Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

Phase I study on pegylated liposomal doxorubicin in combination with docetaxel for patients with platinum-resistant or partially platinum-sensitive epithelial ovarian cancer: The Kansai Clinical Oncology Group study

Context: In platinum-resistant ovarian cancer, single-agent chemotherapy is recommended for the reduction of adverse events. However, in clinical practice, some patients can tolerate drug-specific adverse events. Aims: We assessed the safety of pegylated liposomal doxorubicin (PEG-LD) and docetaxel regimen in the first cycle of ovarian cancer. Settings and Design: We performed a phase I study to evaluate the combination therapy of PEG-LD and docetaxel. Materials and Methods: We recruited five patients with recurrent ovarian cancer within 12 months of first-line platinum-based chemotherapy. All patients had measurable disease severity. PEG-LD and docetaxel were intravenously administered on day 1 and every 21 days using three dose levels: 25 mg/m2 PEG-LD and 50 mg/m2 docetaxel; 30 mg/m2 PEG-LD and 50 mg/m2 docetaxel; and 30 mg/m2 PEG-LD and 60 mg/m2 docetaxel. Statistical Analysis Used: We defined the maximum tolerated dose of the combination therapy based on the modified Fibonacci method. Results: Five patients were enrolled in this study. The median treatment-free interval was 5.5 months. Two dose-limiting toxicities (Grade 4 neutropenia) were observed in two patients. One complete response, one partial response, one stable disease, and two progressive disease cases were observed. The overall response rate was 2/5, and the disease control rate was 3/5. The median overall survival was 7.4 months. Conclusions: We determined that 25 mg/m2 of PEG-LD and 50 mg/m2 of docetaxel were safe and effective doses. This preliminary efficacy and safety data should be further investigated in a Phase II trial.

Antioxidation of Picroside Ⅱ on Cerebral Ischemic Injury in Rats and Its Optimum Dosage and Time Window / 中国中医药信息杂志

Objective To optimize the therapeutic dose and time window of picroside Ⅱ in treating cerebral ischemic injury in rats by orthogonal test. Methods The forebrain ischemia models were established by bilateral common carotid artery occlusion (BCCAO) method. The successful models were randomly grouped according to orthogonal experimental design and treated by injecting picroside Ⅱintraperitoneally at different ischemic time with different doses. The concentrations of MDA, NO and H2O2 in serum and brain tissue were respectively determined by thiobarbituric acid assay, nitratase reductase assay and chemiluminescence immunoassay. Results The optimized composition of the therapeutic dose and time window of picroside Ⅱ in cerebral ischemic injury were ischemia 1.5 h with 10 mg/kg, 1.5 h with 20 mg/kg and 1.5 h with 10 mg/kg body weight according to the expressions of MDA, NO and H2O2 in serum, and ischemia 1.5 h with 10 mg/kg, 1.5 h with 20 mg/kg and 1.5 h with 20 mg/kg body weight according to the expressions of MDA, NO and H2O2 in brain tissue. Conclusion On the basis of the principle of lowest therapeutic dose with longest time window, the optimized composition of the therapeutic dose and time window in cerebral ischemic injury is injecting picroside Ⅱ intraperitoneally with 10-20 mg/kg body weight at ischemia 1.5 h.

Prospective study of increasing doses of tamsulosin in lower urinary tract symptoms of benign prostatic hyperplasia / 中华泌尿外科杂志

ObjectiveTo evaluate the effect of increasing doses of tamsulosin in lower urinary tract symptom (LUTS) of benign prostatic hyperplasia (BPH).MethodsA prospective self-controlled clinical trail was performed.Two hundred and sixty-one patients who had LUTS of BPH were enrolled in this prospective 4 weeks study of tamsulosin.The patients were randomly divided into 2 groups:took tamsulosin 0.2 mg QN (n =126,group A) and 0.4 mg QN (n =135,group B) respectively.The IPSS score and maximum flow rate before and after treatment were compared between the 2 groups.ResultsThe IPSS score of group A decreased from 17.72 ± 2.50 to 10.21± 1.95,average decreased 7.59 ± 2.74 ； maximum flow rate was elevated from (8.78 ± 3.70) ml/s to ( 12.74 ± 2.99 ) ml/s,average increased (4.31 ± 3.01 )ml/s.The IPSS score of group B decreased from 19.24 ± 3.22 to 11.21 ± 3.02,average decreased 8.49 ±3.73； maximum flow rate was elevated from (7.74 ± 1.97) ml/s to ( 12.04 ± 2.46) ml/s,average increased (4.73 ± 2.97) ml/s.There was no significant difference of the changes of IPSS score between the 2 groups ( P ＞ 0.05 ),but there was a significant difference of the changes of maximum flow rate between the 2 groups ( P ＜ 0.05 ).The results was further analyzed by sub grouped ( by patient body weight,divided into ≤55.0 kg,55.1 -65.0 kg,65.1 -75.0 kg,＞75.0 kg group).There were significant differences of the changes of IPSS score and maximum flow rate between the 2 groups in 65.1 - 75.0 kg and ＞ 75.0 kg subgroups ( P ＜ 0.05 ).The incidence of side effects between the 2 groups was not significantly different (P ＞ 0.05).ConclusionsFor most patients,the use of high-dose tamsulosin in improving LUTS caused by BPH can not bring significant benefits.But if the patient's weight is more than 65.0 kg,increasing the dose of tamsulosin is suggested for consideration.

Severe acute renal injury in the need for greater therapeutic dose of CRRT / 中国实用内科杂志

The optimal intensity of continuous renal-replacement therapy in severe acute kidney injury is uncertain,but the establishment of optimal dose of CRRT is the key to successful treatment.In this paper,the basis for setting dose of CRRT starts analysis of the current CRRT dose and the efficacy of the evidence in evidence-based medicine and problems and presents the need of severe acute renal injury for greater CRRT dose.The purpose is to guide clinicians to set an optimal CRRT dose and improve the prognosis of severe acute renal injury.