days or more. Of the infected group, 5 out of 13 cases (38.5%) received a flow rate less than 0.10 g/kg/hr. However, in the non-infected group, 8 out of 10 cases (80.0%) had been administered a flow rate that was less than 0.10 g/kg/hr (P = 0.046). Therefore, we believe the risk of infection can be suppressed by managing the intravenous lipid emulsion flow rate at less than 0.10 g/kg/hr.

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Stable isotope ratios of nitrogen (δ¹⁵N) and carbon (δ¹³C) in scalp hair of elderly patients who received enteral nutrition for long periods were analyzed to assess nutritional status: the δ¹⁵N and δ¹³C in the hair of patients who received enteral nutrition were compared with those of healthy persons, respectively. The average values of the δ¹⁵N and δ¹³C in the hair of patients who received enteral nutrition (n = 19) were higher and lower than those of healthy persons (n = 17), respectively. A negative correlation was observed between the δ¹⁵N in the hair of patients and the dose of energy (r = -0.490, P < 0.05), whereas positive correlation was found between the δ¹³C and the dose of energy (r = 0.563, P < 0.05). The δ¹⁵N and δ¹³C in scalp hair may be good indicators for assessing the nutritional status of the elderly patients who received enteral nutrition for long period.

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The dosage and administration of renally excreted drugs to patients with decreased renal function need to be optimized in accordance with their renal function. However, drug package inserts do not necessarily have sufficient information. Therefore, we identified and classified the issues regarding this lack of information and investigated the percentage of affected package inserts.
We investigated 341 oral drugs in the Clinical Practice Guidebook of Chronic Kidney Disease 2012.
1. The shortcomings in the description of urinary excretion parameters, which is needed for dose adjustment in accordance with renal function, are classified as follows: (1) unchanged drugs and metabolites are not indicated (28%, 95/341), (2) bioavailability for oral dosage is not taken into account (84%, 286/341), and (3) sufficient recovery time for urinary excretion is not acknowledged (3.5%, 12/341).
2. With respect to the dosage regimen of renally excreted drugs, the following information was absent: (1) dosage and dosing interval in accordance with renal function are not described (63%, 70/111) and (2) considerations for dose reduction are not provided (32%, 36/111).
3. A major shortcoming in the description of drug administration for anuric dialysis patient is that nephrotoxic drugs, such as, nonsteroidal anti-inflammatory drugs, are described as being contraindicated (100%, 11/11).
We found that the current information in package inserts of several drugs is insufficient to understand the required dose adjustment or the correct method of administration to patients with decreased renal function. We aim to improve the information in drug package inserts to allow for effective and safe pharmacotherapy.

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One of the serious adverse effects of the antithrombotic agents is intracerebral hemorrhage (ICH). We aimed to evaluate whether antithrombotic agents influence the outcome at the time of hospital discharge in patients with acute phase of ICH. Of the 353 patients with acute phase of ICH, 90 (25.5％) had been treated with antithrombotic agents. Modified rankin scale (mRS) at the time of hospital discharge in patients taking antiplatelet plus antithrombotic agents (combined antiplatelet and anticoagulant therapy: Combined) was higher than those taking antiplatelet agents only (single antiplatelet therapy: SAPT) or anticoagulant agents only (single anticoagulant therapy: SACT). Multiple logistic regression analysis showed that male sex [odds ratio (OR), 2.670; 95% confidence interval (CI), 1.115 - 6.392; P = 0.027)], hemodialysis (OR, 4.165; 95%CI, 1.572-11.033; P = 0.004), Combined (OR, 10.145; 95%CI, 2.520-40.849; P = 0.001), D-dimer > 1.9 μg/mL (OR, 5.271; 95%CI, 2.327-11.942; P < 0.001), NIHSS ≧ 15 (OR, 4.627; 95%CI, 1.888-11.339;P = 0.001) were associated with the death at the time of hospital discharge. This study shows that the onset of ICH taking Combined is associated with an increased risk of death.

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Fall accidents, in which psychotropic polypharmacy is sometimes involved, are serious in medical safety management. We, clinical pharmacists, started to participate in the multi-disciplinary care team for inpatients at the psychiatric unit in Kyoto University Hospital in April 2012. After the patient interview on admission day, we propose a suitable prescription for the proper use of psychotropic drugs. In this study, we investigated the impacts of clinical pharmacy interventions aiming to reduce the psychotropic polypharmacy by evaluating fall accidents during hospitalization. We calculated the dosages of hypnotics, anxiolytics, antipsychotics, antidepressants and antiparkinson agents prescribed at the psychiatry unit in Kyoto University Hospital, as corresponding values, which were diazepam, chlorpromazine, imipramine and biperiden equivalents, respectively, from the computerized electronic records for the period 2011 - 2014. We found a significant reduction in the dosages of long and short-acting hypnotics, anxiolytics, typical antipsychotics (but not atypical antipsychotics) and antiparkinsonian drugs after the introduction of the pharmacist intervention. In contrast, there was a trend toward increased dosages of antidepressants. The numbers of concomitant drugs of each of hypnotics and antipsychotics were decreased significantly. Furthermore, the number of fall accidents reported in the incident reports was decreased to 43-45 from 55 accidents/year after the intervention. These results suggest that clinical pharmacist intervention could contribute to the reduction of the doses used and prevention of polypharmacy in psychotropic drug use, and might be associated with the decrease in the number of fall accidents.

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Although mFOLFOX6 and FOLFIRI are both categorized as moderately emetogenic chemotherapies, they may have a different prevalence of chemotherapy-induced nausea and vomiting (CINV). The optimal strategy to prevent CINV remains uncertain when patients receive mFOLFOX6 followed by FOLFIRI. Of 100 clinical cases executed with mFOLFOX6 and FOLFIRI, we retrospectively investigated the contents of prophylactic antiemetic therapy and the incidence of CINV, and evaluated the efficacy of them when the regimen was changed. Addition of aprepitant, change of 5-HT₃RA to panolosetron, or an increase of the dose of dexamethasone are defined as the intensification of the prophylactic antiemetic therapy (IAT). Around a half of patients who experienced CINV in mFOLFOX6 had intensified prophylactic antiemetic therapy, but over 60％ of them experienced CINV even in FOLFIRI. In order to clearly evaluate the efficacy of IAT, patients were divided into a guideline non-adherent group in which dexamethasone was administered only on Day 1, and a guideline adherent group in which dexamethasone was administered for 3 or 4 days after chemotherapy. Without IAT, the incidence of CINV was significantly increased only by changing chemotherapy from mFOLFOX6 to FOLFIRI (30.8%, 47.6%, respectively, P = 0.048). The incidence of CINV was significantly lower in the guideline adherent group than in the guideline non-adherent group when antiemetic therapy was intensified (25.0%, 81.8%, respectively, P = 0.024). These findings suggest the necessity of IAT and the importance of adhering to the antiemetic guideline concerning the period of dexamethasone administration in patients who receive mFOLFOX6 followed by FOLFIRI.

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Education for medications was integrated into the Japanese junior high school health and physical education (HPE) guidelines in 2012, in tandem with revisions to the Course of Study. To assess knowledge and awareness of the proper use of medications among students who completed courses pertaining to them, a questionnaire survey was administered at 38 high schools in Gifu Prefecture. The questionnaire's recovery and effective response rates were both 99.7% (1,403/1,407 and 1,399/1,403, respectively).
Further, 86.6% of respondents sought advice from their parents or grandparents when using medicines, with 85.4% responding “No” to a question on whether they had ever purchased medicine based on their own self-judgment. A total of 21.4% of respondents had received medicine from friends, and 21.3% had given medicine away. Responding to a question on whether they were aware of the class content regarding medicines, 31.0% of the students answered “Yes,” 48.0% “I don't know,” and 19.5% “No.” Many of these students who were aware of the class content regarding medicines, however, were found to have never received medicine from nor given it to friends, suggesting the importance of medication-related lessons.
The results of this survey clarified the current state of knowledge and awareness regarding the correct use of medicines among students who have taken the junior high school HPE classes on medicines introduced in 2012. In future, further development of both the classes and the instructions are required, to accomplish the purpose given in the Course of Study.

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We report the case of a 35-year-old pregnant woman treated with the calcium channel blocker, nifedipine, for maintenance tocolysis. She was hospitalized due to preterm labor at 21 weeks of gestation by her previous physician. A rash appeared following ritodrine hydrochloride administration for maintenance tocolysis. After changing to magnesium sulfate, a rash appeared again. As these rashes were suspected to have been induced by ritodrine hydrochloride and magnesium sulfate independently, consecutive treatment with these drugs was difficult. Therefore, she was transferred to our hospital for follow-up. At 28 weeks 6 days of gestation, treatment with nifedipine for maintenance tocolysis was started after receiving written informed consent, and the medication was approved by the institutional review board of our hospital. The attending pharmacist considered fetal/neonatal adverse effects of nifedipine, such as teratogenicity, fetotoxicity, and neonatal complications, as well as maternal side effects, such as headache, constipation, and excessive blood pressure drop. The pharmacist provided drug information about nifedipine to the attending physicians and nurses, and gave medication counseling to the patient. Following oral administration of 80 mg of nifedipine daily (20 mg every 6 hours), headache and constipation were evident but gradually improved. Neither excessive blood pressure drop nor exacerbated uterine contraction was observed throughout the period of nifedipine treatment. This medication was finished at 34 weeks 5 days of gestation and the patient was discharged at 36 weeks 2 days of gestation. She delivered a baby at 40 weeks 3 days of gestation.

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Recent guidelines issued by the Japanese Society of Hospital Pharmacists recommend the use of biological safety cabinets (BSCs) and personal protective equipment (PPE) to prevent medical staff from being exposed to antineoplastic drugs during drug preparation. However, wearing PPE costs pharmacists additional time and labor during the preparation process. Since 2012, Nagoya City University Hospital has instituted the use of compounding aseptic containment isolators (CACIs, ChemoSHIELD) and a robotic system (CytoCare) for use during antineoplastic drug preparation. We investigated the effects of introducing CACIs and CytoCare on preventing antineoplastic drug exposure and on pharmacist efficiency. To evaluate workplace contamination, antineoplastic drug residues were measured using the wipe method. We also measured antineoplastic drug urine levels in pharmacists involved in the work. The levels of three antineoplastic drugs (cyclophosphamide, ifosfamide, gemcitabine) were measured using ultra-performance liquid chromatography-tandem mass spectrometry. Further, we investigated the stand-by time of pharmacists involved in the preparation of chemotherapeutic drugs. The results demonstrated that, compared with conventional class II BSCs, CACIs demonstrated decreased workplace contamination. Before CACIs introduction, antineoplastic drugs were detected in 3 of 12 urine samples, whereas after CACIs introduction, antineoplastic drugs were not detected in the urine of pharmacists. Additionally, the CACI and CytoCare systems significantly reduced the stand-by time of pharmacists, compared with BSCs (P < 0.001). Therefore, a combination of CACIs and robotic systems allows safe and efficient chemotherapeutic preparation.

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