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Toshinobu Hayashi,1,2 Mototsugu Shimokawa,3 Koichi Matsuo,2 Takanori Miyoshi,4 Yoko Toriyama,4 Chiaki Yokota,5 Jun Taniguchi,6 Kiyonori Hanada,7 Kyouichi Tsumagari,8 Noriko Okubo,9 Yoshimichi Koutake,10 Kohei Sakata,11 Yosei Kawamata,12 Takashi Goto,13 Yasufumi Tsurusaki,14 Makiko Koyabu1 1Department of Pharmacy, Clinical Research Institute, National Kyushu Medical Center, Fukuoka, Japan; 2Department of Pharmaceutical and Health Care Management, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; 3Cancer Biostatistics Laboratory, Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan; 4Department of Pharmacy, National Hospital Organization Beppu Medical Center, Oita, Japan; 5Department of Pharmacy, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan; 6Department of Pharmacy, National Hospital Organization Ureshino Medical Center, Saga, Japan; 7Department of Pharmacy, National Hospital Organization Kumamoto Saishunso National Hospital, Kumamoto, Japan; 8Department of Pharmacy, National Hospital Organization Miyakonojo Medical Center, Miyazaki, Japan; 9Department of Pharmacy, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan; 10Department of Pharmacy, National Hospital Organization Fukuoka National Hospital, Japan; 11Department of Pharmacy, National Hospital Organization Kumamoto South National Hospital, Kumamoto, Japan; 12Department of Pharmacy, National Hospital Organization Kagoshima Medical Center, Kagoshima, Japan; 13Department of Pharmacy, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan; 14Department of Pharmacy, National Hospital Organization Saga National Hospital, Saga, Japan Purpose: Improvement in the control of delayed chemotherapy-induced nausea and vomiting (CINV) is needed. There is limited information on antiemetic prophylaxis for patients undergoing low-emetic-risk chemotherapy (LEC), and the optimal antiemetic treatment is not well understood. Therefore, we analyzed the risk factors for delayed CINV to aid in the development of individualized treatments. Patients and methods: This prospective multicenter study was conducted in 13 hospitals and included patients with solid cancers undergoing LEC. A total of 222 patients were enrolled between September 2013 and November 2014. The participants completed a daily diary for 5 days after the commencement of the first cycle of LEC to describe the daily incidence of CINV (yes/no). Furthermore, the participants described the severity of nausea and the amount of food intake with the help of VAS. Results: Two hundred and ten patients provided their data that were analyzed using multivariate logistic regression to examine the risk factors for delayed CINV. History of CINV, Eastern Cooperative Oncology Group performance status score ≥1, acute CINV, and single-day antiemetic prophylaxis were identified as independent risk factors for delayed CINV. Conclusion: The current use of antiemetic prophylaxis according to the recommended guideline appears to effectively control delayed CINV in patients undergoing LEC. Therefore, patients with the abovementioned risk factors should be carefully observed, and their treatment should be adjusted according to their symptoms. The use of multiple-day dexamethasone may be beneficial for those patients who develop acute CINV, especially when it is accompanied by anorexia. Keywords: adverse effects, antiemetics, prophylaxis, quality of life

Background: In Japan, the supply of one generic meropenem product was restricted from August 2022 to March 2023., Objective: To determine the effects of meropenem (MEPM) restriction., Methods: We conducted a multicenter retrospective study comparing antimicrobial use, bacteremia mortality, and drug-resistant bacteria detected before the restriction of MEPM (control period), from September 2021 to February 2022, and after the restriction of MEPM (MEPM supply restriction period), from September 2022 to February 2023, in five institutions., Results: The number of carbapenem days of therapy (DOTs) were decreased in all five institutions. Fourth-generation cephalosporin DOTs increased in all facilities, and piperacillin/tazobactam DOTs increased in four facilities. The 30-day and 90-day mortality rates were significantly higher during the MEPM supply restriction period than those during the control period. Moreover, survival time was significantly shorter during the MEPM supply restriction period than that during the control period. Multivariable analysis revealed that MEPM supply restriction, age >80 years, Pitt Bacteremia Score ≥4, platelet count <10 × 10 4 /μL, serum albumin level <2.5 g/dL, and methicillin-resistant Staphylococcus aureus bloodstream infection were independent risk factors for 30-day mortality. The detection rates of carbapenem-resistant Pseudomonas aeruginosa and Enterobacteriaceae did not differ significantly between the two periods., Conclusions: MEPM supply restriction decreased the use of carbapenems and increased the use of other broad-spectrum antimicrobial agents, which worsened the prognosis of bacteremia. Overall, carbapenems are important drugs for the treatment of infectious diseases and are difficult to replace in unforeseen situations such as drug supply outages., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Context: Tramadol is conditionally recommended for cancer pain and is a less expensive drug compared to strong opioids. Thus, tramadol may help reduce health care costs., Objectives: To investigate factors that predict the clinical efficacy of tramadol for cancer pain., Methods: A retrospective study using electronic medical records was conducted on patients who received tramadol for cancer pain from January 2016 to December 2020. Patients who continued tramadol for >28 days or discontinued tramadol before 28 days owing to pain improvement were considered as clinical efficacy cases., Results: We identified 183 eligible patients; 104 cases had clinical efficacy. The median starting tramadol daily dose was 100 mg, and the median administration duration was 22 days. Overall, 169 patients (92.3%) discontinued tramadol; pain improvement was the most common reason (34.9%). Age (>70 years), a performance status of 0-1, and an albumin-bilirubin grade of 1 were independent predictors for the clinical efficacy of tramadol. Patients with multiple predictors had significantly higher achievement rates than those without., Conclusion: Tramadol could have greater clinical efficacy for cancer pain in patients who are elderly, have good performance status, and have good liver function., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy., Methods: This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors., Results: Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence., Conclusion: Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). They cause immune-related adverse events (irAEs), but the underlying mechanisms and predictors remain to be fully elucidated. In this retrospective study, we investigated the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and the occurrence of irAEs., Methods: The study involved 115 patients with NSCLC who started ICI-only treatment in our hospital between January 2016 and April 2020., Results: Forty-five patients (39.1%) had irAEs, and pretreatment NLR was significantly lower in the irAEs group than in the non-irAEs group (2.8 vs. 4.1; p = 0.036). The cutoff value of the NLR was 2.86 (area under curve, 0.62; sensitivity, 0.56; specificity, 0.71), and the incidence rate of irAEs was significantly higher in the NLR < 2.86 group than in the NLR ≥2.86 group (p = 0.004; odds ratio [OR]: 3.12; 95% confidence interval [CI]: 1.43-6.84). The multivariate analysis showed that the NLR was significantly associated with the occurrence of irAEs (p = 0.016; OR: 2.69; 95% CI: 1.21-6.01)., Conclusions: Low pretreatment NLR may be a predictive factor for the occurrence of irAEs. By focusing on the potential risk of irAEs in patients with a low pretreatment NLR, irAEs can be appropriately managed from an early period., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

We evaluated the effect of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) on the efficacy and safety of dasatinib for chronic-phase chronic myeloid leukemia (CP-CML). Retrospective analyses were performed for patients with CP-CML who received dasatinib at seven hospitals between April 2009 and December 2016. Seventy-three patients were identified, 16 of whom received PPIs or H2RAs concurrently with dasatinib. Major molecular response at 12 months was observed in 13 of 13 patients (100%) with concurrent PPIs or H2RAs (combination group), and in 23 of 51 patients (45.1%) who received only dasatinib (dasatinib-alone group; P < 0.001). Deep molecular response at 12 months was observed in four of six patients (66.7%) in the combination group, and seven of 38 patients (18.4%) in the dasatinib-alone group (P = 0.027). Dasatinib chemotherapy was stopped after 18 months for 25 patients (43.9%) from the dasatinib-alone group, but for none from the combination group. Combination treatment with PPIs or H2RAs did not reduce the efficacy of dasatinib. PPIs and H2RAs reduce the incidence of dasatinib discontinuation due to adverse events and increase the efficacy of dasatinib chemotherapy for patients.

Febrile neutropenia(FN)occurs in 3-25% of patients with castration-resistant prostate cancer(CRPC)receiving docetaxel( DTX). Therefore, the need for granulocyte colony-stimulating factor with DTX as prophylaxis has not been established. Herein, we report the efficacy of primary prophylaxis with pegfilgrastim after DTX in patients with CRPC. The subjects were 30 CRPC patients who received DTX at our hospital between January 2013 and October 2017. Twelve patients underwent primary prophylaxis with pegfilgrastim(Peg-G group), whereas the other 18 did not(control group). FN developed in 1(8.3%) and 8(44.4%)patients in the Peg-G and control groups, respectively(p=0.049). No significant differences were observed in RDI between the 2 groups. The average medical cost per course of DTX was lower in the Peg-G group than in the control group. These results demonstrate that primary prophylaxis with pegfilgrastim is useful because DTX induces FN at a high frequency in patients with CRPC, and pegfilgrastim significantly reduces its incidence without increasing the medical cost.

Purpose: The incidence of and the risk factors for nausea and vomiting in patients undergoing low emetic risk chemotherapy (LEC) are unclear. The aim of the study was to provide information on these topics by performing a multicenter, observational, prospective study., Methods: The study consisted of patients who were administered first-time LEC that was consistent or inconsistent with current guidelines. Using the visual analog scale, patients recorded their daily food intake and the occurrence and severity of nausea over a 5-day treatment period., Results: The overall incidence of chemotherapy-induced nausea and vomiting did not differ significantly between patients undergoing guideline-consistent (n = 89) or guideline-inconsistent (n = 121) prophylaxis (30.3 vs. 22.3%, respectively; P = 0.19). Logistic regression analysis identified a history of nausea and LEC other than taxanes as independent risk factors associated with nausea and vomiting in patients undergoing LEC. The mean daily visual analog scale scores for nausea severity and a decrease in food intake were <25 mm throughout the entire observation period., Conclusions: Guideline-consistent prophylaxis appeared to control nausea and vomiting effectively in patients undergoing LEC. However, patients with a history of nausea and receiving LEC other than taxanes should be carefully observed and treatment should be adjusted according to their symptoms.

Although many physiological studies have been reported on the symbiosis between hydra and green algae, very little information from a molecular phylogenetic aspect of symbiosis is available. In order to understand the origin and evolution of symbiosis between the two organisms, we compared the phylogenetic relationships among symbiotic green algae with the phylogenetic relationships among host hydra strains. To do so, we reconstructed molecular phylogenetic trees of several strains of symbiotic chlorella harbored in the endodermal epithelial cells of viridissima group hydra strains and investigated their congruence with the molecular phylogenetic trees of the host hydra strains. To examine the species specificity between the host and the symbiont with respect to the genetic distance, we also tried to introduce chlorella strains into two aposymbiotic strains of viridissima group hydra in which symbiotic chlorella had been eliminated in advance. We discussed the origin and history of symbiosis between hydra and green algae based on the analysis., (Copyright © 2012 Elsevier Inc. All rights reserved.)