BACKGROUND & AIMS: BACKGROUND:Characterisation of risk groups who may benefit from pneumococcal vaccination is essential for the generation of recommendations and policy. METHODS:We reviewed the literature to provide information on the incidence and risk of invasive pneumococcal disease (IPD) in at-risk children in Europe and North America. The PubMed database was searched using predefined search terms and inclusion/exclusion criteria for papers reporting European or North American data on the incidence or risk of IPD in children with underlying medical conditions. RESULTS:Eighteen references were identified, 11 from North America and 7 from Europe, with heterogeneous study methods, periods and populations. The highest incidence was seen in US children positive for human immunodeficiency virus infection, peaking at 4167 per 100,000 patient-years in 2000. Studies investigating changes in incidence over time reported decreases in the incidence of IPD between the late 1990s and early 2000s. The highest risk of IPD was observed in children with haematological cancers or immunosuppression. Overall, data on IPD in at-risk children were limited, lacking incidence data for a wide range of predisposing conditions. There was, however, a clear decrease in the incidence of IPD in at-risk children after the introduction of 7-valent pneumococcal conjugate vaccine into immunisation programmes, as previously demonstrated in the general population. CONCLUSION:Despite the heterogeneity of the studies identified, the available data show a substantial incidence of IPD in at-risk children, particularly those who are immunocompromised. Further research is needed to determine the true risk of IPD in at-risk children, particularly in the post-PCV period, and to understand the benefits of vaccination and optimal vaccination schedules.

背景与目标： 背景：可能从肺炎球菌疫苗接种中受益的风险人群的表征对于产生建议和政策至关重要。
方法：我们回顾了文献，以提供有关欧洲和北美高危儿童的侵袭性肺炎球菌疾病（IPD）的发生率和风险的信息。使用预定义的搜索词和纳入/排除标准对PubMed数据库进行了搜索，以检索报告欧洲或北美患有基础疾病的儿童中IPD发生率或风险的数据。
结果：共确定了18篇参考文献，其中11篇来自北美，7篇来自欧洲，其研究方法，时期和人群各不相同。在人类免疫缺陷病毒感染呈阳性的美国儿童中发生率最高，在2000年达到峰值，每10万患者年中有4167名。调查随时间变化的研究报告说，在1990年代末至2000年代初，IPD发生率下降。在患有血液系统癌症或免疫抑制的儿童中，发生IPD的风险最高。总体而言，高危儿童的IPD数据有限，缺乏各种易患病情况的发病率数据。但是，将7价肺炎球菌结合疫苗引入免疫接种计划后，高危儿童IPD发生率明显下降，这在以前的一般人群中已得到证实。
结论：尽管已确定研究的异质性，但现有数据显示高危儿童，特别是免疫受损儿童的IPD发生率很高。需要进一步的研究来确定高危儿童中IPD的真正风险，尤其是在PCV后时期，并了解疫苗接种的好处和最佳的疫苗接种时间表。

BACKGROUND & AIMS: INTRODUCTION:25 years ago was first reported in Cuba and in the western hemisphere an emergent disease: eosinophilic meningoencephalitis due to Angiostrongylus cantonensis larvae. AIM:To collect in a summary form the accumulated experience and the findings of the study of this parasitosis during the period in the Western hemisphere. DEVELOPMENT AND CONCLUSIONS:There have been collected the first evidences, the parasitological and malacological findings, the experimental and molecular studies on immunology and neuroimmunology, the clinic-pathological findings in children and adults with the particularities of this diseases in our environment with special emphasis in the never-before scientific findings reported. It has been documented the testimony, the main findings among the malacological studies, the role of the immunoglobulin E and the mechanism involved in the central nervous system, the intrathecal synthesis patterns of immunoglobulins and the clinical elements in children and adults.

背景与目标： 简介：25年前首次在古巴和西半球报道了一种新出现的疾病：由于广州管圆线虫幼虫引起的嗜酸性脑膜脑炎。
目的：以汇总的形式收集西半球时期该寄生虫病的积累经验和研究结果。
发展与结论：收集了第一批证据，寄生虫学和乳汁学发现，免疫学和神经免疫学的实验和分子研究，儿童和成人的临床病理学发现，特别是在我们环境中这种疾病的特殊性报告了前所未有的科学发现。已有证词，乳汁学研究的主要发现，免疫球蛋白E的作用和中枢神经系统所涉及的机制，免疫球蛋白的鞘内合成模式以及儿童和成人的临床要素的文献证明。

BACKGROUND & AIMS: Objective:Characterize areas of interinstitutional cooperation and converging health agendas of the Pan American Health Organization/World Health Organization (PAHO/WHO), the Health Council of the Union of South American Nations (UNASUR), and the Amazon Cooperation Treaty Organization (ACTO) in South America based on social determinants of health. Methods:A qualitative study based on official documentary sources from the three organizations, using a comparative analysis of the health agendas of these agencies and the Rio Political Declaration on Social Determinants of Health (2011). Information was systematized using an analytical matrix that identifies convergences in the respective agendas. Results:Development of the health agendas of these agencies is influenced by various international forces such as Member States' foreign policy, international cooperation strategies and models, and the institutions' political and strategic guidelines. These agendas reveal efforts to strengthen blocs, cooperation mechanisms, and coordinated programmatic actions. Conclusions:The agendas of PAHO/WHO, the UNASUR Health Council, and ACTO point towards opportunities for convergence in various programmatic areas, emphasizing social determinants of health. Based on the overall agreements of the Rio Declaration as an analytical framework with recommendations in five decision-making spheres, structural cooperation actions can be carried out in the region's countries, jointly mediated by these agencies.

背景与目标： 目标：确定泛美卫生组织/世界卫生组织（PAHO / WHO），南美国家联盟卫生委员会（UNASUR）和亚马逊合作条约组织（ACTO）的机构间合作领域和融合卫生议程的特征在南美基于健康的社会决定因素。
方法：基于对这三个组织的卫生议程进行的比较分析以及对这三个组织的卫生议程的里约政治宣言（2011年）的定性研究，对这三个组织的卫生议程进行比较。信息通过分析矩阵系统化，该矩阵确定了各个议程中的趋同点。
结果：这些机构的卫生议程的制定受到各种国际力量的影响，例如会员国的外交政策，国际合作战略和模式以及机构的政治和战略指导方针。这些议程揭示了为加强集团，合作机制和协调的计划行动所做的努力。
结论：泛美卫生组织/世卫组织，UNASUR卫生理事会和ACTO的议程指出了在各个计划领域融合的机会，强调了健康的社会决定因素。根据《里约宣言》的总体协定作为一个分析框架，并在五个决策领域提出建议，在这些机构的共同推动下，可以在该区域各国采取结构性合作行动。

BACKGROUND & AIMS: :A conceptual framework is presented, expressing the relationship between food availability and the food and nutritional status of a population. As element of the model, the generation and transfer of appropriate food technologies were included. Based on the conceptual framework, three successful cases of food technology transfer in the Central American area were analyzed. The most important aspects of each case were identified, and a critical review of the characteristics and conditions required to generate and transfer appropriate technologies, was carried out. An inventory was made of those factors which are essential for a food technology to be appropriate; this analysis resulted in the postulation of a model describing the life cycle of appropriate food technologies. On these bases, several guidelines are postulated, which could constitute a conceptual framework to help guide actions in the generation and transference of appropriate food technologies in Central America and Panama. Essential elements of the proposed framework are: identification and characterization of the problem of the group of "users" of the technology; problem solution by a multidisciplinary group; test of the technology and evaluation of its feasibility (technical, economical, political, social and cultural), and controlled transference to the group of "users".

背景与目标： ：提出了一个概念框架，表达了粮食供应与人口粮食和营养状况之间的关系。作为模型的组成部分，包括了适当食品技术的产生和转让。在概念框架的基础上，分析了中美洲地区成功进行食品技术转让的三个案例。确定了每个案例的最重要方面，并对产生和转让适当技术所需的特征和条件进行了严格审查。对适当的食品技术必不可少的那些因素进行了盘点；该分析得出了描述适当食品技术生命周期的模型的假设。在此基础上，提出了几项准则，这些准则可以构成一个概念框架，以帮助指导中美洲和巴拿马的适当食品技术的产生和转让方面的行动。拟议框架的基本要素是：确定和表征技术“用户”群体的问题；多学科小组的问题解决方案；测试技术并评估其可行性（技术，经济，政治，社会和文化），并控制向“用户”组的转移。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND:Systematic repetition postures adopted during trainings could generate alterations in the sagittal spinal curvatures. OBJECTIVE:The purposes were: 1) to analyse the sagittal spinal curvatures and pelvic tilt in Latin American style dancers; 2) to compare the spinal sagittal mobility and hamstring muscle extensibility between Latin American style dancers and non-dancers; and 3) to evaluate the influence of wearing dance shoes upon the sagittal spine posture in standing. METHODS:A total of 20 Latin American style professional dancers and 20 non-dancers (control group) were evaluated during standing, relaxed sitting, maximal trunk flexion with knees flexed and extended, lying prone, and maximal trunk extension. Additionally, dancers were analysed while standing barefoot, and wearing heeled-shoes, during forward walking and the paso-doble posture. The hamstring muscle extensibility was evaluated by the active knee extension test. RESULTS:The spinal morphology in Latin American style professional dancers is characterised by lower thoracic kyphosis, lumbar lordosis and anterior pelvic tilt in the standing posture as well as a flexible spine, especially in flexion postures, in addition to suitable hamstring muscle extensibility. CONCLUSIONS:The spinal morphology of Latin American style professional dancers is characterised by lower thoracic kyphosis and lumbar lordosis and anterior pelvic tilt in the standing posture as well as a flexible spine, especially in flexion postures, and suitable hamstring muscle extensibility.

背景与目标： 背景：在训练过程中采用的系统性重复姿势可能会导致矢状脊柱弯曲的改变。
目的：目的是：1）分析拉丁美洲风格舞蹈演员的矢状脊柱弯曲度和骨盆倾斜度； 2）比较拉丁美洲舞者和非舞者的脊柱矢状活动度和绳肌的伸展性； 3）评估穿着舞蹈鞋对站立时矢状脊柱姿势的影响。
方法：在站立，放松坐姿，最大屈膝屈膝，屈膝伸直，俯卧，最大伸直躯干的过程中，对总共20名拉丁美洲风格的专业舞蹈演员和20名非舞蹈演员（对照组）进行了评估。此外，还对舞者进行了分析，他们在赤脚站立的过程中赤脚站立，穿着高跟鞋。 the绳肌的可伸展性通过主动膝关节伸展试验进行评估。
结果：拉丁美洲风格的专业舞者的脊柱形态的特征是站立姿势下胸椎后凸，腰椎前凸和前骨盆倾斜，以及灵活的脊柱，尤其是屈曲姿势，此外还具有适当的绳肌可伸展性。
结论：拉丁美洲风格的专业舞者的脊柱形态特征是下胸驼背和腰椎前凸和站立姿势的前骨盆倾斜以及灵活的脊柱，特别是在屈曲姿势中，并且适当的绳肌可伸展性。

BACKGROUND & AIMS: BACKGROUND:One main practice gap in allergology that has been detected in several regions of the world is the application of specific immunotherapy (SIT). The prescription and practice of SIT should characterize allergologic specialists, but there are regional discrepancies in such practice. A detailed knowledge of the regulatory and legislation aspects and drawbacks would help improve and harmonize SIT practice. OBJECTIVE:To describe in Latin America the level of allergy training and the characteristics of the use of SIT, including the medical and legal aspects. METHODS:Three sources were used: a 24-item questionnaire sent to 22 allergologic leaders in 11 Latin American countries, 2 face-to-face meetings, and information from health authorities involved in the approval of medical substances. RESULTS:In 56% of countries, the specialty of allergology is a third-level care specialty and/or a subspecialty. Two countries have a special training program for pediatric allergists. Passing a board examination is mandatory in 3 countries, and recertification every 2 to 5 years occurs without examination. Sublingual and subcutaneous SITs are available in all Latin American countries. No legislation restricts SIT prescription and it can be performed by nonspecialists in 7 of 11 countries. In 90% of countries, allergists use allergen extracts from the United States (subcutaneous immunotherapy) and Europe (sublingual and subcutaneous immunotherapies), and 50% also manufacture extracts locally. Only 1 country has legal requirements for the quality of raw materials. CONCLUSION:The present analysis helps to identify gaps in the field of allergologic training and SIT in Latin America, many of them amendable.

背景与目标： 背景：在世界上几个地区发现的过敏学方面的一个主要实践空白是特异性免疫疗法（SIT）的应用。 SIT的处方和做法应以过敏科专家为特征，但这种做法存在地区差异。对法规和立法方面以及弊端的详细了解将有助于改善和统一SIT实践。
目的：描述拉丁美洲的过敏训练水平和使用SIT的特征，包括医学和法律方面。
方法：使用了三种来源：向拉丁美洲11个国家的22名过敏学领导者发送的24项问卷，两次面对面的会议以及来自参与批准医疗物质的卫生当局的信息。
结果：在56％的国家中，过敏科专业为三级护理专业和/或亚专业。有两个国家为小儿过敏症患者提供了特殊的培训计划。必须在3个国家/地区通过董事会考试，并且每2至5年进行一次重新认证，而无需进行考试。所有拉丁美洲国家都提供舌下和皮下SIT。没有法律限制SIT处方，并且11个国家中有7个国家的非专业人员可以执行该处方。在90％的国家中，过敏症患者使用来自美国（皮下免疫疗法）和欧洲（舌下和皮下免疫疗法）的过敏原提取物，还有50％的过敏原也在当地生产。只有一个国家/地区对原材料的质量有法律要求。
结论：本分析有助于查明拉丁美洲的变态反应训练和SIT领域的差距，其中许多差距是可以修正的。

BACKGROUND & AIMS: OBJECTIVE:The objective of this guideline is to provide recommendations for treating patients with the more common forms of histoplasmosis. PARTICIPANTS AND CONSENSUS PROCESS: A working group of 8 experts in this field was convened to develop this guideline. The working group developed and refined the guideline through a series of conference calls. OUTCOMES:The goal of treatment is to eradicate the infection when possible, although chronic suppression may be adequate for patients with AIDS and other serious immunosuppressive disorders. Other important outcomes are resolution of clinical abnormalities and prevention of relapse. EVIDENCE:The published literature on the management of histoplasmosis was reviewed. Controlled trials have been conducted that address the treatment of chronic pulmonary and disseminated histoplasmosis, but clinical experience and descriptive studies provide the basis for recommendations for other forms of histoplasmosis. VALUE: Value was assigned on the basis of the strength of the evidence supporting treatment recommendations, with the highest value assigned to controlled trials, according to conventions established for developing practice guidelines. BENEFITS AND COSTS: Certain forms of histoplasmosis cause life-threatening illnesses and result in considerable morbidity, whereas other manifestations cause no symptoms or minor self-limited illnesses. The nonprogressive forms of histoplasmosis, however, may reduce functional capacity, affecting work capacity and quality of life for several months. Treatment is clearly beneficial and cost-effective for patients with progressive forms of histoplasmosis, such as chronic pulmonary or disseminated infection. It remains unknown whether treatment improves the outcome for patients with the self-limited manifestations, since this patient population has not been studied. Other chronic progressive forms of histoplasmosis are not responsive to pharmacologic treatment. TREATMENT OPTIONS:Options for therapy for histoplasmosis include ketoconazole, itraconazole, fluconazole, amphotericin B (Fungizone; Bristol-Meyer Squibb, Princeton, NJ), liposomal amphotericin B (AmBisome; Fujisawa, Deerfield, IL), amphotericin B colloidal suspension (ABCD, or Amphotec; Seques, Menlo Park, CA), and amphotericin B lipid complex (ABLC, or Abelcet; Liposome, Princeton, NJ).

背景与目标： 目的：本指南的目的是为治疗更常见的组织胞浆菌病患者提供建议。参与者和共识过程：召集了一个由该领域的8位专家组成的工作组来制定此指南。工作组通过一系列电话会议制定并完善了指南。
结果：治疗的目标是在可能的情况下根除感染，尽管对艾滋病和其他严重免疫抑制疾病的患者进行慢性抑制可能就足够了。其他重要结果是临床异常的解决和预防复发。
证据：回顾了有关组织胞浆菌病处理的公开文献。已经进行了针对慢性肺和弥漫性组织胞浆菌病的治疗的对照试验，但是临床经验和描述性研究为其他形式的组织胞浆菌病的推荐提供了基础。价值：根据为制定治疗指南制定的惯例，根据支持治疗建议的证据的强度来分配价值，将最高价值分配给对照试验。收益和成本：某些形式的组织胞浆菌病会危及生命，并导致相当大的发病率，而其他表现形式则不会引起任何症状或轻微的自我限制疾病。然而，非渐进性的组织胞浆菌病可能会降低功能能力，从而影响工作能力和数月的生活质量。对于患有渐进形式的组织胞浆菌病（例如慢性肺部或弥漫性感染）的患者，治疗显然是有益且具有成本效益的。由于该患者人群尚未得到研究，因此治疗是否能改善具有自限性表现的患者的结局仍是未知的。其他慢性进行性组织胞浆菌病对药物治疗无反应。
治疗方案：组织胞浆菌病的治疗方案包括酮康唑，伊曲康唑，氟康唑，两性霉素B（Fungizone; Bristol-Meyer Squibb，Princeton，NJ），脂质体两性霉素B（AmBisome; Fujisawa，Deerfield，IL），两性霉素B胶体（CDCD）或Amphotec； Seques，Menlo Park，CA）和两性霉素B脂质复合物（ABLC或Abelcet；脂质体，普林斯顿，新泽西州）。

BACKGROUND & AIMS: UNLABELLED:In the first population-based study of vertebral fractures in Latin America, we found a 11.18 (95% CI 9.23-13.4) prevalence of radiographically ascertained vertebral fractures in a random sample of 1,922 women from cities within five different countries. These figures are similar to findings from studies in Beijing, China, some regions of Europe, and slightly lower than those found in the USA using the same standardized methodology. INTRODUCTION:We report the first study of radiographic vertebral fractures in Latin America. METHODS:An age-stratified random sample of 1,922 women aged 50 years and older from Argentina, Brazil, Colombia, Mexico, and Puerto Rico were included. In all cases a standardized questionnaire and lateral X-rays of the lumbar and thoracic spine were obtained after informed consent. RESULTS:A standardized prevalence of 11.18 (95% CI 9.23-13.4) was found. The prevalence was similar in all five countries, increasing from 6.9% (95% CI 4.6-9.1) in women aged 50-59 years to 27.8% (95% CI 23.1-32.4) in those 80 years and older (p for trend < 0.001). Among different risk factors, self-reported height loss OR = 1.63 (95% CI: 1.18-2.25), and previous history of fracture OR = 1.52 (95% CI: 1.14-2.03) were significantly (p < 0.003 and p < 0.04 respectably) associated with the presence of radiographic vertebral fractures in the multivariate analysis. In the bivariate analyses HRT was associated with a 35% lower risk OR = 0.65 (95% CI: 0.46-0.93) and physical activity with a 27% lower risk of having a vertebral fracture OR = 0.73 (95% CI: 0.55-0.98), but were not statistically significant in multivariate analyses CONCLUSION:We conclude that radiographically ascertained vertebral fractures are common in Latin America. Health authorities in the region should be aware and consider implementing measures to prevent vertebral fractures.

背景与目标： 在拉丁美洲进行的第一项基于人群的脊椎骨折研究中，我们从五个国家/地区的1,922名妇女中随机抽取了X线照片确定的脊椎骨折患病率，分别为11.18（95％CI 9.23-13.4）。这些数字与在中国北京，欧洲某些地区的研究结果相似，但略低于在美国使用相同标准化方法得出的结果。
简介：我们报告了拉丁美洲的首例放射学性脊椎骨折研究。
方法：采用年龄分层的随机抽样方法，对来自阿根廷，巴西，哥伦比亚，墨西哥和波多黎各的1,922名年龄在50岁以上的女性进行了抽样。在所有情况下，经过知情同意后，可获得一份标准化的问卷以及腰椎和胸椎的X线片。
结果：标准化患病率为11.18（95％CI 9.23-13.4）。这五个国家的患病率相似，从50-59岁女性的6.9％（95％CI 4.6-9.1）上升到80岁以上女性的27.8％（95％CI 23.1-32.4）（趋势

结论：我们得出结论，放射照相确定的椎体骨折在拉丁美洲很常见。该地区的卫生部门应了解并考虑采取预防椎骨骨折的措施。

BACKGROUND & AIMS: OBJECTIVE:In this paper we review progress as well as challenges encountered in Canada, the United States and England with regard to ensuring safety of health information technology. METHOD:A review of major programs and initiatives for ensuring safety of health information technology in the three countries was conducted. Published literature and Web resources from national programs were reviewed for relevant information. RESULTS:It was found that in all three countries the issue of technology-induced error has been recognized as being of critical importance. The three countries have developed approaches for dealing with the issue that have some commonalities; however, they are at varying different stages of maturity, with England having the longest standing and most well developed safety programs, while Canada and the United States are at earlier stages. The types of approaches employed have included work on developing standards related to usability and interface design, certifications, directives from regulatory bodies, educational initiatives in health information technology (HIT) safety as well as research into safer HIT design and implementation methods. CONCLUSIONS:HIT promises to lead to improved patient safety. However, it has become recognized that if not designed and deployed appropriately, such systems can lead to new types of errors. Based on this recognition, a variety of initiatives are being undertaken in Canada, the United States and England to promote the safe design, procurement and deployment of HIT. It is concluded that improved approaches to system design, testing, regulation, error reporting, safety education and cross-country collaboration will be needed to further promote safer HIT.

背景与目标： 目的：在本文中，我们回顾了在确保健康信息技术安全方面在加拿大，美国和英国所取得的进步以及所面临的挑战。
方法：对确保这三个国家健康信息技术安全的主要计划和举措进行了审查。审查了来自国家计划的已出版文献和网络资源，以获取相关信息。
结果：发现在所有三个国家中，技术引起的错误问题已被认为是至关重要的。这三个国家已经制定了处理这一问题的方法，这些方法具有一些共同点。但是，它们处于不同的成熟阶段，英格兰的历史最悠久，安全计划也最完善，而加拿大和美国则处于较早的阶段。所采用的方法类型包括：开发与可用性和界面设计有关的标准，认证，监管机构的指令，健康信息技术（HIT）安全方面的教育计划以及对更安全的HIT设计和实施方法的研究。
结论：HIT有望改善患者的安全性。但是，人们已经认识到，如果设计和部署不当，此类系统可能会导致新型错误。基于这种认识，加拿大，美国和英国正在采取各种举措来促进HIT的安全设计，采购和部署。结论是，将需要改进的系统设计，测试，法规，错误报告，安全教育和跨国合作的方法，以进一步促进更安全的HIT。

BACKGROUND & AIMS: OBJECTIVE:To assesses the safety and rationale of antibacterial fixed-dose combinations in the private sector in Latin America and determine the extent of their use. METHODS:Analysis of FDCs was based on retail sales data for eight Latin American countries (Argentina, Brazil, Chile, Colombia, Mexico, Peru, Uruguay and Venezuela) between 1999 and 2009. FDCs were classified according to the pre-defined criteria. Use was expressed as daily defined doses per 1000 inhabitants per day (DDD/TID). RESULTS:A total of 175 antibacterial FDCs contained a mean of 1.3 antibacterial substances and 3.2 other active substances. Thirty-seven (21%) FDCs were classified as unsafe, 124 (70%) as lacking sufficient evidence for efficacy and only 14 (9%) of all FDCs were considered rational, for example amoxicillin and clavulanic acid. Consumption of unsafe FDCs decreased by 0.011 DDD/TID (95% CI: -0.012 to -0.009) annually, from 0.173 DDD/TID in 1999 to 0.070 DDD/TID in 2009 (overall decrease, 59.7%). Consumption of FDCs lacking sufficient evidence decreased by 30.3% (-0.018 DDD/TID [95% CI: -0.028 to -0.008] annually), while use of rational FDCs increased by 17.1% (from 1.283 DDD/TID to 1.497 DDD/TID annually). CONCLUSION:The majority of antibacterial FDCs in the private sector lack therapeutic benefit. Despite the decrease in the consumption of unsafe antibacterials and those lacking sufficient evidence, their use remains high and their marketing does not fit into strategies of prudent use of antibiotics to contain antibacterial resistance.

背景与目标： 目的：评估拉丁美洲固定部门中抗菌固定剂量组合的安全性和基本原理，并确定其使用范围。
方法：FDC的分析基于1999年至2009年之间八个拉丁美洲国家（阿根廷，巴西，智利，哥伦比亚，墨西哥，秘鲁，乌拉圭和委内瑞拉）的零售数据。FDC根据预先定义的标准进行分类。使用量表示为每天每1000居民定义的剂量（DDD / TID）。
结果：总共175个抗菌FDC含有平均1.3种抗菌物质和3.2种其他活性物质。三十七（21％）个FDC被归类为不安全，124个（70％）被认为缺乏足够的疗效证据，所有FDC中只有14个（9％）被认为是合理的，例如阿莫西林和克拉维酸。每年，不安全FDC的消费量下降了0.011 DDD / TID（95％CI：-0.012降至-0.009），从1999年的0.173 DDD / TID下降到2009年的0.070 DDD / TID（总体下降了59.7％）。缺乏足够证据的FDC的消费量下降了30.3％（-0.018 DDD / TID [95％CI：-0.028至-0.008]每年），而合理FDC的使用量则增长了17.1％（从1.283 DDD / TID到1.497 DDD / TID每年）。
结论：私营部门中的大多数抗菌FDC缺乏治疗益处。尽管不安全的抗菌药物的消费有所减少，并且缺乏足够的证据，但它们的使用仍然很高，并且其行销也不适合谨慎使用含有抗菌素耐药性的抗生素的策略。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVES:Ranolazine was approved by the US Food and Drug Administration in January 2006 for the treatment of chronic angina pectoris, and is the first approved agent from a new class of anti-anginal drugs in almost 25 years. The primary objective of this study was to determine the concentration of ranolazine in human plasma using the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and to compare the pharmacokinetic properties of ranolazine after administration of single and multiple doses of ranolazine in healthy Chinese adult volunteers. METHODS:A randomized, open-label, single- and multiple-dose study design was used in the study. Subjects were randomized to receive a single dose of 500, 1,000, or 1,500 mg of ranolazine. Those who received the single dose continued on to the multiple-dose phase and received 500 mg twice daily for 7 days. In the single-dose phase, blood samples were collected from 0 to 48 h after drug administration. In the multiple-dose phase, samples were obtained before drug administration at 8:00 am and 8:00 pm on days 6 and 7 to determine the minimum steady-state plasma concentration (C(min,ss)) of ranolazine; on day 8, samples were collected from 0 to 48 h after drug administration. All values were expressed as means (standard deviations [SDs]). Adverse events (AEs) were monitored throughout the study via subject interview, vital signs, and blood sampling. RESULTS:The LC-MS/MS method was developed and validated. Twelve Chinese subjects (six men, six women) were enrolled in the single-dose phase of the pharmacokinetic study. The mean (SD) age of the subjects was 24.7 (1.6) years; their mean (SD) weight was 61.3 (6.4) kg, their mean (SD) height was 165.7 (4.5) cm, and their mean (SD) body mass index was 21.6 (6.6) kg/m(2). The main pharmacokinetic parameters [mean (SD)] for ranolazine after administration of a single oral dose of 500, 1,000, and 1,500 mg were as follows: maximum plasma concentration (C(max)) 741.5 (253.0), 1,355.0 (502.0), and 2,328.7 (890.5) ng/mL, respectively; area under the concentration-time curve from time zero to 48 h (AUC(48)) 9,071.9 (3,400.0), 16,573.5 (6,806.2), and 29,324.5 (10,857.2) ng·h/mL; AUC from time zero extrapolated to infinity (AUC(∞)) 9,826.7 (3,152.0), 16,882.4 (6,790.8), and 29,923.5 (10,706.3) ng·h/mL; time to reach C(max) (t(max)) 5.3 (1.4), 4.2 (1.2), and 5.9 (2.8) h; elimination half-life (t(½)) 6.4 (3.3), 6.4 (3.5), and 6.7 (4.3) h. Mean (SD) values for the main pharmacokinetic parameters for ranolazine after administration of multiple doses were as follows: steady-state C(max) (C(max,ss)) 1,732.9 (547.3) ng/mL; C(min,ss) 838.1 (429.8) ng/mL; steady-state AUC at time t (AUC(ss,(t))) 14,655.5 (5,624.2) ng·h/mL; average steady-state plasma drug concentration during multiple-dose administration (C(av,ss)) 1,221.3 (468.7) ng/mL; t(max) 3.46 (1.48) h; t(½) 6.28 (2.48) h. CONCLUSION:In this group of healthy Chinese subjects, AUC and C(max) increased proportionally with the dose, whereas t(½) was independent of the dose. The pharmacokinetic properties of ranolazine were linear after administration of single oral doses of 500 to 1,500 mg. Compared with the pharmacokinetic parameters of the subjects who received a single dose, those who received multiple doses (twice daily) of ranolazine had a larger AUC from time zero to the time of the last measurable concentration (AUC(last)), AUC(∞), C(max), and apparent total body clearance of drug from plasma after oral administration (CL/F), and shorter t(max) (all p < 0.05). Furthermore, some of the main pharmacokinetic parameters of ranolazine may reflect ethnic differences. This dosage was generally well tolerated by all the subjects.

背景与目标： 背景与目的：雷诺嗪于2006年1月获得美国食品和药物管理局的批准，用于治疗慢性心绞痛，并且是近25年以来来自新型抗心绞痛药物的首个批准药物。这项研究的主要目的是使用液相色谱/串联质谱法（LC-MS / MS）确定人血浆中雷诺嗪的浓度，并比较雷诺嗪单次和多次给药后雷诺嗪的药代动力学特性。健康的中国成人志愿者。
方法：本研究采用随机，开放标签，单剂量和多剂量研究设计。受试者被随机分配接受单剂量的雷诺嗪500、1,000或1,500毫克。那些接受单剂量的患者继续进入多剂量阶段，并每天两次服用500毫克，共7天。在单剂量阶段，在给药后0到48小时内收集血液样本。在多剂量阶段，在第6天和第7天的上午8:00和晚上8:00给药之前获取样品，以确定雷诺嗪的最小稳态血浆浓度（C（min，ss））；在给药第8天，在给药后0至48小时收集样品。所有值均表示为平均值（标准偏差[SDs]）。在整个研究过程中，通过受试者访谈，生命体征和血液采样监测不良事件（AE）。
结果：LC-MS / MS方法得到了开发和验证。药代动力学研究的单剂量阶段招募了十二名中国受试者（六名男性，六名女性）。受试者的平均（SD）年龄为24.7（1.6）岁；它们的平均（SD）重量为61.3（6.4）千克，平均（SD）高度为165.7（4.5）厘米，其平均（SD）体重指数为21.6（6.6）kg / m（2）。雷诺嗪单次口服500、1,000和1,500 mg的主要药代动力学参数[平均值（SD）]如下：最大血浆浓度（C（max））741.5（253.0），1,355.0（502.0），和2,328.7（890.5）ng / mL；从时间零到48小时的浓度-时间曲线下的面积（AUC（48））9,071.9（3,400.0），16,573.5（6,806.2）和29,324.5（10,857.2）ng·h / mL；从零时的AUC外推至无穷（AUC（∞））9,826.7（3,152.0），16,882.4（6,790.8）和29,923.5（10,706.3）ng·h / mL；达到C（max）（t（max））5.3（1.4），4.2（1.2）和5.9（2.8）h的时间;消除半衰期（t（1/2））6.4（3.3），6.4（3.5）和6.7（4.3）h。雷诺嗪多次给药后主要药代动力学参数的平均值（SD）如下：稳态C（max）（C（max，ss））1,732.9（547.3）ng / mL; C（min，ss）838.1（429.8）ng / mL;在时间t的稳态AUC（AUC（ss，（t）））14,655.5（5,624.2）ng·h / mL;多剂量给药期间的平均稳态血浆药物浓度（C（av，ss））1,221.3（468.7）ng / mL; t（最大值）3.46（1.48）h; t（1/2）6.28（2.48）小时
结论：在这组健康的中国受试者中，AUC和C（max）与剂量成比例增加，而t（1/2）与剂量无关。雷诺嗪的药代动力学特性在单次口服剂量为500至1,500 mg后呈线性。与接受单剂量受试者的药代动力学参数相比，接受雷诺嗪多次给药（每天两次）的受试者从零时间到最后可测量浓度（AUC（last）），AUC（∞）的AUC较大），C（max）和口服给药后药物从血浆中的表观总体清除率（CL / F），以及t（max）较短（所有p <0.05）。此外，雷诺嗪的一些主要药代动力学参数可能反映出种族差异。所有受试者通常都很好地耐受该剂量。

BACKGROUND & AIMS: BACKGROUND:North American indigenous populations experience higher rates of obesity and chronic disease compared with nonindigenous populations. Improvements in musculoskeletal fitness can mitigate negative health outcomes, but is not well understood among indigenous populations. This review examines musculoskeletal fitness measures among North American indigenous populations. METHODS:A total of 1632 citations were evaluated and 18 studies were included. RESULTS:Comparisons of musculoskeletal fitness measures between North American indigenous men and boys and women and girls were generally not reported. The greatest left and right combined maximal grip strength and maximal leg strength among Inuit boys and men and girls and women were observed among 20-29 years age group. Maximal combined right and left grip strength declined from 1970 to 1990, by an average of 15% among adults and 10% among youth. Maximal leg extension among Inuit has declined even further, averaging 38% among adults and 27% among youth from 1970 to 1990. Inuit men demonstrate greater grip strength and lower leg strength than Russian indigenous men, whereas Inuit women demonstrate greater leg strength. CONCLUSIONS:Further research is needed to better understand physical fitness among indigenous peoples and the potential for improving health and reducing chronic disease risk for indigenous peoples through physical fitness.

背景与目标： 背景：与非土著居民相比，北美土著居民的肥胖和慢性病发病率更高。肌肉骨骼适应性的改善可以减轻负面的健康后果，但在土著居民中尚未得到很好的理解。这项审查审查了北美土著人口中的肌肉骨骼适应措施。
方法：总共对1632篇文献进行了评估，包括18项研究。
结果：一般没有报道北美土著男子和男孩与妇女和女孩之间的肌肉骨骼健身措施的比较。在20至29岁年龄段的人群中，因纽特人男女中最大的左右最大握力和最大腿部力量相结合。从1970年到1990年，左右手的最大组合力量下降了，成年人平均下降15％，青年平均下降10％。因纽特人的最大伸腿幅度甚至进一步下降，从1970年到1990年，成年人平均平均伸腿38％，青年平均27％。因纽特人男性比俄罗斯土著男子表现出更大的握力和更低的腿部力量，而因纽特人女性则表现出更大的腿部力量。
结论：需要进行进一步的研究，以更好地了解土著人民的身体适应性，以及通过身体适应性改善土著人民健康和减少慢性病风险的潜力。

BACKGROUND & AIMS: :In this article, one of the novel mutations, c.208_209+ 8del10, was incorrectly given as c.69_70+8del10. It corresponds to patient 64 in Table 4.

背景与目标： ：在本文中，一种新颖的突变c.208_209 8del10被错误地命名为c.69_70 8del10。它对应于表4中的患者64。

BACKGROUND & AIMS: :We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.

背景与目标： ：我们之前在秘鲁描述了肝细胞癌（HCC）的不同临床表现和分子表现。本研究旨在进一步表征与这种单一的肝癌病原学形式相关的组织特征，以便深入了解该疾病的自然病史。我们对50例秘鲁HCC患者的肿瘤和非肿瘤肝（NTL）组织的组织学进行了探索性分析，并将其与75例非HCC肝肿瘤或良性肝病患者的NTL特征基线进行了比较。我们在一部分NTL组织样本中通过转录组分析对这种方法进行了补充，并且还在患者的肝组织中进行了超灵敏的乙型肝炎病毒（HBV）检测。总体而言，结果表明，尽管潜在的HBV感染率很高（约67％），但在年轻患者队列（中位年龄：40岁）中，肝实质改变的发生率较低。肝透明细胞病变的细胞真正与肝癌相关，并伴随着免疫和G蛋白偶联受体基因表达本体的某些变化。我们的研究结果证实了南美肝癌的特殊背景，肝癌的病理生理学在很大程度上尚待探索。