Evaluation of factors influencing the ratio of the trough blood concentration to dose level of everolimus in Japanese kidney transplant recipients.

BACKGROUND: No factors influencing the blood everolimus (EVL) concentrations has been identified until date. Our aim was to identify factors that can affect the ratio of the trough blood concentration to dose level (C0/D ratio) of EVL in kidney transplant recipients. METHODS: We retrospectively analyzed 448 patients who had undergone kidney transplantation and were subsequently being managed as our hospital between 2011 and 2015. Multivariate analysis were performed in an attempt to identify factors affecting the EVL C0/D ratio. RESULTS: The numbers of patients receiving calcineurin inhibitor (CNI)-free regimen and regimen containing cyclosporine (CsA) or tacrolimus (TAC) were 47, 137 and 264 respectively. The EVL C0/D ratio did not differ significantly between the TAC(+) group and the CNI-free group, while it was significantly higher in the CsA(+) group than the TAC(+) group (p < 0.0001) and CNI-free group (p = 0.0003). In the multivariate analysis, age, gender, diabetes mellitus as a cause of the end-stage renal disease (ESRD), CsA, serum creatinine, and hemoglobin were selected as factors affecting the EVL C0/D ratio (R2 = 0.269, p < 0.0001). Using the stepwise method, although mycophenolate mofetil treatment was selected, did not differ significantly according to multiple linear regression analysis. Furthermore, concomitant use of CsA was identified as the most impactful factor, based on the standardized partial regression coefficients (ß = 0.341). CONCLUSIONS: We obtained an indication of patient characteristics that influences the EVL C0/D ratio. But the accuracy of the regression equation obtained from multiple regression analysis was poor (R2 = 0.269), and it was not accurate enough to predict the EVL C0/D ratio and use it for therapeutic drug monitoring.

[Effectiveness of Pharmacist-convened Multidisciplinary Clinical Team Meetings in Promoting Appropriate Benzodiazepine Receptor Agonist Use].

Benzodiazepine receptor agonists (BZRAs) are used in the treatment of a wide variety of clinical conditions. Although clinical practice guidelines discourage high dosage or long-term use of BZRAs, they are prescribed in clinical settings. This study aimed to investigate whether the pharmacists at multidisciplinary clinical team meetings can help reduce BZRA use and promote appropriate use of these drugs. The psychiatric unit of the Tokyo Women's Medical University Hospital occupies two floors, with 31 beds on Floor A and 34 beds on Floor B. The multidisciplinary clinical team meetings were held once a week in each ward. During the meetings, the pharmacists comprehensively assessed the number of BZRA doses administered and the equivalent diazepam doses, presented their prescription recommendations aimed at dosage reduction, and shared their views with the entire clinical team. This intervention was commenced on Floor A in 2014 and on Floor B in 2015. The average number of BZRAs in each period and equivalent diazepam doses were assessed for 273 psychiatric inpatients hospitalized from April to June in 2013, 2014, and 2015. Changes in the number of BZRA doses administered were assessed per floor per year. The results showed a statistically significant decrease between years with and without interventions. The intervention of pharmacists allowed multidisciplinary clinical team members to gain the same understanding about BZRA use and formulation of drug therapy plans. The results suggest that the intervention of pharmacists at clinical team meetings can strategically lead to decreased BZRA dosages and their proper use.

A retrospective study on the risk factors for bleeding events in warfarin therapy, focusing on renal function.

PURPOSE: The anticoagulant effect of warfarin used to treat stroke has been shown to vary with the concomitant use of medications and comorbidity. Concomitant use of antithrombotic drugs and underlying chronic kidney disease (CKD) represent risk factors for bleeding events. We conducted a comprehensive investigation of the background characteristics and concomitant use of drugs to identify the risk factors for warfarin-related bleeding, focusing on renal function. METHODS: The study population consisted of patients prescribed warfarin at the Tokyo Women's Medical University Hospital. A retrospective review of the patient data, including bleeding events, bleeding sites, the patient's background, concomitant use of drugs, and laboratory data was carried out, and the incidence of bleeding events was compared in patient groups stratified according to CKD stage and antithrombotic drug use. Multivariate logistic regression analysis was performed to determine the risk factors for warfarin-related bleeding. RESULTS: Of the 3,831 patients included in the study, the incidence of warfarin-related bleeding was 3.0 events per 100 patient-years. The multivariate logistic regression analysis identified age > 65 years, body mass index (BMI), alanine aminotransferase (ALT), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2, prothrombin time-international normalized ratio (PT-INR), and concomitant use of antithrombotic drugs as risk factors for warfarin-related bleeding. CONCLUSIONS: The present analyses identified age > 65 years, BMI, ALT, eGFR <30 mL/min/1.73 m2, PT-INR, and concomitant use of antithrombotic drugs as independent risk factors for warfarin-related bleeding. We should pay attention to the risk factors associated with warfarin-related bleeding when prescribing warfarin in patients with renal impairment.