Background/Aim: Measures to control adverse events (AEs) in the use of oral multi-kinase inhibitors (OMI) are important for the continuation of treatment. Patients and Methods: In this study, oncology pharmacists monitored symptoms of patients receiving outpatient therapy with OMIs in real-time using a smartphone Web app for the early detection/early treatment of AEs. This feasibility study evaluated the effects of using the app in 10 patients compared with data from 10 patients who did not use the app. Results: In the app group, grade 3 AEs were reported in all patients on the day of their occurrence. In contrast, in the no-app group, it took 1-22 days for pharmacists to detect these AEs, among whom 2 patients needed emergency consultations and admissions due to grade 3 AEs. In the app group, 1 patient had an emergency consultation, without admission. The percentage of patients requiring 10 minutes or more for symptom checking during the interview before the physician's examination was significantly lower (p=0.001), and the frequency of telephone calls was also significantly lower (p=0.029) in the app group compared to the no app group. Conclusion: Using the Web app facilitates the early detection of AEs, contributing to reducing the need for emergency consultations and admissions, and minimizing the time pharmacists spend confirming symptoms with patients.
Essential thrombocythemia (ET) is a Philadelphia chromosome-negative myeloproliferative disorder that is characterized by the overproduction of platelets and a marked increase in the numbers of mature megakaryocytes present in the bone marrow. Thrombohemorrhagic disorders are major morbidities of ET, especially those with mutations in the gene encoding Janus kinase 2 (JAK2). In this study, we report the case of an 18-year-old patient with ET carrying JAK2 mutation who developed acute ST-elevation myocardial infarction (STEMI) 5 months after a commencement of anagrelide. Coronary endothelial dysfunction confirmed by positive acetylcholine provocation test lasted a year after the occurrence of STEMI. Furthermore, intracoronary imaging using optical coherence tomography demonstrated non-atheromatous intimal fibrosis possibly due to chronic endothelial damage. The coronary pathologies reflected chronic change potentially associated with properties of ET and JAK2 mutation in addition to hyperviscosity. These observations suggest that the side effect of anagrelide in our patient was considered causative, while underlying chronic endothelial dysfunction and adverse endothelial remodeling may be predisposing factors to his fatal cardiovascular events.
Thrombohemorrhagic disorders are the main cause of morbidities and mortalities of essential thrombocythemia (ET), which are typically observed at age 50–60 years and rarely encountered in adolescence or childhood. Recently, anagrelide, a quinazinolone derivative, has been used as a therapeutic agent for ET. Although it is used to reduce platelet count, its cardiotoxicity has been reported. Here, we present an 18-year-old boy with ET who was treated with anagrelide and developed acute myocardial infarction. This was presumed to be an effect of anagrelide administration and, specifically, damage to the coronary arterial endothelial cell exacerbated by ET.
Introduction Pembrolizumab cause immune‐related adverse events. We herein report a case of advanced bladder cancer, who treated with pembrolizumab and exhibited intriguing clinical course. Case presentation A 63‐year‐old man with bladder carcinoma was treated by radical cystectomy, however, the bladder carcinoma recurred and invaded to the rectum. He was treated by combination therapy using gemcitabine and cisplatin, which were not effective for the tumor. He subsequently underwent treatment with pembrolizumab. In several 30 days, he suffered from the symptoms of myasthenia gravis. Serum levels of creatine kinase, its isozyme creatine kinase‐myocardial band, and troponin I were elevated. Electrocardiography showed a right bundle branch block. These findings suggested that he was myasthenia gravis with general myositis and presumable myocarditis. Oral prednisolone administration significantly attenuated these findings. The tumor drastically shrunk only by the single injection of pembrolizumab. Conclusion Early intervention with corticosteroid was effective for neuromuscular complications due to pembrolizumab.
Severe hypercalcemia (serum calcium, 4.25-5.25 mmol/l), in association with osteolytic bone lesions, was found in a girl aged 2 yr 7 mo with common acute lymphoblastic leukemia (ALL). Hormonal studies excluded the possibility of the hypercalcemia being caused by primary hyperparathyroidism or ectopic parathyroid hormone secretion. Increased plasma prostaglandin E2 (PGE2) levels (130 ng/l), probably produced by leukemic cells, were considered to be one of the pathogenic mechanisms responsible for the occurrence of hypercalcemia in this patient. Both the hypercalcemia and the abnormal plasma PGE2 level returned to normal after chemotherapy.
Background: Pazopanib is an effective treatment option for renal cell carcinoma (RCC). However, the therapy is often limited by the appearance of adverse events (AEs), including nausea/vomiting, hepatic impairment, hand-foot syndrome, diarrhea, hypertension and oral mucositis. Early management of AEs is, therefore, extremely important in order to maximize treatment outcomes. Patients and Methods: This non-randomized controlled before-and-after study was carried out to evaluate the effectiveness of our comprehensive pharmaceutical interventions in 37 outpatients receiving pazopanib for RCC (experimental group). Data were compared with those obtained from 13 patients before the start of pharmaceutical intervention (control group). Results: The incidence rates of grade 2 or more nausea and anorexia were significantly lower in the experimental, than in the control group (3% versus 38% for nausea, respectively, p=0.003; 8% versus 46% for anorexia, respectively, p=0.005). Importantly, non-adherence based on patient self-assessment was not observed with intervention (0% versus 38%, p<0.001). Consequently, the median total dose of pazopanib was increased by the intervention (72,600 versus 18,200 mg, p=0.002). Moreover, the median time to treatment failure was significantly longer with intervention than before (10.2 versus 1.7 months, HR=0.23, 95% CI=0.110-0.499, p<0.001). These findings suggest that our interventions are highly effective for enhancing treatment outcomes.
This study aimed to clarify diverse values toward career visions for hospital pharmacists. A self-administered online questionnaire survey was delivered to live and on-demand release attendees at a symposium about sustainable career paths for pharmacists at the 32nd annual meeting of the Japanese Society of Pharmaceutical Health Care and Sciences between September 23rd and November 14th, 2022. Correspondence analyses of text mining were conducted to assess the association between the participants' perspectives on career visions and their backgrounds consisting of sex and generation. The recovery rate was 81.9% (136/166). The majority of respondents were women (61.4%), aged ≥40 years (66.1%). Correspondence analysis of career vision for pharmacists showed that respondents who were ≥20-30 years were associated with the research topic, whereas those who were ≥40 years were associated with the director of a pharmacy and worked until retirement age. In contrast, there was no difference in career visions for pharmacists based on sex. The median satisfaction score of the symposium was 6 [interquartile range (IQR): 5-6] in the entire population, as conveyed using a seven-point Likert scale. Interestingly, the median satisfaction scores of the symposium were significantly higher for men in management positions than women in non-management and management positions (p=0.0106 and p=0.0031, respectively). In conclusion, we believe that career support tailored to everyone's values could enable hospital pharmacists to realize their career visions.
Introduction Pazopanib, a tyrosine kinase inhibitor, and nivolumab, an immune checkpoint inhibitor, are both considered to cause hepatotoxicity with different pathophysiology. We report a case in which a patient died of severe hepatotoxicity who was presumed to have been caused by the administration of nivolumab followed by pazopanib for metastatic renal cell carcinoma. Case presentation A 74‐year‐old male with metastatic renal cell carcinoma was treated with nivolumab as a third‐line treatment. However, nivolumab was subsequently discontinued, as it caused severe thyroiditis. About 2 months after the final dose of nivolumab was administered, pazopanib was initiated as a fourth‐line treatment. The patient suffered from lethal hepatic failure and died 18 days after the initiation of pazopanib treatment. An autopsy revealed that CD8‐positive lymphocytes had infiltrated the thyroid gland and liver. Conclusion The patient was considered to have died of severe hepatic failure due to the aggravation of mild nivolumab‐induced immune‐related hepatitis by pazopanib.
