Volatile anticancer drug determination by thermal desorption technique with polydimethylsiloxane-coated macroporous silica adsorbent in gas chromatography-mass spectrometry.

An analytical method for quantifying the volatile anticancer drugs ifosfamide (IF) and cyclophosphamide (CP) in air was developed on the basis of thermal desorption (TD)-gas chromatography-mass spectrometry. Polydimethylsiloxane-coated macroporous silica was used as the adsorbent. The extraction tube was prepared by packing 0.2 g of adsorbent particles into a glass tube. The extraction and desorption efficiencies of the proposed method were quantitatively investigated in this study. The limits of detection of the proposed method for IF and CP were 3.3 ng L-1 at an air sampling volume of 3.0 L (30 min). The sensitivity of the proposed method was compared with using a Tenax TA packed tube that is widely used as the extraction medium in TD analysis. Finally, detection of IF and CP that evaporated from aqueous standard solution was investigated.

Cost and healthcare utilization of methicillin-resistant Staphylococcus aureus bacteremia estimated from linked antimicrobial resistance surveillance and hospital claims data in Japan.

Objective: To compare the incremental costs and healthcare utilization of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with those of methicillin-susceptible S. aureus (MSSA) bacteremia. Design: Retrospective cohort study using data from April 2014 to March 2015. Setting: Antimicrobial resistance surveillance and hospital claims data from 16 Japanese hospitals. Patients: The study included 73 patients with S. aureus bacteremia: 23 with MRSA and 50 with MSSA. Methods: MRSA bacteremia was identified using blood cultures and drug-susceptibility tests. MRSA- and MSSA-related medical practices were evaluated. The costs were calculated and compared. All the medical costs were classified into empirical and definitive therapy periods and expressed in Japanese yen (JPY, 1 USD = 106 JPY). Additionally, costs at aggressive and passive bacterial test-performing facilities were compared. Results: No significant differences existed in MRSA-related resource use per patient episode between MRSA and MSSA bacteremia during empirical therapy. However, during definitive therapy, in MRSA bacteremia compared with MSSA bacteremia, this difference was higher. The average MRSA-related costs of empirical therapy for MRSA and MSSA were 13,380 and 9,140 JPY (126 and 86 USD) per patient, and for definitive therapy, they were 69,810 and 29,510 JPY (659 and 278 USD) per patient, respectively. No significant differences were noted. Conversely, the average examination costs during definitive therapy differed significantly: 9,740 vs 3,850 JPY (92 vs 36 USD), respectively (P = .0294). Furthermore, the incremental costs in aggressive facilities were lower for the definitive therapy period than those in passive facilities. Conclusions: In the definitive therapy period, MRSA bacteremia had higher incremental costs and greater use of healthcare resources. In addition, the incremental costs in aggressive facilities were lower than those in passive facilities.

Clinical Implication of the Relationship between Antimicrobial Resistance and Infection Control Activities in Japanese Hospitals: A Principal Component Analysis-Based Cluster Analysis.

There are few multicenter investigations regarding the relationship between antimicrobial resistance (AMR) and infection-control activities in Japanese hospitals. Hence, we aimed to identify Japanese hospital subgroups based on facility characteristics and infection-control activities. Moreover, we evaluated the relationship between AMR and hospital subgroups. We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in 124 hospitals from April 2016 to March 2017. Hospitals were classified using cluster analysis based the principal component analysis-transformed data. We assessed the relationship between each cluster and AMR using analysis of variance. Ten variables were selected and transformed into four principal components, and five clusters were identified. Cluster 5 had high infection control activity. Cluster 2 had partially lower activity of infection control than the other clusters. Clusters 3 and 4 had a higher rate of surgeries than Cluster 1. The methicillin-resistant Staphylococcus aureus (MRSA)/S. aureus detection rate was lowest in Cluster 1, followed, respectively, by Clusters 5, 2, 4, and 3. The MRSA/S. aureus detection rate differed significantly between Clusters 4 and 5 (p = 0.0046). Our findings suggest that aggressive examination practices are associated with low AMR whereas surgeries, an infection risk factor, are associated with high AMR.

Estimated medical costs of methicillin-resistant Staphylococcus aureus infection classified by polymerase chain reaction-based open reading frame typing in Japan.

This retrospective, observational cohort study investigated the economic impact of genotype by classifying methicillin-resistant Staphylococcus aureus (MRSA) by using the polymerase chain reaction-based open reading frame typing (POT) method. Using administrative claims and bacteriological data for April 2016 to March 2021 from the University of Yamanashi Hospital, we ascertained the POT1 numbers and classified MRSA as either "hospital-derived" or "community-derived". We defined MRSA-associated medical practices and estimated the associated medical costs. After applying inverse probability of treatment weighting (IPTW)-based adjustment for patient characteristics between the two groups, we estimated the differences in medical costs during the "total therapy period" (defined as the interval from specimen submission to Day 42 after the susceptibility report) and the "definitive therapy period" (defined as the interval from susceptibility reporting to Day 42). Among the 135 MRSA-infected patients, 54 and 81 were classified as having hospital-derived and community-derived MRSA infections, respectively. Significant differences in patient characteristics were observed with regard to age (p = 0.0478), sex (p = 0.0422), surgery (p = 0.0349), chemotherapy (p = 0.0457) and immunosuppressive drug use (p = 0.0222). The median duration of the definitive therapy was 29 and 27 days, and the mortality rate during this period was 11% and 5% for the hospital-derived and community-derived types, respectively. After IPTW-based adjustment, the medical costs for the total therapy period were 324,480 and 296,462 Japanese yen (JPY) per patient for the hospital-derived and community-derived types, respectively, whereas the medical costs for the definitive therapy period were 279,635 and 256,542 JPY per patient for the hospital-derived and community-derived types, respectively. No statistically significant difference was detected (p = 0.5813 and p = 0.6355, respectively). In this study, MRSA healthcare costs were compared according to the POT scores, and no statistically significant differences were observed between hospital-derived and community-derived MRSA infections.

Extraction of Volatile Anticancer Drugs in Air Using a Solid-Phase Extraction Type Device Followed by Gas Chromatography-Mass Spectrometric Analysis.

Ifosfamide (IF), cyclophosphamide (CP), and bendamustine (BD) are widely used anticancer drugs. These drugs have slight volatility; therefore, medical-staff exposure is of concern in the medical field. However, an accurate and quantitative detection method of these volatile drugs in air has not been reported. In this study, we developed the quantitative extraction and detection method of these volatile anticancer drugs in air. For the extraction of analytes, a solid-phase extraction-type collection device packed with styrene-divinylbenzene polymer particles was used. The extracted analytes were quantitatively eluted with 5 mL of ethanol, and the solution was concentrated to 100 µL with nitrogen purging. The analytes were analyzed using gas chromatography-mass spectrometry (GC-MS). The limit of detection of the proposed method for IF and CP was 0.017 and 0.033 ng L-1, respectively in air at an air sampling volume of 300 L. IF and CP showed slight volatility, whereas BD was not detected in GC-MS due to its lower volatility. The spiked recoveries of IF and CP in the proposed method were within the range of 95.5 to 101%. Finally, the proposed method was applied to determine the exposure of IF and CP during the dispensing of CP within a hospital dispensary room. The investigated volatile anticancer drugs were not detected in real air samples, indicating that the protection measures employed are sufficient.

[Clinical Preparations: Status Quo and Challenges in the Future].

Dispensing clinical preparations requires the professional ability of pharmacists as specialists who understand the physicochemical properties of drugs. Clinical preparations contribute to the support of drug therapy and to commercialization by pharmaceutical companies. The Japanese Society of Hospital Pharmacists published the Guidelines on Hospital Preparations and Use in 2012. Those guidelines were designed to improve the safety and utility of hospital preparations, indicate the standard procedures for treatment in hospitals, and show how to ensure the quality of hospital preparations. The expiration dates for clinical preparations should be determined, although this is not done for most because of the numerous hospitals and differences in their approaches to quality control. Furthermore, the acquisition of informed consent for the use of clinical preparations is inadequate. After the guidelines were released, some problems have occurred, such as the underfilling of prescriptions for progesterone vaginal suppositories and overdoses of selenium injections. It therefore appears necessary to consider the development of a new procedural manual on clinical preparations. In this symposium, I discuss relief or safety measures for clinical preparations.

Formulation study on retinoic acid gel composed of iota-carrageenan, polyethylene oxide and Emulgen® 408.

In the present study, all-trans retinoic acid (RA) gels formulated with various compositions of polyethylene oxide (Emulgen®) and iota-carrageenan (ι-CG) were prepared and their physicochemical properties were evaluated. The compression energy, which is the work required to compress the product through a fixed distance, increased with increasing amount of ι-CG or Emulgen®. The adhesion energy and displacement decreased with increasing amount of ι-CG or Emulgen® due to the progression of gel formation. From the results of the sensory tests, the properties of RA gels such as adhesiveness, gel strength and spreadability seemed to be adjustable depending on the condition of skin by varying the components of RA gels. Through photostability study, the expiration date and storage conditions of RA gels were determined as "4°C for 28 d with no exposure to light."

Development of patient-friendly preparations: preparation of a new allopurinol mouthwash containing polyethylene(oxide) and carrageenan.

Stomatitis is a harmful side effect induced by high and/or multiple dosing of cytotoxic drugs such as 5-fluorouracil. Allopurinol mouthwash has been used to prevent stomatitis induced by cancer chemotherapy. In the present study, the pharmaceutical utility of allopurinol mouthwash (Alkox-mw), which consists of polyethylene(oxide) (Alkox) and iota-carrageenan (INA), was investigated as a possible material for a new oral dosage preparation for improving the adhesiveness onto the oral mucosa. From the observation of the gel formation, which was studied as a function of the variety of the added Alkox and/or INA, the preferential compositions of Alkox-mw (Alkox:INA % ratio) seemed to be 1.0:(0-1.0) and (0-3.0):0.4, respectively. The adhesiveness and the spinnability of various allopurinol mouthwashes were also investigated using a creep meter. The adhesiveness of Alkox-mw increased with the increase in the amount of added Alkox. Furthermore, the adhesion force of Alkox-mw was greater than that of allopurinol mouthwash consisting of sodium carboxymethylcellulose (CMC-Na). From the in vitro assessment of mimicking the effusion of the allopurinol mouthwashes from the surface of the oral mucosa, the effusion of Alkox-mws was retarded by the added Alkox. The results obtained in the present study suggest that Alkox-mws may be useful as a new dosage form that adheres to the oral mucosa.