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. 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 4^th and April 25^th, 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. 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. 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.

Methicillin-resistant Staphylococcus aureus (MRSA), the most commonly detected drug-resistant microbe in hospitals, adheres to substrates and forms biofilms that are resistant to immunological responses and antimicrobial drugs. Currently, there is a need to develop alternative approaches for treating infections caused by biofilms to prevent delays in wound healing. Silver has long been used as a disinfectant, which is non-specific and has relatively low cytotoxicity. Silver sulfadiazine (SSD) is a chemical complex clinically used for the prevention of wound infections after injury. However, its effects on biofilms are still unclear. In this study, we aimed to analyze the mechanisms underlying SSD action on biofilms formed by MRSA. The antibacterial effects of SSD were a result of silver ions and not sulfadiazine. Ionized silver from SSD in culture media was lower than that from silver nitrate; however, SSD, rather than silver nitrate, eradicated mature biofilms by bacterial killing. In SSD, sulfadiazine selectively bound to biofilms, and silver ions were then liberated. Consequently, the addition of an ion-chelator reduced the bactericidal effects of SSD on biofilms. These results indicate that SSD is an effective compound for the eradication of biofilms; thus, SSD should be used for the removal of biofilms formed on wounds.

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.

Background and objectives: Skin grafting is a method usually used in reconstructive surgery to accelerate skin regeneration. This method results frequently in unexpected scar formations. We previously showed that cutaneous wound-healing in normal mice is accelerated by a micrograft (MG) technique. Presently, clinical trials have been performed utilizing this technology; however, the driving mechanisms behind the beneficial effects of this approach remain unclear. In the present study, we focused on five major tissue reactions in wound-healing, namely, regeneration, migration, granulation, neovascularization and contraction. Methods: Morphometrical analysis was performed using tissue samples from the dorsal wounds of mice. Granulation tissue formation, neovascularization and epithelial healing were examined. Results: The wound area correlated well with granulation sizes and neovascularization densities in the granulation tissue. Vascular distribution analysis in the granulation tissue indicated that neovessels extended and reached the subepidermal area in the MG group but was only halfway developed in the control group. Moreover, epithelialization with regeneration and migration was augmented by MG. Myofibroblast is a known machinery for wound contraction that uses α-smooth muscle actin filaments. Their distribution in the granulation tissue was primarily found beneath the regenerated epithelium and was significantly progressed in the MG group. Conclusions: These findings indicated that MG accelerated a series of wound-healing reactions and could be useful for treating intractable wounds in clinical situations.

Change in the Antimicrobial Resistance Profile of Extended-Spectrum β-Lactamase-Producing Escherichia coli

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.