Analysis of Regional Timelines To Set Up a Global Phase III Clinical Trial in Breast Cancer: The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Experience

Purpose.

This study measured the time taken for setting up the different facets of Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO), an international phase III study being conducted in 44 participating countries.

Methods.

Time to regulatory authority (RA) approval, time to ethics committee/institutional review board (EC/IRB) approval, time from study approval by EC/IRB to first randomized patient, and time from first to last randomized patient were prospectively collected in the ALTTO study. Analyses were conducted by grouping countries into either geographic regions or economic classes as per the World Bank''s criteria.

Results.

South America had a significantly longer time to RA approval (median: 236 days, range: 21–257 days) than Europe (median: 52 days, range: 0–151 days), North America (median: 26 days, range: 22–30 days), and Asia-Pacific (median: 62 days, range: 37–75 days). Upper-middle economies had longer times to RA approval (median: 123 days, range: 21–257 days) than high-income (median: 47 days, range: 0–112 days) and lower-middle income economies (median: 57 days, range: 37–62 days). No significant difference was observed for time to EC/IRB approval across the studied regions (median: 59 days, range 0–174 days). Overall, the median time from EC/IRB approval to first recruited patient was 169 days (range: 26–412 days).

Conclusion.

This study highlights the long time intervals required to activate a global phase III trial. Collaborative research groups, pharmaceutical industry sponsors, and regulatory authorities should analyze the current system and enter into dialogue for optimizing local policies. This would enable faster access of patients to innovative therapies and enhance the efficiency of clinical research.     

雷帕霉素联合顺铂对宫颈癌Hela细胞生长和对HIF-1α与VEGF表达影响的观察

目的:探讨mTOR抑制剂雷帕霉素与顺铂联合应用对宫颈癌Hela细胞生长的抑制作用及对HIF-1α和VEGF表达的影响。方法:分别以雷帕霉素、顺铂及雷帕霉素联合顺铂处理体外培养人宫颈癌Hela细胞,采用MTT比色法检测人宫颈癌Hela细胞的抑制率,金氏公式评价两药联合用药的效果,采用RT-PCR法、蛋白质印迹法检测各组细胞HIF-1α和VEGF mRNA和蛋白的表达。结果:雷帕霉素和顺铂对宫颈癌Hela细胞的生长有明显的抑制作用,并呈剂量依赖性,分别联合应用2种浓度雷帕霉素(10和20nmol/mL)与顺铂(0.25和0.5mg/mL)协同治疗指数q值均>1.15,两者有协同作用。雷帕霉素与顺铂联合用药HIF-1αmRNA的表达为0.242±0.048,单独用药雷帕霉素组为0.428±0.068,顺铂组为0.357±0.051;雷帕霉素与顺铂联合用药组VEGF mRNA的表达为0.498±0.093,单独用药雷帕霉素组为0.651±0.112,顺铂组为0.623±0.125,联合用药组与单独用药组比较表达量明显降低,P<0.05;雷帕霉素与顺铂联合用药组HIF-1α蛋白的表达为0.514±0.092,单独用药雷帕霉素组为0.625±0.132,顺铂组为0.635±0.120;雷帕霉素与顺铂联合用药组VEGF蛋白的表达为0.409±0.082,单独用药雷帕霉素组为0.650±0.114,顺铂组为0.623±0.102,联合用药组与单独用药组比较表达量明显降低,P<0.05。结论:单独及联合应用雷帕霉素与顺铂对宫颈癌Hela细胞的生长均有抑制作用,两药联合应用有明显的协同作用,雷帕霉素联合顺铂具有明显下调HIF-1α、VEGF基因和蛋白表达的作用。     

宫颈特殊染色法在宫颈病变筛查中价值的研究

目的探讨叶酸受体介导的宫颈特殊染色法在宫颈癌及癌前病变筛查中的应用价值。方法选取2014年1月-2015年7月来医院就诊的患者同时行FRD宫颈特殊染色检测、液基细胞学(TCT)检测,两者任一项提示异常(FRD提示阳性、细胞学提示AGC或≥LSIL)者行阴道镜检查,以病理结果为金标准,比较两者临床诊断价值。结果纳入病例204例,在宫颈癌及癌前病变的筛查中FRD特殊染色、TCT检查两种检验技术敏感度分别为91.20%、84.00%,特异性分别为62.03%、63.29%,诊断符合率分别为79.90%、75.98%,阳性预测值分别为79.17%、78.36%,阴性预测值分别为81.67%、71.43%,Kappa值分别为0.56、0.48。FRD特殊染色与TCT检查结果差异无统计学意义(P0.05)。结论 FRD特殊染色、TCT检查两种检验技术在宫颈病变中的筛查意义无明显差异,但FRD特殊染色操作简便、结果快速、成本低廉,值得应用于临床。     

A case of eruption guidance for eruption disturbances of the bilateral second molars caused by supernumerary teeth

We report a rare case of eruption disturbance of the bilateral second molars caused by supernumerary teeth in a 7-year-old Japanese boy. The supernumerary teeth were detected by radiographic examination. Computed tomography (CT) was used to examine the positional relationship of the supernumerary teeth and neighboring second molars. CT images showed conical-shaped supernumerary teeth on the upper buccal side of the unerupted mandibular second molars. The cusps of the supernumerary teeth pointed toward the lingual side. Because the two supernumerary teeth threatened to disturb the eruption of the second molars, they were surgically removed at 2 years and 4 months after diagnosis. After removal of the supernumerary teeth, the mandibular second molars erupted at a normal age and aligned normally within the dentition. To the best of our knowledge, this is only one case report of eruption guidance for eruption disturbances of the bilateral second molars caused by supernumerary teeth.     

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

Aim:

We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME).

Methods:

SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses.

Results:

Pretreatment with the combination of ligustrazine (27 mg·kg⁻¹·d⁻¹) and berberine (90 mg·kg⁻¹·d⁻¹) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg⁻¹·d⁻¹).

Conclusion:

The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.     

Aplastic anemia associated with pregnancy: maternal and fetal complications

Objective: To analyze obstetric complications associated with aplastic anemia (AA) among pregnant women and analyze the underlying factors.

Methods: A retrospective analysis of 60 pregnancies with AA. Thirty four of these patients were grouped as complicated group having obstetric complications and the rest 26 without complications as the control group. Comparative analysis was conducted to access the related risk factors, which may affect the maternal and fetal complications.

Results: The major maternal complications in this study were premature labor, gestational diabetes, pre-eclampsia, acute heart failure, postpartum hemorrhage, and severe postpartum infection. Premature birth, fetal growth restriction and stillbirths accounted for 27.3%, 5.0% and 6.7% of prenatal mortality. Twenty six of patients had uncomplicated pregnancies. Patients without complications had higher mean hemoglobin concentration (75.38?±?16.19?g/L) and platelet counts (23.92?±?14.82?×?10⁹ cells/L) than did women with complications (mean hemoglobin concentration, 61.47?±?15.15?g/L, p?=?0.001; mean platelet counts, 12.11?±?7.87?×?10⁹ cells/L, p?<?0.001).

Conclusion: Pregnancies associated with AA can carry the risk of multiple maternal and fetal complications. Low hemoglobin concentration and platelet counts may be the primary risk factors for obstetric complications in pregnancies associated with AA.     

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??OBJECTIVE To investigate the effect of solvent pH on the physical/chemical properties and clinical use of four drugs commonly used in gynecology and obstetrics, including aminophylline, ambroxol, labetalol and ritodrine, through simulation and evidence-based evaluation to provide theoretical guidance and quantitative reference for clinical use. METHODS By searching PubMed compound and Martindale:The Complete Drug Reference, the physical/chemical and clinical information of the four drugs were obtained. The logP, pK_a, logD, and solubility were simulated using ACD/LAB 6.0 software. RESULTS The solvent pH had effects on the logD and solubility of the four drugs to a certain degree in an exponential manner. The four drugs are compatible with dextrose injection or 0.9% sodium chloride injection, but special care needs to be taken in the clinical use. CONCLUSION Solvent pH has influence on the dissolution balance of the four drugs. Simulation of the physical/chemical properties of drugs will provide theoretical guidance and reference for clinicians with more detailed information.     

北京市无痛人工流产育龄妇女接受流产服务的现状调查

目的:了解选择行无痛人工流产术的育龄妇女接受流产服务的现状。方法:采用分层随机抽样的方法在北京市18个区县中抽取6个区县的18家开展计划生育技术服务的医疗机构,在门诊对早孕后选择终止妊娠的育龄妇女进行问卷调查。结果:在至少有1次流产史的1 005例行无痛人工流产调查对象中,前次流产有49.2%的人选择了无痛人工流产,在前次流产时有77.9%接受了避孕宣传教育,只有50.1%获得了避孕药具,前次流产告知流产后需避孕者其流产后首次性生活避孕的比例明显高于未告知者,而且提供避孕宣传教育服务与流产的地点有关。本次流产83.6%为意外妊娠,外地户籍、大学或大专学历、收入>3 000元、丈夫或性伴年龄<25岁的育龄妇女选择无痛人工流产的比例较高,选择无痛人工流产的育龄妇女中有29.0%存在高危因素,仅有61.9%被告知无痛人工流产可能发生并发症。结论:无痛人工流产育龄妇女高危流产的比例较高,其流产前、后获得的知识和信息不足,应开展多种形式的生殖健康知识宣传教育,落实避孕措施,减少非意愿妊娠。     

Follicle-stimulating hormone associates with metabolic factors in postmenopausal women

Abstract

Current studies have focused more on the relationships among estrogen, androgen, and metabolic syndrome (MetS). The main aim of the study was to investigate whether the variation of FSH is associated with metabolic factors in postmenopausal women. A total of 561 postmenopausal women aged 39–69 years were selected. FSH, estradiol, fasting blood glucose, and lipid profiles were analyzed. Compared with women in the highest FSH quartile, women in the lowest quartile had higher body mass index (BMI), fast blood glucose (FBG), triglyceride (TG), blood pressure, and serum estradiol (E₂) but lower high-density lipoprotein (HDL) (all p?<?.05). Compared with women in the groups of normal levels of MetS biomarkers, women in the abnormal groups had lower FSH (all p?<?.01). Increased quartiles of FSH were associated with significantly decreased rates of abnormal levels of metabolic factors (all p?<?.05). High FSH levels had protective effects regarding SBP, DBP, and FBG, with odds ratios (ORs) of 0.84 (95% CI 0.76–0.92, p?<?.001), 0.85 (95% CI 0.78–0.94, p?<?.01), 0.90 (95% CI 0.83–0.98, p?<?.01), respectively. Low FSH appears to be a risk factor of all domains of MetS in postmenopausal women, which merits further study.