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INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN. METHODS AND ANALYSIS: We will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B12, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ2, Cochran's Q test and I² statistic. ETHICS AND DISSEMINATION: This review does not require ethical approval. The research will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022371829.

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BACKGROUND: Early monitoring and feedback on the treatment of infectious diseases are some of the methods for optimising antimicrobial treatment throughout the treatment period. Prospective audits and feedback interventions have also been shown to improve antimicrobial use and reduce antimicrobial resistance. We examined the appropriate use of antimicrobials by focusing on the initial timing for audits and feedback intervention of antimicrobial prescription by Infection Control Team pharmacists. METHODS: We conducted a retrospective observational study in a university hospital in Tokyo, Japan from 1 January 2019 to 31 May 2021. We retrospectively enrolled patients with infections and those patients suspected of having an infection, who were administered vancomycin and assessed at our hospital. The definition of primary outcome was the maintenance of target vancomycin trough blood concentrations of 10-20 µg/ml during treatment. Multivariable logistic regression and multivariate linear regression analyses were performed to test the effectiveness of the initial timing of the intervention by Infection Control Team pharmacists as the explanatory variable. RESULTS: A total of 638 patients were included in this study, with a median age of 69 years (interquartile range: 54-78 years). Multivariable logistic regression revealed that the maintenance of target vancomycin trough concentrations was not associated with the timing of the audit and the initiation of monitoring by Infection Control Team pharmacists (adjusted odds ratio: 0.99, 95% confidence interval: 0.99-1.00, p = 0.990). Multivariate linear regression revealed that the duration of vancomycin administration was significantly correlated with the timing of initiation of monitoring by Infection Control Team pharmacists (adjusted estimate: 0.0227, standard error: 0.0051, p = 0.012). CONCLUSIONS: Our study showed that early initiation of a comprehensive audit and monitoring by Infection Control Team pharmacists did not affect the maintenance of the target vancomycin trough blood concentration. However, it reduced the duration of vancomycin administration.

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OBJECTIVES: Alternative dosing strategies for ß-lactams - the most common antibiotics used to treat critically ill patients with respiratory tract infections - have been recommended to maximize the duration of exposure and reduce drug resistance. The objective of this study was to evaluate whether extended infusion of antipseudomonal ß-lactams improves mortality and clinical efficacy. METHODS: Two independent authors identified eligible trials by searching the PubMed, Cochrane Library, Scopus, and ICHUSHI databases, in both English and Japanese, up to June 2019. Data were extracted from both randomized controlled and observational trials comparing extended infusion (≥3h) with intermittent infusion in critically ill patients. The primary outcome was all-cause mortality. Risk differences (RD) and 95% confidential intervals (CI) were calculated using a random-effects model and subgroup analyses were performed. Sensitivity and heterogeneity were also evaluated. RESULTS: Nine studies involving 1508 participants were included in the meta-analysis. Mortality was lower for extended infusion than for intermittent infusion (RD -0.10; 95% CI -0.15 to -0.04). However, no significant between-group differences in clinical success, length of ICU stay, length of hospital stay, and antibiotic duration were observed. CONCLUSIONS: Extended infusions of ß-lactams were associated with reduced mortality rates but not with clinical success.

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OBJECTIVE: The aim of this study is to assess prophylactic prescriptions for febrile neutropenia(FN)caused by chemotherapy. INVESTIGATION: We retrospectively surveyed prophylactic antibiotic prescriptions administered to 930 cancer treatment naive outpatients at Showa University Hospital. Factors associated with prophylactic antibiotic prescriptions were assessed based on patient characteristics, intensity of chemotherapy regimens, laboratory data and diagnoses using logistic regression analysis. RESULTS: The number of patients given prophylactic antibiotic prescriptions was significantly higher in high-risk regimens(n= 349)compared to low-risk regimens(n=288), with an odds ratio of 8.93(6.07-13.14). In logistic regression analysis, significant factors affecting the prophylactic prescription of antibiotics were high-risk regimens(OR: 2.05, p=0.009), age(+ 1 year, OR: 0.98, p=0.002), female sex(OR: 7.10, p<0.001), WBC count(+1.0×10 / 3mL, OR: 1.19, p=0.013)and operation history before and after chemotherapy(OR: 23.19, p<0.001). CONCLUSIONS: Physicians(including pharmacists)should therefore pay attention to the prophylactic prescriptions especially in high-risk female cancer patients with operation history. This prescription pattern provides basic information needed for the proper use of antibiotics in cancer patients.

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It has been suggested that low health literacy (HL) is associated with poor medication adherence. This study aimed to examine the effect of a text message-based HL intervention to promote medication adherence, compared with text messages that only sent medication reminders, in patients with type 2 diabetes. This was a single-center, open-label, randomized (1:1) controlled pilot study. The study period was 6 months. Intervention group was sent HL related text messages, compared to the reminder messages that were sent to the control group. The primary outcome was the difference in the change rate of scores on the Morisky Eight-Item Medication Adherence Scale (MMAS-8). Forty-one participants were randomized into the intervention (n = 21) and control (n = 20) groups and completed the 6-month follow-up. Although almost participants read and understood the information provided in the messages, no significant difference was observed between groups for the primary outcome (p = 0.78). Our results suggested that medication adherence at 6 months after discharge in patients with type 2 diabetes did not significantly change by text messages, which aimed to improve their HL levels.

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Epidermal growth factor receptor (EGFR) mediated mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway was isolated as invasion-metastasis related factor in pancreatic cancer in our previous studies. Matrix metalloproteinase-7 (MMP-7) and tight junction (TJ) proteins are indicated to be involved in cancer invasion-metastasis. To clarify the underlying mechanism of involvement of MMP-7 in cancer invasion, western blotting, invasion assay and immunohistochemistry were performed in dissociated (PC-1.0 and AsPC-1) and non-dissociated (PC-1 and Capan-2) pancreatic cancer cells, as well as pancreatic cancer tissues. Intracellular MMP-7 protein presented as pre-proenzyme and its expression was decreased by AG1478 (EGFR inhibitor) or U0126 (MEK inhibitor) treatment in pancreatic cancer cells. Activated MMP-7 protein was only detected in the medium of PC-1.0 and AsPC-1 cells, but not detected in the medium of PC-1 and Capan-2 cells. Moreover, MMP-7 treatment significant induced the dissociation of cell colonies in PC-1 and Capan-2 cells. Synchronously, TJ structure was apparently disrupted and translocation of TJ proteins to cytoplasm or extracellular medium was induced in PC-1 and Capan-2 cells. Furthermore, MMP-7 treatment markedly increased the in vitro invasion of PC-1 and Capan-2 cells. In addition, MMP-7 expression at the invasive front was obviously stronger than that at the center of pancreatic cancer tissues. Activation of MMP-7 protein is closely involved in disruption of TJ structure and consequent induction of cell dissociation as well as invasion in pancreatic cancer. EGFR mediated MEK/ERK signaling pathway is implied to be involved in regulation of MMP-7 expression in pancreatic cancer cells.

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A 50-year-old Japanese fish dealer presented with painful and swollen fingers. Infectious flexor tenosynovitis with Mycobacterium marinum was suspected. Range of motion was restored after tenosynovectomy and after ofloxacin and clarithromycin were administered. Two years after the operation, the patient presented again with acute inflammation in the same fingers. Histopathological examination revealed gouty tenosynovitis. The preconception that mycobacterial infection occurs often in fish dealers caused us to miss the correct diagnosis of gouty tenosynovitis.