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Pseudomonas aeruginosa bacteremia is associated with a high mortality rate, and meropenem (MEPM) is commonly used to treat it. However, the relationship between the time above the minimum inhibitory concentration ( f T >MIC ) of MEPM and its therapeutic efficacy in P. aeruginosa bacteremia has not been explored. This study aimed to investigate this relationship by defining the target % f T >MIC of MEPM as 75%. The retrospective study spanned 14 years and included hospitalized patients treated with MEPM for P. aeruginosa bacteremia. Monte Carlo simulation was used to calculate the probability of target attainment (PTA) for each patient, and the threshold for a PTA of 75% f T >MIC associated with in-hospital survival was determined using receiver operating characteristic (ROC) curves. The ROC curve-derived PTA associated with improved in-hospital survival was 65.0%, a significant finding in multivariate logistic regression analysis adjusted for patient background factors (odds ratio: 20.49, 95% confidence interval: 3.02-245.23, p = 0.005). This result suggests a dosing regimen that achieves a PTA of at least 65% when the target f T >MIC of MEPM for treating P. aeruginosa bacteremia is defined as 75%.

Background: Immune-checkpoint inhibitors (ICIs) are effective against various cancers; however, immune-related adverse events (irAEs) have been reported and the timing and risk factors are unknown. Therefore, we examined the incidence and timing of irAE occurrence., Methods: Patients who received ICIs at our hospital between 1 April 2016 and 31 March 2020 were enrolled. Patients were classified into an irAE group or non-irAE group. In addition, we examined the onset time and symptoms of irAEs for each ICI type., Results: A total of 80 patients received ICIs, of which 27 (33.8%) developed irAEs. The incidence of irAEs was 35.3% for nivolumab, 35.5% for pembrolizumab, and 28.6% for atezolizumab. The incidence of pneumonitis was 12.5%, 8.8% for dermatologic adverse events, and 6.3% for thyroid dysfunction. The earliest case of onset was after the 1st course, and the latest cases occurred after the 66th course. By the sixth course, 69% of the irAEs occurred. The positive rates for anti-thyroid peroxidase and anti-thyroglobulin antibodies were higher in the irAE group compared to the non-irAE group., Conclusions: Our findings suggest a high probability of irAEs occurring early in ICI treatment, with a diverse range of symptoms. This underscores the need for vigilant monitoring and tailored patient management during the initial courses of ICI therapy.

Background: The causative microorganisms of bloodstream infections (BSIs) in patients with inflammatory bowel disease (IBD) and the clinical characteristics of these patients have not yet been fully identified. Therefore, this study investigated IBD patients who developed BSI to determine their clinical characteristics and identify the BSI-causing bacteria., Methods: The subjects were IBD patients who developed bacteremia between 2015 and 2019 at Fukuoka University Chikushi Hospital. The patients were divided into two groups according to IBD type (Crohn's disease (CD) or ulcerative colitis (UC)). The medical records of the patients were reviewed to determine their clinical backgrounds and identify the BSI-causing bacteria., Results: In total 95 patients, 68 CD and 27 UC patients were included in this study. The detection rates of Pseudomonas aeruginosa ( P. aeruginosa ) and Klebsiella pneumoniae ( K. pneumoniae ) were higher in the UC group than in the CD group (18.5% vs. 2.9%, P = 0.021; 11.1% vs. 0%, P = 0.019, respectively). Immunosuppressive drugs use was higher in the CD group than in the UC group (57.4% vs. 11.1%, P = 0.00003). Hospital stay length was longer in the UC group than in the CD group (15 vs. 9 days; P = 0.045)., Conclusions: The causative bacteria of BSI and clinical backgrounds differed between patients with CD and UC. This study showed that P. aeruginosa and K. pneumoniae had higher abundance in UC patients at the onset of BSI. Furthermore, long-term hospitalized patients with UC required antimicrobial therapy against P. aeruginosa and K. pneumoniae., Competing Interests: The authors declare that they have no competing interests., (Copyright 2023, Kamada et al.)

A nucleic acid amplification test (NAAT) is recommended to determine whether or not patients have a Clostridioides difficile infection (CDI) when the glutamate dehydrogenase activity assay is positive and the rapid membrane enzyme immunoassays for toxins is negative. In our hospital, a NAAT was introduced to diagnose CDI precisely in April 2020. This study aimed to investigate the impact of a NAAT on the clinical outcomes in patients with CDI at our hospital. Seventy-one patients diagnosed with CDI between April 2017 and March 2022 were included in our study. Patients with CDI were divided into two groups: before (pre-NAAT) and after (post-NAAT) the introduction of NAAT. The clinical outcome was compared between the two groups. Of the 71 patients with CDI, 41 were sorted into the pre-NAAT group and 30 into the post-NAAT group. The clinical cure rate was significantly higher in the post-NAAT group compared to the pre-NAAT group (76.7% vs. 48.8%, p = 0.018). In the multivariable analysis, the clinical cure was significantly associated with the introduction of NAAT ( p = 0.022). Our findings suggest that the introduction of NAAT can improve the clinical outcomes in CDI patients.

Background and Objectives : Remdesivir (RDV) is the first antiviral agent approved in Japan for the treatment of coronavirus disease 2019 (COVID-19). The aim of our study was to assess the efficacy and safety of RDV treatment in mildly to moderately ill patients with COVID-19. Materials and Methods: A single-center, retrospective study was performed in Fukuoka University Chikushi Hospital. Patients admitted to our hospital from June to October 2021 for RDV treatment against COVID-19 were enrolled. The primary end point was clinical status on days 10 and 14, using a 6-point ordinal scale ranging from death (category 6) to discharge (category 1). Adverse events were assessed and graded using the Japanese version of Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results : In total, 47 COVID-19 patients receiving RDV treatment were assessed during the study period. Thirty-four (72.3%) out of 47 patients required oxygen therapy. Out of these 34 patients, 30 (88.2%) showed a 2-point clinical improvement on day 14 after RDV was initiated. Serum alanine aminotransferase levels were elevated in three patients (6.4%) (CTCAE Grade 3) and neutropenia was detected in one patient (2.1%) out of the 47 patients. Conclusions : RDV may be highly effective, with good safety profiles, in patients with COVID-19 requiring oxygen therapy.

Background: The substantial increase in the use of expensive anticancer drugs has been accompanied by an increase in the amount of disposing residual liquid from drug preparations. Many Western countries, including the United States, have implemented drug vial optimization (DVO) to prevent the waste of anticancer drugs and have reported the reductions in the total drug costs. This study was designed to estimate the expected reduction in spending on anticancer drugs by Japanese cancer hospitals when DVO was implemented instead of individual preparations and to test the effectiveness of this approach., Methods: We investigated the doses of drugs used and quantity specifications for individually prepared vials for patients who received anticancer drug treatment in December 2017 at the Outpatient Treatment Center of the National Cancer Center Hospital East. Based on these findings, we calculated the total quantity of each drug used on a given day, and the minimum cost for preparation of the number of specified combinations corresponding to the total cost (DVO preparation). Based on the differences in these two costs, we estimated the economic impact of implementing DVO., Results: While the cost for anticancer drugs for the 1-month study period was US$3,305,595 (US$1 = \110) for individual preparations, the estimated cost for DVO preparations was US$3,092,955, equivalent to a reduction of US$212,640., Conclusions: Based on these study results, implementation of DVO-based preparation of injectable anticancer drugs in Japan in 2017 would have resulted in saving approximately US$460 million. This calculation revealed the need for the Japanese government to modify the methods employed to calculate drug costs in the insurance system and develop policies for the proper and optimal use of medical resources.

Background: Polypharmacy (PP) and potentially inappropriate medications (PIMs) cause problematic drug-related issues in elderly patients; however, little is known about the association between medication adherence and PP and PIMs. This study evaluated the association of self-reported medication adherence with PP and PIMs in elderly patients., Methods: A cross-sectional pilot study was conducted using data collected from electronic medical records of 142 self-administering patients aged ≥65 years, excluding emergency hospitalization cases. Self-reported medication adherence was assessed using the visual analogue scale (VAS)., Results: Of the 142 patients, 91 (64.1%) had PP and 80 (56.3%) used at least one PIM. In univariate analysis, patients with a VAS score of 100% had a significantly higher number of female patients and ≥1 PIM use compared to other patients. We found no association between the VAS score and PP. In multivariable analysis, the use of PIMs was significantly associated with a VAS score of 100% (odds ratio = 2.32; 95% confidence interval = 1.16-4.72; p = 0.017)., Conclusions: Use of PIMs by elderly patients is significantly associated with self-reported medication adherence. Pharmacists should pay more attention to prescribed medications of self-administering elderly patients in order to improve their prescribing quality.

Background: Inappropriate dosing of direct oral anticoagulants (DOACs) has been associated with clinical safety and efficacy; however, little is known about clinical data associated with an inappropriate DOAC dosing in Japan. In addition, there is no report in which the appropriateness of DOAC dosing between prescription for inpatients and for outpatients was examined. In this study, we aimed to investigate the prevalence and factors associated in the inappropriate dosing of DOACs in patients with atrial fibrillation (AF)., Methods: The retrospective cohort study was conducted at a single Japanese university hospital. Both inpatients and outpatients, who were diagnosed with AF and for whom treatment with either dabigatran, rivaroxaban, apixaban, or edoxaban was initiated between April 1, 2014 and March 31, 2018, were enrolled in the study. Appropriateness of DOAC dosing was assessed according to the manufacturer's labeling recommendations (dose reduction criteria) of each DOAC. Inappropriate reduced dose, namely, underdosing, was defined as prescription of a reduced dose of DOAC despite the patient not meeting the dose reduction criteria. Inappropriate standard dose, namely, overdosing, was defined as prescription of a standard dose of DOAC despite the patient meeting the dose reduction criteria. Inappropriate DOAC dosing was defined as a deviation of the recommended dose (both underdosing and overdosing)., Results: A total of 316 patients (dabigatran, 28; rivaroxaban, 107; apixaban, 116; and edoxaban, 65) were included, with a median (interquartile range) age of 75 (66-81) years and 62.3% male. DOACs were prescribed at an appropriate standard dose in 39.2% of patients, an appropriate reduced dose in 36.7%, an inappropriate standard dose in 2.5%, and an inappropriate reduced dose in 19.3%. Multivariate analysis revealed that the inappropriate dosing of DOACs was significantly associated with prescriptions for outpatients (vs. inpatients; odds ratio [OR] 2.87, 95% confidence interval [CI] 1.53-5.62, p  < 0.001) and those with higher HAS-BLED scores (OR 1.87, 95% CI 1.42-2.51, p < 0.001)., Conclusions: Our results demonstrated that the inappropriate dosing of DOACs occurred in approximately 20% of AF patients, and was more frequent in outpatients (vs. inpatients) and in those with a higher risk of bleeding. It is recommended that pharmacists play a greater role in assisting in the prescription process to help physicians make better decisions., Competing Interests: Competing interestsThe author(s) declare no competing interests., (© The Author(s). 2020.)

Background: This study aimed to investigate the trends and antimicrobial resistance profile of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) clinical isolates., Methods: A total of 1,303 E. coli isolates from January 2012 to December 2017 at Fukuoka University Chikushi Hospital, Japan, were analyzed. The rate of resistance to cefmetazole (CMZ), flomoxef (FMOX), imipenem (IPM), meropenem (MEPM), amikacin (AMK), gentamicin (GM), minocycline (MINO), ciprofloxacin (CPFX), and levofloxacin (LVFX) was compared between non-ESBL-producing E. coli (non-ESBL-EC) and ESBL-EC., Results: The proportion of ESBL-EC among all the E. coli isolates was 24.6% (320/1,303), and the proportion remained stable throughout the study period. There was no difference in the rate of resistance to CMZ, FMOX, IPM, MEPM, and AMK between non-ESBL-EC and ESBL-EC; however, the rate of resistance to GM, MINO, CPFX, and LVFX was higher in ESBL-EC than in non-ESBL-EC (17.5% vs. 10.0%, 19.1% vs. 7.7%, 87.5% vs. 24.2%, and 87.5% vs. 23.5%, respectively; P < 0.01). The rate of resistance to CPFX and LVFX in ESBL-EC increased throughout the study course. The rate of E. coli isolates susceptible to all the antibiotics was significantly higher in non-ESBL-EC than in ESBL-EC (68.2% vs. 7.5%; P < 0.01), and this rate decreased significantly from 10.0% in 2012 to 3.8% in 2017 in ESBL-EC (P < 0.01)., Conclusions: Our findings indicate a changing antimicrobial resistance profile of ESBL-EC, particularly to fluoroquinolones. Determination of the prevalence and antimicrobial resistance of ESBL-EC will help physicians in selecting the initial empirical treatment for patients with ESBL-EC infections., Competing Interests: The authors declare that they have no conflict of interest.

Objective: The aim of this study was to examine the association between medication adherence and illness perceptions, and to explore the factors associated with poor medication adherence in atrial fibrillation (AF) patients receiving direct oral anticoagulants (DOACs) in a real-world clinical setting., Methods: An observational cross-sectional pilot study was conducted at a single Japanese university hospital. One hundred and twenty-nine patients who were diagnosed with AF and who were taking DOACs were recruited from outpatients between January 4th and April 25th, 2017. We evaluated medication adherence to DOACs using the Morisky Medication Adherence Scale-8 (MMAS-8) and illness perceptions using the Brief Illness Perception Questionnaire (BIPQ). The patients' characteristics and clinical data were collected from electronic medical records., Results: Ninety-nine (76.7%) patients (male, n = 74; mean age, 71.4±9.8 years) participated in this study. According to the MMAS-8, 21 (21.2%) of the patients were classified into the poor adherence group (MMAS-8 score of <6), and 78 (78.8%) were classified into the good adherence group (MMAS-8 score of 6-8). A multivariate logistic regression analysis revealed that age (per year, odds ratio [OR] 0.912, 95% confidence interval [CI] 0.853-0.965, p = 0.001), a history of warfarin use (OR 0.181, 95% CI 0.033-0.764, p = 0.019), duration of DOAC exposure (per 100 days, OR 1.245, 95% CI 1.084-1.460, p = 0.001), and the BIPQ emotional response score (per 1 point, OR 1.235, 95% CI 1.015-1.527, p = 0.035) were significantly associated with poor medication adherence in AF patients receiving DOACs., Conclusion: Poor medication adherence to DOACs was strongly associated with a stronger emotional response (i.e. stronger feelings of anger, anxiety, and depression), as well as younger age, the absence of a history of warfarin treatment, and longer DOAC exposure. Further evaluation of the factors associated with medication adherence in AF patients and the development and execution of strategies for improving poor adherence are warranted in the real-world clinical setting., Competing Interests: The authors have declared that no competing interests exist.

BACKGROUND Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening syndrome comprising severe skin eruption, fever, eosinophilia, lymphadenopathy, and involvement of internal organs. Here, we describe a case of DRESS syndrome caused by cross-reactivity between vancomycin and subsequent teicoplanin administration. CASE REPORT A 79-year-old male was admitted to our hospital for the treatment of injuries incurred in a traffic accident. Eosinophilia and lung dysfunction appeared after vancomycin administration. These symptoms were improved temporarily by withdrawal of vancomycin and administration of corticosteroid, but exacerbated by subsequent teicoplanin administration. These symptoms disappeared after discontinuation of teicoplanin. Based on comprehensive assessment of the overall clinical course, we judged that DRESS syndrome was induced by cross-reactivity between vancomycin and subsequent teicoplanin administration. Using the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system, we categorized DRESS syndrome related to vancomycin and teicoplanin as "probable." We describe, for the first time, DRESS syndrome (defined using the RegiSCAR scoring system) caused by cross-reactivity between vancomycin and subsequent teicoplanin administration. CONCLUSIONS Clinicians should be aware that DRESS syndrome can be induced by cross-reactivity between vancomycin and teicoplanin.

Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients.

Aims: The present study aimed to evaluate the associations between medication use and falls and to identify high risk medications that acted as a trigger for the onset of falls in an acute care hospital setting., Methods: We applied a case-crossover design wherein cases served as their own controls and comparisons were made within each participant. The 3-day period (days 0 to -2) and the 3-day periods (days -6 to -8, days -9 to -11 and days -12 to -14) before the fall event were defined as the case period and the control periods, respectively. Exposures to medications were compared between the case and control periods. Odds ratios (OR) and 95% confidence intervals (CI) for the onset of falls with respect to medication use were computed using conditional logistic regression analyses., Results: A total of 349 inpatients who fell during their hospitalization were recorded on incident report forms between March 2003 and August 2005. The initial use of antihypertensive, antiparkinsonian, anti-anxiety and hypnotic agents as medication classes was significantly associated with an increased risk of falls, and these ORs (95% CI) were 8.42 (3.12, 22.72), 4.18 (1.75, 10.02), 3.25 (1.62, 6.50) and 2.44 (1.32, 4.51), respectively. The initial use of candesartan, etizolam, biperiden and zopiclone was also identified as a potential risk factor for falls., Conclusions: Medical professionals should be aware of the possibility that starting a new medication such as an antihypertensive agent, including candesartan, and antiparkinsonian, anti-anxiety and hypnotic agents, may act as a trigger for the onset of a fall.