Advantages with prophylactic PEG-rhG-CSF versus rhG-CSF in breast cancer patients receiving multiple cycles of myelosuppressive chemotherapy: an open-label, randomized, multicenter phase III study.

BACKGROUND: PEG-rhG-CSF reduces neutropenia and improves chemotherapy safety. In China's registration trial (CFDA: 2006L01305), we assessed its efficacy and safety against rhG-CSF, and prospectively explored its value over multiple cycles of chemotherapy. METHODS: In this open-label, randomized, multicenter phase 3 study, breast cancer patients (n = 569) were randomized to receive PEG-rhG-CSF 100 µg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 µg/kg/d after chemotherapy. The primary endpoints were the incidence and duration of grade 3/4 neutropenia during cycle 1. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia during cycles 2-4, the incidence of febrile neutropenia, and the safety. RESULTS: A once-per-cycle PEG-rhG-CSF at either 100 µg/kg or 6 mg was not different from daily injections of rhG-CSF for either incidence or duration of grade 3/4 neutropenia. Interestingly, a substantial difference was noted during cycle 2, and the difference became bigger over cycles 3-4, reaching a statistical significance at cycle 4 in either incidence (P = 0.0309) or duration (P = 0.0289) favoring PEG-rhG-CSF. A significant trend toward a lower incidence of all-grade adverse events was noted at 129 (68.98%), 142 (75.53%), and 160 (82.47%) in the PEG-rhG-CSF 100 µg/kg and 6 mg and rhG-CSF groups, respectively (P = 0.0085). The corresponding incidence of grade 3/4 drug-related adverse events was 2/187 (1.07%), 1/188 (0.53%), and 8/194 (4.12%), respectively (P = 0.0477). Additionally, PFS in metastatic patients preferred PEG-rhG-CSF to rhG-CSF despite no significance observed by Kaplan-Meier analysis (n = 49, P = 0.153). CONCLUSIONS: PEG-rhG-CSF is a more convenient and safe formulation and a more effective prophylactic measure in breast cancer patients receiving multiple cycles of chemotherapy.

A phase 2 study of methotrexate, etoposide, dexamethasone, and pegaspargase chemotherapy for newly diagnosed, relapsed, or refractory extranodal natural killer/T-cell lymphoma, nasal type: a multicenter trial in Northwest China.

The nasal type of extranodal natural killer/T-cell lymphoma is a rare aggressive lymphoma with poor prognosis. To discover a successful treatment, we investigated the efficacy and safety of chemotherapy with methotrexate, etoposide, dexamethasone, and polyethylene glycol-asparaginase (MESA). Three cycles of MESA were administered to 46 patients with new or relapsed/refractory natural killer/T-cell lymphoma. Complete response after 3 treatment cycles was 43.5%, the overall response rate was 87%, and 2-year overall survival was 83.4%. Complete response was significantly better for newly diagnosed patients than for patients with relapsed/refractory disease. Patients with newly diagnosed disease had a significantly better overall response rate after 1, but not after 2 or 3 treatment cycles. Overall survival and progression-free survival did not differ over 2 years. Grade 1/2 toxicities were frequent, but MESA was associated with fewer grade 3/4 events or treatment-related deaths. These results will require confirmation in larger prospective trials.

[Influence of the effect of general anaesthesia and restraint during dental treatment on dental anxiety and behavior in children].

OBJECTIVE: To compare the level of dental anxiety and dental behavior between dental fear children with dental treatment under general anaesthesia (GA) and those under restraint. METHODS: The GA group included 31 dental fear children aged 4-6-year-old who received dental treatment under the GA. The restraint group included 31 dental fear children aged 4-6-year-old who received dental treatment under the restraint. Age, gender, parent's education level, decayed-missing-filled-tooth (dmft) and face version of the Modified Child Dental Anxiety Scale (MCDASf) score before treatment were matched between the two groups. The Chinese version of MCDASf was used to evaluate the level of dental anxiety in each child before treatment, right after treatment and before examination at recall visit 2-3 weeks after treatment. And the Chinese version of Venham Clinical Anxiety and Cooperative Behavior Scale was used to evaluate children's dental behavior in each child before treatment and before examination at recall visit 2-3 weeks after treatment. RESULTS: The average scores of MCDASf in GA group right after treatment and before recall were lower than that before treatment. The difference was statistically significant (P<0.05). Furthermore, the average score of MCDASf before recall was lower than those after treatment, and the difference was statistically significant (P<0.05). The average scores of MCDASf in restraint group right after treatment and 2-3 weeks after treatment were higher than those before treatment, but the difference was not statistically significant (P>0.05). Children's dental behavior was significantly improved at recall visit in both groups (P<0.01). CONCLUSION: Dental fear could be reduced by treatment under GA. The children's dental behavior was improved after GA. Restraint did not result in the significant elevation of dental anxiety level, but dental behavior was improved after restraint during the short-term recall.

[A retrospective study of 693 children's dental treatment under general anesthesia].

OBJECTIVE: To retrospectively analyze the clinical features of children who received dental treatment under general anesthesia (GA) and the characteristics of dental treatment. METHODS: The records of 693 patients treated under GA in the Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, between Jan. 2001 and Dec. 2012 were collected and analyzed. RESULTS: The numbers of patients treated under GA increased year-to-year. Most of them were under 4-year-old. The main reasons of dental treatment under GA were uncooperative and disabled. The average number of teeth treated was 12±4 for each child, and the average time for treating one tooth was 12 min. The 3 months follow-up rate was 60.31%, and the older, the fewer treated tooth number and out-of-town associated with the less follow-up rate. CONCLUSION: The main reasons of dental treatment under GA are uncooperative and disabled. GA is an effective and safe method for dental rehabilitation in children.

[Application of percutaneous vertebroplasty with the second injection for poor dispersion bone cement of Kümmel disease].

OBJECTIVE: To investigate clinical effect of percutaneous vertebroplasty with second injection for poor dispersion bone cement of Kümmel disease. METHODS: Eighty-eight patients with Kümmel disease were treated with vertebroplasty from February 2014 to December 2017, and 16 patients were found cement dispersion unsatisfactory during initial cement injection and were undertaken second cement injection during operation. Among patients, there were 1 male and 15 females aged from 63 to 82 years old with an average age of 72.7 years old. Distribution of fractured vertebrae were followed: 1 patient was on T10, 1 patient was on T11, 3 patients were on T12, 8 patients were on L1, 1 patient was on L2, and 2 patients were on L3. VAS and ODI score were compared before operation, 2 days after operation and the latest following-up, anterior vertebral height and local kyphosis angle of fractured vertebrae with intravertebral cleft were also observed. Postoperative complication was recorded. RESULTS: All patients were followed up from 5 to 22 months with average of 14.1 months. ODI score before operation, 2 days after operation and the latest following-up were 72.3±12.1, 56.8±5.0 and 12.1±5.3 respectively; VAS score before operation, 2 days after operation and the latest following-up were 7.8±0.6, 3.0±0.4 and 2.4±0.7, respectively; ODI score at 2 days was improved compared with before operation, while ODI and VAS score at the latest following-up was improved than that of 2 days after operation. Vertebral anterior compression rate and Cobb angle of the fractured vertebrae with intravertebral cleft were respectively corrected from (37.8±5.4)% and (15.1±2.0)°preoperative, to (4.7±1.4)% and (4.4±2.2)° at 2 days after operation, (4.9±1.5)% and (4.8±2.4)° at the latest following-up, there was significant difference between before operation and 2 days after operation, while there was no difference between 2 days after operation and the latest following-up. Three patients occurred cement leakage without pulmonary embolism and neurological impairment. Four patients occurred adjacent vertebrae fracture. There was no incidence of recollapsed vertebrae during follow-up period. CONCLUSIONS: Percutaneous vertebroplasty for Kümmel disease could receive satisfactory clinical results when cement dispersion was inadequate during initial cement injection by the second injection, and effectively prevent occurrence of vertebral re-collapse.

Enhanced brain delivery of lamotrigine with Pluronic(®) P123-based nanocarrier.

BACKGROUND: P-glycoprotein (P-gp) mediated drug efflux across the blood-brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG). METHODS: LTG-loaded Pluronic(®) P123 (P123) polymeric micelles (P123/LTG) were prepared by thin-film hydration, and brain penetration capability of the nanocarrier was evaluated. RESULTS: The mean encapsulating efficiency for the optimized formulation was 98.07%; drug-loading was 5.63%, and particle size was 18.73 nm. The solubility of LTG in P123/LTG can increase to 2.17 mg/mL, making it available as a solution. The in vitro release of LTG from P123LTG presented a sustained-release property. Compared with free LTG, the LTG-incorporated micelles accumulated more in the brain at 0.5, 1, and 4 hours after intravenous administration in rats. Pretreatment with systemic verapamil increased the rapid brain penetration of free LTG but not P123/LTG. Incorporating another P-gp substrate (Rhodamine 123) into P123 micelles also showed higher efficiency in penetrating the BBB in vitro and in vivo. CONCLUSION: These results indicated that P123 micelles have the potential to overcome the activity of P-gp expressed on the BBB and therefore show potential for the targeted delivery of AEDs. Future studies are necessary to further evaluate the appropriateness of the nanocarrier to enhance the efficacy of AEDs.

[The effect of H2O2 surface treatment of posts on the bond strength between glass fiber posts and the resin cement].

PURPOSE: To evaluate the effect of H2O2 on the push-out bond strength between glass fiber posts and the resin cement. METHODS: Eighteen Tenax glass fiber posts and 18 Macthpost glass fiber posts were randomly assigned to 6 groups according to the surface treatments. Group A, no surface treatment (control group); Group B, treated with silane agent; Group C, treated with 3% H2O2, then with silane agent; Group D, treated with10% H2O2, then with silane agent; Group E, treated with20% H2O2, then with silane agent; Group F, treated with 30% H2O2, then with silane agent. The posts were adhered using the resin cement to form cylindrical resin block. Each resin block was sectioned to 7 sections of 1 mm thick. A push-out test was performed on other sections of each post to measure bond strengths. The date was recorded and analyzed with SPSS13.0 software package. The failure modes were examined with stereomicroscope. RESULTS: The bond strengths of Tenax post from A1 to F1 were (22.35±3.43) MPa, (22.75±1.92) MPa, (27.21±3.60) MPa, (32.32±2.19) MPa, (36.15±2.32) MPa and (40.51±2.37) MPa, respectively. The bond strengths of Macthpost post from A2 to F2 were (17.29±3.23) MPa, (17.01±3.18) MPa, (20.48±2.11) MPa, (23.60±2.60) MPa, (27.65±3.77) MPa and (30.52±2.99) MPa, respectively. No significantly difference (P>0.05) was found between Group A and Group B, except other groups. CONCLUSIONS: Treatment with H2O2 followed with silane agent can significantly improve the bond strength between Tenax and Macthpost glass fiber posts and resin cement. The group treated with 30% H2O2 has the highest bond strength, and the treatment procedure is more useful to improve the adhesion of the glass fiber post. Supported by Science and Technology Plan Project of Department of Health of Jiangxi Province (20131084).

[Chinese version of a face version of the modified child dental anxiety scale: transcultural adaptation and evaluation].

OBJECTIVE: To develop the Chinese version of a face version of the modified child dental anxiety scale (MCDASf) and test the reliability and validity of MCDASf. METHODS: The English version of MCDASf was translated and back-translated, as well as crosscultural adapted by the method of psychometrics to develop the Chinese version of MCDASf. Subsequently the Chinese version schedule was randomly investigated among 245 kindergarten children and school children aged greater than 4 and less than 12 years on two separate occasions 3 weeks apart to determine the reliability. A total of 248 children attending Pediatrics Dentistry of Peking University School and Hospital of Stomatology aged greater than 4 and less than 12 years old were selected and completed the Chinese version of MCDASf and the Chinese version of modified Children's fear survey schedule-dental subscale (CFSS-DS) before treatment to determine the validity. Then we rated the children's behavior during dental treatment by Venham's clinical anxiety rating scale and cooperative behavior rating scale to evaluate the relation between self-assessed dental anxiety scores and the behavioral reaction during the dental treatment. RESULTS: In reliability study, 98.0% of 250 children completed the MCDASf. In validity study, 99.2% of 248 children completed the MCDASf. Cronbach's alpha coefficient of the translated scale was 0.814 and the test-retest reliability was 0.907. Principal component analysis of the translated scale confirmed that the scale consisted of a single unidimensional construct. The Chinese version of MCDASf significantly was correlated with the Chinese version of modified CFSS-DS (r = 0.843, P < 0.01) . It was also correlated with Venham's clinic anxiety rating scale and cooperative behavior rating scale (r = 0.675, P < 0.01). CONCLUSIONS: The Chinese version of MCDASf demonstrated good reliability and validity and can be used as a simple self-report measurement of dental anxiety in Chinese children aged 4-11 years.