Impact of Pharmacists' audit on improving the quality of prescription of dabigatran etexilate methanesulfonate: a retrospective study.

BACKGROUND: Appropriate prescription of dabigatran etexilate methanesulfonate (JAN) is more complicated than assumed, because there are totally 10 items of contraindications and instructions for dosage reduction depending on patients' characteristics. We aimed to study whether the routine audit of first-time prescriptions of dabigatran performed by pharmacists is effective in improving the quality of prescription. METHODS: A retrospective re-audit was performed on all the prescriptions of dabigatran issued at Kitahara International Hospital, Tokyo between March 2011 and February 2014, by evaluating the prescriptions rigorously against the approved prescribing information of the drug. The original routine audit of the prescriptions for inpatients was performed by hospital pharmacists using electronic medical records (EMR), whereas the audit for ambulant patients receiving external prescriptions was performed by community pharmacists using information obtained mainly by questioning patients. The frequencies of inappropriate prescriptions detected by the re-audit in the two groups were compared. RESULTS: Two hundred and twenty-eight patients (131 ambulant patients and 97 inpatients) were prescribed dabigatran for the first time during the study period. All patients met the approved indications. While 33% of the prescriptions for ambulant patients showed at least one violation of the approved usage, only 11% of the prescriptions for inpatients showed violations (p < 0.001). Two ambulant patients with creatinine clearance < 30 mL/min were dispensed dabigatran, whereas no such case was found among inpatients. A significantly greater proportion of ambulant patients aged ≥70 years showed violation of the instruction for dosage reduction compared to inpatients of the same age group (18 and 4%, respectively). CONCLUSION: The present study suggests that pharmacists may achieve better performance in auditing prescriptions of dabigatran when medical records are fully available than when information is available mainly by questioning patients. Further large-scale studies are required to clarify whether the audit of dabigatran prescriptions improves ultimate therapeutic outcomes or complications.

Nuclear export of the influenza virus ribonucleoprotein complex: Interaction of Hsc70 with viral proteins M1 and NS2.

The influenza virus replicates in the host cell nucleus, and the progeny viral ribonucleoprotein complex (vRNP) is exported to the cytoplasm prior to maturation. NS2 has a nuclear export signal that mediates the nuclear export of vRNP by the vRNP-M1-NS2 complex. We previously reported that the heat shock cognate 70 (Hsc70) protein binds to M1 protein and mediates vRNP export. However, the interactions among M1, NS2, and Hsc70 are poorly understood. In the present study, we demonstrate that Hsc70 interacts with M1 more strongly than with NS2 and competes with NS2 for M1 binding, suggesting an important role of Hsc70 in the nuclear export of vRNP.

A phase I trial of concurrent chemoradiotherapy with non-split administration of docetaxel and cisplatin for dry stage III non-small-cell lung cancer (JCOG9901DI).

PURPOSE: This study aimed to establish the maximum tolerated dose of concurrent chemoradiotherapy (cCRT) with conventional administration of the docetaxel (D) plus cisplatin (P) (conv-DP) regimen. METHODS: Patients (aged ≤70 years) with unresectable dry stage III non-small-cell lung cancer (NSCLC) and having performance status 0 or 1 and adequate organ function were eligible. They received radiotherapy (60 Gy in 30 fractions) once daily starting on day 2. Concurrent P (day 1; 60 mg/m(2) at Levels 1-3, 80 mg/m(2) at Level 4) and D (day 1; 30 mg/m(2) at Level 1, 40 mg/m(2) at Level 2, 50 mg/m(2) at Levels 3-4) were administered every 4 weeks for 2-4 courses. RESULTS: Eighteen patients were enrolled (stage IIIA/IIIB, 5/13 patients). Three cases of dose-limiting toxicity were observed in this study, although another 3 cases were added at Levels 2 and 3. Radiotherapy was completed in 15 patients. Seventeen patients received more than 2 courses of chemotherapy. Neither Grade 3/4 esophagitis nor severe hematological events were observed at Levels 1-4. However, dose escalation to Level 5 (P [80 mg/m(2)], D [60 mg/m(2)]) was stopped because the Level 5 dose was the recommended dose (RD) of chemotherapy alone for stage IIIB/IV NSCLC in Japan. Therefore, the RD was determined as D50/P80 mg/m(2) in this cCRT. The objective response rate was 89%, and the median survival time was 23.6 months. CONCLUSIONS: cCRT with non-split DP was a tolerable and effective regimen, and RD was 50/80 mg/m(2) every 4 weeks.

Crucial role of the influenza virus NS2 (NEP) C-terminal domain in M1 binding and nuclear export of vRNP.

The influenza virus genome replicates in the host cell nucleus, and the progeny viral ribonucleoproteins (vRNPs) are exported to the cytoplasm prior to maturation. The influenza virus NS2 protein has a nuclear export signal (NES) and binds to M1. It is therefore postulated that vRNP is exported from the nucleus by binding to NS2 through M1. However, the significance of the association between NS2 and M1 for the nuclear export of vRNP is still poorly understood. We herein demonstrate that the C-terminal domain of NS2 (residues 81-100) is essential for M1 binding and the nuclear export of progeny vRNPs.