Exploratory analysis of target concentration of lenvatinib in the treatment of hepatocellular carcinoma.

PURPOSE: We aimed to evaluate exposure-toxicity/efficacy relationship of lenvatinib by determining its target trough concentration for patients with hepatocellular carcinoma (HCC). METHODS: In this retrospective, observational study, 28 HCC patients who had been treated with lenvatinib were enrolled between August 2018 and April 2020. We evaluated the association between the trough lenvatinib concentration and occurrence of grade ≥ 3 toxicities. Additionally, we estimated the association of the trough lenvatinib concentration with responder status (disease control; complete response, partial response, or stable disease), and progression-free survival (PFS). RESULTS: The mean trough lenvatinib concentration was significantly higher in the group with grade ≥ 3 toxicity (n = 15) than in the group with grade ≤ 2 toxicity (n = 13). Based on the receiver operating characteristic curve, the threshold values of the trough lenvatinib concentrations for predicting grade ≥ 3 toxicities and responder status were 71.4 ng/mL [area under the curve (AUC) 0.86, 95% confidence interval (CI) 0.71-1.00; p < 0.05] and 36.8 ng/mL (AUC 0.95, 95% CI 0.85-1.00; p < 0.05), respectively. Lenvatinib concentrations of 36.8-71.4 ng/mL resulted in longer PFS than concentrations < 36.8 ng/mL and ≥ 71.4 ng /mL [median 13.3 months (36.8-71.4 ng/mL) vs. 3.5 months (< 36.8 ng/mL) and 7.8 months (≥ 71.4 ng /mL), respectively]. CONCLUSIONS: Considering these results, we propose that the target trough concentration of lenvatinib could be 36.8-71.4 ng/mL for maintaining disease control status and reducing grade ≥ 3 toxicity in the treatment of HCC.

[Evaluation of a Two-day Hospital On-site Training Program for Community Pharmacists: Approach to Facilitate Collaboration among Community Healthcare Professionals].

　The importance of community-based care systems has increased due to the highly aging population and diversity of disease. To enhance the cooperation among healthcare professionals in community-based care systems, a two-day on-site training program for community pharmacists based on a multidisciplinary team approach was conducted at the Medical Science Hospital of Shiga University from April 2015 to March 2017. There were two professional courses in this training program: the palliative care course and nutrition support course. Both courses consisted of common pharmaceutical care training as follows: regional cooperation among healthcare professionals, pharmacist's clinical activities in the ward, pressure ulcer care, infection control, and aseptic technique for parenteral solutions. Each course was limited to 2 participants. A questionnaire was given to participants in the training program. Seventy-five pharmacists participated in the training and all of them answered the questionnaire. According to the questionnaire, 86% of participants felt that 2 days was an appropriate term for the training program. Positive answers regarding the content of each program and overall satisfaction were given by 100% and 99% of the participants, respectively. In the categorical classification of free comments regarding the expected change in pharmacy practice after the training, both "support for patients under nutritional treatment" and "cooperation with other medical staff" were answered by 24 participants. These results suggested that the 2-day on-site training for community pharmacists facilitated cooperation among healthcare professionals in the community.

[Anesthetic management of Jehovah's Witnesses patients undergoing open heart surgery with cardiopulmonary bypass].

BACKGROUND: The anesthetic management of Jehovah's Witnesses (JW) patients undergoing open heart surgery with cardiopulmonary bypass (CPB) is associated with a major risk of anemic hypoxia. METHODS: Fifteen patients from the community of JW underwent open heart surgery. The surgical procedures undertaken were aortic valve replacement in 7 patients, mitral valve plasty or replacement in 5 patients, repair of congenital heart diseases in 2 patients, and removal of left atrial myxoma in one patient. Hemoglobin values, cardiac output, and oxygen delivery (Do2) as well as consumption (Vo2) were evaluated during and after surgery. RESULTS: After CPB, the mean hemoglobin (Hb) value decreased to 8.2 g x dl(-1) from the baseline level of 11.6 g x dl(-1) (P = 0.0007); however, it increased to 10.5 g x dl(-1) at the end of surgery Cardiac index remained unchanged. Oxygen delivery (Do2) decreased after CPB from its baseline level, whereas oxygen consumption remained unchanged. Twenty-four hours after surgery, Do2 recovered to its baseline level because of an increase in cardiac output with the Hb value of 10.7 g x dl(-1) . CONCLUSIONS: The decrease in Hb level is unavoidable in cardiac surgery with CPB in these JW patients. This survey showed that the decrease in Hb level may be compensated by conserved cardiac output avoiding the decrease of Do2 to its critical level when hypoxia occurs.