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.     

占永立教授从咽论治IgA肾病的理论与实践探析

本文从理论与临床实践2方面总结了占永立教授从咽论治IgA肾病的经验。占教授将Ig A肾病分为3型进行辨证论治:1)肺气不足,热毒扰咽证; 2)脾气虚弱,热邪客咽证; 3)肾阴亏虚,余热留咽证。治疗上以清热解毒利咽为主,兼以扶正,根据病情灵活选方用药,取得较好的临床疗效。     

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.     

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.     

Implantación de Guías de buenas prácticas en España a través del Programa de Centros Comprometidos con la Excelencia en Cuidados®

The implementation of Best practice guidelines is effective in improving clinical practice and reducing clinical variability. The Best Practice Guidelines of the Ontario Nurses Association have been implemented in Spain since 2012 following the principles of the Canadian programme of the Best Practice Spotlight Organisations® (BPSO®). The Nursing and Healthcare Research Unit (Investén-isciii) coordinates this programme in Spain, having been nominated BPSO Host by the Ontario Nurses Association.Four strategies were followed: translation of the Best Practice Guidelines, dissemination of same and of the programme, implementation of the Best Practice Guidelines and assessment of the results in competitively selected centres, and, finally, the development of sustainability mechanisms.Implementation is based on the theoretical Knowledge to Action model, which establishes a cycle of 6 phases: identification of the problem and training of selected BPSO®; adaptation to the local context; assessment of facilitators and barriers; adaptation and implementation of interventions; monitoring and evaluation of results, and sustainability. Each of these phases incorporate evidence-based elements that promote the effectiveness of implementation, such as the competitive selection of candidates to participate in the programme, selection by the institution of the guidelines to be implemented, leadership by nurses with a multi-professional approach, planning of the process from work structures that are non-vertical but with the support of the institution, the simultaneous use of multiple strategies, ongoing assessment and feedback of results. All of which is mentored and supported by the BPSO Host.There are currently 27 institutions in Spain of different characteristics that implement a total of 20 clinical guidelines. The scope and structure of the programme has recently been extended with regional BPSO Host coordinating centres, which has brought the number of institutions to 36 and the number of implemented clinical guidelines to 22.The programme has had a positive impact on organisations and the system, on care processes and on patient health. This is evidenced by enriched evidence-based professional practice, the promotion of collaborative networking and by improved patient health outcomes and the quality of care provided.