BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND:Attention to evidence-informed policy has grown; however, efforts to strengthen the quality and use of evidence are not starting from a blank slate. Changes in health architectures and financing pose different considerations for investments in evidence-informed policy than in the past. We identify major trends that have shifted the environment in which health policies are made, and use the evolution and future aspirations of National Immunization Technical Advisory Groups (NITAGs) in low- and middle-income countries to identify questions the sector must confront when determining how best to structure and strengthen evidence-informed health policy. DISCUSSION:Trends over the last two decades have resulted in a dense arena with many issue-specific groups, discrete initiatives to strengthen evidence-informed policy and increasing responsibility for subnational institutions. Many countries face a shifting resource base, which for some reduces the amount of resources for health. There is global momentum around universal health coverage, reflecting a broader systems approach, but few examples of how the vast array of stakeholders relate within it are available. NITAG aspirations reflect four interconnected themes related to their scope, their integration in national policy processes, health financing and relationships with ministries of finance, and NITAG positioning relative to other domestic and international entities, raising questions such as, What are the bounds of issue-specific groups and their relationship to allocation decision-making processes across health areas? How do technical advisory groups interface with what are inherently political processes? When are finances considered, by whom and how? What is the future of existing groups whose creation was intended to enhance national ownership but who need continued external support to function? When should new entities be created, in what form and with what mandate? CONCLUSIONS:Countries must determine who makes decisions about resources, when, using what criteria, and how to do so in a robust yet efficient way given the existing and future landscape. While answers to these questions are necessarily country specific, they are collective matters that cannot be addressed by specialised groups alone and have implications for new investments in evidence-informed policy.

背景与目标： 背景：人们越来越重视以证据为依据的政策；但是，增强证据质量和使用证据的努力并非一帆风顺。与过去相比，卫生架构和资金的变化对以证据为依据的政策进行投资提出了不同的考虑因素。我们确定了改变卫生政策制定环境的主要趋势，并利用中低收入国家的国家免疫技术咨询小组（NITAG）的演变和未来愿望，确定该部门在确定如何应对时必须面对的问题最好构造和加强有据可依的健康政策。
讨论：过去二十年来的趋势导致了一个密集的竞技场，其中有许多针对特定问题的团体，采取了一些离散的举措来加强以证据为依据的政策，并增加了对地方机构的责任。许多国家面临着不断变化的资源基础，这在某些方面减少了卫生资源。围绕全民健康覆盖的全球动力，反映了一种更广泛的系统方法，但是很少有有关广泛的利益相关者如何与之联系的例子。 NITAG的愿望反映了四个相互关联的主题，这些主题涉及其范围，它们在国家政策流程中的整合，卫生筹资以及与财政部的关系，以及NITAG在其他国内和国际实体中的定位，引发了诸如以下问题的问题：特定群体及其与跨卫生领域分配决策过程的关系？技术咨询小组如何与固有的政治流程互动？何时考虑财务，由谁以及如何考虑？现有团体的成立是为了增强国家所有权，但需要持续的外部支持才能发挥作用，它们的前景如何？什么时候应该以什么形式和什么任务创建新实体？
结论：在给定现有和未来形势的情况下，国家必须确定谁来决定资源，何时，使用什么标准以及如何以健壮而有效的方式做出决定。尽管对这些问题的回答必然是针对特定国家的，但它们是集体问题，不能由专门小组单独解决，并且对以证据为依据的政策进行新的投资具有影响。

BACKGROUND & AIMS: :As demand for germline genetic testing for cancer patients increases, novel methods of genetic counseling are required. One such method is the mainstream consent pathway, whereby a member of the oncology team (rather than a genetic specialist) is responsible for counseling, consenting, and arranging genetic testing for cancer patients. We systematically reviewed the literature for evidence evaluating mainstream pathways for patients with breast, ovarian, colorectal, and prostate cancer. Medline, EMBASE, and Cochrane Library were searched for studies that met inclusion and exclusion criteria. Article references were checked for additional studies. Trial databases were searched for ongoing studies. Of the 13 papers that met inclusion criteria, 11 individual study groups were identified (two study groups had two publications each). Ten of the 11 studies evaluated the acceptability, feasibility, and impact of BRCA testing for patients and/or clinicians in different clinical settings in breast and ovarian cancer, while the final study explored the attitudes of colorectal specialists toward genetic testing for colorectal cancer. None involved prostate cancer. Overall, mainstream pathways were acceptable and feasible. Medical oncologist- and nurse-driven pathways were particularly successful, with both patients and clinicians satisfied with this process. Although the content of pretest counseling was less consistent compared with counseling via the traditional model, patients were largely satisfied with the education they received. Further research is required to evaluate the mainstream pathway for men with prostate cancer.

背景与目标： 随着对癌症患者种系基因测试的需求增加，需要新的遗传咨询方法。一种这样的方法是主流同意途径，即肿瘤小组的一名成员（而不是遗传专家）负责为癌症患者提供咨询，同意和安排基因检测。我们系统地回顾了文献，以评估乳腺癌，卵巢癌，结肠直肠癌和前列腺癌患者的主流途径。搜索Medline，EMBASE和Cochrane库以查找符合纳入和排除标准的研究。检查了文章参考文献以进行其他研究。在试验数据库中搜索正在进行的研究。在符合纳入标准的13篇论文中，确定了11个单独的研究组（两个研究组各有两个出版物）。 11项研究中的10项评估了BRCA检测对乳腺癌和卵巢癌不同临床环境中的患者和/或临床医生的可接受性，可行性和影响，而最终研究探讨了结直肠专家对结直肠癌基因检测的态度。没有人涉及前列腺癌。总体而言，主流途径是可以接受和可行的。医学肿瘤学家和护士驱动的途径特别成功，患者和临床医生都对此过程感到满意。尽管与通过传统模式进行咨询相比，测试前咨询的内容不太一致，但是患者对他们所接受的教育非常满意。需要进一步的研究来评估男性前列腺癌的主流途径。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: BACKGROUND:Previously, family-based designs and high-risk pedigrees have illustrated value for the discovery of high- and intermediate-risk germline breast cancer susceptibility genes. However, genetic heterogeneity is a major obstacle hindering progress. New strategies and analytic approaches will be necessary to make further advances. One opportunity with the potential to address heterogeneity via improved characterization of disease is the growing availability of multisource databases. Specific to advances involving family-based designs are resources that include family structure, such as the Utah Population Database (UPDB). To illustrate the broad utility and potential power of multisource databases, we describe two different novel family-based approaches to reduce heterogeneity in the UPDB. METHODS:Our first approach focuses on using pedigree-informed breast tumor phenotypes in gene mapping. Our second approach focuses on the identification of families with similar pleiotropies. We use a novel network-inspired clustering technique to explore multi-cancer signatures for high-risk breast cancer families. RESULTS:Our first approach identifies a genome-wide significant breast cancer locus at 2q13 [P = 1.6 × 10-8, logarithm of the odds (LOD) equivalent 6.64]. In the region, IL1A and IL1B are of particular interest, key cytokine genes involved in inflammation. Our second approach identifies five multi-cancer risk patterns. These clusters include expected coaggregations (such as breast cancer with prostate cancer, ovarian cancer, and melanoma), and also identify novel patterns, including coaggregation with uterine, thyroid, and bladder cancers. CONCLUSIONS:Our results suggest pedigree-informed tumor phenotypes can map genes for breast cancer, and that various different cancer pleiotropies exist for high-risk breast cancer pedigrees. IMPACT:Both methods illustrate the potential for decreasing etiologic heterogeneity that large, population-based multisource databases can provide.See all articles in this CEBP Focus section, "Modernizing Population Science."

背景与目标： 背景：以前，基于家庭的设计和高风险谱系为发现高风险和中风险种系乳腺癌易感基因提供了价值。但是，遗传异质性是阻碍进展的主要障碍。新的策略和分析方法对于进一步发展将是必要的。通过改善疾病特征来解决异质性的潜力之一是多源数据库的可用性不断提高。涉及基于家庭的设计的进步所特有的是包括家庭结构在内的资源，例如犹他州人口数据库（UPDB）。为了说明多源数据库的广泛实用性和潜在功能，我们描述了两种不同的新颖的基于家族的方法来减少UPDB中的异构性。
方法：我们的第一个方法侧重于在基因作图中使用谱系信息的乳腺肿瘤表型。我们的第二种方法侧重于识别具有多效性相似的家庭。我们使用一种新颖的网络启发式聚类技术来探索高危乳腺癌家庭的多癌特征。
结果：我们的第一种方法在2q13处确定了全基因组重要的乳腺癌基因座[P = 1.6×10-8，对数的对数（LOD）等于6.64]。在该地区，IL1A和IL1B是引起炎症的关键细胞因子基因，引起了人们的特别关注。我们的第二种方法确定了五种多癌风险模式。这些簇包括预期的共聚集（例如与前列腺癌，卵巢癌和黑色素瘤的乳腺癌），并且还鉴定了新颖的模式，包括与子宫癌，甲状腺癌和膀胱癌的共聚集。
结论：我们的研究结果表明，谱系知悉的肿瘤表型可以定位乳腺癌基因，高危乳腺癌谱系存在多种不同的癌症多效性。
影响：这两种方法都说明了减少基于人群的大型多源数据库可以提供的病因异质性的潜力。请参阅“ CEBP焦点”部分“现代化人口科学”中的所有文章。

BACKGROUND & AIMS: PURPOSE OF REVIEW:We aimed to review literature on the efficacy and tolerability of psychosocial and psychopharmacological interventions in youth with early-onset schizophrenia spectrum disorders (EOS). A rationale for pragmatic psychopharmacology in EOS, including dosing, switching and adverse effect monitoring and management, is provided. RECENT FINDINGS:Three randomized controlled trials (RCTs) over the last 8 years demonstrated benefits of psychosocial interventions (i.e. psychoeducation, cognitive remediation, cognitive behavioural therapy) for EOS without clear advantages of one psychosocial treatment over another. Six large, placebo-controlled, short-term RCTs over the last 4 years demonstrated that aripiprazole, olanzapine, paliperidone, quetiapine and risperidone, but not ziprasidone, were superior to placebo. Except for clozapine's superiority in treatment-refractory EOS, efficacy appeared similar across studied first-generation and second-generation antipsychotics, but tolerability varied greatly across individual agents. SUMMARY:Antipsychotics are efficacious in the treatment of EOS. Given the lack of efficacy differences between antipsychotics (except for clozapine for treatment-refractory EOS), we propose that tolerability considerations need to guide choice of antipsychotics. Further and longer-term efficacy and effectiveness studies are urgently needed that should also explore pharmacologic and nonpharmacologic augmentation strategies.

背景与目标： 审查目的：我们旨在审查有关在早期发作的精神分裂症谱系障碍（EOS）的青年中进行社会心理和心理药物干预的功效和耐受性的文献。提供了EOS中实用的心理药理学原理，包括剂量，转换和不良反应监测与管理。
最近的发现：过去8年中的三项随机对照试验（RCT）证明了针对EOS的心理社会干预措施（即心理教育，认知矫正，认知行为疗法）的益处，而没有一种心理社会治疗方法比另一种方法具有明显优势。过去四年中有六项大型，安慰剂对照的短期RCT表明，阿立哌唑，奥氮平，帕潘立酮，喹硫平和利培酮，而非齐拉西酮优于安慰剂。除了氯氮平在难治性EOS方面的优越性外，在研究的第一代和第二代抗精神病药中疗效相似，但各药物的耐受性差异很大。
摘要：抗精神病药可有效治疗EOS。鉴于抗精神病药之间缺乏疗效差异（氯氮平治疗难治性EOS除外），我们建议应考虑耐受性，以指导抗精神病药的选择。迫切需要进一步和长期的有效性和有效性研究，这也应该探索药理学和非药理学增强策略。

BACKGROUND & AIMS: AIMS:Highlight the use of critical social science theories, practice development principles and a situational leadership framework within transformational leadership to inform Directors of Nursing and Midwifery (DoNM) practices as leaders. BACKGROUND:Healthcare is constantly changing, unpredictable, strives for quality service and cost containment, which can result in stress and crisis for healthcare workers. DoNM leadership is critical to supporting and leading staff through these complex times within healthcare. KEY ISSUES:Understanding theories, frameworks and their application to real-world practice can assist in supporting individuals and teams to navigate through the changing healthcare environment. CONCLUSION:Blending critical social science theories with practice development principles and the situational leadership framework can assist the DoNM to enact transformational leadership to support the development of individuals and teams to meet the complex healthcare needs of patients within the clinical setting. IMPLICATIONS FOR NURSE MANAGEMENT: This article contributes through the practical application of critical social science theories, practice development principles and situational leadership framework within transformational leadership as an approach for enacting DoNM leadership. To further understand and develop in the role of the contemporary DoNM in leadership, these directors are encouraged to publish their work.

背景与目标： 目的：重点介绍在变革型领导中使用批判性社会科学理论，实践发展原则和情境领导框架，以将领导者的护理和助产士（DoNM）行为告知领导。
背景：医疗保健不断变化，变幻莫测，力求提供优质的服务和控制成本，这可能导致医护人员承受压力和危机。在医疗保健领域的复杂时期，DoNM领导层对于支持和领导员工至关重要。
关键问题：了解理论，框架及其在实际操作中的应用可以帮助支持个人和团队在不断变化的医疗环境中导航。
结论：将批判社会科学理论与实践发展原则和情境领导框架相结合，可以帮助DoNM实施变革型领导，以支持个人和团队的发展，以满足临床环境中患者的复杂医疗保健需求。对护士管理的影响：本文通过在批判性领导中实践批判性社会科学理论，实践发展原则和情境领导框架（作为实践DoNM领导的一种方法）的实际应用做出了贡献。为了进一步了解和发展当代DoNM在领导中的作用，我们鼓励这些导演发表他们的作品。

BACKGROUND & AIMS: :Of 997 minority high school students, 8.6% had tattoos and 8% piercings (excluding earlobes); 21% with tattoos and 59% with piercings would not repeat the experience. Fifty-eight percent with tattoos and 43% with piercings reported parental knowledge before the procedure; 75% and 80%, respectively, were asked for proof of parental consent.

背景与目标： ：在997名少数民族高中学生中，有8.6％的人有纹身和8％的穿孔（不包括耳垂）； 21％的纹身和59％的穿孔不会重复体验。在做手术之前，有58％的纹身和43％的穿孔报告了父母的知识；分别要求75％和80％的父母同意证明。

BACKGROUND & AIMS: :Case histories are based on actual medical negligence claims or medicolegal referrals; however certain facts have been omitted or changed by the author to ensure the anonymity of the parties involved. Can children and adolescents consent to their own medical treatment? Do general practitioners owe teenagers a duty of confidentiality? This article examines the legal obligations of GPs when obtaining consent to medical treatment from patients who are under 18 years of age.

背景与目标： 病史是基于实际的医疗过失声明或法医转诊而得出的；但是，作者已经省略或更改了某些事实，以确保所涉各方的匿名。儿童和青少年可以同意自己接受治疗吗？全科医生应负青少年责任吗？本文研究了18岁以下患者获得医疗同意后，GP的法律义务。

BACKGROUND & AIMS: BACKGROUND:All patients with atrial fibrillation (AF) require optimization of their ventricular rate. Factors leading to use of additional rhythm control in clinical practice have not been thoroughly defined. METHODS:The ORBIT-AF registry enrolled patients with AF from a broad range of practice settings and collected data on rate versus rhythm control, as indicated by the treating physician. Multivariable logistic regression analysis was performed to identify factors associated with each strategy. RESULTS:Of 10,061 patients enrolled, 6,859 (68%) were managed with rate only control versus 3,202 (32%) with rhythm control. Patients managed with rate control were significantly older and more likely to have hypertension, heart failure, prior stroke, and gastrointestinal bleeds. They also had fewer AF-related symptoms (41% with no symptoms vs 31% for rhythm control). Systemic anticoagulation was prescribed for 5,448 (79%) rate-control patients versus 2,219 (69%) rhythm-control patients (P < .0001). After multivariable adjustment, patients with higher symptom scores (severe symptoms vs. none, OR 1.62, 95% CI 1.41-1.87) and those referred to electrophysiologists (OR 1.64, 95% CI 1.45-1.85) were more likely to be managed with a rhythm control strategy. CONCLUSIONS:In this outpatient registry of US clinical practice, the majority of patients with AF were managed with rate control alone. Patients with more symptoms and who were treated by an electrophysiologist were more likely to receive rhythm-control therapies. A significant proportion of AF patients, regardless of treatment strategy, were not treated with anticoagulation for thromboembolism prophylaxis.

背景与目标： 背景：所有房颤患者都需要优化心室率。尚未在临床实践中明确导致使用其他节律控制的因素。
方法：按照治疗医师的指示，ORBIT-AF登记系统从广泛的实践环境中招募了AF患者，并收集了其心率与心律控制的相关数据。进行多变量逻辑回归分析以识别与每种策略相关的因素。
结果：在10061名患者中，有6859名（68％）接受了单纯速率控制，而有3202名（32％）接受了节奏控制。进行速率控制的患者年龄较大，并且更有可能患有高血压，心力衰竭，中风和胃肠道出血。他们也有较少的房颤相关症状（41％无症状，节律控制为31％）。相对于2,219（69％）节律患者，对5448（79％）个速率控制的患者进行了全身抗凝治疗（P <.0001）。经过多变量调整后，症状评分较高（严重症状对比无症状，OR 1.62，95％CI 1.41-1.87）和转诊给电生理学家的患者（OR 1.64，95％CI 1.45-1.85）更容易接受节奏控制策略。
结论：在这个美国临床实践的门诊登记中，大多数房颤患者仅通过速率控制进行治疗。症状更多且由电生理师治疗的患者更有可能接受节律控制疗法。不论采用何种治疗策略，相当大比例的房颤患者均未接受抗凝治疗以预防血栓栓塞。

BACKGROUND & AIMS: :The accurate characterization of the diffusion process in tissue using diffusion MRI is greatly challenged by the presence of artefacts. Subject motion causes not only spatial misalignments between diffusion weighted images, but often also slicewise signal intensity errors. Voxelwise robust model estimation is commonly used to exclude intensity errors as outliers. Slicewise outliers, however, become distributed over multiple adjacent slices after image registration and transformation. This challenges outlier detection with voxelwise procedures due to partial volume effects. Detecting the outlier slices before any transformations are applied to diffusion weighted images is therefore required. In this work, we present i) an automated tool coined SOLID for slicewise outlier detection prior to geometrical image transformation, and ii) a framework to naturally interpret data uncertainty information from SOLID and include it as such in model estimators. SOLID uses a straightforward intensity metric, is independent of the choice of the diffusion MRI model, and can handle datasets with a few or irregularly distributed gradient directions. The SOLID-informed estimation framework prevents the need to completely reject diffusion weighted images or individual voxel measurements by downweighting measurements with their degree of uncertainty, thereby supporting convergence and well-conditioning of iterative estimation algorithms. In comprehensive simulation experiments, SOLID detects outliers with a high sensitivity and specificity, and can achieve higher or at least similar sensitivity and specificity compared to other tools that are based on more complex and time-consuming procedures for the scenarios investigated. SOLID was further validated on data from 54 neonatal subjects which were visually inspected for outlier slices with the interactive tool developed as part of this study, showing its potential to quickly highlight problematic volumes and slices in large population studies. The informed model estimation framework was evaluated both in simulations and in vivo human data.

背景与目标： ：伪影的存在极大地挑战了使用弥散MRI对组织中弥散过程的准确表征。对象运动不仅导致扩散加权图像之间的空间失准，而且通常还引起切片信号强度误差。体素鲁棒模型估计通常用于排除强度误差作为异常值。然而，在图像配准和变换之后，切片异常值变得分布在多个相邻切片上。由于部分体积的影响，这对使用体素程序进行离群值检测提出了挑战。因此需要在将任何变换应用于扩散加权图像之前检测离群切片。在这项工作中，我们提出了i）一种由SOLID创造的自动工具，用于在进行几何图像变换之前进行切片离群值检测，以及ii）一个自然解释SOLID的数据不确定性信息并将其包括在模型估计器中的框架。 SOLID使用简单的强度度量，独立于扩散MRI模型的选择，并且可以处理具有几个或不规则分布的梯度方向的数据集。 SOLID通知的估计框架通过降低不确定性程度的测量权重来防止完全拒绝扩散加权图像或单个体素测量的需要，从而支持迭代估计算法的收敛性和良好条件。在全面的模拟实验中，SOLID以较高的灵敏度和特异性检测异常值，并且与基于其他更复杂，更耗时的方案的工具相比，可以实现更高或至少相似的灵敏度和特异性。 SOLID在来自54个新生儿受试者的数据上进行了进一步验证，这些数据已通过本研究的一部分开发的交互式工具进行了视觉检查，以检测异常值，显示出其在大型人群研究中快速突出问题体积和切片的潜力。在模拟和体内人类数据中都评估了该知情的模型估计框架。

BACKGROUND & AIMS: :The promises of precision medicine are often heralded in the medical and lay literature, but routine integration of genomics in clinical practice is still limited. While the "last mile' infrastructure to bring genomics to the bedside has been demonstrated in some healthcare settings, a number of challenges remain - both in the receptivity of today's health system and in its technical and educational readiness to respond to this evolution in care. To improve the impact of genomics on health and disease management, we will need to integrate both new knowledge and new care processes into existing workflows. This change will be onerous and time-consuming, but hopefully valuable to the provision of high quality, economically feasible care worldwide.

背景与目标： ：在医学和非专业文献中经常提到精确医学的前景，但是基因组学在临床实践中的常规整合仍然有限。虽然在某些医疗机构中已经证明了将基因组学带到床边的“最后一英里”基础设施，但仍然存在许多挑战-既有当今卫生系统的接受性，也有应对医疗保健这一演变的技术和教育准备。为了提高基因组学对健康和疾病管理的影响，我们将需要将新知识和新护理流程整合到现有的工作流程中，这一变化将是繁重且耗时的，但希望对提供高质量，经济上可行的有价值在全球范围内护理。

BACKGROUND & AIMS: OBJECTIVE:To determine how trauma-informed programming affects household food insecurity (HFI) over 12 months. DESIGN:Change was assessed in HFI from baseline to 12 months in response to a single-arm cohort intervention. Measures were taken at baseline and in every quarter. Two participant groups were compared: participation in ≥4 sessions (full participation) vs participation in <4 sessions (low/no participation). SETTING:Community-based setting in Philadelphia, Pennsylvania. PARTICIPANTS:A total of 372 parents of children aged <6 years, participating in Temporary Assistance for Needy Families and the Supplemental Nutrition Assistance Program, recruited from county assistance offices and community-based settings. INTERVENTION:Trauma-informed programming incorporates healing-centered approaches to address previous exposures to trauma. Sixteen sessions addressed emotional management, social and family dynamics related to violence exposure and childhood adversity, and financial skills. MAIN OUTCOME MEASURES:Household food insecurity, as defined by the US Department of Agriculture Household Food Security Survey Module. ANALYSIS:Mixed-effects logistic regression models were used to compare groups from baseline to 12 months, controlling for adverse childhood experiences, depression, and public assistance. RESULTS:Those with full participation had 55% lower odds of facing HFI compared with the low/no participation group (adjusted odds ratio = 0.45; 95% confidence interval, 0.22-0.90). CONCLUSIONS AND IMPLICATIONS:Trauma-informed programming can reduce the odds of HFI and may reduce trauma-related symptoms associated with depression and poverty.

背景与目标： 目的：确定在未来12个月内，受创伤影响的编程如何影响家庭粮食不安全（HFI）。
设计：对HFI从基线到12个月的变化进行了评估，以应对单臂队列干预。在基线和每个季度都采取了措施。比较了两个参与者组：≥4次会议（完全参与）与<4次会议（低/无参与）的参与。
地点：宾夕法尼亚州费城的社区环境。
参与者：共有372名6岁以下儿童的父母参加了有需要的家庭的临时援助和营养补充计划，这些活动是从县援助办公室和社区机构招募的。
干预：创伤知情的编程结合了以治疗为中心的方法，以解决以前遭受的创伤。第十六届会议讨论了情绪管理，与暴力暴露和童年逆境有关的社会和家庭动态以及理财技巧。
主要观察指标：美国农业部家庭粮食安全调查模块定义的家庭粮食不安全。
分析：采用混合效应逻辑回归模型比较从基线到12个月的组，控制不良的儿童经历，抑郁症和公共援助。
结果：与低/无参与组相比，完全参与的人面对HFI的几率低55％（调整后的优势比= 0.45； 95％置信区间为0.22-0.90）。
结论和意义：创伤知情的程序设计可以减少HFI的几率，并可以减轻与抑郁症和贫困相关的创伤相关症状。

BACKGROUND & AIMS: :Although aspirin is a well-established antiplatelet agent, the mechanisms of aspirin resistance remain poorly understood. Metabolomics allows for measurement of hundreds of small molecules in biological samples, enabling detailed mapping of pathways involved in drug response. We defined the metabolic signature of aspirin exposure in subjects from the Heredity and Phenotype Intervention Heart Study. Many metabolites, including known aspirin catabolites, changed on exposure to aspirin, and pathway enrichment analysis identified purine metabolism as significantly affected by drug exposure. Furthermore, purines were associated with aspirin response, and poor responders had higher postaspirin adenosine and inosine levels than did good responders (n = 76; both P < 4 × 10(-3)). Using our established "pharmacometabolomics-informed pharmacogenomics" approach, we identified genetic variants in adenosine kinase associated with aspirin response. Combining metabolomics and genomics allowed for more comprehensive interrogation of mechanisms of variation in aspirin response--an important step toward personalized treatment approaches for cardiovascular disease.

背景与目标： ：尽管阿司匹林是一种公认​​的抗血小板药，但对阿司匹林抗药性的机制仍知之甚少。代谢组学可测量生物样品中的数百个小分子，从而详细绘制涉及药物反应的途径。我们从遗传和表型干预心脏研究中定义了阿司匹林暴露的代谢特征。暴露于阿司匹林后，许多代谢物（包括已知的阿司匹林分解代谢物）发生了变化，途径富集分析确定嘌呤的代谢受药物暴露的影响很大。此外，嘌呤与阿司匹林反应有关，不良反应者的阿司匹林后腺苷和肌苷水平高于良好反应者（n = 76； P <4××10（-3））。使用我们建立的“药代代谢组学信息化的药物基因组学”方法，我们确定了与阿司匹林反应相关的腺苷激酶的遗传变异。将代谢组学和基因组学相结合，可以更全面地研究阿司匹林反应变异的机制，这是迈向心血管疾病个性化治疗方法的重要一步。

BACKGROUND & AIMS: :Consent must be undertaken prior to any dermatological procedure; however, in doing this, the clinician needs to ensure consent is valid and satisfies the principles of determining material risk. We aimed to assess variations in obtaining consent in the UK and understanding of material risk through a nationally distributed survey to members of the British Society for Dermatological Surgery and British Association of Dermatologists. Of 165 responses, we found that written consent was being obtained for all procedures in 73.9% of cases and typically at the time of procedure in the operating room/theatre (78.8%). Fifty-seven per cent of respondents were not familiar with the term 'material risk' and almost one-third were not aware of the Montgomery vs. Lanarkshire ruling, which replaced the Bolam test in 2015. We would encourage readers to be aware of these changes to consent law in the UK and how it might affect their approach to obtaining consent.

背景与目标： ：必须在任何皮肤病学程序之前进行同意；但是，这样做时，临床医生需要确保同意有效并满足确定重大风险的原则。我们旨在通过对英国皮肤病外科学会和英国皮肤科医生协会成员进行的全国性调查来评估在英国获得同意和对重大风险的理解的差异。在165份答复中，我们发现73.9％的病例（通常是在手术室/手术室中）在所有手术中均获得了书面同意（78.8％）。 57％的受访者对“重大风险”一词不熟悉，几乎三分之一的受访者不了解蒙哥马利诉拉纳克郡裁定，该裁定在2015年取代了博拉姆测验。我们鼓励读者注意这些规定。英国同意书法律的变更及其可能如何影响他们获取同意书的方式。