Objective: Almost half of all patients with cancer experience dyspnea, which can have various causes. Although systemic corticosteroids are administered to relieve symptoms, their efficacy has not been established. This systematic review aims to determine the efficacy of systemic corticosteroids for dyspnea in patients with cancer. Methods: CENTRAL, MEDLINE, EMBASE, and Ichushi-Web databases were searched for articles published from their inception to September 23, 2019, on studies of systemic corticosteroid administration for dyspnea in patients with cancer. The primary outcome measure was dyspnea intensity, as assessed by patient-reported outcomes. Secondary outcome measures were quality of life, delirium, and severe adverse events. Results: Two RCTs were included in the meta-analysis. With regard to alleviating dyspnea, the systematic corticosteroid group was associated with significantly greater dyspnea relief than the placebo group (mean difference: −0.71 [95% CI: −1.4 to −0.03]). However, a meta-analysis of quality of life and delirium could not be performed due to insufficient data. Analysis of severe adverse events showed no significant difference in their incidence between the corticosteroid and control groups (relative rate: 0.96 [95% CI: 0.19-4.93]). Conclusions: Systemic corticosteroids may be effective in treating dyspnea in patients with cancer, particularly those with lung involvement. Limiting the conditions for which corticosteroids are approved is expected to promote their appropriate use and minimize their adverse effects. However, further investigation is needed to determine the appropriate dosage, and the conditions in which corticosteroids are effective.

Objective: The wrong dose of high-risk drugs such as oral steroids is a serious issue that needs to be addressed. This study aims to determine the appropriate upper tolerable dose threshold and to develop a multi-variable logistic regression model to detect dose-errors in oral prednisolone tablets.Methods: Data on Prednisolone prescriptions were obtained from a single center. Out of the data collected, positive cases consisted of cases where dose-related modifications were made. A univariate logistic regression model was developed with the current daily dose. In the model, the Youden Index was used to determine the upper tolerable dose threshold. The investigation was done to determine whether the performance of the multivariate model was improved by adding clinical department and previous prescription information as variables.Results: Univariate models (AUC: 0.645) with only current daily doses and estimated optimal thresholds of 6 mg/day or 11 mg/day, respectively were determined to be appropriate. Including variables improved the performance of the predictive model; the best performing model (AUC: 0.840) was derived when the following variables were entered: “current daily dose,” “current prescription days,” “clinical department,” “daily dose of the previous prescription,” and “prescription days of the previous prescription”.Conclusion: A single upper tolerance limit is insufficient to determine dose adequacy for prednisolone tablets owing to their broad clinical dose range. Itmay be possible to develop a high-performance dose audit support model by adding information.

Objective: To evaluate the efficacy of high-flow nasal cannula oxygen (HFNC) for dyspnea in patients with advanced disease. Methods: A literature search was conducted using MEDLINE, Cochrane Library, EMBASE, and Ichu-shi Web. Inclusion criteria were: 1) randomized controlled trials evaluating the effect of HFNC on dyspnea; 2) aged 18 years or older with advanced disease with hypoxemia; 3) control group was conventional oxygen therapy or noninvasive positive pressure ventilation. Exclusion criteria were: 1) patients in intensive care unit, 2) weaning from ventilator. Results: Six studies (4 from database searches, and 2 from hand searches) were included. In the 2 studies evaluating short-term intervention, one showed HFNC was more efficacious, and the other conventional oxygen was more efficacious. In the 2 studies evaluating long-term interventions: one showed HFNC was more efficacious, and the other showed no significant difference. In the 2 studies evaluating the intervention during exercise, one showed HFNC was more efficacious, and the other showed no significant difference. Conclusion: HFNC may be effective for dyspnea in patients with advanced disease associated with hypoxemia.

Objective: To evaluate the efficacy of fan therapy for the relief of dyspnea in patients with chronic progressive disease. Methods: A systematic electronic database search of all available articles published before October 23, 2019 was conducted using Ichushi-Web of the Japan Medical Abstract Society databases, CENTRAL, EMBASE, and MEDLINE. In addition, a hand-search for updates was performed using PubMed on June 30, 2020 and December 7, 2021. The inclusion criteria were: 1) any RCTs comparing the effect of fan therapy with any other intervention, and 2) patients aged ≥18 years. Exclusion criteria were: 1) duplicate references, and 2) conference presentations. Results: We identified 110 studies, of which 10 met our criteria for inclusion. Finally, five studies were used in the meta-analysis. Fan therapy significantly improved dyspnea in patients with chronic progressive disease compared to control groups with a standardized mean difference of −1.43 (95% confidence interval: −2.70 to −0.17, I2=94%, p<0.0001). Conclusion: Fan therapy was found to be effective in reducing dyspnea in chronic progressive disease.

Background/Aims: A subgroup analysis was conducted in Japanese patients with moderate to severe ulcerative colitis (UC) enrolled in the phase 3 VISIBLE 1 study, which evaluated the safety and efficacy of a new vedolizumab subcutaneous (SC) formulation. Methods: Eligible patients received open-label infusions of vedolizumab 300 mg intravenous (IV) at weeks 0 and 2 in the induction phase. Patients with clinical response by complete Mayo score at week 6 entered the double-blind maintenance phase and were randomized to vedolizumab 108 mg SC every 2 weeks, placebo, or vedolizumab 300 mg IV every 8 weeks. The primary endpoint was clinical remission (complete Mayo score ≤ 2 points; no individual subscore > 1 point) at week 52. Results: Of 49 patients who entered the induction phase, 22 out of 49 patients (45%) had clinical response at week 6 and were randomized to vedolizumab 108 mg SC (n = 10), placebo (n = 10), or vedolizumab 300 mg IV (n = 2). At week 52, 4 out of 10 patients (40%) who received vedolizumab SC had clinical remission versus 2 out of 10 patients (20%) who received placebo (difference: 20% [95% confidence interval, –27.9 to 61.8]). Two patients (2/10, 20%) who received vedolizumab SC experienced an injection-site reaction versus none who received placebo. Conclusions Our results indicate that the efficacy of vedolizumab SC in a subgroup of Japanese patients with UC are similar with those in the overall VISIBLE 1 study population, and with those established with vedolizumab IV. The safety and tolerability of vedolizumab SC were generally similar to that established for vedolizumab IV. (ClinicalTrials.gov ID NCT02611830; EudraCT 2015-000480-14)

Introduction: Antiepileptic drugs were occasionally administered to manage seizures in terminally-ill cancer patients. When enteral route is no longer feasible due to dysphagia or depressed level of consciousness, subcutaneous route could be an option. We reported three cases of terminally cancer patients who received subcutaneous levetiracetam (LEV) due to an inability to administer via intravenous route. Cases: The age of 3 cases was 83, 75, 82 years, respectively. In all cases, the prognosis prediction at the start of subcutaneous LEV was about 1 month. In all cases, the route of administration of LEV was changed from intravenous to subcutaneous. No exacerbation of convulsions, or injection site reaction was confirmed after subcutaneous LEV administration. Discussion: We believe that subcutaneous LEV administration may be one of the treatment options for seizures in patients with terminal cancer for whom intravenous administration of LEV is no longer feasible.

An 84-year-old woman treated for tuberculosis in childhood presented to our emergency department with chronic cough and massive hemoptysis. Contrast-enhanced computed tomography (CT) on admission revealed a bronchial-pulmonary artery fistula (BPAF) for which she underwent bronchial artery embolization (BAE) and developed hemoptysis postoperatively. Contrast-enhanced CT on admission revealed a connection between the right coronary and a bronchial artery, suggesting coronary-to-bronchial artery communication. Hemoptysis persisted despite coiling of a branch of the right coronary artery. Therefore, we were consulted to perform thoracic endovascular aortic repair (TEVAR), which we performed as a semi-emergency. She did not show hemoptysis or paraplegia postoperatively and was discharged on postoperative day 40. TEVAR is effective for a BPAF in patients in whom BAE cannot control hemoptysis.

Introduction: Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of non-Hodgkin lymphoma. Patients with IVLBCL frequently have neurological symptoms associated with cerebrovascular infarction or central nervous system involvement of malignant lymphoma. Case: A 67-year-old man consulted the Department of Hematology at our hospital because of fever of unknown origin, anemia and increased serum lactate dehydrogenase. Although IVLBCL was strongly suspected, no lymphoma cells were found by multiple bone marrow aspirations and skin biopsies. Two months later, he developed hyperactive delirium, which was difficult to manage using antipsychotic agents. Brain MRI revealed multiple hyper-intense infarct-like lesions on diffusion-weighted images. After assessment of bone marrow aspiration and skin biopsies, he was administered an enough dose of prednisolone to manage malignant lymphoma. Hyperactive delirium rapidly improved. Discussion: In patients with IVLBCL, corticosteroids may be useful to manage hyperactive delirium due to cerebrovascular infarction or central nervous system involvement of IVLBCL.

Objective: The use of generic drugs is promoted to reduce medical costs and copayments. However, tumor agents are expensive and generic drugs are not widelyused. Thus, it is necessaryto evaluate the safetyof generic drugs in more detail. We compared the incidence of adverse events between the original drug (Gemzar®: GEM) and generic drug (Gemcitabine [Sandoz]: GE-GEM) using propensityscore (PS) matching.Methods: We investigated adverse events in patients who received one course of GEM or GE-GEM. The patient background (age,sex, BSA, cancer type, stage, metastasis, surgical history, and radiotherapy) and administration status (administration route and RDI) were used to calculate the PS.Results: Among all patients (GEM: 51, GE-GEM: 54), a significantlygreater number in the GE-GEM group had cancer metastasis. On comparison of adverse events, there were significantlymore cases of vascular pain (p＜0.05) in the GEM group, and manycases of nausea (p＝0.08) and rash (p＝0.08). Fortypatients in each group were extracted byPS matching. There were no significant differences in the patient background between the groups, and on comparison of adverse events, the two groups did not significantly differ.Conclusion: Our studysuggested that there is no difference in side effects between Gemzar® and gemcitabine [Sandoz]. To compare the incidence of adverse events, it is useful to use PS matching in clinical practice.

Objective: Risk Management Plan (RMP) is created and submitted by a pharmaceutical company while applying for new drug approval; it is published to be used by healthcare professionals. For example, healthcare professionals utilize RMP when considering whether to adopt a drug. However, there is no stipulation for the release date of RMPs; moreover, surveys regarding this are limited. We conducted a cross-sectional survey on the relationship between RMP-related timing and regulatory affairs-related timing.Methods: The surveyed drugs were those for which the first version of RMP was notified by PMDA Medinavi (mail delivery service) in FY2014 and FY2018. We examined regulatory affairs-related timing (i.e., “manufacturing and marketing approval date,” “drugprice standards listing date,” and “release date”) and RMP-related timing (i.e., “RMP creation date” and “Medinavi delivery date”).Results: For 7 of 43 items in FY2014 and 5 of 41 items in FY2018, the “RMP creation date” occurred later than the “drug-price standards listing date.” For one item in FY2014, the “RMP creation date” occurred later than the “release date.” For 12 items in FY2014 and 13 items in FY2018, the “Medinavi delivery date” occurred later than the “release date.”Conclusion: No considerable difference was confirmed between FY2014 and FY2018 regarding RMP-related timing and regulatory affairs timing. It was confirmed that there were several items for which the RMP creation occurred later than drug-price standard listing and items for which the publishing notice by Medinavi was delayed for drug marketing release. To promote the utilization of RMPs by healthcare professionals, RMPs must be created and published without delay.