Journal of Pharmaceutical Health Care and Sciences最新文献

Background: Tedizolid is an oxazolidinone anti-MRSA drug with included in the National Health Insurance Drug Price List in 2018. The effect of hemodialysis on tedizolid phosphate concentrations has been reported; pre-dialysis concentrations decreased by 10% compared to post- dialysis concentrations. However, the material of the dialysis membrane remains unknown. In addition, there have been no reports on the effects of continuous hemodiafiltration. In this study, we investigated the effects of continuous hemodiafiltration on tedizolid using two types of dialysis membranes made of different materials.

Methods: The adsorption of tedizolid, linezolid, and vancomycin to two different dialysis membranes was investigated, and the clearance of each drug was calculated by experiments using an in vitro continuous hemodiafiltration model.

Results: The adsorption of tedizolid, linezolid, and vancomycin on the dialysis membranes was examined, and no adsorption was observed. Experimental results from the continuous hemodiafiltration model showed that linezolid and vancomycin concentrations decreased over time: after two hours, the respective decreases were 26.48 ± 7.14% and 28.51 ± 2.32% for polysulfone membranes, respectively. The decrease was 23.57 ± 4.95% and 28.73 ± 5.13% for the polymethylmethacrylate membranes, respectively. These results suggested that linezolid and vancomycin were eliminated by continuous hemodiafiltration. In contrast, tedizolid phosphate and tedizolid concentrations decreased slightly in the polysulfone and polymethylmethacrylate membranes. The decrease in concentrations were 2.10 ± 0.77% and 2.97 ± 0.60% for the polysulfone membranes, respectively. For the polymethylmethacrylate membranes, the decrease in concentration were 2.01 ± 0.88% and 1.73 ± 0.27%, respectively.

Conclusion: These results suggested that tedizolid should not be considered for dose control during continuous hemodiafiltration.

Background: The loading dose of teicoplanin (TEIC) is recommended for implementation. However, there is significant discrepancy between the dose settings in the package insert and, in the guidelines, and the actual status of loading doses in Japan is unclear. Furthermore, TEIC causes liver injury as side effect. Although the risk of developing liver injury has not been reported to be increased following a loading dose based on the guidelines, there is a lack of reports in large populations. Therefore, we evaluated the trend in the loading dose and factors affecting the efficacy and safety of TEIC administration.

Methods: A Japanese administrative claims database was used in this study. Trends in loading doses were evaluated in target populations administered TEIC between 2010 and 2019. Patient characteristics were adjusted by propensity score matching based on the guideline group (total dose of 3 days > 1,600 mg) and non-guideline group (≤ 1,600 mg) of the loading dose. Finally, univariable and multivariable conditional logistic regression analysis was performed to evaluate factors affecting 30-day mortality and liver injury.

Results: A total of 10,030 patients were selected based on these criteria. The proportion of loading doses based on the recommended guidelines showed an increase over time, regardless of the implementation of therapeutic drug monitoring (TDM), but especially so in cases where TDM was implemented, the loading doses were administered in accordance with the recommendations of the guidelines. Conditional logistic regression analysis showed a relationship between drug management and guidance fees (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.36‒0.55), a reimbursement indicating pharmacist intervention, and a reduction in 30-day mortality. In addition, loading doses based on the recommended guidelines had no influence on liver injury, and other factors were not significantly associated with increased incidence of liver injury.

Conclusion: Thus, this study implies the benefits of pharmacological management as indicated by drug management and guidance fee and supports the implementation of loading doses based on the guideline on TEIC administration.

Background: We previously demonstrated that in a Japanese national university's medical faculty, overall paper publication frequency increased between 1979-1980 and 2017-2018, while original paper publication did not increase. Further, publication language changed from predominantly Japanese to English. However, whether these trends are specific to medicine or representative of other faculties remains unclear.

Methods: We diachronically analyzed annual university library-produced publication reports for four pharmaceutical and three medical units between 1979-1980 and 2019-2020, elucidating how publication frequency, type, and language medium changed.

Results: All publication types increased for the pharmaceutical faculty, from 2.87 per faculty member per year to 10.77. Publication of original papers more than doubled, from 1.06 per faculty member per year to 2.37. This increase was exclusively in English publication, with no publication of Japanese original papers in 2019-2020. This contrasts with medicine, which, while it demonstrated similar increases in all publication types combined, from 4.92 papers per faculty member per year to 12.78, did not demonstrate as striking an increase in total original paper publication (English and Japanese), from 1.21 papers per faculty member per year to 1.30. However, these two faculties observed similar trends in that English largely replaced Japanese original paper publication. That both faculties' Japanese original paper publication decreased suggests English language original paper publication comes at the expense of publishing in Japanese. Concerning both faculties together, the increase in publishing frequency for all publication types more than tripled from 4.01 to 12.38. This was largely driven by changes in conference paper publication for the pharmaceutical sciences faculty, where English publication increased 2,775% (0.06 to 1.7 papers per faculty member per year) and Japanese language publication 258% (1.33 to 4.77). While conference paper publication did increase for the medical sciences, its change in total publication frequency was largely driven by 'other' types of publication, which increased from 0.51 publications per faculty member per year in 1979-1980 to 5.41 in 2019-2020, largely driven by Japanese language publication.

Conclusion: In 2019-2020, pharmaceutical sciences faculty members largely published original papers in English, so postgraduate education should consider the future likelihood of graduates needing to publish in English.

Background: Tedizolid is a new oxazolidinone antibiotic with high potency for the treatment of infections caused by methicillin-resistant Staphylococcus aureus and other species.

Case presentation: Two patients with osteoarthritis (women aged 79 and 73 years, cases 1 and 2, respectively) infected with S. aureus were successfully treated with tedizolid after administration of 200 mg once daily via intravenous infusion. The synovial fluid and plasma concentrations of tedizolid during surgery in case 1 at day 7 were 2.1 and 1.6 µg/mL, respectively, yielding a ratio of synovial fluid/plasma of 130%. Those in case 2 at day 2 were 2.9 and 3.3 µg/mL, respectively, corresponding to a ratio of synovial fluid/plasma of 88%.

Conclusions: These results imply very similar concentrations of tedizolid in the synovial fluid and plasma of osteoarthritis patients with acute S. aureus infection.

Background: Among Japanese pharmacists, there is a gap in their commitment to self-improvement and a possible gap in their ability to identify and solve problems. However, the factors causing this situation have not yet been clarified. This study was conducted to identify factors that influence the abilities of Japanese pharmacists to identify and solve problems, which are skills considered essential for this profession. A prior history of presenting at academic conferences was set as a surrogate outcome to clarify whether having this experience affects the factors.

Methods: A nationwide internet-based survey was conducted among 300 participating hospitals and 300 community pharmacists. The survey was discontinued when the sample size of each group reached 300. The respondents were categorized into two groups on the basis of their experience of presenting at academic conferences in the survey item "status of self-improvement after employment." Their association with other survey items was determined using univariate and multivariate logistic regression analyses.

Results: The multivariate analysis revealed that 152 (50.7%) hospital pharmacists and 41 (13.7%) community pharmacists had presented at academic conferences. Among the hospital pharmacists, the experience of presenting at academic conferences was significantly associated with the "age 30 s (*references 20 s)," "presence of pharmacists to consult," "experience supervising interns," and "number of types of self-improvement" factors. For the community pharmacists, prior conference presentation experience was significantly associated with "age over 70 s," "highest educational background (doctoral or master's degree)," and "number of types of self-improvement."

Conclusion: This pioneering study suggests that having prior experience of presenting at academic conferences as a surrogate outcome of pharmacists' problem-finding and problem-solving skills may be related to the support provided by human environmental factors at the facility, the status of self-improvement, and the highest educational background.

Background: In-hospital therapeutic drug monitoring (TDM) requires a suitable quantification method for target drugs from the viewpoint of precision, throughput, and testing costs. We previously developed a practical HPLC-UV platform for quantification of serum levels of various drugs. In this report, the platform was effectively applied to the quantification of patient serum levels of five different drugs by clinical professionals in our hospital during their daily work.

Methods: The residual sera of patients receiving carbamazepine (CBZ), phenytoin (PHT), lamotrigine (LTG), vancomycin (VCM), or voriconazole (VRCZ) were used in the present clinical study. The quantification method for each drug consisted of rapid solid-phase extraction (SPE) of each drug in the patient serum, followed by optimized HPLC-UV analysis of the drug in the SPE eluate. Furthermore, patient serum levels of PHT, CBZ, and VCM were also measured by ligand-binding assay using a cobas^® analyzer in our hospital, and those of LTG and VRCZ were measured by HPLC-MS/MS at an outsourced provider. Passing-Bablok regression analysis and Bland-Altman analysis were employed to analyze the agreement of drug levels in patient sera, which was separately quantified using two different methods-our HPLC-UV platform and the cobas analyzer, or HPLC-UV and HPLC-MS/MS.

Results: All analytical conditions of the present method using our HPLC-UV platform were well optimized for each target drug quantification in the patient's serum, and the quantification method for each drug was fully validated for accuracy, precision and reproducibility. Furthermore, Passing-Bablok regression analysis and Bland-Altman analysis revealed that patient serum levels of PHT, CBZ, and VCM quantified by our HPLC-UV platform were closely correlated with those quantified by the cobas^® analyzer, and the levels of LTG and VRCZ quantified by our HPLC-UV platform were also correlated with those quantified by HPLC-MS/MS.

Conclusions: Our HPLC-UV platform can be performed without requiring special analytical techniques. This platform is expected to be used for the measurement of blood levels of multiple drugs for in-hospital routine TDM.

Background: We conducted a systematic review and meta-analysis to summarize the available literature and comprehensively appraise the renal profiles of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in Japanese patients with type 2 diabetes mellitus (T2DM).

Methods: The electronic databases MEDLINE, Ichushi-web, and ClinicalTrials.gov were searched for studies without language restrictions from their inception until 20 July 2023 and CENTRAL until 21 September 2021. Studies were included if they were double-masked randomized controlled trials (RCTs) (1) including Japanese patients with T2DM aged > 18 years who received SGLT2i or a placebo, (2) reporting at least one renal outcome of serum creatinine or the estimated glomerular filtration rate (eGFR), and (3) with a follow-up of > 12 weeks. Cross-over and open label trials were excluded. The risk of bias based on the Cochrane risk-of-bias tool for randomized trials (RoB 2) was appraised. We computed the weighed mean difference with 95%CI for each renal outcome and used a random-effects model (inverse variance method).

Results: We ultimately retrieved 13 RCTs including 2687 individuals in our review. The durations of RCTs ranged between 12 and 104 weeks. Only one trial had a longer duration of more than one year. Ten out of 13 RCTs reported serum creatinine, while nine included eGFR. Serum creatinine and eGFR were slightly worse with SGLT2i than with a placebo [mean difference 0.01 (95%CI 0.00 to 0.02) mg/dL, p = 0.002, mean difference - 1.30 (95%CI -2.23 to -0.37) mL/min/1.73 m², p = 0.006, respectively]. Merged results revealed insignificant heterogeneity (I² < 30%).

Conclusion: These results suggest that SGLT2i slightly worsens serum creatinine and eGFR in Japanese patients with T2DM. However, since the durations of most RCTs were short, the effects of eGFR in particular may be transient. Further evidence is needed from rigorous studies that focus on renal outcomes with a longer duration to confirm the present results.

Background: Optimised antithrombotic therapy requires clinical experience and an understanding of the current guidelines. This retrospective study aimed to evaluate whether pharmacist interviews and interventions with patients taking oral antithrombotic drugs in the pharmaceutical outpatient cardiology clinic had favourable clinical outcomes including decreased bleeding.

Methods: The participants included patients visiting the outpatient clinic of cardiovascular internal medicine at the Kobe University Hospital from January-December 2017, and were taking oral antithrombotic medication. The observation period was from the first visit to the outpatient clinic to October 2021 or death. Patients who received pharmacist intervention more than twice were defined as the pharmacist intervention group. Two control patients per one pharmacist intervention group individual were selected from the non-intervention pool matched for age, gender and antithrombotic medication type.

Results: Of the 895 eligible patients, 132 were in the pharmacist intervention group and 264 were selected for the matched non-intervention group. Bleeding events according to the Bleeding Academic Research Consortium criteria over type 2 were significantly lower in the pharmacist intervention group compared with the non-intervention group (17.4% versus 28.4%, P = 0.019). There were no significant differences in mortality and heart failure hospitalisation frequency, stroke, or cardiovascular events between the groups. Multivariate analysis identified age (≥ 65 years) and pharmacist intervention as factors associated with bleeding (odds ratio = 2.29 and 0.51, respectively).

Conclusion: Pharmacist intervention in the outpatient clinic of cardiovascular internal medicine was effective in reducing the risk of bleeding in patients undergoing antithrombotic therapy.

Background: Enteral nutritional supplements are used in many medical facilities and home care, but require appropriate management because they are nutrient-rich products. Recently, infection control methods for Ready To Hang (RTH) preparations, which are widely used and are expected to reduce the risk of infection, have not been established in Japan and are dependent on caregivers. Therefore, we evaluated the difference in the growth of microorganisms depending on the type of enteral nutrients following contamination with microorganisms.

Methods: Nine types of enteral nutrition were used. Escherichia coli (E. coli) W3110, Serratia marcescens (S. marcescens) NBRC3046, and Candida albicans (C. albicans) IFM61197 were used as test bacteria. The bacterial solution was added to the enteral nutritional supplement, adjusted, and the number of bacteria was measured at 0, 4, 8, and 24 h after the addition of the bacterial solution at 25 °C and in the dark.

Results: E. coli and S. marcescens grew in RACOL^®-NF SemiSolid for Enteral Use, Hine_® Jerry AQUA, and Mermed Plus_® over a 24-h period; however, a decrease was observed for other enteral nutrition products. In contrast, C. albicans grew in all enteral nutrition products.

Conclusion: Because the viscosity and calorie content vary among enteral nutrition preparations in which growth was observed, we found that pH had the greatest effect on the differences in bacterial growth. Nonetheless, C. albicans growth occurred in all nine types of enteral nutrients, indicating that unlike bacteria, its growth was independent of pH. If semi-solid enteral nutrients are contaminated with microorganisms for any reason, microorganisms will grow, so appropriate infection control is necessary to prevent infection.

Background: Epilepsy is a common neurological disorder. Lacosamide is a third-generation antiepileptic drug used to treat partial-onset seizures. Limited information is currently available on the transfer of lacosamide to breast milk. To facilitate studies on the safety of lacosamide use during breastfeeding, we aimed to develop a method to quantify lacosamide in human breast milk and plasma using ultra-performance liquid chromatography/tandem mass spectrometry.

Methods: Fifty microliters of breast milk or plasma was used, and samples were prepared by protein precipitation using methanol containing lacosamide-d₃ as an internal standard (IS). Chromatography was performed using an ACQUITY HSS T3 column with an isocratic flow of 10 mM ammonium acetate solution/methanol (70:30, v/v). Lacosamide and IS were detected by multiple reaction monitoring in positive ion electrospray mode. The run time was 3.5 min.

Results: Calibration curves were linear and in the range of 0.5 to 100 ng/mL both in breast milk and plasma. The validation assessment indicated that precision, accuracy, matrix effects, selectivity, dilution integrity, and stability were acceptable. The developed method was successfully applied to quantify lacosamide in breast milk and plasma obtained from a volunteer who had been orally administered lacosamide twice a day (100 mg × 2). Relative infant dose of lacosamide was estimated to be 14.6% in breast milk at five time points.

Conclusions: We developed a simple and robust method to quantify of lacosamide in human breast milk and plasma. This method could be useful for in future studies investigating the safety of lacosamide use during breastfeeding.