Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models

Despite the many benefits of breast milk, mothers taking medication are often uncertain about the risks of drug exposure to their infants and decide not to breastfeed. Physiologically based pharmacokinetic models can contribute to drug‐in‐milk safety assessments by predicting the infant exposure and subsequently, risk for toxic effects that would result from continuous breastfeeding. This review aimed to quantify breast milk intake feeding parameters in term and preterm infants using literature data for input into paediatric physiologically based pharmacokinetic models designed for drug‐in‐milk risk assessment. Ovid MEDLINE and Embase were searched up to July 2, 2019. Key study reference lists and grey literature were reviewed. Title, abstract and full text were screened in nonduplicate. Daily weight‐normalized human milk intake (WHMI) and feeding frequency by age were extracted. The review process retrieved 52 studies. A nonlinear regression equation was constructed to describe the WHMI of exclusively breastfed term infants from birth to 1 year of age. In all cases, preterm infants fed with similar feeding parameters to term infants on a weight‐normalized basis. Maximum WHMI was 152.6 ml/kg/day at 19.7 days, and weighted mean feeding frequency was 7.7 feeds/day. Existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency. Milk feeding parameters were quantified for preterm infants, a vulnerable population at risk for high drug exposure and toxic effects. A high‐risk period of exposure at 2–4 weeks of age was identified and can inform future drug‐in‐milk risk assessments.     

医疗保险制度对老年群体死亡风险的影响——基于CLHLS的生存分析

目的:探讨医疗保险制度对老年群体死亡风险的影响,为我国医疗保障制度的改革与完善提供参考依据。方法:基于中国老年健康影响因素跟踪调查(CLHLS)2011—2014年的追踪数据,以添加脆弱因子的Weibull模型与Gompertz模型进行生存分析,并且分年龄组进行异质性分析。结果:相对于无医保的老人,有医保老人的死亡风险随医保制度的不同而发生不同程度的变化,具体而言,新农合、城镇居民基本医疗保险以及城镇职工基本医疗保险分别降低了约20%、25%以及31%的死亡风险。通过分年龄组进一步分析发现,医疗保险对高龄组老人死亡风险有显著影响,而对低龄组老人的死亡风险的影响不显著。结论:医疗保险制度有助于降低老年群体的死亡风险,但影响程度各异,表现为城镇职工医疗保险最高,城镇居民医疗保险次之,新农合最低。基于此,我国医疗保险制度改革的重点方向在于继续扩大医保覆盖面,并弥合不同医保之间的待遇差异,在统筹城乡居民医疗保险的基础上,进一步推进城镇职工医疗保险与居民医疗保险的整合,最终实现城乡医疗保险制度的一体化发展。     

Improved dynamic connection detection power in estimated dynamic functional connectivity considering multivariate dependencies between brain regions

To estimate dynamic functional connectivity (dFC), the conventional method of sliding window correlation (SWC) suffers from poor performance of dynamic connection detection. This stems from the equal weighting of observations, suboptimal time scale, nonsparse output, and the fact that it is bivariate. To overcome these limitations, we exploited the kernel‐reweighted logistic regression (KELLER) algorithm, a method that is common in genetic studies, to estimate dFC in resting state functional magnetic resonance imaging (rs‐fMRI) data. KELLER can estimate dFC through estimating both spatial and temporal patterns of functional connectivity between brain regions. This paper compares the performance of the proposed KELLER method with current methods (SWC and tapered‐SWC (T‐SWC) with different window lengths) based on both simulated and real rs‐fMRI data. Estimated dFC networks were assessed for detecting dynamically connected brain region pairs with hypothesis testing. Simulation results revealed that KELLER can detect dynamic connections with a statistical power of 87.35% compared with 70.17% and 58.54% associated with T‐SWC (p‐value = .001) and SWC (p‐value <.001), respectively. Results of these different methods applied on real rs‐fMRI data were investigated for two aspects: calculating the similarity between identified mean dynamic pattern and identifying dynamic pattern in default mode network (DMN). In 68% of subjects, the results of T‐SWC with window length of 100 s, among different window lengths, demonstrated the highest similarity to those of KELLER. With regards to DMN, KELLER estimated previously reported dynamic connection pairs between dorsal and ventral DMN while SWC‐based method was unable to detect these dynamic connections.     

Prognostic value of preoperative inflammatory markers in resectable biliary tract cancer – Validation and comparison of the Glasgow Prognostic Score and Modified Glasgow Prognostic Score in a Western cohort

IntroductionEstablished preoperative prognostic factors for risk stratification of patients with biliary tract cancer (BTC) are lacking. A prognostic value of the inflammation-based Glasgow Prognostic Score (GPS) and Modified Glasgow Prognostic Score (mGPS) in BTC has been indicated in several Eastern cohorts. We sought to validate and compare the prognostic value of the GPS and the mGPS for overall survival (OS), in a large Western cohort of patients with BTC.Material and methodsWe performed a retrospective single-center study for the period 2009 until 2017. 216 consecutive patients that underwent surgical exploration with a diagnosis of perihilar cholangiocarcinoma (PHCC), intrahepatic cholangiocarcinoma (IHCC), or gallbladder cancer (GBC) were assessed. GPS and mGPS were calculated where both CRP and albumin were measured pre-operatively (n = 168/216). Survival was analyzed by Kaplan-Meier estimate and uni-/multivariate Cox regression.ResultsGPS and mGPS were negatively associated with survival (p < 0.001/p < 0.001), and the association was significant in all three subgroups. GPS, but not the mGPS, identified an intermediate risk group: with GPS = 1 having better OS than GPS = 2 (p = 0.003), but worse OS than GPS = 0 (p = 0.008). In multivariate analyses of resected patients, GPS (p = 0.001) and mGPS (p = 0.03) remained significant predictors of survival, independent of postoperatively available risk factors.ConclusionsPreoperative GPS and mGPS are independent prognostic factors in BTC. The association to OS was shown in all patients undergoing exploration, in resected patients only, and in both cholangiocarcinoma and gallbladder cancer. Furthermore, GPS – which weights hypoalbuminemia higher – could identify an intermediate risk group.     

海安市七星湖社区H型高血压患病率调查及危险因素分析

目的调查海安市七星湖社区H型高血压的发生情况及相关危险因素,为未来社区高血压防治工作的开展提供新的参考依据。方法2019-01/03调查海安市七星湖社区卫生服务中心的居民健康档案登记在册的所有高血压患者,采用自制的调查问卷收集调查对象的一般情况、疾病史和行为生活方式等资料,采用卡方检验及独立样本t检验进行组间比较,采用二元Logistic回归分析影响H型高血压发生的危险因素。结果本次共有908例高血压患者纳入统计分析。空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白、血肌酐、血尿素氮和血尿酸均值分别为(6.26±1.87)mmol/L、(4.79±2.52)mmol/L、(1.85±1.44)mmol/L、(2.79±0.84)mmol/L、(1.71±0.61)mmol/L、(77.68±22.89)mmol/L、(5.61±2.91)mmol/L和(383.07±94.13)mmol/L。调查对象同型半胱氨酸(Hcy)水平为(15.73±9.03)mmol/L,根据Hcy结果筛查出H型高血压患病率为4.46%,占所有高血压患者的41.03%。多因素分析显示,患者男性(OR=1.97,95%CI:1.52~2.95)、高龄(OR=1.076,95%CI:1.057~1.096)、有吸烟史(OR=1.182,95%CI:1.081~1.292)、血尿酸水平高(OR=1.002,95%CI:1.000~1.004)、血肌酐水平高(OR=1.033,95%CI:1.023~1.043)相比于低龄患者、无吸烟史、低尿酸水平、低血肌酐水平的H性高血压发生风险更大。结论七星湖社区高血压患者的Hcy水平偏高,尽管H型高血压患病率较低,但其在高血压中占较高的比例,且存在较多的危险因素较多。社区防治需进行针对性的健康教育及干预,将对心血管事件的防范产生积极的影响。