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Background Sleep disturbance is a common psychiatric disorder in patients with cancer. However, many patients with incurable cancer have difficulty receiving oral administrations, which limits treatment options during disease progression. The aim of the present study was to assess the efficacy and safety of intravenous chlorpromazine treatment for sleep disturbances in patients with incurable cancer, with oral administration difficulty. Methods A prospective observational study was conducted among 52 patients with incurable cancer, with oral administration difficulty received daily intravenous chlorpromazine treatment for sleep disturbance from 2018 to 2020 at a single-unit university hospital. St. Mary's Hospital Sleep Questionnaire (SMHSQ) compared sleep before and after intravenous chlorpromazine administration. The primary endpoint was the efficacy rate of sleep quality [defined as a score of ≥4 (range: 1-6)] 7 days after receiving chlorpromazine. Results Beginning the day after receiving chlorpromazine, sleep quality significantly improved from a mean score of 1.6±0.7 to 4.3±1.2, and 80.8% [95% confidence interval (CI): 66.5-89.1%] and 69.2% (95% CI: 53.8-79.6%) of patients reported good sleep quality 3 and 7 days after receiving chlorpromazine, respectively. The patients reported increased total sleep time and fewer awakenings during sleep, and satisfaction with sleep and difficulty falling asleep improved. Some adverse events occurred [akathisia (n=2), dry mouth (n=2), and somnolence (n=3)]; all were Grade 1 (CTCAE ver5.0) and improved with chlorpromazine discontinuation. Systolic blood pressure and heart rate displayed no clinically problematic changes. Conclusions Intravenous chlorpromazine has a high tolerability and effectively treats sleep disturbances in patients with incurable cancer with oral administration difficulties.

A 67-year-old man with dilated cardiomyopathy and renal insufficiency was admitted to our hospital with dyspnea secondary to end-stage heart failure. We introduced oxycodone for medically refractory dyspnea instead of morphine because of the patient's renal insufficiency. After the administration of oxycodone, his dyspnea was alleviated without any adverse opioid effects, such as respiratory depression. After treating his heart failure, he was able to leave the intensive care unit. Oxycodone may therefore be a reliable agent for the treatment of dyspnea in patients with end-stage heart failure and renal insufficiency.

Nivolumab, an anti-programmed cell death 1 antibody, has been approved for the treatment of unresectable advanced non-small-cell lung cancer (NSCLC). Although immune-related adverse events (irAEs) such as dermatologic, digestive, endocrine, hepatic, and pulmonary toxicities are known to occur upon administration of immune checkpoint inhibitors, case reports of polymyalgia rheumatica (PMR) associated with nivolumab use are rare. We report a case of an NSCLC patient who developed PMR during treatment with nivolumab and received corticosteroids. A 74-year-old man without a history of autoimmune diseases received nivolumab at a dosage of 3 mg/kg once every 2 weeks for the treatment of stage IIIB squamous cell carcinoma. After 12 cycles of nivolumab treatment, he developed grade 3 muscle pain and arthralgia, requiring hospitalization and discontinuation of nivolumab. A bone scintigraphy revealed no bone metastasis. Serological tests showed that although creatine phosphokinase did not increase, C-reactive protein and the erythrocyte sedimentation rate were both high. Tests for the rheumatoid factor, anti-cyclic citrullinated peptide antibody, and anti-nuclear antibody were negative. In addition to the serological findings, joint ultrasonography data and clinical symptoms were evaluated, leading to the diagnosis of PMR. Oral prednisolone 20 mg/d was started to treat the PMR without giant-cell arteritis. The patient's symptoms improved within 5 d of the initiation of treatment. Prednisolone was tapered to 5 mg/d without recurrence of PMR. Although grade 3 or 4 irAEs (except in type 1 diabetes) are generally treated with high-dose corticosteroids, grade 3 PMR associated with nivolumab use may be treatable with low-dose corticosteroids.

Background: In February 1999 we encountered our first patient with rhab domyolysis treated with the combination of bezafibrate and simvastatin, and realized the need to prevent adverse reactions when combining bezafibrate with HMG-CoA reductase inhibitors. In early March 1999 bezafibrate labeling for adverse reactions was revised, prohibiting combination therapy with HMG-CoA reductase inhibitors when serum creatinin levels reached>1.5 mg/dl. We have subsequently investigated the influences of the bezafibrate labeling changes on prescription trends for HMG-CoA reductase in hibitors combined with bezafibrate.Methods: We identified all patients within the period May 1998 to March 1999 who had visited the cardiovascular department at Kansai Medical University Hospital (Osaka, Japan) and received bezafibrate with HMG-CoA reductase inhibitors, as recorded in the computerized prescription data.Results: The number of patients who had received bezafibrate with HMG-CoA reductase inhibitors was 97 (mean age 60.2±9.9 years), of whom 78 had previously received HMG-CoA reductase inhibitors prior to additional bezafibrate. In these 78 patients, the mean serum total cholesterol and triglyceride levels after adding bezafibrate had decreased by 5.5±17.6% and 33.4±33.0%, respectively. For patients receiving both lipid-lowering agents, the results of periodic measurement of serum creatinine and creatin kinase levels were considered insufficient, and these parameters had not been measured for more than 4 months in 57% and 76% of the cases, respectively. Of the 97 patients, either bezafibrate or HMG-CoA reductase inhibitors had been withdrawn from treatment in 15 patients (15.5%) by the end of March 1999. By the end of March 2000, one year after the bezafibrate labeling changes, no patient had commenced the combina tion therapy of both lipid-lowering agents, and within that year 37 patients (38.1%) discontinued treatment with either bezafibrate or HMG-CoA reductase inhibitors (total 52 patients, 53.6%).Conclusions: The hospital pharmacy caution issued regarding the prevention of adverse reactions is seen as contributing to the decrease by approximately one-half the number of patients receiving bezafibrate with HMG-CoA reductase inhibitors. In the near future, the combination therapy of bezafibrate and HMG-CoA reductase inhibitors can be eliminated by selective usage, and by the establishment of an appropriate dosage setting for, HMG-CoA reductase inhibitors.

Aspirin is widely used as an antiplatelet drug for the secondary prevention of cardiovascular event in patients with myocardial infarction. However, gastrointestinal complications (ulceration, bleeding, perforation) as adverse drug reactions may also be associated with aspirin use. Low-dose aspirin is very widely used for the secondary prevention of cardiovascular event that clinicians may not be aware of gastrointestinal complications. We report 5 patients with gastrointestinal bleeding associated with low-dose aspirin for the prevention of cardiovascular events.All 5 patients were males, and the mean age was 68 ± 9.6 years. They had been treated with low-dose aspirin (81mg daily) from 17 days-2 years. At hospital admission, all patients had severe anemia, and complained of anorexia, tarry stool, melena, and light-headedness, but none reported stomachache. A gastroendoscopic examination showed active A 1 stage ulcers in four patients, and an active A 2 stage ulcer in one patient. Endoscopic hemostatic procedures were performed in four patients. In all patients, the gastrointestinal complications improved after the administration of proton pump inhibitor and the discontinuation of aspirin.Although every patient had been administered low-dose aspirin (81mg daily), severe gastrointestinal bleeding which required hospitalization developed in all 5 patients. They did not complain of pain, and their hemorrhagic ulcers were suspected to be due to severe anemia or melena. Their symptoms were consistent with the features of “silent ulcer” associated with aspirin or other nonsteroidal antiinflammatory drugs. All but one patient was elderly and more than 60 years of age. In 3 patients, hemorrhagic ulcers developed within 2 months after aspirin initiation. Therefore, gastrointestinal bleeding associated with aspirin does not necessary occur only after long term use.When aspirin is used for the secondary prevention of cardiovascular events in patients with myocardial infarction, the risk of gastrointestinal bleeding can not be ruled out even with low-dose administration. Especially for elderly patients, clinicians should therefore include such a possibility in the follow-up of such patients.