In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.     

Patients with Gastric Antral Vascular Ectasia (GAVE) Are at a Higher Risk of Gastrointestinal Bleeding in the Absence of Cirrhosis

Background and Aims: Gastric antral vascular ectasia (GAVE) is commonly found in patients with cirrhosis, but it is also associated with other diseases in the absence of cirrhosis. Whether GAVE confers a different severity of gastrointestinal (GI) bleeding between patients with and without cirrhosis remains unknown. We aim to examine whether there is a difference in clinically significant GI bleeding due to GAVE in patients with or without cirrhosis. Methods: This is a retrospective case-control study of patients who were diagnosed with GAVE between January 2000 and June 2014. Patients were categorized into cirrhosis and noncirrhosis groups, and those with an additional GI bleeding source were excluded. Univariate comparisons and multivariable models were constructed using logistic regression. Results: In total, 110 patients diagnosed with GAVE on esophagogastroduodenoscopy (EGD) were included in our analysis; 84 patients had cirrhosis (76.4%) and 26 (23.6%) did not. Active GI bleeding was more prevalent in patients without cirrhosis (63.4% vs. 32.1%, p=0.003) despite similar indications for EGD, and endoscopic treatment with argon plasma coagulation (APC) was required more often in this group, approaching statistical significance (27% vs. 10.7%, p=0.056). There was no difference in bleeding severity, as evidenced by similar re-bleeding rates, surgery, or death attributed to uncontrolled bleeding. The strongest independent risk factor for GI bleeding was the absence of cirrhosis (odds ratio (OR): 5.151 (95% confidence interval (CI): 1.08-24.48, p=0.039). Conclusions: Patients with GAVE in the absence of cirrhosis are at higher risk for active GI bleeding and require more frequent endoscopic treatment than similar patients with cirrhosis. It may be worthwhile to treat GAVE in this population even in the absence of active bleeding.     

黄石、荆门地区产妇母乳喂养自我效能影响因素分析

目的 探究黄石、荆门地区产后妇女母乳喂养自我效能的现状及影响因素,为改善母乳喂养率提供更多理论依据。方法 对2017年12月—2018年3月在湖北省黄石市、荆门市的三所医院住院分娩的产妇进行问卷调查,获得产妇社会人口特征、孕产相关资料、母乳喂养相关情况。采用多元线性回归分析母乳喂养自我效能的影响因素。结果 共1 023名产妇纳入分析,平均年龄(29.0±5.7)岁。已婚占98.3%,初产占54.0%,大专及以上学历占53.9%。研究对象的母乳喂养自我效能平均得分为(45.5±12.3)分。多元线性回归的结果显示:当前不存在乳腺问题(B=2.08,P=0.036)、有母乳喂养经历(B=3.62,P<0.001)、家人提供母乳喂养指导或经验(B=3.20,P=0.001)、丈夫支持母乳喂养(B=5.87,P=0.001)及产后30 min内有医护母乳喂养帮助(B=3.02,P=0.003)的产妇母乳喂养自我效能得分更高。结论 产后妇女的母乳喂养自我效能可能与其健康状况、母乳喂养经历、社会支持及母乳喂养卫生服务有关。应对产后妇女提供广泛的社会支持,加强母乳喂养卫生服务提供,以提高其母乳喂养的自我效能,促进母乳喂养。     

Serum growth factor stability in different eye drop packaging systems during storage

Serum eye drops (SED) have shown beneficial effects in patients suffering from dry eye syndrome and are manufactured for an increasing number of patients in Australia every year. Previous studies have examined the stability of serum growth factors during storage in either experimental vessels not used as the final packaging system or in eye drop bottles. To ensure the quality and safety of SED product manufactured in Australia, the stability of growth factors in serum packaged into two different systems during storage at different temperatures was examined. Healthy blood donors provided a whole blood donation, from which serum was prepared, diluted to 20% and dispensed into either a tube or a vial packaging system. The stability of growth factors, fibronectin and total protein in tube segments was comparable to matched vials samples during storage at −30 °C, 4 °C, 22 °C and 37 °C, with the exception of EGF and fibronectin in 20% SED stored in tube segments, which were more sensitive to storage conditions at 4 °C and 22 °C when compared to vials. Additionally, the growth factor, fibronectin and total protein concentration in both tube segments and vials was stable during storage at −30 °C for at least 9 months. This study highlights the impact of different manufacturing procedures on serum growth factor stability during storage.     

Early onset scoliosis and current treatment methods

ObjectiveProvide an update of the management options for early onset scoliosis patients, including general assessment, conservative and surgical options.MethodsWe included the updated information about the assessment and management options of Early Onset Scoliosis, taking into consideration the non-fusion methods, including the burden on the patient and their family.ResultsWith the heterogeneity of this population, it is difficult to get a consensus about a unified protocol for management. Accordingly, the surgeon dealing with these cases needs to be aware of the broad range of surgical and non-surgical methods when treating these patients.ConclusionThe main aim of early onset scoliosis treatment is to gain a flexible spine associated with normal lung development and thoracic growth. Management needs to be individualized between the surgeon and patient in relation to the etiology and patient conditions.     

嘉兴市新居民儿童心理发育行为问题及影响因素分析

目的调查嘉兴市新居民儿童心理发育行为问题及影响因素，为改善新居民儿童心理健康提供理论依据。方法随机抽取新居民儿童548例，本地儿童1248例，采用自编量表评估儿童家庭影响因素，长处与困难问卷评估儿童心理发育行为问题，心理痛苦温度计评估主观心理痛苦程度，儿童心理虐待与忽视量表评估家庭教养方式，社会支持量表评估社会支持程度。结果新居民儿童主观评定心理痛苦程度高于本地儿童（P=0.002）。新居民儿童亲社会化行为低于本地儿童（P=0.000），多动/注意缺陷问题高于本地儿童（P=0.011）。儿童忽视虐待量表本地儿童5个因子得分低于新居民儿童：责骂因子（P=0.000）、恐吓因子（P=0.000）、情感忽视因子（P=0.000）、教育忽视因子（P=0.000）、身体忽视因子（P=0.000）。社会支持量表本地儿童3个因子得分均高于新居民儿童：客观支持（P=0.032）、主观支持（P=0.000）、对支持的利用度（P=0.000）。新居民儿童在新居民儿童学校、混合学校、本地儿童学校的3类学校中亲社会化行为、忽视因子、虐待因子、社会支持均有统计学差异（均P＜0.05）。结论新居民儿童较本地儿童心理发育行为明显落后，良好的家庭教养方式和有效的社会支持系统能够更快更好地促进其身心发育。     

Endothelial function,regulation of angiogenesis and embryonic central hemodynamics in ART-conceived pregnancies

Abstract

This study was undertaken to compare the concentrations of pro- and anti-angiogenic growth factors, nitric oxide (NO) stable metabolites in maternal serum and embryonic left ventricular (LV) isovolumic relaxation time (IRT, ms) during the first trimester in two groups of women: with pregnancy conceived by assisted reproductive technologies (ART, n?=?39) and normally conceived (control group, n?=?68) pregnancy. The concentration of vasoconstrictor endothelin 1 was 45.5 times more in ART than in control group. On the contrary, the concentrations of NO stable metabolites in ART were 1.9 times less than in control women. The assessment of angiogenic suppressors in ART women demonstrates the decrease in s-endoglin concentration was 1.6 times and in soluble receptor to vascular endothelial growth factor concentration was 2.0 times in comparison with control group. There was a significant increase in LV IRT in ART embryos in comparison to control ones. These data suggest significant changes in pro- anti-angiogenic factors balance and increase in vascular impedance in ART-conceived embryos.