Identification of target small molecule tyrosine kinase inhibitors that need monitoring and clinical application of protocol for early detection of cancer therapeutics-related cardiac dysfunction using signal detection: An investigation of real world data.

PURPOSE: In order to detect cancer therapeutics-related cardiac dysfunction (CTRCD) early, we identified which drugs were to be monitored using signal detection and the package insert, and created and applied a protocol to address this. METHODS: Adverse event data recorded in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and January 2018 were used. Among small molecule tyrosine kinase inhibitors that are not described in the serious side-effects section of the package insert despite signal detection, tyrosine kinase inhibitors with severe side-effects in the background of cases reported by JADER database were selected to be monitored in clinical practice. We applied our findings clinically by creating a protocol to detect CTRCD early. All cases at Tosei General Hospital where the target tyrosine kinase inhibitors were administered from when they were first released in November 2019 were included. We compared the results from before and after we began the protocol to clarify its effects. RESULTS: We found that CTRCD was not described in the serious side-effect section of the package inserts for Bosutinib, Alectinib, and Osimertinib even though CTRCD signals were detected for them. Therefore, it is possible that we may have previously overlooked CTRCD. When we applied our protocol using Osimertinib as the target drug, we were able to detect CTRCD early in 5/21 (24%) patients. CONCLUSIONS: It was clarified that the drug identification method used in this study for early detection of adverse events leads to early detection of adverse events when applied clinically.

Efficacy of baloxavir marboxil on household transmission of influenza infection.

BACKGROUND: Baloxavir marboxil (baloxavir) is a new anti-influenza virus agent that is comparable to oseltamivir phosphate (oseltamivir). Since the efficacy of baloxavir in preventing household transmission of influenza is not well established, we compared the secondary household influenza virus transmission rates between patients on baloxavir vs oseltamivir. METHODS: Between October 2018 and March 2019, we enrolled index patients (diagnosed with influenza and treated with baloxavir or oseltamivir) and household members. The secondary attack rate of household members was compared between index patients treated with baloxavir vs oseltamivir. Risk factors of household transmission were determined using multivariate logistic analyses. RESULTS: In total, 169 index patients with influenza type A were enrolled. The median age was 27.0 (interquartile range; 11-57) years. The number of index patients treated with baloxavir and oseltamivir was 49 and 120, respectively. The secondary attack rate was 9.0% (95% confidence interval [CI]: 4.6-15.6) in the baloxavir group and 13.5% (95% CI: 9.8-17.9) in the oseltamivir group. In the multivariate analysis, independent risk factors were 0-6 years of age (odds ratio [OR] 2.78, 95% CI: 1.33-5.82, p < 0.01) and not being on baloxavir treatment. (OR: 0.63, 95% CI: 0.30-1.32, p = 0.22). CONCLUSION: The household secondary attack rate of influenza was comparable in patients treated with baloxavir vs oseltamivir. Therefore, baloxavir can be used as an alternative therapy to oseltamivir in reducing household transmission of influenza. TRIAL REGISTRATION: Patients in this study were retrospectively registered. https://www.tosei.or.jp/clinical/pdf/2_influenza.pdf.

Efficacy of prolonged tapered and pulsed vancomycin regimen on recurrent Clostridioides difficile infection in the Japanese setting: a case control study.

BACKGROUND: According to the Clinical Practice Guidelines for Clostridioides difficile, oral vancomycin is to be used in vancomycin tapered and pulsed regimen (VCM-TP) for recurrent Clostridium difficile infection (CDI). However, data on the efficacy of VCM-TP in Japanese patients with recurrent CDI are scarce. To address this gap, we investigated the efficacy of VCM-TP and performed a case-controlled study to assess the risk factors associated with treatment failure in these patients. FINDINGS: We conducted this study on all patients who were administered VCM-TP for recurrent episodes of CDI between January 2008 and December 2018 at Tosei General Hospital. All patients had documented follow-ups within 90 days after completion of the VCM-TP. Data were obtained for comparative analysis of treatment success or failure. Thirty-six patients were eligible for this study, and treatment success was documented in 23 patients (63.9%) following VCM-TP treatment. Treatment success was documented in 22 of 30 (73.3%) patients who received the recommended therapy according to the Clinical Practice Guidelines. The frequency of patients treated with the recommended therapy was higher in the treatment success group (95.7%) than in the treatment failure group (61.5%) (OR: 13.75, 95% CI: 1.39-136.39, p = 0.016). Vancomycin-resistant enterococci culture tests were performed in 20 patients (55.6%), and all results were negative. CONCLUSIONS: Our findings suggest that VCM-TP is a good therapeutic option for recurrent CDI in Japanese patients. Furthermore, administration of the recommended VCM-TP is important for achieving a high rate of treatment success. Hence, antimicrobial stewardship teams should support the implementation of recommended VCM-TPs.

Effectiveness of pharmaceutical support by pharmacists in urinary care teams.

To facilitate timely removal of urinary catheters and promote self-voiding among inpatients, urinary care teams have been established in some Japanese medical institutions. However, direct evidence of the effectiveness of pharmacist intervention in urinary care teams is limited. We evaluated the efficacy of pharmaceutical support by a pharmacist in a urinary care team. Between September 2017 and August 2018, 84 patients met the criteria for initiating continuous intervention. Patients with (20 cases) and without (8 cases) adoption of pharmaceutical support (initiation or discontinuation of treatment for dysuria) were scored for urinary function (including degree of independence of urination and score of lower urinary tract disorder) and for urinary situation. Comparative analysis results showed that pharmacist intervention in the adoption cases resulted in significantly improved scores for urinary function than in non-adoption cases. Similarly, pharmaceutical support resulted in improved overall urinary situation in the patients (85.0% of adoption cases compared to 37.5% of the non-adoption cases). The most common pharmaceutical support was a recommendation to discontinue drugs that induce dysuria (65.0% of the cases). Taken together, our findings suggested that pharmacists are important members of urinary care teams.

[Cetuximab-associated skin ulceration in patient with metastatic colorectal cancer: a case report].

An 82-year-old female was diagnosed with rectal cancer. Hartmann's procedure was performed and a curative resection was successfully achieved. Postoperative staging according to the classification of the Japanese Society for Cancer of the Colon and Rectum(The 7th Edition)was stage III. She received adjuvant chemotherapy after surgery with tegafur(UFT 300 mg/body/day)orally for 6 months. One year after the surgery, paraaortic lymph node metastasis and a local recurrence were diagnosed. She was treated with modified FOLFOX6 chemotherapy combined with bevacizumab. After 13 courses of treatment with FOLFOX6 and bevacizumab, multiple lung metastases were found. Therefore, we changed the chemotherapy regimens to FOLFIRI plus cetuximab. After 18 weeks of this new treatment she had two skin ulcerations around her stoma, a known side effect associated with cetuximab. We stopped cetuximab and continued chemotherapy with FOLFIRI alone. Seven weeks after cetuximab withdrawal, her skin ulcer healed with the support of a dermatologist and a wound ostomy continence nurse. We reintroduced cetuximab in a chemotherapy regimen with a reduced dose. After two infusions of cetuximab, skin ulceration recurred. We stopped cetuximab again and continued chemotherapy with FOLFIRI. Nine weeks later we resumed cetuximab, but this time the skin ulcer did not occur, and we were able to continue the chemotherapy regimen with FOLFIRI and cetuximab.