2009-2019年西安市肺结核流行特征及治疗转归分析

目的 了解2009-2019年西安市肺结核的流行特征及治疗转归情况，为完善西安市肺结核防治策略提供依据。方法 收集2009-2019年《传染病信息管理系统》中登记的肺结核患者病案信息数据，通过描述性研究方法对肺结核流行病学特征和治疗转归情况进行分析。结果 2009-2019年间西安市肺结核年平均发病率为49.06/10万。郊县、郊区、城区肺结核年平均发病率分别为54.13/10万、47.46/10万和46.19/10万；男性发病率是女性的1.85倍。职业分布排在前5位的为农民（47.48%），家政、家务及待业（14.65%），离退人员（9.55%），学生（8.63%）和工人（5.23%）。利福平敏感或耐药性未知患者的成功治疗率平均为98.03%，利福平耐药患者治疗成功率为51.47%。结论 西安市近年来肺结核发病率和治疗率呈增长趋势，利福平耐药患者治疗成功率较低，要加强对重点人群的健康促进工作，加大肺结核发现力度及患者治疗管理工作。     

Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

1. Download : Download high-res image (187KB)
2. Download : Download full-size image

     

Validation of PATHFx 2.0: An open-source tool for estimating survival in patients undergoing pathologic fracture fixation

Treatment decisions in patients with metastatic bone disease rely on accurate survival estimation. We developed the original PATHFx models using expensive, proprietary software and now seek to provide a more cost-effective solution. Using open-source machine learning software to create PATHFx version 2.0, we asked whether PATHFx 2.0 could be created using open-source methods and externally validated in two unique patient populations. The training set of a well-characterized, database records of 189 patients and the bnlearn package within R Version 3.5.1 (R Foundation for Statistical Computing), was used to establish a series of Bayesian belief network models designed to predict survival at 1, 3, 6, 12, 18, and 24 months. Each was externally validated in both a Scandinavian (n = 815 patients) and a Japanese (n = 261 patients) data set. Brier scores and receiver operating characteristic curves to assessed discriminatory ability. Decision curve analysis (DCA) evaluated whether models should be used clinically. DCA showed that the model should be used clinically at all time points in the Scandinavian data set. For the 1-month time point, DCA of the Japanese data set suggested to expect better outcomes assuming all patients will survive greater than 1 month. Brier scores for each curve demonstrate that the models are accurate at each time point. Statement of Clinical Significance: we successfully transitioned to PATHFx 2.0 using open-source software and externally validated it in two unique patient populations, which can be used as a cost-effective option to guide surgical decisions in patients with metastatic bone disease.     

替考拉宁在中国成人患者中的群体药动学研究

目的建立中国成年患者的替考拉宁(teicoplanin,TEC)群体药动学(population pharmacokinetics,PPK)模型,考察TEC药动学参数的影响因素。方法前瞻性收集139例革兰阳性球菌感染患者静脉注射TEC后的222份常规监测血药浓度和相关信息,采用一级消除的一室模型进行数据拟合,并应用非线性混合效应模型(nonlinear mixed effect model,NONMEM)程序建立PPK模型。采用Bootstrap、正态预测分布误差法(normalized predictive distribution error,NPDE)进行最终模型评价。利用蒙特卡洛模拟法对给药方案进行优化。结果确定了肌酐清除率(creatinine clearance,CLcr)、白蛋白(albumin,ALB)为影响TEC清除率的主要因素。最终模型为:CL(L·h^-1)=1.24×(CLcr/77)0.564×31/ALB;V(L)=69.2。验证表明,模型稳定、有效,且有较好的预测效能。对于不同ALB和CLcr的多数患者起始负荷剂量400 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案可达有效治疗谷浓度。严重感染者需调整负荷剂量至800 mg/q12h,iv,3次,维持剂量400~800 mg·d^-1的给药方案来确保血药浓度达到15 mg·L^-1以上。结论本实验报道了CLcr、ALB对TEC清除率有显著影响,所建模型对TEC在中国成人患者中实现个体化给药具有重要应用价值。     

C.B‐17 SCID mice develop epicardial calcinosis with unaltered cardiac function

Inbred mouse strains are the most widely used mammalian model organism in biomedical research owing to ease of genetic manipulation and short lifespan; however, each inbred strain possesses a unique repertoire of deleterious homozygous alleles that can make a specific strain more susceptible to a particular disease. In the current study, we report dystrophic cardiac calcinosis (DCC) in C.B‐17 SCID male mice at 10 weeks of age with no significant change in cardiac function. Acquisition of DCC was characterized by myocardial injury, fibrosis, calcification, and necrosis of the tissue. At 10 weeks of age, 38% of the C.B‐17 SCID mice from two different commercial colonies exhibited significant calcinosis on the ventricular epicardium, predominantly on the right ventricle. The frequency of calcinosis was more than 50% for mice obtained from Taconic's Cambridge City colony and 25% for mice obtained from Taconic's German Town colony. Interestingly, the DCC phenotype did not affect cardiac function at 10 weeks of age. No differences in echocardiography or electrocardiography were observed between the calcinotic and non‐calcinotic mice from either colony. Our findings suggest that C.B‐17 SCID mice exhibit DCC as early as 10 weeks of age with no significant impact on cardiac function. This strain of mice should be cautiously considered for the study of cardiac physiology.     

Predictors of condom use behaviour among male street labourers in urban Vietnam using a modified Information-Motivation-Behavioral Skills (IMB) model

HIV risk in vulnerable groups such as itinerant male street labourers is often examined via a focus on individual determinants. This study provides a test of a modified Information-Motivation-Behavioral Skills (IMB) model to predict condom use behaviour among male street workers in urban Vietnam. In a cross-sectional survey using a social mapping technique, 450 male street labourers from 13 districts of Hanoi, Vietnam were recruited and interviewed. Collected data were first examined for completeness; structural equation modelling was then employed to test the model fit. Condoms were used inconsistently by many of these men, and usage varied in relation to a number of factors. A modified IMB model had a better fit than the original IMB model in predicting condom use behaviour. This modified model accounted for 49% of the variance, versus 10% by the original version. In the modified model, the influence of psychosocial factors was moderately high, whilst the influence of HIV prevention information, motivation and perceived behavioural skills was moderately low, explaining in part the limited level of condom use behaviour. This study provides insights into social factors that should be taken into account in public health planning to promote safer sexual behaviour among Asian male street labourers.     

Nonproportional hazards and unobserved heterogeneity in clustered survival data: When can we tell the difference?

Multivariate survival data are frequently encountered in biomedical applications in the form of clustered failures (or recurrent events data). A popular way of analyzing such data is by using shared frailty models, which assume that the proportional hazards assumption holds conditional on an unobserved cluster-specific random effect. Such models are often incorporated in more complicated joint models in survival analysis. If the random effect distribution has finite expectation, then the conditional proportional hazards assumption does not carry over to the marginal models. It has been shown that, for univariate data, this makes it impossible to distinguish between the presence of unobserved heterogeneity (eg, due to missing covariates) and marginal nonproportional hazards. We show that time-dependent covariate effects may falsely appear as evidence in favor of a frailty model also in the case of clustered failures or recurrent events data, when the cluster size or number of recurrent events is small. When true unobserved heterogeneity is present, the presence of nonproportional hazards leads to overestimating the frailty effect. We show that this phenomenon is somewhat mitigated as the cluster size grows. We carry out a simulation study to assess the behavior of test statistics and estimators for frailty models in such contexts. The gamma, inverse Gaussian, and positive stable shared frailty models are contrasted using a novel software implementation for estimating semiparametric shared frailty models. Two main questions are addressed in the contexts of clustered failures and recurrent events: whether covariates with a time-dependent effect may appear as indication of unobserved heterogeneity and whether the additional presence of unobserved heterogeneity can be detected in this case. Finally, the practical implications are illustrated in a real-world data analysis example.     

A conceptual model and detailed framework for stress-related,strain-related,and overuse athletic injury

A multitude of athletic injuries occur when the various tissues that make up the human body experience stresses and strains that exceed their material strength. The precise amount of stress and strain that any given tissue can withstand is determined by the mechanical properties and resultant strength of that particular tissue. These mechanical properties are directly determined by an individual’s physiology and acute regulation of these properties. A number of theoretical frameworks for athletic injury occurrence have been proposed, however, a detailed conceptual framework for injury aetiology that considers the interplay between the physiological and mechanical factors and outlines the causal pathways to tissue damage and injury is needed. This will guide injury research towards a more thorough investigation of causal mechanisms and understanding of risk factors. Further, it is important to take into account the considerable differences in loading patterns which can result in varying injury outcomes such as acute stress-related, strain-related, or overuse injury. Within this article a simplified conceptual model of athletic injury is proposed along with a detailed, evidence-informed, conceptual framework for athletic injury aetiology that focuses on stress-related, strain-related, and overuse injury.     

A new mouse model for the neurodevelopmental ciliopathy Joubert syndrome

Recent recognition of the key role of primary cilia in orchestrating human development and of the dire consequences of their dysfunction on human health has placed this small organelle in the spotlight. While the causal link between mutations in ciliary genes and central nervous system malformations and dysfunction is well established, the mechanisms by which primary cilia dysfunction acts on development and function of the CNS remain partly unknown. The recent article by Bashford and Subramanian in The Journal of Pathology describes a new mouse model for the neurodevelopmental ciliopathy Joubert syndrome, supporting a role for ciliary-mediated Hedgehog signaling on proliferation, survival, and differentiation of cerebellar granule cell progenitors. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.