A Survey of Near-Miss Dispensing Errors in Hospital Pharmacies in Japan: DEPP-J Study-Multi-Center Prospective Observational Study-

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

[Elucidation of Influential Factors on Nausea Associated with Olaparib Administration].

Olaparib, an anticancer drug, requires daily administration, frequently causing nausea. Elucidation of the influential factors for nausea is important for continuing treatment. We retrospectively examined 23 patients who received olaparib treatment and were divided into nausea and no-nausea groups, according to antiemetic prescriptions during treatment. We compared the patients' background and laboratory values between the 2 groups. Nine patients developed nausea and 14 did not, with mean body weights at treatment initiation of 49.9±9.8 kg and 60.0±13.9 kg, respectively. Body weights were significantly lower in the nausea than in the no-nausea group. Four weeks after olaparib administration, the logarithmic difference in the fluctuation of the neutrophil count was -0.145±0.154 and 0.095±0.242, while the fluctuation of the lymphocyte count was -0.169±0.053 and -0.060±0.110 in the nausea and no-nausea groups, respectively, with the former significantly lower than the latter. The treatment period for the nausea group was significantly longer than that for the no-nausea group. Since olaparib is administrated as a flat dose, the dose per body weight increased in underweight patients. Thus, being underweight might have impacted the efficacy of olaparib, including the development of side effects such as nausea and hematotoxicity.

[Effect of Hypoalbuminemia on Severe Neutropenia Induced by Paclitaxel Monotherapy and Paclitaxel plus Ramucirumab Combination Therapy in Patients with Gastric Cancer].

Hypoalbuminemia is often observed in patients receiving chemotherapy for gastric cancer. The risk of hematologic toxicity is increased by the pharmacokinetic alteration of paclitaxel(PTX)owing to high serum protein binding in patients with hypoalbuminemia. Here, we examined the relationshipbetween the frequency of GradeB3 neutropenia and serum albumin concentration in 30 patients receiving PTX monotherapy, and 29 patients receiving PTX plus ramucirumab(RAM)combination therapy-a second-line treatment for advanced/recurrent gastric cancer. The number of patients who developed GradeB3 neutropenia was 8(27%)and 14(48%)of those who received monotherapy and combination therapy, respectively, with mean serum albumin concentrations of 3.31 g/dL and 3.15 g/dL, respectively. Serum albumin concentrations were significantly lower in the GradeB3 neutropenia group than in the non-GradeB3 neutropenia group in both regimens. When the serum albumin concentration of patients receiving PTX or PTX plus RAM was below the cut-off values of 3.75 g/dL and 3.45 g/dL, respectively, the odds ratio of GradeB3 neutropenia was 12.25 and 7.33, respectively. Hypoalbuminemia was associated with the development of chemotherapy-induced GradeB3 neutropenia, in patients with gastric cancer treated with either PTX monotherapy or PTX plus RAM combination therapy. Therefore, not only neutrophils but also serum albumin concentration should be monitored during chemotherapy.

Decreased Prevalence of qacA-Positive Methicillin-Resistant Staphylococcus aureus in Hospitalized Patients in Tokyo, Japan.

Presence of methicillin-resistant Staphylococcus aureus (MRSA) strains carrying plasmid-borne multidrug efflux pump-encoding gene, qacA/B, is a serious issue for infection control in hospitals, because they can survive hand hygiene. The qacA/B genes are divided into five subtypes: qacA, qacBI, qacBII, qacBIII, and qacBIV. The aim of this study was to investigate the prevalence and risk factors of hospitalized patients infected by respective qacA/B-positive MRSA strains between 2010 and 2016 in Tokyo, Japan. Of the 600 total MRSA strains observed, the qacA/B-positive strains constituted 19.8% (199 isolates), of which 56.8% (113 isolates), 28.6% (57 isolates), and 14.6% (29 isolates) were classified as qacA, qacBIII, and qacBII-positive strains, respectively. The prevalence of qacA-positive MRSA strains significantly decreased from July 2010 to June 2011 (34.0%) to July 2015 to May 2016 (5.3%) (p < 0.05). When staphylococcal cassette chromosome (SCC)mec types of the respective qacA/B-positive strains were determined, 81.4% of the qacA-positive strains were classified into SCCmec type II, which has recently been decreasing in hospital-acquired MRSA in Japan. Risk factor analysis showed that there were no specific clinical departments associated with the presence of qacA-positive strains. Our findings suggest that change in the MRSA clonal lineages impact to decrease the prevalence of qacA-positive strains in Japanese hospitals.

[Identification of the Risk Factors for Cabazitaxel-Induced Neutropenia with Preventive Administration of Pegfilgrastim].

Prophylaxis using pegfilgrastim is recommended to prevent cabazitaxel-induced neutropenia. We observed GradeB3 neutropenia in a patient after administration of cabazitaxel, despite prophylaxis using pegfilgrastim. To identify the risk factors associated with GradeB3 neutropenia, we retrospectively investigated the records of 10 patients who received prophylaxis with pegfilgrastim after administration of cabazitaxel. They were divided into GradeB3 neutropenia and non-GradeB3 neutropenia groups, and we compared the background data and laboratory values between the 2 groups. A univariate analysis revealed that hypoalbuminemia was significantly observed in patients with cabazitaxel-induced GradeB3 neutropenia. The incidence of GradeB3 neutropenia was significantly high in patients with serum albumin levels<3.6 g/dL. Cabazitaxel has a high rate of protein binding; moreover, serum albumin levels<3.6 g/dL might be associated with high concentrations of unbound cabazitaxel, and thus an increase in the incidence of GradeB3 neutropenia. Therefore, hypoalbuminemia at the time of administration of cabazitaxel may be a risk factor related to the development of GradeB3 neutropenia.

[Retrospective Investigation of the Risk Factors for Severity in Panitumumab-Induced Hypomagnesemia].

Hypomagnesemia caused by panitumumab can often lead to severe adverse effects, such as arrhythmia. However, the risk factors are still controversial. To clarify the risk factors and time to onset of panitumumab-induced hypomagnesemia, we retrospectively investigated the records of 30 patients who had received panitumumab. They were divided into Grade B2 hypomagnesemia and non-Grade B2 hypomagnesemia groups, according to their serum magnesium levels, and we compared patients' backgrounds, laboratory values, and concomitant drugs between the 2 groups. Univariate analysis revealed that hypocalcemia and non-administration of an oral magnesium preparation were significantly associated with Grade B2 hypomagnesemia induced by panitumumab. Incipient grade 1 hypocalcemia was observed after incipient Grade 1 hypomagnesemia in both groups. The occurrence of these complications was significant in the Grade B2 hypomagnesemia group. Thereafter, in all patients of the Grade B2 hypomagnesemia group that exhibited both complications, hypomagnesemia developed to Grade 2 or higher. The development of Grade 3 and Grade 4 hypomagnesemia without the development of Grade 2 hypomagnesemia was observed in 2 patients each. Thus, aggravation of hypomagnesemia can be expected upon the administration of panitumumab, and therefore, not only serum magnesium levels, but also serum calcium levels need to be monitored.

Predictability of serum vancomycin concentrations using the kinetic estimated glomerular filtration rate formula for critically ill patients
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OBJECTIVE: To evaluate the predictability of serum vancomycin concentrations of critically ill patients using the new kinetic estimated glomerular filtration rate (KeGFR) and other three established eGFR formulae. MATERIALS AND METHODS: We calculated serum vancomycin concentrations using software provided by the manufacturer of vancomycin. RESULTS: Data were collected from 122 hospitalized adults. The mean error and mean absolute error of KeGFR were 0.81 µg/mL and 4.46 µg/mL, respectively. The root mean squared prediction error of KeGFR was the highest (6.67 µg/mL) among the four formulae. CONCLUSION: The predictability of KeGFR formula did not show good accuracy in critically ill patients.
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Change in genotype of methicillin-resistant Staphylococcus aureus (MRSA) affects the antibiogram of hospital-acquired MRSA.

Recently, the dissemination of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) into hospitals has frequently been reported worldwide. Hospital-acquired MRSA (HA-MRSA) strains exhibit high-level resistance to multiple antimicrobial agents, whereas CA-MRSA strains are usually susceptible to non-ß-lactams. Thus, it is predicted that the antibiogram of the HA-MRSA population would change along with the change in genotype of MRSA. Here, we investigated the changes in the MRSA population along with the MRSA antibiogram in a hospital between 2010 and 2016. Staphylococcal cassette chromosome (SCC) mec typing showed that the predominant HA-MRSA strains in the hospital dramatically changed from SCCmec type II, which is the major type of HA-MRSA, to SCCmec type IV, which is the major type of CA-MRSA. Multilocus sequence typing revealed that the predominant SCCmec type IV strain was a clonal complex (CC) 8 clone, which is mainly found among CA-MRSA. Furthermore, the CC1-SCCmec type IV (CC1-IV) clone significantly increased. Both the CC8-IV and CC1-IV clones exhibited high antimicrobial susceptibility. The antibiogram change of the HA-MRSA population was consistent with the antimicrobial susceptibilities and increased prevalence of the CC8-IV and CC1-IV clones. Our data reveal that the change in the genotypes of MRSA strains could impact the antibiogram of HA-MRSA population.

A disposable voltammetric cell for determining the titratable acidity in vinegar.

A disposable voltammetric cell using three pencil leads as working, reference, and counter electrodes was developed for determining the titratable acidity, i.e. the acid content in vinegar. The materials of the pencil leads were graphite-reinforcement carbons (GRCs). A voltammetric determination of acid was made by measuring the reduction prepeak current of 3,5-di-t-butyl-1,2-benzoquinone (DBBQ) due to the presence of acids in unbuffered solution. The potential stability of the pseudo-reference electrode of GRC was examined. The prepeak current was found to be proportional to the acetic acid concentration from 0.05 to 2.7 mM with a correlation coefficient of 0.999. The cell-to-cell reproducibility for 1 mM acetic acid was evaluated with ten individual disposable cells. The RSD of the prepeak current and the SD of the prepeak potential were 2.56% and 0.008, respectively. The titratable acidity in five vinegar samples was determined by voltammetry using disposable cells and compared with that of the titratable acidity determined by the conventional potentiometric titration method. We then observed the results by both methods, and found a correlation coefficient of 0.972. As such, the voltammetry using disposable-cell required only one thousandth the volume of a vinegar sample for the titration method. The disposable cell was superior to the conventional electrochemical cell, in terms of facility, environment-friendly, and economy, and thus a sensor using the present cell would be useful for routine work in the quality control of vinegar.