The increasing prevalence of antimicrobial-resistant organisms is a global public health problem and is a particular concern for hospitals. Multidrug-resistant bacteria contribute to increased morbidity, patient length of stay, and, ultimately, mortality rates. Accumulating data on antimicrobial consumption and resistance from a variety of institutions are increasingly recognized because the association between antimicrobial consumption and resistance is now regarded as a useful indicator of the selection pressure exerted by antimicrobials in the hospital setting. Therefore, the first national surveillance study of antimicrobial consumption was performed in Japan through pharmacists belonging to the Japanese Society of Hospital Pharmacists.
This review summarizes the evaluation of interventions in a single facility, and that of the relationship between antimicrobial consumption and resistance in Japanese hospitals, to explore the benchmark of infection control. Our results demonstrate that the total consumption of antimicrobials in Japan might be lower than that in other countries, and that the incidence of Pseudomonas aeruginosa resistance is associated with advanced-treatment hospitals, piperacillin/tazobactam, quinolones, and/or total consumption. Our results potentially play a useful role in the next generation of studies in the field of infection because we show the measurement of the total effect of exposure at the time.

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Several case reports of hepatitis B virus reactivation after rituximab administration have been documented. We investigated the association between hepatitis B and C and 15 kinds of molecular-targeted drugs for cancer. We compared two databases, the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency (PMDA). Quantitative analysis involved calculating the reporting odds ratio (ROR) and 95％ confidence interval (95% CI) as a measure of disproportionality. ROR is a tool that detects signals of adverse events for individual drugs, with signals detected when the lower limit of the 95% CI of ROR is > 1. We also investigated the timing of the adverse events and the age of the patients. There were 29,017,485 reports in FAERS and 2,079,653 reports in JADER. Signals were detected for rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B. In FAERS, hepatitis B often occurred within 1 month, whereas rituximab-associated hepatitis B often occurred 2-6 months after administration. In JADER, hepatitis B and rituximab-associated hepatitis B often occurred 1-3 months after administration. We conclude that signals of rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B are marked. Analyzing the timing and age of the patient at the occurrence of adverse events may suggest a relationship between drugs and these events.

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Patients who received percutaneous coronary intervention (PCI) should be treated with dual anti-platelet therapy (DAPT). DAPT significantly lowers the risk of the incidence of major adverse cardiac events (MACE). However, the risk factors for the incidence of MACE are unclear. We investigated the relationship between the incidence of MACE in PCI treated patients who underwent combined therapy by clopidogrel and aspirin, and patient background, present clinical history, lifestyle, and concomitant drugs. Between the MACE symptom group and non-MACE group, there were no significant differences in terms of patient background and lifestyle. In the MACE-symptom group, the percentage of treatments using concomitant drugs that inhibits cytochrom P450 (CYP)3A4 activity was significantly higher than in the non-MACE group (odds ratio 2.70). The present study also demonstrated that diabetes was an important risk factor (odds ratio 3.16, P = 0.001) of MACE symptoms. A significant positive correlation was found between diabetes and hypertension morbidity, and the administration ratio of concurrent drugs with CYP3A4 inhibition activity. The present study suggests that diabetes morbidity may be associated with MACE symptoms in antiplatelet therapy with DAPT.

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Amitiza^® is available as an oval, soft gelatin capsule containing 24 μg of lubiprostone dissolved in a medium-chain triglyceride. Lubiprostone is a chloride channel activator indicated for the treatment of chronic idiopathic constipation in adults. Although Amitiza^® capsules should be swallowed whole and not broken apart or chewed, the capsules have been administered by a simple suspension method to recipients unable to ingest food or drugs orally. The administration of Amitiza^® capsule suspension through nasoenteric feeding tubes has not been investigated. Therefore, we evaluated whether the capsules are appropriate for administration through nasogastric tubes. The capsules disintegrated and dispersed after 10 min in 30 mL of hot water at 55°C. The suspension was transferred into a syringe or suspension bottle and passed through nasoenteric feeding tubes (8 Fr) without obstruction. Lubiprostone levels in each sample were determined by liquid chromatography/mass spectrometry. More than 93% of the lubiprostone was contained in suspension with flash solution through the feeding tubes administered through both the tubes. In conclusion, this study suggests that Amitiza^® capsules can be administered to patients by a simple suspension method through nasoenteric feeding tubes.

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Graft-versus-host diseases (GVHD) are the main complications after stem cell transplantations. The use of systemic steroids remains the standard for first-line treatment of such complications despite the severe adverse side effects such as the risk of opportunistic infections, glucose intolerance, and bone demineralization. Many of the adverse side effects associated with systemic steroids can be avoided through the use of beclomethasone dipropionate (BDP) as BDP is promptly metabolized in the liver after absorption from the intestines. The BDP is an activated form of steroid that exerts a strong anti-inflammatory action and may be expected to have an effect on gastrointestinal GVHD (GI-GVHD).
This retrospective study verified such an effect for 29 cases diagnosed with alimentary GI-GVHD from June 2008 to July 2013 in order to clarify an effective case. The BDP was administered to 21 patients with acute GVHD and 8 patients with chronic GVHD. The GI-GVHD improved in 20 patients and the condition worsened with 9 patients. The BDP was also effective with acute and chronic GI-GVHD. With lighter conditions of the disease at the time of the BDP internal administration, it was more effective. In 15 cases where systemic steroids were administered there were no new infections. It may be concluded that BDP is an effective medication for GI-GVHD when administered at an early stage.

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To ensure the proper use of pharmaceutical products, it is very important to check outpatient prescriptions brought by patients when they are hospitalized. However, in recent years, this checking has become a huge task for medical staff to manage, especially with the increase in the number of generic medicines. On April 2010, the chief of the Health Policy Bureau, Ministry of Health, Labour and Welfare, released an important statement, “Implementation of team medical care by the cooperation and linkage of medical staff,” indicating legal pharmaceutical activities to promote team medicine. The Ministry has established a new role for ward-pharmacists related to medical fees. In Kyoto University Hospital, we established a protocol for outpatient medication management, which clarifies the division of the roles played by doctors, nurses and pharmacists, according to the statement of the chief of the Health Policy Bureau (protocol-based pharmacotherapy management, PBPM). In this protocol, ward-pharmacists check outpatient prescriptions and propose the most suitable prescription to physicians by entering the physician order-entry system. Although it is an examination in only one ward, the introduction of this protocol effectively reduced doctors' and nurses' workloads by about 20 minutes per patient. Ward-pharmacists increased the frequency of prescription interventions, and also obviated errors committed by doctors. The practice of this PBPM on the management of outpatient medications greatly contributed to a reduction in the burden on doctors and nurses, and simultaneously improved medication safety in our hospital. This report presents an example of how medical team care can ensure high-quality patient treatment in a hospital.

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In this study, we examined the stability of Artist, Ubretid, Cardenalin, J Zoloft, Nu-Lotan, Micardis and Renivace tablets after removal from the press through package (PTP). Stability information for these tablets after removal from PTP is insufficient, although these tablets are frequently in clinical use. Test formulations were stored for 3 and 6 months at room temperature and humidity without artificial control, under fluorescent light and exposed to the atmosphere. These stabilities were evaluated by visual inspection, residual rate, a hardness test and a dissolution test. The content of the unchanged drug in Nu-Lotan tablets was significantly decreased at the 3rd and 6th months. Moreover, the tendency of content decreasing in Cardenalin and Renivace tablets was observed at the 3rd and 6th months. Hardness change was observed in Ubretid tablets at the 6th month. A significant reduction in hardness and an appearance change at the 3rd and 6th months were observed in the Renivace tablets. Moreover, mean dissolution time (MDT) of these tablets was significantly shortened. The change in quality of tablets after removal from PTP could cause a change in the effects and pharmacokinetic profiles of these drugs. Therefore, it is considered that the stability information in the unpackaged state requires enhancement.

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A retrospective survey of a database containing patient backgrounds and prescribed drugs was conducted to elucidate the detailed characteristics and risk factors of adverse effects caused by topical dermatological formulations of diclofenac. A total of 145,478 patients who had been dispensed topical dermatological formulations of diclofenac at 466 community pharmacies belonging to Nihon Chouzai were included in the study. Of these, 580 patients had adverse effects. The incidence of adverse effects was significantly higher in the elderly (more than 65 years old) and in female patients. A variety of systemic adverse effects were evident in 19 patients. Approximately half of these adverse effects were related to the respiratory system, eg, asthma, but the other adverse effects (eg, edema, decreases in urinary volume, tremor and others) were not described in the drug package inserts. Data from patients with systemic adverse effects, and an age- and gender-matched control group of patients underwent multivariate logistic regression analysis. Asthma (odds ratio: 13.3, 95% confidence interval: 2.40 - 95.5, P = 0.004) and the number of co-administered drugs (odds ratio: 1.25, 95% confidence interval: 1.02 - 1.55, P = 0.035) were identified as risk factors for systemic adverse effects of topical dermatological formulations of diclofenac. Moreover, many of the co-administered drugs affected P450 enzymes other than P450 2C9, the main metabolizer of diclofenac. Therefore, to manage the risk of adverse events, it was concluded that various characteristics of concomitant medications and patient's medical history should be evaluated properly before topical dermatological formulations of diclofenac are prescribed.

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