Creation of the first regional medical resource map for use in a disaster.

Background: Japan is located on the Pacific Ring of Fire and experiences frequent earthquakes. In addition, as the climate is changing due to global warming, heavy rains have caused frequent floods recently. Following the occurrence of disasters, citizens often experience confusion regarding access to healthcare services. Moreover, health professionals often face uncertainty regarding the availability of medical services in their local area. The Tokyo Kita city Pharmacist Association (KPA) independently developed the pharmacist safety confirmation (PSC) and pharmacy status confirmation (PSTC) systems to provide information regarding pharmaceutical resources during a disaster. These systems are very useful; however, they only provide information about pharmacies. Using this system as a base, a regional medical resource (RMR) map was created in cooperation with the Medical Association and Dental Association to provide useful medical resource information for clinicians and citizens during a disaster. Objectives: The study aimed to assess the effectiveness and reliability of the RMR map. Methods: The PSC and PSTC systems were originally invented by the KPA. The systems were employed in the event of actual earthquakes and flood damages and have produced positive results. An RMR map was created as a new resource map system by updating the software and platform of PSC and PSTC, and its reliability and efficacy were verified using drills. Drills were conducted seven times from 2018 to 2021. Results: Out of the 527 member facilities, 450 were registered. The response rate ranged from 49.4% to 73.8% and the system successfully created useful maps. Conclusion: This is the first report on the creation of an effective RMR map that can be used for helping people during disasters in Japan.

Administration of Kampo medicine through a tube at an advanced critical care center.

n emergency and critical care medical centers, tube administration is employed for patients who have difficulty swallowing oral drugs owing to decreased consciousness or mechanical ventilation. However, tube clogging due to drug injection is a concern. We compared the crushing method with the simple suspension method for the passage of amlodipine, an antihypertensive drug, in combination with rikkunshito, which has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux in emergency and critical care medical centers, to ascertain the effect of Kampo products on the passage of other drugs during tube administration. When the crushing method was employed, poorly water-soluble solid products were formed, while a uniformly dispersed suspension was obtained using the simple suspension method. In addition, the passage rate of amlodipine through the tube was 64% and 93% in the crushing and simple suspension methods, respectively, thereby indicating that the simple suspension method provided more favorable than the crushing method. The results of this study suggested that the passage rate of amlodipine for patients who received Kampo products concurrently was higher when the simple suspension method was used, and an appropriate drug amount might well be able to administered to patients using this method. J. Med. Invest. 65:32-36, February, 2018.

Evaluation of the Benefits of De-Escalation for Patients with Sepsis in the Emergency Intensive Care Unit.

PURPOSE: Although the 2016 Japanese guidelines for the management of sepsis recommend de-escalation of treatment after identification of the causative pathogen, adherence to this practice remain unknown. The objective of this study was to evaluate the benefits of de-escalating treatment for sepsis patients at an advanced critical care and emergency medical centre. METHODS: Based on electronic patient information, 85 patients who were transported to the centre by ambulance, and diagnosed with sepsis between January 2008 and September 2013 were enrolled and evaluated. Patients were divided into two groups with and without de-escalation, and comparisons were conducted for several variables, including length of hospital stay, and length of antibiotic administration. Two types of subgroup analysis were conducted between patients with septic shock or positive blood cultures. Statistical analysis was conducted using chi-square and Mann-Whitney U tests. RESULTS: The length of hospital stay after diagnosis was significantly shorter for the de-escalation group than for the non-de-escalation group. In the subgroup analysis, de-escalation for blood culture-positive patients was beneficial in terms of the length of hospital stay and length of antibiotic administration. CONCLUSIONS: The findings of this study suggest that sepsis treatment de-escalation is beneficial for treatment efficacy and appropriate use of antibiotics. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Meta-analysis of the efficacies of amiodarone and nifekalant in shock-resistant ventricular fibrillation and pulseless ventricular tachycardia.

Amiodarone (AMD) and nifekalant (NIF) are used in the treatment of ventricular fibrillation or tachycardia; however, only few studies have been conducted on their efficacies. Therefore, a meta-analysis was conducted. Relevant sources were identified from PubMed, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi. The outcomes were short-term and long-term survival in patients with shock-resistant ventricular fibrillation /pulseless ventricular tachycardia. Thirty-three studies were analysed. The results showed that, compared to the control treatment, AMD did not improve short-term survival (odds ratio (OR): 1.25, 95% confidence interval (CI): 0.91-1.71) or long-term survival (OR: 1.00, 95% CI: 0.63-1.57). However, compared to the control treatment, NIF significantly improved short-term survival (OR: 3.23, 95% CI: 2.21-4.72) and long-term survival (OR: 1.88, 95% CI: 1.36-2.59). No significant difference was observed in short-term survival (OR: 0.85, 95% CI: 0.63-1.15) or long-term survival (OR: 1.25, 95% CI: 0.67-2.31) between AMD- and NIF-treated patients. The results suggest that NIF is beneficial for short-term and long-term survival in shock-resistant ventricular fibrillation/pulseless ventricular tachycardia; however, the efficacy of AMD in either outcome is not clear.

Pharmaceutical Education Focused on Pharmacotherapy in Emergency Medical Care.

Pharmacists are expected to be active members of the healthcare team in emergency medicine, because many pharmaceuticals are administered to patients with life-threatening conditions. However, adequate education for pharmacists and pharmacy students is not provided. The "Emergency Pharmaceutical Sciences" course was introduced for the first time in Japan by the Department of Pharmacy, Okayama University, to offer advanced education in emergency medicine and research related to critical care. We offer an emergency pharmaceutical training program with high-performance simulators and have succeeded in improving the clinical skills and confidence of pharmacy students. In this review, we introduce our activities intended to mold pharmacy students into emergency pharmacists who can contribute to emergency medicine.

[Role of pharmacists in disaster medicine: required knowledge and skills].

Immediately after the Great East Japan Earthquake of March 2011, Okayama University dispatched a medical assistance team based on the request of Iwate Prefecture. The first team was followed by 12 medical teams. I was one of the members of the fourth and fifth medical teams sent to Rikuzen-takata and Ofunato for a week beginning March 16th to support medical relief operations as a pharmacist during the sub-acute phase of the disaster. As a member of the team at the temporary clinic in Rikuzen-takata, pharmacists such as myself required physical assessment skills to perform related tasks, along with expertise in drug dispensing and consultation. In my next medical team, which headed the pneumonia unit at Oofunato Hospital, I played a critical role in the effective use of medicine reserved/provided for disasters, including antibiotics. Throughout the relief operations, strong clinical reasoning and decision making, as well as good teamwork, proved vital, especially in emergency situations. For future community medical systems, emergency/disaster medicine should be included in pharmacy education. The School of Pharmacy at Okayama University will establish emergency medicine program in the next school year, in cooperation with the Medical, Dental and Health Care Departments.

[Usefulness of group work as a teaching strategy for long-term practical training in the 6-year pharmaceutical education].

At the initiation of long-term practical training in the 6-year pharmaceutical education, there are many issues to be solved. For example, it is necessary for teaching pharmacists, who are in charge of both staffing and teaching pharmacy students, to manage their workload with other staff pharmacists. To overcome this situation and to improve the motivation of teaching pharmacists towards student practical training, we twice held group work (GW) sessions for teaching pharmacists, and then evaluated whether such training was effective for their understanding of the Model Core Curriculum for Practical Training and for promoting a higher level of motivation. During the two-day GW discussions, teaching pharmacists, who work daily in the dispensing area, were separated into two groups to discuss teaching skills. A questionnaire survey was completed by participants before and after each GW session. According to the survey, more than 90% of the pharmacists had a higher motivation level for practical training after the sessions. Particularly in the second GW training, the response rate of "being actively involved" improved from 40% to 70%. Furthermore, "The Educational Evaluation Testing" was conducted, which confirmed the increased participant comprehension. The median scores of the comprehensive exams significantly (p<0.01) improved in twice GW, respectively. Therefore, we conclude that GW sessions are a useful tool for both improving professional knowledge about the Model Core Curriculum and motivating teaching pharmacists involved in the practical training of students. We hope that this exercise will lead to higher student motivation and satisfaction during their practical training.

[Clinical usefulness of the new Japanese glomerular filtration rate equation for initial and individualized dosage adjustment concentrations of vancomycin].

To clarify whether the new Japanese glomerular filtration rate (eGFR) equation was able to accurately determine the initial and individualized dosage adjustment concentrations of vancomycin (VCM), the predictive performance for VCM concentrations using the eGFR and Cockcroft-Gault (CG) equations was compared. Data were retrospectively collected from clinical records of 90 patients with MRSA infection whose trough and peak VCM concentrations had been determined. The predicted VCM initial and individualized dosage adjustment concentrations were performed with the 2-compartment linear model using pharmacokinetic parameter means and their individual values via Bayesian estimation, respectively. The prediction error (PE) and its absolute value (APE) between the observed and predicted VCM concentrations were calculated as indices of bias and accuracy in predictive performance, respectively. In the initial dosage adjustment of VCM, the PE value, calculated with the eGFR equation in trough and peak VCM concentrations of patients whose BMI were 18.5 kg/m(2) and higher, was significantly smaller than that calculated with the CG equation. In particular, both PE and APE values obtained from the eGFR calculated concentrations from nonelderly patients (younger than 65 years old) were significantly improved compared with those from the CG equation. In the individualized dosage adjustment of VCM, the eGFR equation gave a significantly smaller PE value in nonelderly patients' trough concentrations than the CG equation. These findings provide useful information for adjusting the VCM dosage to achieve optimal therapeutic efficacy in patients with MRSA infection.

Regio- and stereoselective oxidation of propranolol enantiomers by human CYP2D6, cynomolgus monkey CYP2D17 and marmoset CYP2D19.

Toxic and pharmacokinetic profiles of drug candidates are evaluated in vivo often using monkeys as experimental animals, and the data obtained are extrapolated to humans. Well understanding physiological properties, including drug-metabolizing enzymes, of monkeys should increase the accuracy of the extrapolation. The present study was performed to compare regio- and stereoselectivity in the oxidation of propranolol (PL), a chiral substrate, by cytochrome P450 2D (CYP2D) enzymes among humans, cynomolgus monkeys and marmosets. Complimentary DNAs encoding human CYP2D6, cynomolgus monkey CYP2D17 and marmoset CYP2D19 were cloned, and their proteins expressed in a yeast cell expression system. The regio- and stereoselective oxidation of PL enantiomers by yeast cell microsomal fractions were compared. In terms of efficiency of expression in the system, the holo-proteins ranked CYP2D6=CYP2D17>>CYP2D19. This may be caused by the bulky side chain of the amino acid residue at position 119 (leucine for CYP2D19 vs. valine for CYP2D6 and CYP2D17), which can disturb the incorporation of the heme moiety into the active-site cavity. PL enantiomers were oxidized by all of the enzymes mainly into 4-hydroxyproranolol (4-OH-PL), followed by 5-OH-PL and N-desisopropylpropranolol (NDP). In the kinetic analysis, apparent K(m) values were commonly in the µM range and substrate enantioselectivity of R-PL

The mechanism causing the difference in kinetic properties between rat CYP2D4 and human CYP2D6 in the oxidation of dextromethorphan and bufuralol.

The capacity to oxidize bufuralol (BF) and dextromethorphan (DEX) was compared kinetically between human CYP2D6 and four rat CYP2D (CYP2D1, -2D2, -2D3 and -2D4) isoenzymes in a yeast cell expression system. In BF 1''-hydroxylation and DEX O-demethylation, only CYP2D4 showed hook-shaped Eadie-Hofstee plots, the other four CYP2D enzymes exhibiting linear plots. In DEX N-demethylation, rat CYP2D2 did not show any detectable activity under the conditions used, whereas the other four enzymes yielded linear Eadie-Hofstee plots. To elucidate the mechanisms causing the nonlinear kinetics, four CYP2D4 mutants, CYP2D4-F109I, -V123F, -L216F and -A486F, were prepared. CYP2D4-V123F, -L216F and -A486F yielded linear or linear-like Eadie-Hofstee plots for BF 1''-hydroxylation, whereas only CYP2D4-A486F exhibited linear plots for DEX O-demethylation. The substitution of Phe-109 by isoleucine did not have any effect on the oxidative capacity of CYP2D4 for either BF or DEX. These results suggest that the introduction of phenylalanine in the active-site cavity of CYP2D4 simplifies complicated interactions between the substrates and the amino acid residues, but the mechanisms causing the simplification differ between BF and DEX.

Toxin production by Aeromonas sobria in natural environments: river water vs. seawater.

Aeromonas are water-borne pathogens. They are halotolerant, which means that they can survive in environments whose salt content corresponds to that of seawater (3.0% NaCl). However, the presence of Aeromonas in seawater is extremely rare compared with that in river water. In this study, we tested the ability of Aeromonas sobria to produce toxins in river water and seawater. First, we cultured A. sobria on skim milk agar plates supplemented with either river water (SARW) or seawater (SASW). The bacteria grew on both plates. A clear zone around the bacteria was generated in SARW. However, such a zone was not observed in SASW, suggesting that proteases were not generated in SASW. Subsequently, we cultured A. sobria in a nutrient broth supplemented with either river water (NRW) or with seawater (NSW), and examined the protease activity of their culture supernatants. The protease activity of the culture supernatant from NSW was extremely low compared to that from NRW. The immunoblotting analysis showed that serine protease (ASP) was not produced by the culture in NSW. By contrast, aerolysin-like hemolysin was produced in all conditions examined in this study. This indicates that the salinity of water is deeply involved in the production of ASP by A. sobria.

Total analysis and purification of cellular proteins binding to cisplatin-damaged DNA using submicron beads.

A high-performance affinity purification technique has been developed for cisplatin (CDDP)-damaged DNA binding proteins directly from crude nuclear extracts of HeLaS3 cell using novel submicron beads synthesized by copolymerization of styrene and glycidyl methacrylate (GMA). The beads dramatically decreased both nonspecific protein adsorption on solid surfaces and elution volume and simplified the handling procedure. Preparation of the beads for purification was carried out by immobilization of telomeric repeats, (TTAGGG)(n), on the surface after the reaction with CDDP. At least nine proteins clearly showed higher affinity to CDDP-DNA and were identified by amino acid sequence analysis including HMGB (high mobility group), hUBF (human upstream binding factor), and Ku autoantigen, which were previously reported to be components of CDDP-damaged DNA binding proteins.