研究型医院发展战略的科学内涵

本文探讨新形势下医院的创新发展之路,主要是围绕深化医院管理创新、加快研究型医院建设,对研究型医院发展模式的内涵解读。     

Adapting Certified Safe Farm to North Carolina Agriculture: An Implementation Study

Certified Safe Farm (CSF) is a multimodal safety and health program developed and assessed through multiple controlled intervention studies in Iowa. Although developed with the intent to be broadly applicable to agriculture, CSF has not been widely implemented outside the midwestern United States. This article describes the CSF implementation process in North Carolina (NC), as piloted on a large-scale in three agriculturally diverse and productive counties of NC, and reports its effectiveness using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. Implementation involved (1) capacity building through safety and health training, (2) adaptation of components of Iowa’s CSF model to NC agriculture, (3) marketing and recruitment, and (4) formative evaluation, including an online survey and focus group discussion. From 2009 to 2012, 113 farms participated in at least one component of the CSF intervention, representing a NC farm participation rate of 3.1% in the study area. A major adaptation of NC implementation was the utilization of NC Cooperative Extension as the local driver of implementation in contrast to local AgriSafe clinics in Iowa. The most innovative adaptation to CSF components was the development of a defined economic incentive in the form of a cost-share program. The RE-AIM framework was found to be useful and relevant to the field of agricultural health and safety translational research. This study provides effectiveness measures and implementation alternatives useful for those considering implementing CSF. It informs current efforts to move CSF from research to practice through the National Sustainable Model CSF Program initiative.     

Healthcare for migrants,participatory health research and implementation science—better health policy and practice through inclusion. The RESTORE project

Background: This is a time of unprecedented mobility across the globe. Healthcare systems need to adapt to ensure that primary care is culturally and linguistically appropriate for migrants. Evidence-based guidelines and training interventions for cultural competence and the use of professional interpreters are available across European healthcare settings. However, in real-world practice migrants and their healthcare providers ‘get by’ with a range of informal and inadequate strategies. RESTORE is an EU FP7 funded project, which is designed to address this translational gap.

Objectives: The objective of RESTORE is to investigate and support the implementation of guidelines and training initiatives to support communication in cross-cultural consultations in selected European primary care settings.

Design: RESTORE is a qualitative, participatory health project running from 2011–2015. It uses a novel combination of normalization process theory and participatory learning and action research to follow and shape the implementation journeys of relevant guidelines and training initiatives. Research teams in Ireland, England, the Netherlands, Austria and Greece are conducting similar parallel qualitative case study fieldwork, with a complementary health policy analysis led by Scotland. In each setting, key stakeholders, including migrants, are involved in participatory data generation and analysis.

Expected results: RESTORE will provide knowledge about the levers and barriers to the implementation of guidelines and training initiatives in European healthcare settings and about successful, transferrable strategies to overcome identified barriers. RESTORE will elucidate the role of policy in shaping these implementation journeys; generate recommendations for European policy driving the development of culturally and linguistically appropriate healthcare systems.     

A critical assessment of edaravone acute ischemic stroke efficacy trials: is edaravone an effective neuroprotective therapy?

Importance of the field: Edaravone (Radicut^®) is a free radical scavenger marketed in Japan by Mitsubishi Tanabe Pharma Corp. to treat acute ischemic stroke (AIS) patients presenting within 24 h of the attack. Injectable edaravone ampoules (30 mg b.i.d., i.v., 14 days) were first approved on 23 May 2001. On 19 January 2010, as a new innovation, the Radicut BAG (Intravenous BAG) was approved by the Japanese Ministry of Health and Welfare. Efficacy of edaravone ranges from large significant clinical improvements to only modest improvements in clinical function measured using standard stroke scales when administered 6 – 72 h following an ischemic stroke. With almost 17 years of edaravone clinical experience, a few adverse events – including acute renal failure – have been noted.

What the reader will gain: This is the only article to date to critically review available clinical efficacy and toxicology data published in the literature to ascertain whether edaravone should be further pursued as a candidate for development worldwide.

Areas covered in this review: This review covers clinical studies carried out over the period 1993 – 2008.

Take home message: Edaravone may be a useful neuroprotective agent to treat the > 15 million victims worldwide who are devastated by stroke annually. Additional clinical studies are necessary to verify the efficacy of edaravone.     

In vitro models of pancreatic cancer for translational oncology research

Background: Pancreatic cancer is a disease of near uniform fatality and the overwhelming majority of patients succumb to their advanced malignancy in a few months of diagnosis. Despite considerable advances in our understanding of molecular mechanisms underlying pancreatic carcinogenesis, this knowledge has not yet been fully translated into clinically available treatment strategies that yield significant improvements in disease free or overall survival. Objective: Cell line-based in vitro model systems provide powerful tools to identify potential molecular targets for therapeutic intervention as well as for initial preclinical evaluation of novel drug candidates. Here, we provide a brief overview of recent literature on cell line-based model systems of pancreatic cancer and their application in the search for novel therapeutics against this vicious disease. Conclusion: Although in vitro models of pancreatic cancer are of tremendous value for genetic studies and for initial functional screenings in drug discovery, they carry several immanent drawbacks and are often poor in predicting therapeutic response in humans. Therefore, in most instances, they are successfully exploited to generate hypothesis and identify molecular targets for novel therapeutics, which are subsequently subject to further in-depth characterization using more advanced in vivo model systems and clinical trials.     

What Aspects of Human Alcohol Use Disorders Can Be Modeled Using Selectively Bred Rat Lines?

The use of selective breeding to produce animal models for the study of alcohol abuse and alcoholism represents one of the major advances in the field of alcohol research. Rats selectively bred for alcohol preference and alcohol nonpreference have been useful to both preclinical and clinical investigators in the alcohol research community for studying the behavioral, neurobiological, and molecular basis of alcohol drinking, for identifying the genes that may contribute to the development of alcohol abuse and alcoholism, and for evaluating the utility of drugs aimed at reducing alcohol intake and preventing alcohol relapse. Rats selectively bred for alcohol preference (alcohol preferring or “P” line) have enhanced responsiveness to the low dose reinforcing effects of alcohol, less aversion to moderate/high doses of alcohol, and are able to develop tolerance to the aversive effects of alcohol more rapidly and to maintain tolerance longer than rats selectively bred for alcohol nonpreference (alcohol nonpreferring or “NP” line). The increased potency of low-dose alcohol as a reinforcer for P rats might be expected to foster and maintain alcohol drinking. Weaker aversion to the pharmacological effects of moderate/high doses of alcohol in the P line would allow P rats to drink more alcohol than NP rats before the postingestional effects become aversive. Rapid induction of tolerance to the aversive effects of alcohol with repeated bouts of voluntary alcohol drinking, as well as persistence of alcohol tolerance in rats of the P line might serve to maintain alcohol drinking. These are powerful mechanisms that may serve to promote and maintain a high alcohol drinking behavior. Although these rat lines have been used to address several characteristics of excessive alcohol consumption in humans, they have not yet been used to model several aspects of human alcohol use disorders. New applications of these selectively bred rat lines are discussed which may further our understanding of the factors contributing to alcohol abuse and alcoholism.     

Drug-like delivery methods of stem cells as biologics for stroke

ABSTRACT

Introduction: Stem cell therapy is an experimental treatment for brain disorders. Although a cellular product, stem cells can be classified as biologics based on the cells’ secretion of therapeutic substances. Treatment with stem cell biologics may appeal to stroke because of the secondary cell death mechanisms, especially neuroinflammation, that are rampant from the onset and remain elevated during the progressive phase of the disease requiring multi-pronged biological targets to effectively abrogate the neurodegenerative pathology. However, the optimal delivery methods, among other logistical approaches (i.e. cell doses and timing of intervention), for stem cell therapy will need to be refined before stem cell biologics can be successfully utilized for stroke in large scale clinical trials.

Areas covered: In this review, we discuss how the innate qualities of stem cells characterize them as biologics, how stem cell transplantation may be an ideal treatment for stroke, and the various routes of stem cell administration that have been employed in various preclinical and clinical investigations.

Expert opinion: There is a need to optimize the delivery of stem cell biologics for stroke in order to guide the safe and effective translation of this therapy from the laboratory to the clinic.     

The reproducibility issue and preclinical academic drug discovery: educational and institutional initiatives fostering translation success

ABSTRACT

Introduction: Drug discovery depends critically upon published results from the academy. The reproducibility of preclinical research findings reported by academia in the peer-reviewed literature has been called into question, seriously jeopardizing the value of academic science for inventing therapeutics.

Areas covered: The corrosive effects of the reproducibility issue on drug discovery are considered. Purported correctives imposed upon academia from the outside deal mainly with expunging fraudulent literature and imposing punitive sanctions on the responsible authors. The salutary influence of such post facto actions on the reproducibility of discovery-relevant preclinical research data from academia appears limited. Rather, intentional doctoral-scientist education focused on data replicability and translationally-meaningful science and active participation of university entities charged with research innovation and asset commercialization toward ensuring data quality are advocated as key academic initiatives for addressing the reproducibility issue.

Expert opinion: A mindset shift on the part of both senior university faculty and the academy to take responsibility for the data reproducibility crisis and commit proactively to positive educational, incentivization, and risk- and reward-sharing practices will be fundamental for improving the value of published preclinical academic research to drug discovery.     

克山病监测之转化流行病学

将流行病学基本理论和技术规范地应用到疾病监测和防控实践,是疾病监测和防控实践最基本的转化流行病学和创新。能够发现疾病监测和防控实践中的新问题,并能够以新技术解决问题,是高一个层次的转化流行病学和创新。为解决实践中的关键问题,发明新技术或促进了疾病监测和防控理论和方法的发展,则是很高层次的转化流行病学和创新。10年来,我们要求克山病病区省上报克山病监测的原始数据,以PPS方法调查克山病患病率,通过增加病例搜索改进哨点监测方法,调查非病区扩心病患病水平,这些都是对我国克山病防控实践的深刻思考后,自觉或不自觉地将转化研究的理念应用于中国克山病监测的实践。     

年龄和离体翻译后修饰对兔α-晶状体蛋白分子伴娘活性的影响

目的：探讨年龄和离体翻译后翻译对兔α－晶状体蛋白分子伴娘活性的影响。方法：（1）用凝胶过滤法分离幼年、成年和老年3个组兔水溶性晶状体蛋白,观察不同年龄兔α－晶状体蛋白蛋白抑制β-low晶状体蛋白凝集和变性作用的程度差异。（2）孵育α－晶状体蛋白使之氧化和糖基化,观察修饰和未修饰的α－晶状体蛋白抑制β-low晶状体蛋白凝集和变性作用的程度差异。结果：（1）3个年龄组α－晶状体蛋白抑制热诱导β-low晶状体蛋白抑制凝集和变性作用的程度差异有显著意义（F＝29．100,P＜0．01）,成年组兔α－晶状体蛋白的抑制作用强于老年组,弱于幼年组,差异有显著意义（q＝4．1924,4．339,P＜0．05）。（2）离体氧化和糖基化修饰的α－晶状体蛋白抑制β-low晶状体蛋白凝集和变性的作用均弱于未修饰的α－晶状体蛋白,差异有显著意义（q＝26．9171,11．6404;P＜0．01）。结论：（1）随着年龄的增加,兔α－晶状体蛋白的分子伴娘活性呈下降趋势。（2）离体翻译后修饰可使兔α－晶状体蛋白的分子伴娘活性下降。