MCD2030-week6-2009
美国《消费品安全改进法案》(儿童产品安全)
中华人民共和国扬州进出口玩具检验所
PAHs 相关的法令法规
中华人民共和国扬州进出口玩具检验所
PAHs 相关的法令法规
德国GS (Geprufte Sicherheit): 德国安全认证 • 表明产品符合《德国产品安全法》规定 • 与CE认证不同，GS认证并非强制性的法 规，但由于它确实能最大化地降低产品质 量方面的风险，因此在欧洲甚至世界范围 内得到了消费者和企业广泛的认可，具有 巨大的市场竞争力
条款要求：
一、标准 1、安全标准：SPSC将对现行的标准进行审核和评估。第二 步将采取更为严格的自愿性标准。 2、在CPSIA颁布后一年内的每6个月至少颁布2种婴幼儿耐 用品和儿童学步车的标准。 二、注册 1、随产品一起为消费者提供一份已付邮资的消费者登记表 2、制造商应保存产品持有人的登记表，包括持有人的姓 名、地址、电子邮箱及其它联系信息，以提高产品召回的 效率 3、在婴幼儿耐用品和儿童学步车上永久标注制造商的名 称和联系方式、产品名称及数量、生产日期等信息 4、制造商应保存登记表至少6年
美国《消费品安全改进法案》 （儿童产品安全）
中华人民共和国扬州进出口玩具检验所
美国《消费品安全改进法案》的背 景
中华人民共和国扬州进出口玩具检验所
《美国消费品安全改进法案》的主要 内容
在全美建立统一的强制性国家标准。 进一步规范含铅玩具 玩具上加贴可追溯性标签。 将自愿性标准ASTM F963转化为强制性标 准。 对某些儿童产品实行强制性第三检测 对玩具中的6种邻苯二甲酸盐实施控制
介绍
多环芳烃(Polycyclic Aromatic Hydrocarbons PAHs) 指两个及两个以上苯环连在一起的化合物，如萘、蒽等 是煤，石油及其制品，木材，烟草，塑料等不完全燃烧或连续高温处 理时产生的
美国食品标签指南
食品标签指南行业指南2009年10月目录包括非约束性建议 1.2.3. 序言44 背景材料一般食品标签要求行业指南食品标签指南本《指南》代表食品和药物管理局（FDA）在该问题上的当前观点，并未产生或赋予任何人任何权利，亦未对食品和药物管理局或公众产生任何约束力。
您亦可采用另一种方法，只要该方法符合当前适用法律和条例的要求。
如果您想讨论另一种方法，请联系负责落实本《指南》的食品和药物管理局工作人员；如果您未能与适当的食品和药物管理局工作人员取得联系，可拨打本《指南》扉页上的电话号码。
4. 食品名称7 果汁5. 内容物净含量声明146. 配料名单17色素食品致敏原标签7. 营养成分标签25基本信息营养素标示带有单独包装配料的食品/食品分类标签格式/图表一般信息特殊标签格式反式脂肪贴标其他服食量免除情况/特殊贴标规定8. 说明72营养成分说明健康说明合格健康说明结构/功能说明9. 附录A：营养成分说明的定义8710. 附录B：营养成分说明的附加要求9111. 附录C：健康说明9512. 附录D：合格健康说明10413. 附录E：其他食品和药物管理局参考信息12314. 附录F：计算适当营养物质每日使用量百分比12415. 附录G：四岁以下婴幼儿、孕妇及哺乳期妇女每日所需量12516. 附录H：根据食品和药物管理局四舍五入规定进行数值的四舍五126 入1. 序言在一本类似本《指南》的文件中，不太可能事无巨细地回答所提出的每一个关于食品标签方面的问题，一般采用“问答”的形式解决最经常出现的问题。
我们认为本《指南》对绝大多数食品标签方面的问题给与了解答，并将这些问题根据所关心的食品标签区域进行分类，其中本文件的目录可帮助您找到您所关注的食品标签问题。
根据食品和药物管理局的法律和规定，食品和药物管理局不得事先批准食物产品的标签。
有关食物产品标签方面的问题，可咨询食品和药物管理局，食品安全和应用营养中心，营养产品、标识和膳食补充剂办公室的食品标签和标准工作人员（HFS-820），地址是5100 Paint Branch Parkway, College Park, MD 20740-3835, 电话：（301）436-2371。
解读 2012 年儿童哮喘国际共识
解读2012 年儿童哮喘国际共识2014-05-26 11:06 来源：中华实用儿科临床杂志作者：向莉字体大小-|+来自于欧洲变态反应和临床免疫学会(EAAcI)、美国变态反应哮喘和免疫学会(AAAAI)、美国变态反应哮喘和免疫学院(AcAAI) 以及世界变念反应组织(wAO) 的专家组成的哮喘变态反应和免疫国际联合会(IcAALL) 于20l2 年 6 月发表儿童哮喘国际共识(IcoN)。
ICAAELL 的委员对：2006 年以来修订或颁布的国际代表性或区域性儿童哮喘指南分析比较，这些指南文件包括澳大利亚哮喘管理手册2006 版、哮喘管理和预防的全球策略20l1 年更新版、5 岁以下儿童哮喘诊断与管理的全球策略2009 年版、日本儿童哮喘指南2008 版、美国心肺血液研究所关于国家哮喘教育和预防计划的专家组报告一3 的2007 年版、儿童哮喘诊断和治疗的pRAcTALL 共识报告2008 年版、英国哮喘管理指南2011 年修订版(sIGN)。
IcON 强调了以上各项指南关于儿童哮喘管理理念的共同点一一哮喘治疗目标为疾病控制，达到哮喘控制的目标需要将教育患儿及其父母与卫生服务的专业人士的教育共同结合起来。
应规律进行评估和监测以便精细调整治疗方案。
大多数儿童经合理的药物治疗能控制症状和减少未来患病风险。
表型特异性哮喘治疗是未来发展趋势。
1 哮喘的定义和分类通过比较不同指南文件在定义哮喘的差异性和共性，指出在慢性炎症这一病理本质上已经达成共识。
并在使用描述性定义中，不同程度地涵盖了症状、表现类型和潜在机制。
但由于迄今为止，有关慢性呼吸道炎症、支气管高反应性、症状三者之问的关系仍小清楚，因此，IcON 认为在哮喘的定义中增加更加细化的描述，例如细胞类型、症状时程、可逆性及其触发因素，并不能增加在哮喘认知方面的敏感性和特异性。
因此住临床应用中，使用一个简化的哮喘的工作定义更为实用，即哮喘是与多变的气流阻塞和支气管高反应性相关的慢性炎症病变。
MG2009指南
重症肌无力诊断和治疗指南发表时间：2009-12-14 发表者：李醒亚(访问人次：1373)重症肌无力是乙酰胆碱受体抗体介导，细胞免疫依赖，补体参与的，发生于神经肌接头的自身免疫性疾病。
诊断：（1）横纹肌易疲劳性。
晨轻暮重，活动后肌无力加重，经休息后减轻、缓解。
（2）药理学特征。
胆碱酯酶抑制剂可迅速缓解肌无力症状。
（3）电生理学特征。
低频重复频率刺激可使波幅衰竭50%以上。
（4）血清学特征。
在80-90%的全身型重症肌无力患者血中可检测到特异性的致病因子-乙酰胆碱受体抗体；约在60%左右的单纯眼肌型重症肌无力患者血中可检测到乙酰胆碱受体抗体。
近年来，在乙酰胆碱受体抗体阴性的全身型重症肌无力患者血中检测到抗-MuSK抗体，阳性率约为60%。
（5）影像学特征。
约80%重症肌无力患者伴有胸腺增生；约25%左右的重症肌无力患者同时伴有胸腺瘤；约20-25%胸腺瘤患者出现重症肌无力症状。
重症肌无力治疗：一、不同类型重症肌无力患者的药物选择。
（1）单纯眼肌型重症肌无力患者病初用胆碱酯酶抑制剂即可；如果单用胆碱酯酶抑制剂疗效不佳者可考虑应用糖皮质激素或者甲基强的松龙冲击。
胆碱酯酶抑制剂剂量应个体化。
激素在预防单纯眼肌型重症肌无力向全身型重症肌无力转化中的可能作用。
近年来有文献报道，单纯眼肌型重症肌无力患者早期使用糖皮质激素可预防眼肌型重症肌无力向全身型重症肌无力的转化。
但，直到目前还没有明确证据证明糖皮质激素能够预防眼肌型向全身重症肌无力的转化。
（2）全身型重症肌无力。
一般只用胆碱酯酶抑制剂不足以完全改善症状，需要联合用药治疗。
在应用胆碱酯酶抑制剂的基础上，加用糖皮质激素或者联合应用免疫抑制剂，如硫唑嘌呤、环孢酶素A等。
部分全身型重症肌无力患者需要甲基强的松龙冲击。
在冲击过程中应严密观察病情变化。
部分全身型重症肌无力患者在甲基强的松龙冲击过程中病情一过性加重，甚至需行气管插管或气管切开。
经甲基强的松龙冲击后疗效后仍不佳者，考虑大剂量丙种球蛋白冲击。
FDA指南 混合均匀性接受标准
Powder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and AssessmentDRAFT GUIDANCEThis guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit comments to Dockets Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the docket number listed in the notice of availability that publishes in the Federal Register.For questions regarding this draft document contact Jon E. Clark, 301-594-5613 or Mike Gavini, 301-827-9053.U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)October 2003Pharmaceutical CGMPsPowder Blends and Finished Dosage Units — Stratified In-Process Dosage Unit Sampling and AssessmentAdditional copies are available from:Office of Training and CommunicationDivision of Drug Information, HFD-240Center for Drug Evaluation and ResearchFood and Drug Administration5600 Fishers LaneRockville, MD 20857(Tel) 301-827-4573/cder/guidance/index.htmU.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Office of Pharmaceutical Science (OPS)Office of Compliance (OC)October 2003Pharmaceutical CGMPsDraft — Not for ImplementationTABLE OF CONTENTSI.INTRODUCTION (1)II.BACKGROUND (1)III.SCOPE (2)IV.CORRELATION OF IN-PROCESS STRATIFIED SAMPLING WITH POWDER MIX AND FINISHED PRODUCT (4)A.Assessment of Powder Mix Uniformity (4)B.Correlation of Powder Mix Uniformity with Stratified In-Process Dosage Unit Data (5)C.Correlation of Stratified In-Process Samples with the Finished Product (6)V.EXHIBIT/VALIDATATION BATCH POWDER MIX HOMOGENEITY (6)VI.VERIFICATION OF MANUFACTURING CRITERIA (7)A.In-Process Dosage Unit Sampling and Analysis (7)B.Criteria to Meet the Readily Pass Classification (8)C.Criteria to Meet the Marginally Pass Classification (8)D.Sample Locations for Routine Manufacturing (9)VII. ROUTINE MANUFACTURING BATCH TESTING METHODS (9)A.Standard Criteria Method (SCM) (9)1.Stage 1 Test (10)2.Stage 2 Test (10)B.Marginal Criteria Method (MCM) (10)C.Switching to Standard Test Method from Marginal Test Method (11)VIII.REPORTING THE USE OF STRATIFIED SAMPLING (11)A.Applications Not Yet Approved (11)B.Postapproval Change (12)GLOSSARY (13)ATTACHMENT 1: VERIFICATION OF MANUFACTURING CRITERIA (14)ATTACHMENT 2: ROUTINE MANUFACTURING BATCH TESTING (15)Guidance for Industry112Powder Blends and Finished Dosage Units — Stratified In-Process 3Dosage Unit Sampling and Assessment4567This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 8thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 9bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of 10the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA 11staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call 12the appropriate number listed on the title page of this guidance.13.141516I.INTRODUCTION1718This guidance is intended to assist manufacturers of human drug products in meeting the19requirements of 21 CFR 211.110 for demonstrating the adequacy of mixing to ensure uniformity of in-process powder blends and finished dosage units. This guidance describes the procedures 2021for assessing powder mix adequacy, correlating in-process dosage unit test results with powder 22mix test results, and establishing the initial criteria for control procedures used in routine23manufacturing.2425FDA's guidance documents, including this guidance, do not establish legally enforceable26responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should 27be viewed only as recommendations, unless specific regulatory or statutory requirements are28cited. The use of the word should in Agency guidances means that something is suggested or 29recommended, but not required.3031II.BACKGROUND323334This guidance is the result of an Agency effort to achieve a science-based policy and regulatory enforcement. Experts from industry, academia, and the FDA developed the principles3536underlying this guidance after extensive public discussion. A brief history of the evolution of 37this guidance is provided in the following paragraphs.1 This guidance has been prepared by the Office of Pharmaceutical Science and the Office of Compliance in theCenter for Drug Evaluation and Research (CDER) at the Food and Drug Administration in cooperation with the Product Quality Research Institute (PQRI) (see footnote 3). This guidance document represents the Agency'scurrent thinking on assessment of the uniformity of powder blends and finished dosage units in the absence of new technology development or implementation.3839In response to industry concerns regarding regulations for demonstrating the adequacy of in-40process powder mixing, the FDA published a draft guidance for industry on blend uniformity 41analysis in August 1999.2 Comments submitted to the docket resulted in the formation of the 42Blend Uniformity Working Group (BUWG) by the Product Quality Research Institute (PQRI).3 43The PQRI BUWG conducted a public meeting, PQRI Workshop on Blend Uniformity, on44September 7 and 8, 2000.4546Using the consensus reached by participants in this workshop, the BUWG developed a draft47recommendation, The Use of Stratified Sampling of Blend and Dosage Units to DemonstrateAdequacy of Mix for Powder Blends. The draft recommendation received examination and peer 4849review in multiple scientific and public venues. In addition, the Advisory Committee for50Pharmaceutical Science (ACPS) reviewed the draft recommendation and received public51comment during scheduled meetings of the committee.4 The draft recommendation was revised 52to incorporate the results of peer review and public comment and was presented to CDER's53Center Director in final form on December 30, 2002. The recommendation was subsequently 54published in the PDA Journal of Pharmaceutical Science and Technology.5 This draft guidance 55reflects CDER's effort to incorporate the draft recommendation into regulatory policy.565758III.SCOPE5960Stratified sampling is the process of sampling dosage units at predefined intervals and collecting representative samples from specifically targeted locations in the compression/filling operation 6162that have the greatest potential to yield extreme highs and lows in test results. These test results 63are used to monitor the manufacturing process output that is most responsible for causing64finished product variability. The test results can be used to develop a single control procedure to 65ensure adequate powder mix and uniform content in finished products.6667The methods described in this guidance are not intended to be the only methods for meeting68Agency requirements to demonstrate the adequacy of powder mix. Traditional powder blend 69sampling and testing, in conjunction with testing for uniformity of content in the finishedproduct, can be used to comply with current good manufacturing practice requirements702 The FDA withdrew the guidance for industry ANDAs: Blend Uniformity Analysis o n May 17, 2002.3 PQRI is a collaborative body involving FDA's Center for Drug Evaluation and Research (CDER), industry, andacademia. Since its inception in January 1996, the mission of PQRI has been to generate scientific information in support of regulatory policies through research. Additional information about PQRI is available at .4 The PQRI BUWG recommendation appeared on the public ACPS agenda on November 28, 2001 (introduction),May 8, 2002 (distribution and comment), and October 22, 2002 (final comment).5 G Boehm, J Clark, J Dietrick, L Foust, T Garcia, M Gavini, L Gelber, J Geoffry, J Hoblitzell, P Jimenez, GMergen, F Muzzio, J Planchard, J Prescott, J Timmermens, and N Takiar, "The Use of Stratefied Sampling of Blend and Dosage Units to Demonstrate Adequacy of Mix for Powder Blends, PDA J. Pharm. Sci Technol,. 57:59-74, 2003.71(CGMPs). Use of at-, in-, or on-line measurement systems can also be appropriate and are72described in other guidance documents.67374This guidance provides recommendations on how to:7576•Conduct powder blend sampling and analyses.77•Establish initial criteria for stratified sampling of in-process dosage units7 and evaluation 78of test results.79•Analyze the stratified samples and evaluate data.•Correlate the stratified sample data with the powder blend data.8081•Assess powder mix uniformity.•Correlate the stratified sample data with the finished dosage unit data and assess8283uniformity of content.•Test exhibit and validation batches for adequacy of powder mix.8485•Test and evaluate routine manufacturing batches.86•Report the use of stratified sampling in the application.8788The methods described in this guidance can be used to monitor active ingredient homogeneity of 89powder blends and to ensure uniform content of the finished product for solid oral drug products. 90These methods are only one way to satisfy the CGMP and application review requirements for 91in-process testing to demonstrate adequacy of powder mix and uniform content of the finished 92product. The method assumes appropriate monitoring of all manufacturing steps as required by 93the regulations or application commitments. This guidance does not discuss the assessment of the potency and other attributes that can affect the finished dosage units, or the homogeneity of 9495inactive ingredients. Formulations with extremely low dose and/or high potency may call for96more rigorous sampling than that described in this guidance to assess the uniformity of powder 97blends or the uniformity of content of the finished dosage units.9899When using the methods described in this guidance, certain data or trends may be observed. We 100recommend that manufacturers scientifically evaluate these types of research data to determine if they affect the quality of a product and, if so, how. The FDA does not intend to inspect research 101102data collected on an existing product for the purpose of evaluating the suitability of proposedmethods. Any FDA decision to inspect research data would be based on exceptional situations 1036 In August 2003, the Agency issued the draft guidance for industry PAT – A Framework for InnovativePharmaceutical Manufacturing and Quality Assurance. Once finalized, it will represent the Agency's perspective on this issue.7 The in-process dosage unit is a capsule or tablet as it is formed in the manufacturing process before it is coated orpackaged.similar to those outlined in Compliance Policy Guide Sec. 130.300.8 Those data used to support 104105validation or regulatory submissions will be subject to inspection in the usual manner.106107108IV.CORRELATION OF IN-PROCESS STRATIFIED SAMPLING WITH POWDER 109MIX AND FINISHED PRODUCT110111If you plan to follow the procedures described in this guidance document, we recommend that 112you first complete the process development procedures described in this section before using the methods described in sections V, VI, VII. The subsections below describe how to assess the 113114adequacy of powder mix, uniformity of content of the in-process and finished dosage unitsthrough correlation and assessment of data from development, validation and manufacturing 115116batches. These procedures can reveal deficiencies in the blending operation that may not have 117been previously detected. We recommend that manufacturers correct deficiencies in the118blending operation before implementing the routine manufacturing control methods described in 119this guidance.120121A.Assessment of Powder Mix Uniformity122123We recommend the assessment of powder mix uniformity using the following procedures:124•Conduct blend analysis on batches by extensively sampling the mix in the blender and/or 125126intermediate bulk containers (IBCs).127•Identify appropriate blending time and speed ranges, dead spots in blenders, and locations 128of segregation in IBCs. Determine sampling errors.129•Define the effects of sample size (e.g., 1-10X dosage unit range) while developing a130technique capable of measuring the true uniformity of the blend. Sample quantities larger 131than 3X can be used with adequate scientific justification. Appropriate blend sampling 132techniques and procedures should be developed for each product with consideration to 133various designs of blend powder sampling and the physical and chemical properties of 134the blend components.135•Design blend-sampling plans and evaluate them using appropriate statistical analyses. 136•Quantitatively measure any variability that is present among the samples. Attribute the 137sample variability to either lack of uniformity of the blend or sampling error. Significant 138within-location variance in the blend data can be an indication of one factor or acombination of factors such as inadequacy of blend mix, sampling error9 or1398 FDA/ORA Compliance Policy Guide, Sec. 130.300, FDA Access to Results of Quality Assurance Program Auditsand Inspections (CPG7151.02)9 If blend sampling error is detected, more sophisticated, statistical analyses should be applied to assess the situation,such as the use of methods described in J Berman, DE Elinski, CR Gonzales, JD Hofer, PJ Jimenez, JA Planchard, RJ Tlachac, PF Vogel, “Blend Uniformity Analysis: Validation and In-Process Testing.” Technical Report No. 25, PDA J Pharm. Sci. Technol. 51(Suppl 3i-iii), S1-99, 1997.140agglomeration.10, 11 Significant between-location variance in the blend data can indicate141that the blending operation is inadequate.142143B.Correlation of Powder Mix Uniformity with Stratified In-Process Dosage 144Unit Data145146We recommend the following steps for correlation:147•Conduct periodic sampling and testing of the in-process dosage units by sampling them at 148149defined intervals and locations throughout the compression or filling process. Use aminimum of 20 appropriately spaced in-process dosage unit sampling points. There150151should be at least 7 samples taken from each of these locations for a total minimum of at152least 140 samples.153•Take 7 samples from each additional location to further assess each significant event,12 154such as filling or emptying of hoppers and IBCs, start and end of the compression or155filling process and equipment shutdown. This may be accomplished by using processdevelopment batches, validation batches, or by using routine manufacturing batches for 156157approved products.•Significant events may also include observations or changes from one batch to another 158159(e.g., batch scale-up and observations of undesirable trends in previous batch data).160• Prepare a summary of the data and analysis used to correlate the stratified sampling161locations with significant events in the blending process. We recommend you submit this162summary with the application as described in section VIII of this guidance.163•Compare the powder mix uniformity with the in-process dosage-unit data described above.164165•Investigate any discrepancies observed between powder mix and dosage-unit data and establish root causes. At least one trouble-shooting guide is available that may be helpful 166167with this task.13 Possible corrections may range from going back to formulation168development to improve powder characteristics to process optimization. Sampling10OS Sudah, PE Arratia, D. Coffin-Beach, FJ Muzzio, "Mixing of Cohesive Pharmaceutical Formulations in Tote (Bin)-Blenders,” Drug Dev. Ind. Pharm, 28(8): 905-918, 2002.11V Swaminathan, DO Kildsig, “Polydisperse powder mixtures: effect of particle size and shape on mixturestability,” Drug Dev. Ind. Pharm., 28(1):41-48, 2002.12 A s ignificant event is any operation during the solid dosage production process that can affect the integrity of thein-process materials – see section IX Glossary.13 JK Prescott, TJ Garcia, "A Solid Dosage and Blend Content Uniformity Troubleshooting Diagram," Pharm.Technol., 25 (3):68-88, 2001.problems may also be negated by use of alternate state-of-the-art methods of in situ real-169170time sampling and analysis.171C.Correlation of Stratified In-Process Samples with the Finished Product172173174We recommend the following steps:175176•Conduct testing for uniform content of the finished product using an appropriate177procedure or as specified in the Abbreviated New Drug Application (ANDA) or the NewDrug Application (NDA) for approved products.178179•Compare the results of stratified in-process dosage unit analysis with uniform content of the finished dosage units from the previous step. This analysis should be done without 180181weight correction.14182•Prepare a summary of the data and analysis used to conclude that the stratified in-process 183sampling provides assurance of uniform content of the finished product. We recommend184you submit this summary with the application as described in section VIII of thisguidance.185186187188V.EXHIBIT/VALIDATATION BATCH POWDER MIX HOMOGENEITY189This section describes sampling and testing the powder mix of exhibit and process validation 190191batches used to support implementing the stratified sampling method described in this guidance.192193194We recommend that during the manufacture of exhibit and process validation batches, you assess195the uniformity of the powder blend, the in-process dosage units, and the finished product196independently. We recommend you use the following steps to identify sampling locations and197acceptance criteria prior to the manufacture of the exhibit and/or validation batches.151981991.Carefully identify at least 10 sampling locations in the blender to represent potential areas200of poor blending. For example, in tumbling blenders (such as V-blenders, double cones,or drum mixers), samples should be selected from at least two depths along the axis of 201202the blender. For convective blenders (such as a ribbon blender), a special effort should203be made to implement uniform volumetric sampling to include the corners and discharge204area (at least 20 locations are recommended to adequately validate convective blenders).2052062.Collect at least 3 replicate samples from each location. Samples should meet the207following criteria:14 Weight correction is a mathematical correction to eliminate the effect of potentially variable tablet weight onmeasurement of mix adequacy—see Glossary, Section IX.15 This is described in Section IV of this guidance.208209•Assay one sample per location (number of samples (n) ≥ 10)210(n = 20 for ribbon blender).211212•RSD (relative standard deviation) of all individual results ≤ 5.0 percent.213214•All individual results are within 10.0 percent (absolute) of the mean of the results. 215216If samples do not meet these criteria, we recommend that you investigate the failure according to 217the flow chart in Attachment 1. We also recommend that you not proceed any further with 218implementation of the methods described in this guidance until the criteria are met.219220Sampling errors may occur in some powder blends, sampling devices, and techniques that make 221it impractical to evaluate adequacy of mix using only the blend data. In such cases, we222recommend that you use in-process dosage unit data in conjunction with blend sample data to 223evaluate blend uniformity.224225Some powder blends may present unacceptable safety risk when directly sampled. The safety 226risk, once described, may justify an alternate procedure. In such cases, process knowledge and 227data from indirect sampling combined with additional in-process dosage unit data may be228adequate to demonstrate the adequacy of the powder mix. Data analysis used to justify using 229these alternate procedures should be described in a summary report that is maintained at the 230manufacturing facility.231232As an alternative, you can substitute the procedures described in the PDA Technical Report No. 23325, (see reference in footnote 8) to ensure that the blend is uniform and that the method meets or 234exceeds the criteria described above.235236237VI.VERIFICATION OF MANUFACTURING CRITERIA238239You should complete the assessment of powder mix uniformity and correlation of stratified in-240process dosage unit sampling development procedures before establishing the criteria andcontrols for routine manufacturing. We also recommend that you assess the normality and241242determine RSD from the results of stratified in-process dosage unit sampling and testing that 243were developed. The RSD value should be used to classify the testing results as either readily 244pass (RSD ≤ 4.0%), marginally pass (RSD ≤ 6.0%) or inappropriate for demonstration of batch 245homogeneity (RSD > 6.0%). The procedures are discussed in the following sections:246247A.In-Process Dosage Unit Sampling and Analysis248249We recommend the following steps:250•Carefully identify locations throughout the compression or filling operation to sample in-251252process dosage units. The sampling locations should also include significant processevents such as hopper changeover, filling or machine shutdown and the beginning and 253254end of the compression or filling operation.16 There should be at least 20 locations with 7 255samples each for a minimum total of 140 samples. These include periodic sampling256locations and significant event locations.257•Sample at least 7 in-process dosage units from each sampling location.258•Assay at least 3 of the 7 and weight correct each result. (The number of samples should 259be specified and justified for a given product and process.)•Conduct an analysis of the dosage unit stratified sampling data to demonstrate that the 260261batch has a normal distribution of active ingredient. Indications of trends, bimodal262distributions, or other forms of a distribution other than normal should be investigated. If 263these occurrences significantly affect your ability to ensure batch homogeneity, they264should be corrected.•Prepare a summary of this analysis. Potential investigation results along with a265description of batch normality should be included in the summary. Submit this summary 266267with the application as described in section VIII of this guidance.268In addition to this analysis of batch normality, we recommend that you classify the test results as 269270readily pass or marginally pass according to the following procedure:271B.Criteria to Meet the Readily Pass Classification272273274For each separate batch, compare the test results to the following criteria:275276•For all individual results (for each batch n ≥ 60) the RSD ≤ 4.0 percent.277•Each location mean is within 90.0 percent to110.0 percent of target strength.278279280•All individual results are within the range of 75.0 percent to 125.0 percent of target strength.281282283If your test results meet these criteria, they are classified as readily pass and you can start routine 284batch testing using the Standard Verification Method (SVM) described in section VII. If your 285test results fail to meet these criteria, we recommend that you compare the results with themarginally pass criteria described below.286287288C.Criteria to Meet the Marginally Pass Classification289290If your dosage unit test results fail to meet the criteria for the r eadily pass classification, you 291should assay the remaining dosage units (all 7 units per location) and compare the test results to 292the following criteria:16 The beginning and end samples are taken from dosage units that would normally be included in the batch.293294•For all individual results (for one batch n ≥ 140) the RSD ≤ 6.0 percent.295•Each location mean is within 90.0 percent to 110.0 percent of target strength.296297298•All individual results are within the range of 75.0 percent to 125.0 percent of target299strength.300301If your test results meet these criteria, results can be classified as marginally pass. If yoursamples do not meet these criteria, we recommend that you investigate the failure, find justified 302303and assignable cause(s), correct the deficiencies, and repeat the powder mix homogeneity304assessment, in-process dosage unit sampling correlation, and initial criteria establishment305procedures. The disposition of batches that have failed the m arginally pass criteria is outside the 306scope of this guidance.307308D.Sample Locations for Routine Manufacturing309310We recommend that you prepare a summary of the data analysis from the powder mixassessment and stratified sample testing. From the data analysis, you should establish the311312stratified sample locations for routine manufacturing, taking into account significant process 313events and their effect on in-process dosage unit and finished dosage unit quality attributes. You should identify at least 10 sampling locations during capsule filling or tablet compression to 314315represent the entire routine manufacturing batch.316317318VII. ROUTINE MANUFACTURING BATCH TESTING METHODS319We recommend that you evaluate the routine manufacturing batches against the following320321criteria after completing the procedures described above to assess the adequacy of the powder 322mix and uniform content in finished dosage form.323324These routine manufacturing batch-testing methods include the Standard Criteria Method (SCM) 325and the Marginal Criteria Method (MCM). The SCM consists of two stages, each with the same accept/reject criteria. The second of the two stages recommends using a larger sample size to 326327meet these criteria. The MCM uses accept/reject criteria that are different from the SCM.328329If the batch data fail to conform to the SCM criteria, we recommend continued sampling and 330testing to intensified criteria (MCM). Both verification methods and the procedures for331switching from one to the other are detailed below and in the flow chart in Attachment 2.332333A.Standard Criteria Method (SCM)334335We recommend using the SCM verification method when either of the following conditions is 336met:•Results of establishing initial criteria are classified as readily pass.337。
增强免疫力功能评价方法(征求意见稿)及修订说明之欧阳道创编
附件1：增强免疫力功能评价方法（征求意见稿）保健食品评价试验项目、试验原则及结果判定Items, Principles and Result Assessment1 试验项目1.1 动物实验1.1.1 体重1.1.2脏器/体重比值测定：胸腺/体重比值，脾脏/体重比值1.1.3细胞免疫功能测定：小鼠脾淋巴细胞转化实验，迟发型变态反应实验1.1.4体液免疫功能测定：抗体生成细胞检测，血清溶血素测定1.1.5单核—巨噬细胞功能测定：小鼠碳廓清实验，小鼠腹腔巨噬细胞吞噬荧光微球实验1.1.6NK细胞活性测定2 试验原则2.1 所列的指标均为必做项目2.2分为正常动物实验方案和免疫功能低下模型动物实验两种方案, 可任选其一进行实验.2.3采用免疫功能低下动物模型实验方案时需做外周血白细胞总数测定3 结果判定3.1采用正常动物实验，受试样品具有增强免疫力作用。
在细胞免疫功能、体液免疫功能、单核－巨噬细胞功能及NK细胞活性四个方面测定中，任两个方面试验结果为阳性，可以判定该受试样品具有增强免疫力作用。
其中细胞免疫功能测定项目中两个实验的结果均为阳性，判定细胞免疫功能试验结果阳性。
体液免疫功能测定项目中两个实验的结果均为阳性，判定体液免疫功能试验结果阳性。
单核—巨噬细胞功能测定项目中两个实验的结果均为阳性，判定单核—巨噬细胞功能试验结果阳性。
NK细胞活性测定实验的一个以上剂量结果阳性，判定NK细胞活性结果阳性。
正常动物实验需进行四个方面的测定。
3.2 采用免疫功能低下动物实验，受试样品对免疫功能低下者具有增强免疫力作用。
在免疫功能低下模型成立条件下，血液白细胞总数、细胞免疫功能、体液免疫功能、单核－巨噬细胞功能及NK细胞活性五个方面测定中，任两个方面试验结果为阳性，判定该受试样品对免疫功能低下者具有增强免疫力作用。
其中细胞免疫功能测定项目中两个实验的结果均为阳性，或任一个实验的两个剂量组结果阳性，可判定细胞免疫功能试验结果阳性。
RoHS基础知识及MCD简介
二、物料成份宣告（MCD）/环境管理物质或 部 件展开表
内容主要是填写我公司具体某款产品 的基本信息，部件名称，料号，原材料，当 然 最 重 要 的 是 原 材 料 的 是 否 含 有 RoHS 限 制 使 用的物质，并提供证据，如RoHS测试报告或 SGS检测报告、其中不同客户的要求填写的文 件名称可能不一样，但内容大致相同。如 供 應商環境危害物質檢測調查表、物料数据表、 产品符合环保申明、環 境 管 理 物 質 成 份 或 部 件 展 開 表、供应商RoHS管理一 览表
或者上游供應商的變更等,要求重新提供 MCD, 并通知富士康 4. 所有的供應商必須 及時簽回 << 富士康供應 商 RoHS 管理調查表 >>
• 淇誉RoHS文件要求： 《供商零部件环保保证书》
• 集成要求的文件：
《供应商RoHS管理一览表》
• 伟创力要求：
填写FBP-RHS005B1060508文件，要 填写材料含有的所有物质成份，并且把资料 填到网上去。
ROHS教材一
提供:张巧平 审核:吴刚
RoHS基础知识
一、RoHS基础知识
1、RoHS指令说明
欧盟议会和欧盟理事会于2003年1月 通过了RoHS指令，全称是The Restriction
of the use of certain Hazardous
substances in Electnical and Electronic Equipment（关于在电子电气设备中禁止使 用某些有害物质的指令）,即2002/95/EC指 令，2005年欧盟又以2005/618/EC决议的 形式对2002/95/EC进行了补充，明确规定 了六种有害物质的最大限量值。其中铅 （Pb）、汞(Hg)、六价铬(Cr6+)、多溴联 苯(PBB)、多溴二苯醚 (PBDE)的最大允许含 量为0.1%(1000ppm)，镉
欧盟医疗器械指令MDDEEC培训
- G. 动物移植物或动物组织或细胞，除非器械是利用不能存活的动物组织或从动 物组织中衍生的不能存活的产品制造的
Note 1:Mass-produced devices which need to be adapted to meet the specific requirements of the medical practitioner or any other professional user ►M5shall
· 上市: 指器械首次供应于社会. · 投入使用: 指器械首次按其预定功能被使用.
16
第十六页，共七十六页。
第1章 定义和范围
· 器械子类别
·‘device subcategory’ means a set of devices having common areas of intended use or common technologmeans a set of devices having common areasof intended use or commontechnology;
be custom made devices 大量生产则不应认为是定制器械
12
第十二页，共七十六页。
第1章 定义和范围
制造商
是指在以其名义将器械投放市场前负责器械的设计、制造、包装和标签的自然人或法人 ，无论这些工作是他自己完成的，还是由第三方代表他完成的。本指令规定制造商必须履
行的义务也适用于负责对一件或几件制成品进行装配，包装、加工、全面整修和/或加贴标志和/或
慢性阻塞性肺疾病诊断、治疗与预防全球策略年版更新解读ppt课件全
目录CONTENTS
定义和概述
诊断和初始评估
预防和维持治疗的证据支持
稳定期慢阻肺治疗药物推荐
急性加重的评估与治疗
慢阻肺和共患疾病
1
2
3
4
5
6
慢阻肺的定义
慢性阻塞性肺疾病（慢阻肺）是一种常见的、可以预防和治疗的疾病，以持续呼吸症状和气流受限为特征，通常是由于明显暴露于有毒颗粒或气体引起的气道和/或肺泡异常所导致。
至首次急性加重的时间
一项双盲、平行组、随机，对照的临床研究，纳入吸入支扩剂后FEV1<50%，过去1年至少1次急性加重史，CAT评分小于10分的患者，以2:2:1的比例接受含倍氯米松/富马酸福莫特罗/格隆溴铵复方制剂、噻托溴铵和倍氯米松/富马酸福莫特罗复方制剂加噻托溴铵的给药方式，评估患者治疗52周后中度、重度急性加重发生率。次要研究终点为第52周FEV1较基线的变化。
肺功能仍然是疾病进展、特殊治疗选择（例如肺减容术、肺移植等）和治疗效果评估的重要依据
3
评估方法是弱化了“肺功能”在慢阻肺诊治中的作用？NO！
支气管扩张剂后FEV1/FVC的值介于0.6-0.8建议复测以明确诊断
4
急性加重史仍是评估未来急性加重风险
最佳的预测因子
GOLD 2011-2016：患者自身的急性加重史是未来急性加重的最佳的预测因子
LABAs 和LAMAs 联合治疗比单独使用（A 类证据）或ICS/LABA（B 类证据）减少急性加重。
对于有急性加重史的中度至极重度慢阻肺患者而言，ICS 联合LABA 治疗改善肺功能、健康状况和降低急性重比二者单药治疗更有效（A 类证据）
在LABA/ICS 的基础上联合LAMA 可以改善肺功能和患者报告结局，尤其是急性加重的风险
ISOCOM OPTOCOUPLER SELECTION GUIDE
OPTOCOUPLER SELECTION GUIDEMicross provides distribution and value added services for all ISOCOM products sold in the USA and India.ISOCOM LIMITED FACILITIES AND CAPABILITIES ISOCOM Limited, based in the North East of England, specialises in custom packaging and hybrid assembly design with clean room manufacturing including wire bonding, die attaching and lid sealing. Our screening facilities and test capabilities include:•ATE and bench test equipment for all component parameters•High temperature handlers•High/Low temperature forcing•Die wafer probing•High magnification inspection station•Acceleration tests to 30,000G•Vibration test to MIL and DESC levels•Solderability tests•Fluorocarbon pressurisation and gross and fine leak tests•Endurance tests and environmental tests, including Temperature Cycling and various Burn-in processes•Particle Impact Noise Detector (PIND) testing•Hermetic Sealing of components•Full production equipment for Hybrid and PCB assemblies•Conceptual design to final production: components and systems•Ceramic and metal product design.We would welcome the opportunity to discuss how we can help you achieve your custom design requirements. Our contact details are set out below.CONTENTSIndex of Radiation Hard Ceramic Optocouplers 4 Ceramic Hermetically Sealed Transistor Optocouplers 6 Ceramic Hermetically Sealed AC Transistor Optocouplers9 Ceramic Hermetically Sealed High-Speed Transistor Optocouplers10 Ceramic Hermetically Sealed High Gain Optocouplers 12 Ceramic Hermetically Sealed High Gain Photon Optocouplers14 Ceramic Hermetically Sealed Zero Crossing Triac Optocouplers16 Ceramic Hermetically Sealed Linear Optocouplers16 Ceramic Hermetically Sealed Photodiode Optocoupler 17 Hermetic Optocoupler Surface Mount Options 18 Package Dimensions 19 Screening Flow MIL-PRF-19500 21 Screening Flow MIL-PRF-38534 22 Radiation Summary 23RADIATION HARD CERAMIC OPTOCOUPLERSDEVICE4N24 6 4N49 6 4N55 10 6N134 14 6N140A 12 CD500 6 CD501 6 CD650 14 CD651 14 CD750 12 CD850 10 CD5731 12 CH100 6 CH300 6 CH301A 7 CH350 14 CH370 12 CH380 10 CH390 12 CS200 7 CS201 7 CS224 7 CS249 7 CS600 14 CS700 12 CS800 10 CS801 10 CS3031 16 CS3032 16 CS3033 16 CS3041 16 CS3042 16 CS3043 16 CS3061 16 CS3062 16 CS3063 16 CS3081 16 DEVICECS3082 16 CS3083 16 CS5700 13 CSL400 16 CSM100 7 CSM120 9 CSM121 9 CSM141A 13 CSM150 17 CSM151 17 CSM160-2 13 CSM160-4 13 CSM161-2 13 CSM161-4 13 CSM162-2 13 CSM162-4 13 CSM165-2 8 CSM165-4 8 CSM166-4 8 CSM168-2 10 CSM168-4 11 CSM169-2 15 CSM169-4 15 CSM200 8 CSM452 13 CSM1200 7 CSM1224 8 CSM1600 14 CSM1601A 14 CSM1700 13 CSM1800 11 CSM1801 11 CSM2224 8 CSMR40 17 IS49 8 MC600 15 MC800 11SPACE HERITAGEAPPLICATION PARTS USED GLONASS TELECOM SATELLITE CD501/L2S, CSM165-4/L2S GLONASS “K” SATELLITE CD501/L2S GLONASS “M” SATELLITE CSM1200/L2S ALPHA MAGNETIC SPECTROMETER (ISS)CD501/L2S, CS200/L2S, CSM165-4/L2S GALILEO TELECOM SATELLITE CD501/L2S SWIR SPECTROMETER CS600/L2S AEROSPACE DIGITAL COMPUTER (ARGON)CD501/L2S E-STAR (EGYPT-SAT) SATELLITE PROGRAM CD501/L2S MOON RESOURCE SPACE PROGRAM CD501/L2S “SPEECH”CD501/L2S#30 UNIVERSAL SPACE PLATFORM SPACECRAFT CD501/L2S, CD501/L2S#30 OBZOR-O CD501/L2S, CSM165-4/L2S SPACE SYSTEM IONOZOND CSM165-4/L2S ELECTRO-L CSM165-4/L2S PANCAM EXOMARS CS249/L2S SOLAR PROBE PLUS PROGRAM CD650/L2S, CD850/L2S ICON (IONOSPHERIC CONNECTION)CS5700/L2S MOMA EXOMARS CSM100/L2S MICROSATELLITE PROPULSION SYSTEM CSM100/L2S YENISEY A1 (LUCH 4)IS49/L2S ENMAP CS600/L2S, 6N134/L2S ANGOSAT 1CD501/L2Senquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed Transistor Optocouplers, manufactured to ISO 9001:2008, with an operating temperaturerange from -55°C to +125°C(RADIATION TESTED)Part No.Functional DiagramPackage DetailsCTR (I F = 10mA) min(%)ContinuousI F max(mA) V F (I F = 10mA) max(V) BV CEO (I C = 1mA) min(V) I CEO (Dark) (V CE = 20V) max(μA)V CE Sat (I F = 10mA, I C = 2mA) max(V)Package Figure No.4N22/4N234N2435050 1.8 100 100 0.3Page 19 Fig.34N497/4N484N49350501.81001000.3Page 19 Fig.3CD500/CD50150501.51001000.22③Page 20 Fig.8CH300350151.530100 ⑥0.25 ①Page 19 Fig.1CH100/CH101150401.8701000.3 ②Please contactIsocomenquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546①I = 2mA, I= 0.2mA②I= 20mA, I= 10mA ③I= 10mA, I = 2.5mA④I = 2mA, I = 1mA ⑤ I = 1mA ⑥V = 10VCeramic Hermetically Sealed Transistor Optocouplers, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C (RADIATION TESTED)Part No.Functional DiagramPackage DetailsCTR (I F = 10mA) min(%)ContinuousI Fmax(mA)V F (I F = 10mA) max(V)BV CEO (I C = 1mA) min(V)I CEO (Dark) (V CE = 20V) max(μA)V CE (Sat) (I F = 10mA, I C = 2mA) max(V)Package Figure No.CH301A350151.530100++0.25 ①Page 19 Fig.1CS200/CS201100501.8 70100 0.3 ③ Page 20 Fig.10CS224350501.8 1000.1 0.3 ③ Page 20 Fig.10CS249200501.8701000.22 ②Page 20 Fig.10CSM100/CSM101350 40 1.6 70 100 0.22 ② Page 19 Fig.4CSM1200350 50 1.8 100 100 0.3 ② Page 20 Fig.6enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546①I= 2mA, I= 0.2mA ②I= 20mA, I= 10mA ③I= 10mA, I= 2.5mA④ I= 2mA, I= 1mA ⑤ I = 1mA ⑥V = 10VCeramic Hermetically Sealed Transistor Optocouplers, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C (RADIATION TESTED)Part No.Functional DiagramPackage DetailsCTR (I F = 10mA) min(%) Continuous I F max(mA)V F(I F = 10mA) max(V)BV CEO (I C = 1mA) min(V)I CEO (Dark) (V CE = 20V) max(μA)V CE (Sat) (I F = 10mA, I C = 2mA) max (V)Package Figure No.CSM1224350501.8 1000.10.3 ②Page 20 Fig.6CSM165-2350501.6100 0.10.22 ② Page 20 Fig.7CSM165-4350501.6100 0.10.22 ② Page 20 Fig.7CSM166-2/CSM166-4100+101.8 500.10.3 ④ Page 20 Fig.8CSM200350501.4 1000.10.22 ② Page 20 Fig.6CSM2224350501.8 1000.1 0.3 ② Page 20 Fig.6IS4935050 1.8 701000.22 ②Page 20 Fig.6enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed AC Transistor Optocoupler, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C (RADIATION TESTED)Part No.Functional DiagramPackage DetailsCTR (I F =10mA) min(%)BV CEO (I C = 1mA) min(V)V F(I F = 10mA) min(V)Transition Times (R L = 100Ω) PackageFigure No.t r max(μS) t f max(μS)CSM120200 40 1.8 2020Page 19 Fig.4CSM121200 40 1.8 20 20 Page 20 Fig.6enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed High Speed Optocouplers, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C (RADIATION TESTED)Part No.FunctionalDiagramPackageDetailsCTR (I F = 16mA) min(%)ContinuousI F max(mA)V F(I F = 16mA) max(V)BW (R L = 100Ω) typ(MHz)Propagation Delay Times(R L = 1.9KΩ,V CC = 5V, I F = 16mA) PackageFigure No.t PHL max (μS) t PLH max (μS)4N55920 1.7 3 2.06.0Page 20 Fig.8CD850typ 1720 1.7 3 0.8 0.8 Page 20 Fig.9CH380typ 1720 1.7 3 0.8 0.8 Page 19 Fig.2CS800920 typ 1.45 ❑ 2 typ 0.5 ☐ typ 0.5 ☐ Page 20 Fig.9CS8011520 typ 1.45 ❑ 2 typ 0.5 ☐ typ 0.5 ☐ Page 20 Fig.9CSM168-2920 1.7 3 typ 0.1 typ 0.3 Page 20 Fig.7☐ R L = 8.2kΩ ❑I F = 20mAenquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed High Speed Optocouplers, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C(RADIATION TESTED)Part No.Functional DiagramPackage DetailsCTR (I F = 16mA) min(%)Continuous I F max(mA) V F(I F = 16mA) max(V)BW(R L = 100Ω) typ(MHz)Propagation Delay Times(R L = 1.9KΩ,V CC = 5V, I F = 16mA) PackageFigure No.t PHL max (μS) t PLH max (μS)CSM168-4920 1.7 3 typ 0.1 typ 0.3 Page 20 Fig.7CSM1800/CSM1801typ 1720 1.7 2 0.8 0.8 Page 20 Fig.6CSM1801typ 1720 1.7 2 0.8 0.8 Page 20 Fig.6MC800920 1.7 2 0.8 0.8 Page 20 Fig.7enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed High Gain Optocouplers, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C(RADIATION TESTED)Part No.FunctionalDiagramPackageDetailsCTR (I F = 1.6mA) min(%)ContinuousI F max(mA)V F(I F = 1.6mA) max(V)Data Rate typ(Kb/s)Propagation Delay Times,(R L = 680Ω, V CC = 5V, I F = 5mA) Package Figure No.t PHL max (μS)t PLH max (μS)6N140A200101.7100 1260Page 20 Fig.8CD5731200101.7100 12 60 Page 20 Fig.9CD750200101.7100 12 60 Page 20 Fig.9CH37020081.9100 12 60 Page 19 Fig.2CH390200101.9100 12 60Please contact ISOCOMCS700200101.7100 10 60 Page 20 Fig.9enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Part No.Functional DiagramPackage DetailsCTR (I F = 1.6mA) min(%)ContinuousI F max(mA)V F(I F = 1.6mA) max(V)Data Rate typ(Kb/s)V CC = 5V, I F = 5mA) Package Figure No.t PHL max(μS)t PLH max(μS)CS5700300101.7100 1060Page 20 Fig.9CSM141A300101.7700 5 20 Page 20 Fig.6CSM160-2/ CSM161-2/CSM162-2200101.7100 5 60 Page 20 Fig.7CSM160-4/ CSM161-4/CSM162-4200101.7100 5 60 Page 20 Fig.7CSM1700200101.7700 12 60 Page 20 Fig.6CSM452100010 ❒1.4100 12 60 Page 19 Fig.4❒ I F = 10mAenquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Part No.Functional DiagramPackage DetailsCTR (I F = 10mA) min(%)ContinuousI Fmax(mA)V F(I F = 20mA) max(V)Data Rate typ(Kb/s)V CC = 5V, I F = 13mA) Package Figure No.t PHL max(ns)t PLH max(nS)6N13410020 1.9 10 9090Page 20 Fig.8CD650/CD651100 ♓201.910 100 90 Page 20 Fig.9CH350100 151.910 200 200 Page 19 Fig.2CS600100 ♓201.910 75 75 Page 20 Fig.9CSM1600100 201.910 300 ♦ 1400 ♦ Page 20 Fig.6CSM1601A100 20 1.9 10 300 ♦ 1400 ♦ Page 20 Fig.6♦ R L = 350Ω, V CC = 5V, I F = 7.5mA, CL= 15pF R L = 350Ω, V CC = 5V, I F = 13mA, CL= 15pF ♓ I F = 5mA ❒enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed High Gain Photon Optocouplers, manufactured to ISO 9001:2008 with an operatingtemperature range from -55°C to +125°C(RADIATION TESTED)Part No.Functional DiagramPackage DetailsCTR (I F = 10mA) min(%)ContinuousI F max(mA)V F(I F = 20mA) max(V)Data Rate typ(Kb/s)Propagation Delay Times (R L = 510Ω, C L = 15pF, V CC = 5V, I F = 13mA) Package FigureNo.t PHL max(ns) t PLH max(nS)CSM169-210020 1.9 10 200200Page 20 Fig.7CSM169-4100201.910 200 200 Page 20 Fig.7MC600100201.910 300 300 Page 19 Fig.3enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Dual channel versions also available. Please contact us for more information.Ceramic Hermetically Sealed Zero Crossing Triac Optocouplers, manufactured to ISO 9001:2008 with an operatingtemperature range from -55°C to +125°CPart No.Functional Diagram Package DetailsV DRM (I DRM = 100nA)min(V)Continuous I F max(mA)V F (I F = 30mA) max(V)I FT(Main Terminal Voltage = 3V) max(mA)dv/dt (C) typ(V/µs)Package Figure No.CS3031/ 32/33250 60 1.8 15 / 10 / 5 2000Page 20 Fig.10CS3041/ 42/43 400 60 1.7 15 / 10 / 5 2000 CS3061/ 62/63 60060 1.5 15 / 10 / 5 1500 CS3081/ 82/83800601.515 / 10 / 51500Ceramic Hermetically Sealed Linear Optocouplers, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C (RADIATION TESTED)Part No.Functional DiagramPackage DetailsBV R(I R = 100μA) typ(V)V F(I F = 10mA) max(V)Transfer Gain (I F = 10mA, V R = 15V)Typ()Transition times (R L = 50Ω, I F = 10mA)max(μS) PackageFigure No.t rt fCSL400D200 1.8 1.0 2 2 Page 20 Fig.9CSL400L200 1.8 1.0 2 2 Page 19 Fig.5enquiries, or further information, please contact our sales office at:ISOCOM Limited • 2 Fern Court • Bracken Hill Business Park • Peterlee • County Durham • SR8 2RR • United KingdomEmail:***************.com•Tel:+44(0)1914166546Ceramic Hermetically Sealed MOSFET Optocoupler, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°CPart No.Functional DiagramPackage DetailsI F max(mA)R(ON)(I F = 10mA, I O = 500mA,t p ≤ 30ms) V F(I F = 10mA) max(V)I O (OFF) (V F = 0.6V, V O = 90V) max(µA)Turn On/Off times (I F = 10mA, V DD = 28V,I O = 800mA) Package Figure No.A typ(Ω)B typ(Ω)t ON max(ms) t OFF max(ms)CSMR40200.8 0.2 1.7 10 6.0 0.25Page 20 Fig.9Ceramic Hermetically Sealed Photodiode Optocoupler, manufactured to ISO 9001:2008 with an operating temperaturerange from -55°C to +125°C (RADIATION TESTED)Part No.Functional DiagramPackage DetailsI D (V R = 5v, R L = 1MΩ) typ(μA)BV R (I R = 1mA) min(V)Transition Times (R L = 3.3KΩ, I F 10mA)CTR (I F = 10mA, V OUT = 5) typ(%)Package Figure No.t rtyp(nS) t ftyp(nS)CSM150100200 200 200 1.56Page 19 Fig.4CSM1511002002002001.56Page 19 Fig.5DIP PACKAGE OPTIONSOption Description10Surface mountable hermetic optocoupler with leads trimmed for butt joint assembly. This option is available on commercial hi-rel product in 8 and 16 pin DIP0.51 (0.02)M in2.29 (0.09)2.79 (0.11)0.51 (0.02)M a x1.14 (0.045)1.40 (0.055)4.32 (0.17)M a x0.51 (0.2)M in 2.29 (0.09)2.79 (0.11)0.51 (0.02)M a x1.14 (0.045)1.40 (0.055)4.32 (0.17)M a x0.2 (0.008)0.33 (0.013)7.36 (0.29)7.87 (0.31)Fig. 1 8 and 16 pin DIP trimmed for butt joint assembly20 Solder Dip Option30Surface mountable hermetic optocoupler with leads cut and bent for gull wing assembly. This option is available on commercial and hi-rel product in 8 and 16 pin DIP.0.51 (0.02)M in 2.29 (0.9)2.79 (0.11)0.51 (0.02)M a x1.4 (0.055)1.65 (0.065)4.57 (0.18)M a x0.51 (0.02)M in 2.29 (0.09)2.79 (0.11)0.51 (0.02)M a x1.4 (0.055)1.65 (0.065)4.57 (0.18)M a x 9.65 (0.38)9.91 (0.39)0.2 (0.008)0.33 (0.013)4.57 (0.18)M a x5 d egM axFig. 2 8 and 16 pin DIP with leads cut and bent for gull wing assembly60Surface mountable hermetic optocoupler with leads trimmed for butt joint assembly. This option is available on commercial hi-rel product in 8 and 16 pin DIP0.51 (0.02)Min2.29 (0.09)2.79 (0.11)1.14 (0.045)1.25 (0.049)0.2 (0.008)0.33 (0.013)7.36 (0.29)7.87 (0.31)3.81 (0.15)Min0.51 (0.02)Min 2.29 (0.09)2.79 (0.11)1.02 (0.04)Typ3.81 (0.15)MaxFig. 3 8 and 16 pin DIP with leads trimmed for butt joint assemblyPACKAGE DIMENSIONSFigure 1: 4/5 Pin HybridFigure 2: 5 Pin Hybrid ArrayFigure 3: 6 Metal CanFigure 4: 4 Pin LCCFigure 6: 6 Pin LCCFigure 7: 16 Pin Flat PackFigure 8: 16 Pin DIPFigure 9: 8 Pin DIPFigure 10: 6 Pin DIPSCREENING FLOW MIL-PRF-19500SCREENING FLOW MIL-PRF-38534ISOCOM LIMITED RADIATION SUMMARY ON OPTOCOUPLERSTOTAL IONIZATION DOSE TESTED Up to 1 Mrad(si)DISPLACEMENT DAMAGE TESTED 1 MeV X 10¹²NEUTRON TESTED Transistors – 1.00E + 11High Speed – 3.00E + 12High Gain – 3.00E +12High Gain Photon – 1.00E + 13Normalized CTR versus the radiation level for the IS49 Transistor optocouplerMicross provides distribution and value added servicesfor all ISOCOM products sold in the USA and India.。
propoxycarbazone
EUROPEAN COMMISSIONHEALTH & CONSUMER PROTECTION DIRECTORATE-GENERALDirectorate E – Food Safety: plant health, animal health and welfare, international questionsE1 - Plant healthPropoxycarbozoneSANCO/4067/2001-Final30 September 2003COMMISSION WORKING DOCUMENT - DOES NOT NECESSARILY REPRESENTTHE VIEWS OF THE COMMISSION SERVICESReview report for the active substance propoxycarbazoneFinalised in the Standing Committee on the Food Chain and Animal Health at its meeting on3 October 2003 in view of the inclusion of propoxycarbazone in Annex I of Directive91/414/EEC.1. Procedure followed for the evaluation processThis review report has been established as a result of the evaluation of the new active substancepropoxycarbazone, made in the context of the work provided for in Articles 5 and 6 of Directive91/414/EEC concerning the placing of plant protection products on the market, with a view tothe possible inclusion of this substance in Annex I to the Directive.In accordance with the provisions of Article 6(2) of Directive 91/414/EEC, the Germanauthorities received on25 January 2000 an application from Bayer AG (now BayerCropScience), hereafter referred to as the applicant, for the inclusion of the active substancepropoxycarbazone in Annex I to the Directive. The German authorities indicated to theCommission on 10 March 2000 the results of a first examination of the completeness of thedossier, with regard to the data and information requirements provided for in Annex II and, for atleast one plant protection product containing the active substance concerned, in Annex III to theDirective. Subsequently, and in accordance with the requirements of Article 6(2), a dossier onpropoxycarbazone was distributed to the Member States and the Commission.The Commission referred the dossier to the Standing Committee on the Food Chain andAnimal Health in the meeting of the working group ‘legislation’ thereof on10 March 2000,during which the Member States confirmed the receipt of the dossier.In accordance with the provisions of Article 6(3), which requires the confirmation at Communitylevel that the dossier is to be considered as satisfying, in principle, the data and informationrequirements provided for in Annex II and, for at least one plant protection product containingthe active substance concerned, in Annex III to the Directive and in accordance with theprocedure laid down in Article 20 of the Directive, the Commission confirmed in its Decision 2000/463/EC 1 of 17 July 2000 that these requirements were satisfied.Within the framework of that decision and with a view to the further organisation of the works related to the detailed examination of the dossier provided for in Article 6(2) and (4) of Directive 91/414/EEC, it was agreed between the Member States and the Commission that Germany would, as rapporteur Member State, carry out the detailed examination of the dossier and report the conclusions of its examination accompanied by any recommendations on the inclusion or non-inclusion and any conditions relating thereto, to the Commission as soon as possible and at the latest within a period of one year.Germany submitted to the Commission on26 March 2001 the report of its detailed scientific examination, hereafter referred to as the draft assessment report, including, as required, a recommendation concerning the possible inclusion of propoxycarbazone in Annex I to the Directive.On receipt of the draft assessment report, the Commission forwarded it for consultation to all the Member States as well as to Bayer AG being the sole applicant on4 May 2001.The Commission organised further an intensive consultation of specialised scientific experts from a representative number of Member States, to review the draft assessment report and the comments received thereon (peer review), in particular on each of the following disciplines :- identity and physical /chemical properties ;- fate and behaviour in the environment ;;- ecotoxicology- mammalian toxicology ;- residues and analytical methods ;questions.- regulatoryThe meetings for this consultation were organised on behalf of the Commission by the Pesticide Safety Directorate (PSD) in York, United Kingdom, from November 2001 to July 2002.The report of the peer review (i.e. full report) was circulated, for further consultation, to Member States and the sole applicant on 11 October 2002.The dossier, draft assessment report and the peer review report (i.e. full report) including in particular an outline resumé of the remaining technical questions, were referred to the Standing Committee on the Food Chain and Animal Health, and specialised working groups of this Committee, for final examination, with participation of experts from the 15 Member States. This final examination took place from March to October 2003, and was finalised in the meeting of the Standing Committee on 3 October 2003.The present review report contains the conclusions of this final examination; given the importance of the draft assessment report, the peer review report (i.e. full report) and the comments and clarifications submitted after the peer review as basic information for the final examination process, these documents are considered respectively as background documents A, B and C to this review report and are part of it.These review did not reveal any open question, which would have required the consultation of the Scientific Committee on Plants.2. Purposes of this review reportThis review report, including the background documents and appendices thereto, have been developed and finalised in support of the Directive 2003/119/EC2 concerning the inclusion of propoxycarbazone in Annex I to Directive 91/414/EEC, and to assist the Member States in decisions on individual plant protection products containing propoxycarbazone they have to take in accordance with the provisions of that Directive, and in particular the provisions of article 4(1) and the uniform principles laid down in Annex VI.This review report provides also for the evaluation required under Section A.2.(b) of the above mentioned uniform principles, as well as under several specific sections of part B of these principles. In these sections it is provided that Member States, in evaluating applications and granting authorisations, shall take into account the information concerning the active substance in Annex II of the directive, submitted for the purpose of inclusion of the active substance in Annex I, as well as the result of the evaluation of those data.In parallel with the provisions of Article 7(6) of Regulation 3600/92 for existing active substances, the Commission and the Member States will keep available or make available this review report for consultation by any interested parties or will make it available to them on their specific request. Moreover the Commission will send a copy of this review report (not including the background documents) to the applicant.The information in this review report is, at least partly, based on information which is confidential and/or protected under the provisions of Directive 91/414/EEC. It is therefore recommended that this review report would not be accepted to support any registration outside the context of Directive 91/414/EEC, e.g. in third countries, for which the applicant has not demonstrated possession of regulatory access to the information on which this review report is based.3. Overall conclusion in the context of Directive 91/414/EECThe overall conclusion from the evaluation is that it may be expected that plant protection products containing propoxycarbazone will fulfil the safety requirements laid down in Article 5(1)(a) and (b) of Directive 91/414/EEC. This conclusion is however subject to compliance with the particular requirements in sections 4, 5, 6 and 7 of this report, as well as to the implementation of the provisions of Article 4(1) and the uniform principles laid down in Annex VI of Directive 91/414/EEC, for each propoxycarbazone containing plant protection product for which Member States will grant or review the authorisation.Furthermore, these conclusions were reached within the framework of the uses which were proposed and supported by the main data submitter and mentioned in the list of uses supported by available data (attached as Appendix IV to this Review Report).Extension of the use pattern beyond those described above will require an evaluation at Member State level in order to establish whether the proposed extensions of use can satisfy the requirements of Article 4(1) and of the uniform principles laid down in Annex VI of Directive 91/414/EEC.4. Specific conclusions which are highlighted in this evaluation4.1 Residues of propoxycarbazone in foodstuffsThe review has established that the residues arising from the proposed uses, consequent on application consistent with good plant protection practice, have no harmful effects on human or animal health. The Theoretical Maximum Daily Intake (TMDI) for a 60 kg adult is0,26% of the Acceptable Daily Intake (ADI), based on the FAO/WHO European Diet (August 1994). This low intake value reflects the current limited use pattern for this active substance.4.2 Exposure of operators, workers and bystandersThe review has identified acceptable exposure scenarios for operators, workers and bystanders, which require, however, confirmation for each plant protection product in accordance with the relevant sections of the above mentioned uniform principles.Ecotoxicology4.3The review has also concluded that under the proposed and supported conditions of use there are no unacceptable effects on the environment, as provided for in Article 4 (1) (b) (iv) and (v) of Directive 91/414/EEC, provided that certain conditions are taken into account as detailed in section 7 of this report.5. Identity and Physical/chemical propertiesThe main identity and the physical/chemical properties of propoxycarbazone are given in Appendix I.The active substance shall have a minimum purity of974g/kg technical product (based on a pilot plant production).The review has established that for the active substance notified by the applicant (Bayer AG), none of the manufacturing impurities considered are, on the basis of information currently available, of toxicological or environmental concern.6. Endpoints and related informationIn order to facilitate Member States, in granting or reviewing authorisations, to apply adequately the provisions of Article 4(1) of Directive 91/414/EEC and the uniform principles laid down in Annex VI of that Directive, the most important endpoints as identified during the evaluation process are listed in Appendix II.7. Particular conditions to be taken into account on short term basis by Member States in relation to the granting of authorisations of plant protection products containing propoxycarbazoneOn the basis of the proposed and supported uses, the following particular issues have been identified as requiring particular and short term (within 12 months at the latest) attention from the Member States, in the framework of any authorisations to be granted, varied or withdrawn, as appropriate:In this overall assessment Member States- should pay particular attention to the potential of propoxycarbazone and its metabolites for groundwater contamination, when the active substance is applied in regions with vulnerable soil and/or climate conditions;- should pay particular attention to the protection of aquatic ecosystems, especially of aquatic plants.Risk mitigation measures should be applied where appropriate.8. List of studies to be generatedNo further studies were identified which were considered at this stage, and under the current inclusion conditions necessary in relation to the inclusion of propoxycarbazone in Annex I.9. Updating of this review reportThe technical information in this report may require periodic updating to take account of technical and scientific developments as well as of the results of the examination of any information referred to the Commission in the framework of Articles 7, 10 or 11 of Directive 91/414/EEC. Such adaptations will be examined and finalised in the Standing Committee on the Food Chain and Animal Health, in connection with any amendment of the inclusion conditions for propoxycarbazone in Annex I of the Directive.APPENDIX IIdentity, physical and chemical propertiesPROPOXYCARBAZONECommon name (ISO) Propoxycarbazone (The given data belong to thesodium salt Propoxycarbazone-sodium if not specifiedotherwise)MKH 65 61Development Code (for new activesonly)Chemical name (IUPAC) parent2-(4,5-dihydro-4-methyl-5-oxo-3-propoxy-1H-1,2,4-triazol-1-yl)carboxamidosulfonylbenzoicacid-methylestersodium saltsodium (4,5-dihydro-4-methyl-5-oxo-3-propoxy-1H-1,2,4-triazol-1-ylcarbonyl)(2-methoxycarbonylphenylsulfonyl)azanideChemical name (CA) parentmethyl 2-[[[(4,5-dihydro-4-methyl-5-oxo-3-propoxy-1H-1,2,4-triazol-1-yl)carbonyl]amino]sulfonyl]benzoatesodium saltbenzoic acid, 2-[[[4,5-dihydro-4-methyl-5-oxo-3-propoxy-1H-1,2,4-triazol-1-yl)carbonyl]amino] sulfonyl]-, methyl ester,sodium saltCIPAC No 655 (parent); 655.011 (sodium salt)CAS No 145026-81-9 (parent); 181274-15-7 (sodium salt)EEC No not assignedFAO SPECIFICATION not availableMinimum purity 974 g/kgMolecular formula C15H18N4O7S (parent); C15H17N4NaO7S (sodium salt) Molecular mass 398.4 g/mol (parent); 420.4 g/mol (sodium salt)Structural formulaMelting point 230 – 240 °C,the melting occurs under decompositionBoiling point Not measurable, decomposition at 230 – 240 °C Appearance odourless and colourless crystalline powder (PAS, TAS) Relative density 1.42 g/cm³ at 20°CVapour pressure Cannot be determined directly due to its extreme low value;upper limit: < 9 ⋅ 10-8 Pa at 70 °C< 1 ⋅ 10-8 Pa at 20 °C (extrapolated)Henry's law constant < 1 ⋅ 10-10 Pa m3 mol-1 at 20 °C (calculated)Solubility in water (g/L) pH 8.8: 42 (unbuffered)pH 9.0: 42pH 7.2: 42pH 4.5: 2.9Solubility in organic solvents (g/L) n-heptane < 0.1xylene < 0.10.11-octanol <2-propanol <0.1ethyl acetate < 0.1polyethylen glycol 5.2acetonitrile 0.90acetone 0.50dichloromethane 1.5dimethylsulfoxide 190Partition co-efficient (log P ow) pH 9: - 1.59pH 7: - 1.55pH 4: - 0.30Hydrolytic stability (DT50) Stable at 25 ° C at pH 4 –9Dissociation constant The free acid of the sodium salt is produced by protonationof the active substance under acidic conditions.It has a pKa-value of 2.1 in aqueous solutions.Quantum yield of direct photo-Φ = 0.75transformation in water at λ >290nmFlammability Not highly flammable in the sense of EU guideline A.10.Does not undergo spontaneous combustion in the sense ofEU guideline A.16 and in 1L BCC-Test.Explosive properties Not explosive in the sense of EU guideline A.14UV/VIS absorption (max.) 230 nmPhotostability in water (DT50) DT50 18.1 days (phenyl-labelled)DT50 40.9 days (triazolinone-labelled)23 June 2003APPENDIX IIEND POINTS AND RELATED INFORMATIONPROPOXYCARBAZONE1 Toxicology and metabolismAbsorption, distribution, excretion and metabolism in mammalsRate and extent of absorption: Rapid but incomplete absorption (25 – 30 %) within48 hoursDistribution: Widely distributed, highest residues in the liverPotential for accumulation: No evidence for accumulationRate and extent of excretion: Rapid and nearly complete excretion (>88 % of theadministered dose within 48 hours) primarily via faeces(>66 %)Toxicologically significant compounds: Parent compound, plant metabolite 2-hydroxypropoxyMKH 6561 (M01) was not of greater toxicologicalsignificance than parentMetabolism in animals: Limited metabolism: unchanged parent compound in urine(>90 %) and faeces (>80 %); metabolism via cleavage ofthe amide bond, sulfonamide methylester (M05),sulfonamide acid (M06) and saccharin (M07)Acute toxicityRat LD50 oral: > 5000 mg/kg bwRat LD50 dermal: > 5000 mg/kg bwRat LC50 inhalation: > 5.03 mg/l airSkin irritation: Non-irritantEye irritation: Non-irritantSkin sensitization (test method used andNot sensitising (M & K)result):Short term toxicityTarget / critical effect: Decreased body weight gain, increased water intake;irritation of forestomach epithelium (rats); decreased foodconsumption and relative heart weights (dog)Lowest relevant oral NOAEL / NOEL: 1yr dog: 2000 ppm (56 mg/kg bw/d)Lowest relevant dermal NOAEL / NOEL: >1000 mg/kg bw/d (rat)Lowest relevant inhalation NOAEL / NOEL:No data – not requiredGenotoxicity No genotoxic potential23 June 2003Long term toxicity and carcinogenicityTarget / critical effect: Decreased body weight gain; increased urine pH value andrenal pelvic mineralization in rats onlyLowest relevant NOAEL: 2yr rat: 1000 ppm (43 mg/kg bw/d)Carcinogenicity: No carcinogenic potentialReproductive toxicityTarget / critical effect - Reproduction: No reproductive toxicity at limit dose level (rat)Lowest relevant reproductive NOAEL /NOEL:>16000 ppm (>1000 mg/kg bw/d; rat)Target / critical effect - Developmental toxicity: Embryotxic effects (reduced fetus number, reduced fetal and placental weights, increased post-implantation loss, retarded skeletal ossification) at a maternally toxic dose (1000 mg/kg bw/d) in rabbitsLowest relevant developmental NOAEL / NOEL: Rabbit:500 mg/kg bw/d (developmental toxicity) 100 mg/kg bw/d (maternal toxicity)Delayed neurotoxicity No acute or subchronic (90-day) neurotoxicity in rats(NOAEL acute: >2000 mg/kg bw; NOAEL subchronic:>1321 mg/kg bw/d)Other toxicological studies Plant metabolite M01 has a very low acute oral toxicity(LD50: >5000 mg/kg bw), was not genotoxic (Ames-Test, invitro chromosome aberration test Chinese hamster V79cells), and caused no effects in the rat after subacutefeeding of 10000 ppmMedical data Limited data (new compound); no human health problemsobservedSummaryValueStudySafetyfactor ADI: 0.4 mg/kg bw Rat, 2yr study 100AOEL systemic: 0.3 mg/kg bw/day Rabbit,developmentalstudy (approx. oralabsorption rate25%)100ARfD (acute reference dose): Not allocated Not necessaryDermal absorption10 % default value (due to physical and chemicalproperties)14 April 2003 2 Fate and behaviour in the environment2.1 Fate and behaviour in soilRoute of degradationAerobic:Mineralization after 100 days: phenyl-label:9.1 to 41.9 % (88-98d); 21.7 to 49.0% (180-361d)(n=4)triazolinone-label:1.3 to 8.9 % (93-117d);2.6 to 12.6 % (182 –365d)(n=4)Non-extractable residues after 100 days: phenyl-label:6.5 to 29.5 % (88-98d); 8.2 to 28.3 % (180-361d)(n=4)triazolinone-label:8.9 to 64.9 %(93-117d); 17.9 to 65.7 % (182-365d)(n=4)Major metabolites above 10 % of applied active substance: name and/or code% of applied rate (range and maximum) sulfonamide methyl ester (M05):Range: <10 % at day 100, max. 20.9 % (day 6) saccharin (M07):Range: 17.3 % at day 100 in 1 soil, max. 26.7 % (day 14)4-Hydroxy saccharin (M08):Range: 9.3 to 18.1 % at day 100, max. 19.5 % (day 36)N-methyl propoxy triazolinone amide (M09): Range: <10 % at day 100, max. 13.2 % (day 253)N-methyl propoxy triazolinone (M10):Range: 12.6 to 34.3 % at day 100, max. 55.2 % (day 182)Supplemental studiesAnaerobic:not required, application in springSoil photolysis:stable to photolysisRemarks:noneRate of degradationLaboratory studiesDT50lab (20 °C, aerobic): DT50lab (20°C, aerobic): propoxycarbazone-sodium:14 April 2003range: 22.8 – 98.8 (220.4*) d (n = 8), 1st order,median: 60.6 d, r²: 0.818 – 0.997,DT50calc (20°C, aerobic): sulfonamide methyl ester(M05):3.0 - 22.3 d(n = 3), 1st order, median: 3.1, r²: 0.898 - 1DT50calc (20°C, aerobic): saccharin (M07):5 - 57 d(n = 3), 1st order, median: 27.3, r²: 0.909 - 1DT50lab (20°C, aerobic): 4-Hydroxy saccharin (M08):178.4 d (r²:0.899), 185.5 d (r²:0.838), 953.8* d(r²:0.227) 1st order (n = 3),DT50lab (20°C, aerobic): N-methyl propoxy triazolinoneamide (M09):83.8 d (r²:0.777), 90.1 d (r²:0.855), >>1 year*(r²:0.025), 1st order (n = 3)DT50lab+calc (20°C, aerobic): N-methyl propoxytriazolinone (M10):38.7 - 75.6 d, 1st order (n = 3)* soil with low microbial activity (not representative) DT90lab (20 °C, aerobic): DT90lab (20°C, aerobic): propoxycarbazone-sodium:range: 76 – 328 (733*) d [n = 8], r²: 0.818 -.0.997,1st order, median: 202 d* soil with low microbial activity (not representative) DT50lab (10 °C, aerobic): DT50lab (10°C, aerobic): calculated from lab (20 °C):50.2 – 217.4 d (485* d), median 133 d (n = 8), 1storder* soil with low microbial activity (not representative)3 field trials with average temperatures ~10 °C in the firweeks after application showed DT50 between 4.9 and20 daysDT50lab (20 °C, anaerobic): DT50lab (20°C, anaerobic): not requiredField studies (country or region)DT50f from soil dissipation studies: DT50f: Southern Europe (France): 2.7 / 9.1d, √1st order[n = 2], recalc. 1st order: 12 and 37 dNorthern Europe (Germany, France, UK): 6.6 - 21.0 d,1st order [n = 4] and 4.9 d √1st order [n = 1], recalc. 1storder: 9.1 dDT50 (total residues):DT50f: Southern Europe (France): 15–29 dDT50f: Northern Europe (Germany, France, UK):12–56 dDT90f from soil dissipation studies: DT90f: Southern Europe (France): 30 / 101 d, √1storder [n = 2], recalc. 1st order: 40 and 123 dNorthern Europe (Germany, France, UK): 22 - 71 d, 1st4] and 54 d √1st order [n = 1], recalc. 1st order: 49 d14 April 2003Soil accumulation studies: not requiredSoil residue studies: Not requiredRemarks:e.g. effect of soil pH on degradation ratenoneAdsorption/desorptionK f / K oc:K d:pH dependence: K oc: propoxycarbazone-sodium:12.9 –106.2 L/kg [n=5], median: 28.8 L/kg sulfonamide methyl ester (M05):K oc: 35 L/kg (column leaching study), 71.1 L/kg (calculated, PCKOCWIN)saccharin (M07):K oc: 4.6 to 15.5 L/kg [n = 5], median: 5.2 L/kg4-Hydroxy saccharin (M08):K oc: 456.9 to 2872.7 L/kg [n = 5], median: 2033.8 L/kg N-methyl propoxy triazolinone amide (M09):K oc: 10.4 to 551.5 L/kg [n = 5], median: 99.9 L/kgN-methyl propoxy triazolinone (M10):K oc: 8.9 to 75.5 L/kg [n = 5], median: 20.6 L/kgpropoxycarbazone-sodium:K d: 0.22 – 1.7. L/kg [n = 5]sulfonamide methyl ester (M05):0.161 L/kg (column leaching study)saccharin (M07):K d: 0.02 to 0.25 L/kg [n = 5]4-Hydroxy saccharin (M08):K d: 7.5 to 46.3 L/kg [n = 5]N-methyl propoxy triazolinone amide (M09):K d: 0.26 to 3.90 L/kg [n = 5]N-methyl propoxy triazolinone (M10):K d: 0.22 to 1.22 L/kg [n = 5]propoxycarbazone-sodium, M05, M07, M08, M09,M10: noMobilityLaboratory studies:Column leaching: not requiredAged residue leaching: Loamy sand (80 % sand, 4 % clay, 0.5 % C org), ageingtime 28 d (phenyl-label) and 29 d (triazolinone-label),irrigation 508 mm, incubation at 20 °C and FC in the14 April 2003darkleachates contained 85.8 % (phenyl-label) and 89.0 %(triazolinone-label) of the applied radioactivity, containin76.5 % propoxycarbazone-sodium, 3.1 - 3.6 % carboxyacid (M04), 0.8 % sulfonamide acid (M06), 4.3 % sacch(M07) and 7.9 % N-methyl propoxy triazolinone (M10).Sulfonamide methyl ester (M05) and N-methyl propoxytriazolinone amide (M09) were not detectedField studies:Lysimeter/Field leaching studies: 70 g as/ha, spring application, 2 lysimeters over 3years, single application in year 1 and 2annual average concentration in leachate (µg/l):propoxycarbazone-sodium: 0.009, 0.004, 0.002N-methyl propoxy triazolinone(M10):0.002,0.018,0007total radioactive residue: 0.061, 0.057, 0.049maximum concentration in leachate (µg/l):propoxycarbazone-sodium: 0.02N-methyl propoxy triazolinone(M10): 0.04total radioactive residue: 0.099Remarks: under vulnerable conditions,propoxycarbazone-sodiumand N-methyl propoxy triazolinone (M 10) might leachinto ground water14 April 2003 2.2 Fate and behaviour in waterAbiotic degradationHydrolytic degradation: pH 4: stable (25°C)pH 7: stable (25°C)pH 9: stable (25°C)Major metabolites: nonePhotolytic degradation: phenyl label: propoxycarbazone-sodium: DT50: 18.1 dtriazolinone label: propoxycarbazone-sodium: DT50: 40. Major metabolites: metabolite saccharin (M07): 22 % of TAR (day 19, endof study)metabolite N-methyl propoxy triazolinone (M10): 13.6 %TAR (day 19, end of study)Biological degradationReadily biodegradable: not required (see water sediment study)Water/sediment study:DT50 water:DT90 water:DT50 whole system:DT90 whole system:Distribution in water / sediment systems (active substance)Distribution in water / sediment systems (metabolites) 10.6 and 90.8 d35.4 and 302.0 d12.0 and 189.0 d39.9 and 627.0 dwater: 97 - 97.9 % AR (0 d)0.7 - 47.2 % AR after 100 dsediment: max. 18.2 % AR (3 d) - 21.4 % AR (100 d) 0.2 - 21.4 % AR after 100 dcarboxylic acid (M04)water: max. 0.1 % AR (30 d) - 50.2 % AR (30 d)0.1 - 34.6 % AR after 100 dsediment: max. 0.0 % AR (0-100 d) - 19.3 % AR (62d)0.0 - 13.2 % AR after 100 dsulfonamide acid (M06)water: max. 1.6 % AR (100d) - 16.2 % AR (100d) sediment: max. 0 (0-100 d)- 3.2 % AR (100d)N-methyl propoxy triazolinone (M10)water: max. 3.1 % AR (100 d) - 21.2 % AR (100 d) 3.1 - 21.2 % AR after 100 dsediment: max. 3.8 % AR (100 d) - 13.2 % AR (100 d) 3.8 - 13.2 % AR after 100 d14 April 2003 Degradation in the saturated zone degradation in the saturated zone: not required Remarks: none14 April 2003 2.3 Fate and behaviour in airVolatilityVapour pressure: Cannot be determined directly due to its extreme lowvalue; upper limit: < 9 ⋅ 10-8 Pa at 70 °C< 1 ⋅ 10-8 Pa at 20 °C (extrapolated)Henry's law constant: < 1 ⋅ 10-10 Pa m3 mol-1 at 20 °C (calculated)Photolytic degradationDirect photolysis in air: no dataPhotochemical oxidative degradation in air DT50: Calculations according to Atkinson (AOPWin 1.75): t½: 4.5 h (c OH = 0.5 · 106 cm-3, 24 h day)Volatilisation: from plant surfaces: < 10 % within 24 hoursfrom soil: < 10 % within 24 hours Remarks: no short or long range transport expected14 April 20033 EcotoxicologyTerrestrial VertebratesAcute toxicity to mammals: LD 50 >5000 mg/kg bw (rat)Acute toxicity to birds: LD 50 >2000 mg/kg bw (bobwhite quail) Dietary toxicity to birds: LC 50 >10000 ppm (bobwhite quail)Reproductive toxicity to birds: NOEL 1250 ppm (bobwhite quail and mallard duck)Aquatic OrganismsGroup Test sub-stanceTime-scaleEnd-pointToxicity (mg/L)Laboratory testsAcute toxicity fish (LC50):O. mykiss a.s. acute (static) mortality>77.6 Long term toxicity fish (NOEC):P.promelasa.s. long-term (flow-through)Mortalit y,hatch, growth, beha-viour 105Bioaccumulation fish:Not relevant (Log P OW : 0.03) D. magna a.s. acute(stat.) mortalit y >107 D. magnaMKH 7017 (M10) acute (stat.) mortalit y >100D. magna MKH 7018 (M04) acute (stat.) mortalit y >100Acute toxicity invertebrate (EC50)D. magna STJ 4934 (M05)acute (stat.)mortalit y>100Chronic toxicity invertebrate (NOEC): D. magnaa.s. chronic (flow-through) Mortalit y,growth,reprodu ction110Acute toxicity algae (EC50):Selenastr umcapricorn utuma.s. chronic biomass 1.57。
荧光酶标仪中英文对照双版
时间分辨荧光
用于珀金埃尔默2030-0040
此配置可用于这两种类型的时间分辨荧光测量值，例如DELFIA®，涉及离解和提高和LANCE均相测定。为增强与LANCE之间的性能，它可以安装一个任选的红色敏感检测单元（光电倍增管）。
在时间分辨荧光，激发光由UV闪光氙灯（- 400纳米的光谱范围230）产生的。光通不像CW-灯轮和发射滤光器滑动那样可以改变滤波器或全轮或滑对。
1420-3050试验2.5数据分析软件包含在模型2030-0030，2030-0040和2030-0050标准，可以作为其他模型的一个选项
单盘模式
在无栈式存储器的模式中，单个微板加载到读卡器。
栈式存储器型号
在堆叠操作中，板被装入输入堆叠与所述第一板为在底部进行测量。空接纸首先安装到多标记酶标仪;它占据了左手位置。然后输入堆垛与板被装配在右侧的位置。在操作过程中，板由输入堆栈至测量位置移动一个接一个。每个板被测量后，它被移动到输出堆叠器。当测量完成时，输出堆栈器可以被删除。快速释放机构能让所述板很容易地从堆叠器排空。
闪光型发光利用分配器选项通过直接分装试剂进入板的孔中以引发反应。请参阅前面所述的分配器选择的信息。
发光法（发光法模型）
用于珀金埃尔默2030-0010
实际操作基于正常珀金埃尔默2030发光法。
振动板
该板输送机也可作为一个振动器。您可以指定多长时间，多快，什么样的幅度。再一个特征是，摇动的方式可以是直链，轨道或双轨道（8字形）。当输送机移动板到测量位置时，该板发生摇晃。
下列选项可用于所有型号：
1420-221条形码阅读器
1420-2550年...1420-2580单一分配器...4个分配器
欧盟食品中重金属限量标准中文
欧盟重金属限量标准中国SPS通报咨询中心提供一、铅1 铅Lead未加工的牛奶, 热处理的牛奶和以牛奶为原料加工的奶制品Raw milk , heat-treated milk and milk forthe man欧盟Foodstuffs listed in thiscategory as defined in2 铅Lead婴儿食品和后续食品Infant formulae and follow-on formulae欧盟The maximum level refersto the products ready to3 铅Lead牛、羊、猪和家禽肉,不包括下Meat excluding offal of bovine animals,sheep, p欧盟Foodstuffs listed in thiscategory as defined in R4 铅Lead牛、羊、猪和家禽的下水Offal of bovine animals, sheep, pig andpoultry欧盟Foodstuffs listed in thiscategory as defined in R5 铅Lead鱼的肌肉Muscle meat of fish欧盟Fish listed in this categoryas defined in categor6 铅Lead甲壳类, 不包括螃蟹的褐色肉、龙虾和大小相当的甲壳类Nephropidae and PalinurCrustaceans, excluding brown meat of craband excl欧盟Foodstuffs falling withincategory © and f of th7 铅Lead双壳类动物Bivalve molluscs欧盟Foodstuffs falling withincategory © and f of th8 铅Lead头足类动物Cephalopods without viscera欧盟Foodstuffs falling withincategory © and f of th9 铅Lead谷类、豆荚和豆科植物Cereals, legumes and pulses欧盟10 铅Lead蔬菜,不包括芸苔蔬菜、叶类蔬菜、新鲜草药和菌类,土豆的最大限量适用于去皮土豆Vegetables, excluding brassica vegetables,leaf ve欧盟The maximum levelapplies after washing ofthe fru11 铅Lead芸苔蔬菜、叶类蔬菜和食用菌Brassica vegetables, leaf vegetables andcultivate欧盟The maximum levelapplies after washing ofthe fru12 铅Lead果实,不包括浆果和小果实Fruit, excluding berries and small fruit欧盟The maximum levelapplies after washing ofthe fru13 铅Lead浆果和小果Berries and small fruit欧盟The maximum levelapplies after washing ofthe fru14 铅Lead脂肪和油,包括奶油Fats and oils, including milk fat欧盟15 铅Lead果汁,作为重新制造的浓缩果汁和果蜜Fruit juices, concentrated fruit juices asreconst欧盟Foodstuffs listed in thiscategory as defined in C16 铅Lead酒包括汽酒,不包括利口酒,苹果酒,梨酒和果酒Wine including sparkling wine, excludingliqueur欧盟Foodstuffs listed in thiscategory as defined in17 铅Lead香酒、加酒芬香的饮料和加酒芬香的鸡尾酒Aromatized wine, aromatized wine-baseddrinks and欧盟Foodstuffs listed in thiscategory as defined in二、镉1 镉Cadmium牛、羊、猪和家禽肉,不包括下水Meat excluding offal of bovine animals,sheep, p欧盟Foodstuffs listed in thiscategory as defined in R2 镉Cadmium马肉,不包括下水Horsemeat, excluding offal 6欧盟Foodstuffs listed in thiscategory as defined in R3 镉Cadmium牛、羊、猪、家禽、马肝脏Liver of bovine animals, sheep, pig,poultry and h欧盟Foodstuffs listed in thiscategory as defined in R4 镉Cadmium牛、羊、猪、家禽、马肾脏Kidney of bovine animals, sheep, pig,poultry and欧盟Foodstuffs listed in thiscategory as defined in R5 镉Cadmium鱼肉,不包括和中列出的那些鱼肉Muscle meat of fish , excluding specieslisted in欧盟Fish listed in thiscategory as defined incategor6 镉Cadmium下列鱼的肉：凤尾鱼Engraulis 种、鲣Sarda sarda、常见的Muscle meat of the followingfish :anchovy Engrau欧盟Fish listed in thiscategory as defined incategor7 镉Cadmium旗鱼的肉Xiphias gladiusMuscle meat of swordfish Xiphias欧盟Fish listed in thiscategory as defined ingladius categor8 镉Cadmium甲壳类, 不包括螃蟹的褐色肉、龙虾和大小相当的甲壳类Nephropidae andPalinurCrustaceans, excluding brown meat ofcrab and excl欧盟Foodstuffs falling withincategory © and f of th9 镉Cadmium双壳类软体动物Bivalve molluscs欧盟Foodstuffs falling withincategory © and f of th10 镉Cadmium头足类软体动物没有内脏Cephalopods without viscera欧盟Foodstuffs falling withincategory © and f of th11 镉Cadmium谷物不包括麸、酵母、小麦和大米Cereals excluding bran, germ, wheat andrice欧盟12 镉Cadmium麸、酵母、小麦和大米Bran, germ, wheat and rice欧盟13 镉Cadmium大豆Soybeans欧盟14 镉Cadmium蔬菜和水果,叶类蔬菜除外,茎类蔬菜,松子,根类蔬菜和马铃薯Vegetables and fruit, excluding leafvegetables, f欧盟The maximum levelapplies after washing ofthe fru15 镉Cadmium叶类蔬菜,新鲜中草药,食用菌和块根芹Leaf vegetables, fresh herbs, cultivatedfungi and欧盟The maximum levelapplies after washing ofthe fru16 镉Cadmium茎类蔬菜,根类蔬菜和番茄,块根芹;土豆的最大限量适用于去皮土豆Stem vegetables, root vegetables andpotatoes, exc欧盟The maximum levelapplies after washing ofthe fru三、汞1 汞Mercury渔类产品和鱼肉,不包括列的那些;最大限量也适用于甲壳类, 不包括螃蟹的褐色肉、龙虾Fishery products and muscle meat offish , excl欧盟Foodstuffs fallingwithin category © and fof2 汞Mercury下列鱼的肌肉: 华脐鱼Lophiusspecies、大西洋鲶鱼Anarhimeat of the following fish : anglerfis欧盟Fish listed in thiscategory as defined incategor四、锡1 锡Tin所有罐装食品饮料除外Canned foods other than beverages200欧盟2 锡Tin罐装饮料,包括果汁和蔬菜汁Canned beverages, including fruit juicesand veget100欧盟3 锡Tin罐装的婴儿食品和婴儿和小孩以谷类为基础加工的食品,不包括干的的和粉末类产品Canned baby foods and processedcereal-based foods50欧盟Foodstuffs listed in thiscategory as defined in C4 锡Tin罐装婴儿食品和婴儿食品的延续物包括婴儿牛奶和延续奶粉, 不包括干燥的和粉末产品Canned infant formulae and follow-onformulae inc50欧盟Foodstuffs listed in thiscategory as defined in C5 锡Tin用于特定婴儿的、特定医疗目的的罐装婴儿食品, 干燥和粉状产品除外Canned dietary foods for special medicalpurposes50欧盟Foodstuffs listed in thiscategory as defined in C。
阿尔茨海默病创新药物临床试验中国专家共识解读(最全版)
阿尔茨海默病创新药物临床试验中国专家共识解读（最全版）阿尔茨海默病（Alzheimer's disease，AD）是一种原因未明的神经退行性疾病，以渐进性记忆障碍、认知功能丧失伴日常生活能力下降和行为改变为特征，其发病率随年龄增加而不断增高[1,2]。
AD是最常见的痴呆类型，占60%～80%。
《世界阿尔茨海默病2015报告》指出，到2050年全球AD患病人数将从目前的4 680万增加至1.315亿[3]。
痴呆及相关认知功能障碍疾病已成为全社会医疗支出及经济负担的重要原因之一，是全人类面临的重大的公共卫生事件。
近年来，AD发病机制研究虽无重大突破，但诊断标准有较大革新。
如由美国神经病学、语言障碍和卒中-老年痴呆和相关疾病学会工作组（NINCDS-ADRDA）诊断标准转变和倾向于美国国家老龄问题研究所-阿尔茨海默病协会（national institute on aging-Alzheimer's Association，NIA-AA）提出的IWG-2诊断标准。
该诊断标准不仅细化了AD的临床表型，强调临床前期AD（pre-clinical AD）的识别，而且将各类生物标志物（脑脊液Aβ、APOE基因型、MRI或淀粉样蛋白PET 扫描等）整合进诊断标准中，使其更适用于临床研究[4]。
目前对AD的治疗仍以改善临床症状为主，代表药物为多奈哌齐、加兰他敏、卡巴拉汀以及美金刚[5]。
对AD具有疾病修饰作用的新药研发已逐步成为抗AD的研究热点，这些药物包括抑制Aβ斑块形成或促进Aβ清除的药物、抑制Tau蛋白纤维缠结形成和促进Tau蛋白清除的药物（如β、γ分泌酶抑制剂或α分泌酶促进剂），以及针对Aβ和Tau蛋白的单/多克隆抗体等。
近年来，几项关于AD的大型药物临床试验（如首个抗Aβ单克隆疫苗AN1792[6]、针对Aβ及纤维缠结的单克隆抗体[7,8]以及γ分泌酶抑制剂Semagacestat[9]等），因不良反应、中期评价疗效不达标等原因而宣告失败。
09年糖尿病指南
Executive Summary:Standards of Medical Care in Diabetes—2009Current Criteria for the Diagnosis of Diabetes●Fasting plasma glucose(FPG)Ն126 mg/dl(7.0mmol/l).Fasting is defined as no caloric intake for at least8h●Symptoms of hyperglycemia and a ca-sual(random)plasma glucoseՆ200 mg/dl(11.1mmol/l).Casual(random) is defined as any time of day without regard to time since last meal.The clas-sic symptoms of hyperglycemia include polyuria,polydipsia,and unexplained weight loss.●2-h plasma glucoseՆ200mg/dl(11.1 mmol/l)during an oral glucose toler-ance test(OGTT).The test should be performed as described by the World Health Organization,using a glucose load containing the equivalent of75g anhydrous glucose dissolved in water.Testing for Pre-Diabetes and Diabetes in Asymptomatic Patients ●Testing to detect pre-diabetes and type 2diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese(BMI Ն25kg/m2)and who have one or more additional risk factors for diabetes).In those without these risk factors,testing should begin at age45years.(B)●If tests are normal,repeat testing should be carried out at least at3-year inter-vals.(E)●To test for pre-diabetes or diabetes,an FPG test or2-h OGTT(75-g glucose load)or both are appropriate.(B)●An OGTT may be considered in pa-tients with impaired fasting glucose (IFG)to better define the risk of diabe-tes.(E)●In those identified with pre-diabetes, identify and,if appropriate,treat other cardiovascular disease(CVD)risk fac-tors.(B)Testing for Type2Diabetes inChildren●Test children who are overweight(BMIϾ85th percentile for age and sex,weight for heightϾ85th percentile,orweightϾ120%of ideal for height)andhave any two of the following risk fac-tors:●Family history of type2diabetes infirst-or second-degree relative●Race/ethnicity of Native American,African American,Latino,AsianAmerican,or Pacific Islander●Signs of insulin resistance or condi-tions associated with insulin resis-t a n c e(a c a n t h o s i s n i g r i c a n s,hypertension,dyslipidemia,polycys-tic ovary syndrome,or small-for-gestational-age birth weight)●Maternal history of diabetes or gesta-tional diabetes mellitus(GDM)dur-ing the child’s gestation(E)●Testing should begin at age10yearsor at onset of puberty,if puberty oc-curs at a younger age,and be re-peated every3years.(E)●FPG is the preferred test.(E)Detection and Diagnosis of GDM●Screen for GDM using risk factor anal-ysis and,if appropriate,use of anOGTT.(C)●Women with GDM should be screenedfor diabetes6–12weeks postpartumand should be followed up with subse-quent screening for the development ofdiabetes or pre-diabetes.(E)Prevention/Delay of Type2Diabetes●Patients with impaired glucose toler-ance(A)or IFG(E)should be referredto an effective ongoing support pro-gram for weight loss of5–10%of bodyweight and increasing physical activityto at least150min per week of moder-ate activity such as walking.●Follow-up counseling appears to be im-portant for success.(B)●Based on potential cost savings of diabe-tes prevention,such counseling shouldbe covered by third-party payors.(E)Glucose Monitoring●Self-monitoring of blood glucose(SMBG)should be carried out three ormore times daily for patients using mul-tiple insulin injections or insulin pumptherapy.(A)●For patients using less frequent insulininjections,noninsulin therapies,ormedical nutrition therapy(MNT)andphysical activity alone,SMBG may beuseful as a guide to the success of ther-apy.(E)●To achieve postprandial glucose tar-gets,postprandial SMBG may be appro-priate.(E)●When prescribing SMBG,ensure thatpatients receive initial instruction in,and routine follow-up evaluation of,SMBG technique and their ability to usedata to adjust therapy.(E)●Continuous glucose monitoring(CGM)in conjunction with intensive insulinregimens can be a useful tool to lowerA1C in selected adults(agedՆ25years)with type1diabetes(A).●Although evidence for A1C lowering isless strong in children,teens,andyounger adults,CGM may be helpful inthese groups.Success correlates with ad-herence to ongoing use of the device.(C)●CGM may be a supplemental tool toSMBG in those with hypoglycemia un-awareness and/or frequent hypoglyce-mic episodes.(E)A1C●Perform the A1C test at least two timesa year in patients who are meeting treat-ment goals(and who have stable glyce-mic control).(E)●Perform the A1C test quarterly in pa-tients whose therapy has changed orwho are not meeting glycemic goals.(E)●Use of point-of-care testing for A1C al-lows for timely decisions on therapychanges,when needed.(E)●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●DOI:10.2337/dc09-S006©2009by the American Diabetes Association.Readers may use this article as long as the work is properly cited,the use is educational and not for profit,and the work is not altered.See http://creativecommons.org/licenses/by-nc-nd/3.0/for details.E x e c u t i v e S u m m a r yGlycemic Goals in Adults●Lowering A1C to below or around7% has been shown to reduce microvascu-lar and neuropathic complications of type1and type2diabetes.Therefore, for microvascular disease prevention, the A1C goal for nonpregnant adults in general isϽ7%.(A)●In type1and type2diabetes,random-ized controlled trials of intensive versus standard glycemic control have not shown a significant reduction in CVD outcomes during the randomized por-tion of the trials.Long-term follow-up of the Diabetes Control and Complica-tions Trial(DCCT)and UK Prospective Diabetes Study(UKPDS)cohorts sug-gests that treatment to A1C targets be-low or around7%in the years soon after the diagnosis of diabetes is associ-ated with long-term reduction in risk of macrovascular disease.Until more evi-dence becomes available,the general goal ofϽ7%appears reasonable for many adults for macrovascular risk re-duction.(B)●Subgroup analyses of clinical trials such as the DCCT and UKPDS and the mi-crovascular evidence from the AD-VANCE(Action in Diabetes and Vascular Disease:Preterax and Diami-cron MR Controlled Evaluation)trial suggest a small but incremental benefit in microvascular outcomes with A1C values closer to normal.Therefore,for selected individual patients,providers might reasonably suggest even lower A1C goals than the general goal of Ͻ7%,if this can be achieved without significant hypoglycemia or other ad-verse effects of treatment.Such patients might include those with short dura-tion of diabetes,long life expectancy, and no significant CVD.(B)●Conversely,less stringent A1C goals than the general goal ofϽ7%may be appropriate for patients with a history of severe hypoglycemia,limited life ex-pectancy,advanced microvascular or macrovascular complications,and ex-tensive comorbid conditions and those with longstanding diabetes in whom the general goal is difficult to attain de-spite diabetes self-management educa-tion,appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin.(C)Medical Nutrition Therapy(MNT) General recommendations●Individuals who have pre-diabetes or diabetes should receive individualizedMNT as needed to achieve treatmentgoals,preferably provided by a regis-tered dietitian familiar with the compo-nents of diabetes MNT.(B)●MNT should be covered by insuranceand other payors.(E)Energy balance,overweight,and obesity●In overweight and obese insulin-resistant individuals,modest weightloss has been shown to reduce insulinresistance.Thus,weight loss is recom-mended for all overweight or obese in-dividuals who have or are at risk fordiabetes.(A)●For weight loss,either low-carbohy-drate or low-fat calorie-restricted dietsmay be effective in the short-term(upto1year)(A).●For patients on low-carbohydrate diets,monitor lipid profiles,renal function,and protein intake(in those with ne-phropathy)and adjust hypoglycemictherapy as needed.(E)●Physical activity and behavior modifica-tion are important components of weightloss programs and are most helpful inmaintenance of weight loss.(B)Primary prevention of diabetes●Among individuals at high risk for de-veloping type2diabetes,structuredprograms that emphasize lifestylechanges and include moderate weightloss(7%body weight)and regularphysical activity(150min/week),withdietary strategies including reducedcalories and reduced intake of dietaryfat,can reduce the risk for developingdiabetes and are therefore recom-mended.(A)●Individuals at high risk for type2diabetesshould be encouraged to achieve the U.S.Department of Agriculture recommenda-tion for dietaryfiber(14gfiber/1,000kcal)and foods containing whole grains(one-half of grain intake).(B)Dietary fat intake in diabetes manage-ment●Saturated fat intake should beϽ7%oftotal calories.(A)●Intake of trans fat should be minimized.(B)Carbohydrate intake in diabetes man-agement●Monitoring carbohydrate,whether bycarbohydrate counting,exchanges,orexperience-based estimation,remains akey strategy in achieving glycemic con-trol.(A)●For individuals with diabetes,the use ofthe glycemic index and glycemic loadmay provide a modest additional bene-fit for glycemic control over that ob-served when total carbohydrate isconsidered alone.(B)Other nutrition recommendations●Sugar alcohols and nonnutritive sweet-eners are safe when consumed withinthe acceptable daily intake levels estab-lished by the Food and Drug Adminis-tration.(A)●If adults with diabetes choose to usealcohol,daily intake should be limitedto a moderate amount(one drink perday or less for adult women and twodrinks per day or less for adult men).(E)●Routine supplementation with antioxi-dants,such as vitamins E and C andcarotene,is not advised because of lackof evidence of efficacy and concern re-lated to long-term safety.(A)●Benefit from chromium supplementa-tion in people with diabetes or obesityhas not been conclusively demon-strated and,therefore,cannot be rec-ommended.(E)Bariatric Surgery●Bariatric surgery should be consideredfor adults with BMIՆ35kg/m2andtype2diabetes,especially if the diabe-tes is difficult to control with lifestyleand pharmacologic therapy.(B)●Patients with type2diabetes who haveundergone bariatric surgery need life-long lifestyle support and medicalmonitoring.(E)●Although small trials have shown gly-cemic benefit of bariatric surgery in pa-tients with type2diabetes and BMI of30–35kg/m2,there is currently insuf-ficient evidence to generally recom-mend surgery in patients with BMIϽ35kg/m2outside of a research protocol.(E)●The long-term benefits,cost-effectiveness,and risks of bariatric sur-gery in individuals with type2diabetesshould be studied in well-designed ran-domized controlled trials with optimalmedical and lifestyle therapy as thecomparator.(E)Diabetes Self-ManagementEducation(DSME)●People with diabetes should receiveDSME according to national standardswhen their diabetes is diagnosed and asneeded thereafter.(B)●Self-management behavior change isExecutive Summarythe key outcome of DSME and should be measured and monitored as part of care.(E)●DSME should address psychosocial is-sues,since emotional well-being is strongly associated with positive diabe-tes outcomes.(C)●DSME should be reimbursed by third-party payors.(E)Physical Activity●People with diabetes should be advised to perform at least150min/week of moderate-intensity aerobic physical ac-tivity(50–70%of maximum heart rate).(A)●In the absence of contraindications, people with type2diabetes should be encouraged to perform resistance train-ing three times per week.(A)Psychosocial Assessment and Care ●Assessment of psychological and social situation should be included as an on-going part of the medical management of diabetes.(E)●Psychosocial screening and follow-up should include,but is not limited to, attitudes about the illness,expectations for medical management and out-comes,affect/mood,general and diabe-tes-related quality of life,resources (financial,social,and emotional),and psychiatric history.(E)●Screen for psychosocial problems such as depression,anxiety,eating disor-ders,and cognitive impairment when adherence to the medical regimen is poor.(E)Hypoglycemia●Glucose(15–20g)is the preferred treatment for the conscious individual with hypoglycemia,although any form of carbohydrate that contains glucose may be used.If SMBG15min after treatment shows continued hypoglyce-mia,the treatment should be repeated. Once SMBG glucose returns to normal, the individual should consume a meal or snack to prevent recurrence of hypo-glycemia.(E)●Glucagon should be prescribed for all individuals at significant risk of severe hypoglycemia,and caregivers or family members of these individuals should be instructed in its administration.Gluca-gon administration is not limited to health care professionals.(E)●Individuals with hypoglycemia un-awareness or one or more episodes of severe hypoglycemia should be advisedto raise their glycemic targets to strictlyavoid further hypoglycemia for at leastseveral weeks to partially reverse hypo-glycemia unawareness and reduce riskof future episodes.(B)Immunization●Annually provide an influenza vaccineto all diabetic patientsՆ6months ofage.(C)●Administer pneumococcal polysaccha-ride vaccine to all diabetic patientsՆ2years of age.A one-time revaccination isrecommended for individualsϾ64years of age previously immunizedwhen they wereϽ65years of age if thevaccine was administeredϾ5yearsago.Other indications for repeat vacci-nation include nephrotic syndrome,chronic renal disease,and other immu-nocompromised states,such as aftertransplantation.(C)Hypertension/Blood PressureControlScreening and diagnosis●Blood pressure should be measured atevery routine diabetes visit.Patientsfound to have systolic blood pressureՆ130mmHg or diastolic blood pres-sureՆ80mmHg should have bloodpressure confirmed on a separate day.Repeat systolic blood pressureՆ130mmHg or diastolic blood pressureՆ80mmHg confirms a diagnosis of hyper-tension.(C)Goals●Patients with diabetes should be treatedto a systolic blood pressureϽ130mmHg.(C)●Patients with diabetes should be treatedto a diastolic blood pressureϽ80mmHg.(B)Treatment●Patients with a systolic blood pressureof130–139mmHg or a diastolic bloodpressure of80–89mmHg may be givenlifestyle therapy alone for a maximumof3months and then,if targets are notachieved,treated with addition of phar-macological agents.(E)●Patients with more severe hypertension(systolic blood pressureՆ140or dia-stolic blood pressureՆ90mmHg)atdiagnosis or follow-up should receivepharmacologic therapy in addition tolifestyle therapy.(A)●Pharmacologic therapy for patientswith diabetes and hypertension shouldbe with a regimen that includes eitheran ACE inhibitor or an angiotensin re-ceptor blocker(ARB).If one class is nottolerated,the other should be substi-tuted.If needed to achieve blood pres-sure targets,a thiazide diuretic shouldbe added to those with an estimatedglomerularfiltration rate(GFR)(see be-low)Ն30ml/min per1.73m2and aloop diuretic for those with an esti-mated GFRϽ30ml/min per1.73m2.(C)●Multiple drug therapy(two or moreagents at maximal doses)is generallyrequired to achieve blood pressure tar-gets.(B)●If ACE inhibitors,ARBs,or diuretics areused,kidney function and serum potas-sium levels should be closely moni-tored.(E)●In pregnant patients with diabetes andchronic hypertension,blood pressuretarget goals of110–129/65–79mmHgare suggested in the interest of long-term maternal health and minimizingimpaired fetal growth.ACE inhibitorsand ARBs are contraindicated duringpregnancy.(E)Dyslipidemia/Lipid ManagementScreening●In most adult patients,measure fastinglipid profile at least annually.In adultswith low-risk lipid values(LDL choles-terolϽ100mg/dl,HDL cholesterolϾ50mg/dl,and triglyceridesϽ150mg/dl),lipid assessments may be re-peated every2years.(E)Treatment recommendations and goals●Lifestyle modification focusing on thereduction of saturated fat,trans fat,andcholesterol intake;weight loss(if indi-cated);and increased physical activityshould be recommended to improvethe lipid profile in patients with diabe-tes.(A)●Statin therapy should be added to life-style therapy,regardless of baselinelipid levels,for diabetic patients:●with overt CVD(A)●without CVD who are over the age of40years and have one or more otherCVD risk factors.(A)●For patients at lower risk than thosementioned above(e.g.,without overtCVD and under the age of40years),statin therapy should be considered inaddition to lifestyle therapy if LDL cho-lesterol remains above100mg/dl or inthose with multiple CVD risk factors(E)●In individuals without overt CVD,theExecutive Summaryprimary goal is an LDL cholesterol Ͻ100mg/dl(2.6mmol/l).(A)●In individuals with overt CVD,a lower LDL cholesterol goal ofϽ70mg/dl(1.8 mmol/l),using a high dose of a statin,is an option.(B)●If drug-treated patients do not reach the above targets on maximal tolerated sta-tin therapy,a reduction in LDL choles-terol ofϳ30–40%from baseline is an alternative therapeutic goal.(A)●Triglyceride levelsϽ150mg/dl(1.7 mmol/l)and HDL cholesterolϾ40 mg/dl(1.0mmol/l)in men andϾ50 mg/dl(1.3mmol/l)in women are desir-able.However,LDL cholesterol–targeted statin therapy remains the preferred strategy.(C)●If targets are not reached on maximally tolerated doses of statins,combination therapy using statins and other lipid-lowering agents may be considered to achieve lipid targets but has not been evaluated in outcome studies for either CVD outcomes or safety.(E)●Statin therapy is contraindicated in pregnancy.(E)Antiplatelet Agents●Use aspirin therapy(75–162mg/day) as a primary prevention strategy in those with type1or type2diabetes at increased cardiovascular risk,includ-ing those who areϾ40years of age or who have additional risk factors(family history of CVD,hypertension,smok-ing,dyslipidemia,or albuminuria).(C)●Use aspirin therapy(75–162mg/day) as a secondary prevention strategy in those with diabetes with a history of CVD.(A)●For patients with CVD and docu-mented aspirin allergy,clopidogrel(75 mg/day)should be used.(B)●Combination therapy with ASA(75–162mg/day)and clopidogrel(75mg/ day)is reasonable for up to a year after an acute coronary syndrome.(B)●Aspirin therapy is not recommended in people under30years of age,due to lack of evidence of benefit,and is con-traindicated in patients under the age of 21years because of the associated risk of Reye’s syndrome.(E)Smoking Cessation●Advise all patients not to smoke.(A)●Include smoking cessation counseling and other forms of treatment as a rou-tine component of diabetes care.(B)Coronary Heart Disease(CHD)Screening and TreatmentScreening●In asymptomatic patients,evaluate riskfactors to stratify patients by10-yearrisk and treat risk factors accordingly.(B)Treatment●In patients with known CVD,ACE in-hibitor(C),aspirin(A),and statin ther-apy(A)(if not contraindicated)shouldbe used to reduce the risk of cardiovas-cular events.●In patients with a prior myocardial in-farction,add-blockers(if not contra-indicated)to reduce mortality.(A)●In patientsϾ40years of age with an-other cardiovascular risk factor(hyper-tension,family history,dyslipidemia,microalbuminuria,cardiac autonomicneuropathy,or smoking),aspirin andstatin therapy(if not contraindicated)should be used to reduce the risk ofcardiovascular events.(B)●In patients with coronary heart failure(CHF),thiazolidinedione use is contra-indicated.(C)●Metformin may be used in patients withstable CHF if renal function is normal.It should be avoided in unstable or hos-pitalized patients with CHF.(C)Nephropathy Screening andTreatmentGeneral recommendations●To reduce the risk or slow the progres-sion of nephropathy,optimize glucosecontrol.(A)●To reduce the risk or slow the progres-sion of nephropathy,optimize bloodpressure control.(A)Screening●Perform an annual test to assess urinealbumin excretion(UAE)in type1dia-betic patients with diabetes duration ofՆ5years and in all type2diabetic pa-tients,starting at diagnosis.(E)●Measure serum creatinine at least annu-ally in all adults with diabetes regard-less of the degree of UAE.The serumcreatinine should be used to estimateGFR and stage the level of chronic kid-ney disease(CKD),if present.(E)Treatment●In the treatment of the nonpregnant pa-tient with micro-or macroalbuminuria,either ACE inhibitors or ARBs shouldbe used.(A)●While there are no adequate head-to-head comparisons of ACE inhibitorsand ARBs,there is clinical trial supportfor each of the following statements:●In patients with type1diabetes,withhypertension and any degree of albu-minuria,ACE inhibitors have beenshown to delay the progression of ne-phropathy.(A)●In patients with type2diabetes,hy-pertension,and microalbuminuria,both ACE inhibitors and ARBs havebeen shown to delay the progressionto macroalbuminuria.(A)●In patients with type2diabetes,hy-pertension,macroalbuminuria,andrenal insufficiency(serum creatinineϾ1.5mg/dl),ARBs have been shownto delay the progression of nephrop-athy.(A)●If one class is not tolerated,the othershould be substituted.(E)●Reduction of protein intake to0.8–1.0g⅐kg body wtϪ1⅐dayϪ1in individualswith diabetes and the earlier stages ofCKD and to0.8g⅐kg body wtϪ1⅐dayϪ1in the later stages of CKD mayimprove measures of renal function(UAE rate,GFR)and is recommended(B)●When ACE inhibitors,ARBs,or diuret-ics are used,monitor serum creatinineand potassium levels for the develop-ment of acute kidney disease and hy-perkalemia.(E)●Continued monitoring of UAE to assessboth response to therapy and progres-sion of disease is recommended.(E)●Consider referral to a physician experi-enced in the care of kidney diseasewhen there is uncertainty about the eti-ology of kidney disease(active urinesediment,absence of retinopathy,rapiddecline in GFR),difficult managementissues,or advanced kidney disease.(B)Retinopathy Screening andTreatmentGeneral recommendations●To reduce the risk or slow the progres-sion of retinopathy,optimize glycemiccontrol.(A)●To reduce the risk or slow the progres-sion of retinopathy,optimize bloodpressure control.(A)Screening●Adults and children aged10years orolder with type1diabetes should havean initial dilated and comprehensiveeye examination by an ophthalmologistor optometrist within5years after theonset of diabetes.(B)Executive Summary●Patients with type2diabetes should have an initial dilated and comprehen-sive eye examination by an ophthalmol-ogist or optometrist shortly after the diagnosis of diabetes.(B)●Subsequent examinations for type1 and type2diabetic patients should be repeated annually by an ophthalmolo-gist or optometrist.Less frequent exams (every2–3years)may be considered following one or more normal eye ex-ams.Examinations will be required more frequently if retinopathy is pro-gressing.(B)●Women with preexisting diabetes who are planning pregnancy or who have become pregnant should have a com-prehensive eye examination and be counseled on the risk of development and/or progression of diabetic retinop-athy.Eye examination should occur in thefirst trimester with close follow-up throughout pregnancy and for1year postpartum.(B)Treatment●Promptly refer patients with any level of macular edema,severe nonproliferative diabetic retinopathy(NPDR),or any proliferative diabetic retinopathy (PDR)to an ophthalmologist who is knowledgeable and experienced in the management and treatment of diabetic retinopathy.(A)●Laser photocoagulation therapy is indi-cated to reduce the risk of vision loss in patients with high-risk PDR,clinically significant macular edema,and in some cases of severe NPDR.(A)●The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection,as this therapy does not increase the risk of retinal hemor-rhage.(A)Neuropathy Screening and Treatment●All patients should be screened for dis-tal symmetric polyneuropathy(DPN)at diagnosis and at least annually thereaf-ter using simple clinical tests.(B)●Electrophysiological testing is rarely needed,except in situations where the clinical features are atypical.(E)●Screening for signs and symptoms of cardiovascular autonomic neuropathy should be instituted at diagnosis of type 2diabetes and5years after the diagno-sis of type1diabetes.Special testing is rarely needed and may not affect man-agement or outcomes.(E)●Medications for the relief of specificsymptoms related to DPN and auto-nomic neuropathy are recommended,as they improve the quality of life of thepatient.(E)Foot care●For all patients with diabetes,performan annual comprehensive foot exami-nation to identify risk factors predictiveof ulcers and amputations.The foot ex-amination should include inspection,assessment of foot pulses,and testingfor loss of protective sensation(10-gmonofilament plus testing any one of:vibration using128-Hz tuning fork,pinprick sensation,ankle reflexes,orvibration perception threshold).(B)●Provide general foot self-care educationto all patients with diabetes.(B)●A multidisciplinary approach is recom-mended for individuals with foot ulcersand high-risk feet,especially those witha history of prior ulcer or amputation.(B)●Refer patients who smoke,have loss ofprotective sensation and structural ab-normalities,or have history of priorlower-extremity complications to footcare specialists for ongoing preventivecare and life-long surveillance.(C)●Initial screening for peripheral arterialdisease(PAD)should include a historyfor claudication and an assessment ofthe pedal pulses.Consider obtaining anankle-brachial index(ABI),as many pa-tients with PAD are asymptomatic.(C)●Refer patients with significant claudica-tion or a positive ABI for further vascu-lar assessment and consider exercise,medications,and surgical options.(C)Children and AdolescentsGlycemic control●Consider age when setting glycemicgoals in children and adolescents withtype1diabetes,with less stringent goalsfor younger children.(E)Nephropathy●Annual screening for microalbumin-uria,with a random spot urine samplefor microalbumin-to-creatinine ratio,should be initiated once the child is10years of age and has had diabetes for5years.(E)●Confirmed,persistently elevated mi-croalbumin levels on two additionalurine specimens should be treated withan ACE inhibitor,titrated to normaliza-tion of microalbumin excretion if pos-sible.(E)Hypertension●Treatment of high-normal blood pres-sure(systolic or diastolic blood pres-sure consistently between the90–95thpercentile for age,sex,and height)should include dietary interventionand exercise,aimed at weight controland increased physical activity,if ap-propriate.If target blood pressure is notreached with6–12months of lifestyleintervention,pharmacologic treatmentshould be initiated.(E)●Pharmacologic treatment of high bloodpressure(systolic or diastolic bloodpressure consistently above the95thpercentile for age,sex,and height orconsistentlyϾ130/80mmHg for ado-lescents)should be initiated along withlifestyle intervention as soon as the di-agnosis is confirmed.(E)●ACE inhibitors should be consideredfor the initial treatment of hyperten-sion.(E)●The goal of treatment is a blood pres-sure consistentlyϽ130/80or below the90th percentile for age,sex,and height,whichever is lower.(E)DyslipidemiaScreening●If there is a family history of hypercho-lesterolemia(total cholesterolϾ240mg/dl)or a cardiovascular event beforeage55years,or if family history is un-known,then a fasting lipid profileshould be performed on childrenϾ2years of age soon after diagnosis(afterglucose control has been established).If family history is not of concern,thenthefirst lipid screening should be per-formed at puberty(Ն10years).All chil-dren diagnosed with diabetes at or afterpuberty should have a fasting lipid pro-file performed soon after diagnosis(after glucose control has been estab-lished).(E)●For both age-groups,if lipids are abnor-mal,annual monitoring is recom-mended.If LDL cholesterol values arewithin the accepted risk levels(Ͻ100mg/dl[2.6mmol/l]),a lipid profileshould be repeated every5years.(E)Treatment●Initial therapy should consist of optimi-zation of glucose control and MNTusing a Step2American Heart Associ-ation diet aimed at a decrease in theamount of saturated fat in the diet.(E)●After the age of10years,the addition ofa statin is recommended in patientswho,after MNT and lifestyle changes,Executive Summary。
2009年ADA最新的糖尿病指南(英文).
Standards of Medical Care in Diabetes—2009 A MERICAN D IABETES A SSOCIATIOND iabetes is a chronic illness that re-quires continuing medical careand patient self-management ed-ucation to prevent acute complications and to reduce the risk of long-term complications.Diabetes care is complex and requires that many issues,beyond glycemic control,be addressed.A large body of evidence exists that supports a range of interventions to improve dia-betes outcomes.These standards of care are in-tended to provide clinicians,patients, researchers,payors,and other inter-ested individuals with the components of diabetes care,treatment goals,and tools to evaluate the quality of care. While individual preferences,comor-bidities,and other patient factors may require modific ation of goals,targets that are desirable for most patients with diabetes are provided.These standards are not intended to preclude more ex-tensive evaluation and management of the patient by other specialists as needed.For more detailed information, refer to references1–3.The recommendations included are screening,diagnostic,and therapeutic actions that are known or believed to favorably affect health outcomes of pa-tients with diabetes.A grading system (Table1,developed by the American Diabetes Association(ADAand mod-eled after existing methods,was utilized to clarify and codify the evidence that forms the basis for the recommenda-tions.The level of evidence that sup-ports each recommendation is listed after each recommendation using the letters A,B,C,orE.I.CLASSIFICATION ANDDIAGNOSISA.ClassificationIn1997,ADA issued new diagnostic and classification criteria(4;in2003,modi-fications were made regarding the diagno- sis of impaired fasting glucose(5.The classification of diabetes includes four clinical classes:●type1diabetes(results from-cell de- struction,usually leading to absolute insulin deficiency●type2diabetes(results from a progres- sive insulin secretory defect on the background of insulin resistance●other specific types of diabetes due to other causes,e.g.,genetic defects in-cell function,genetic defects in insu- lin action,diseases of the exocrine pan- creas(such as cysticfibrosis,and drug-or chemical-induced(such as in the treatment of AIDS or after organ trans-plantation●gestational diabetes mellitus(GDM (diabetes diagnosed during pregnancy Some patients cannot be clearly classified as type1or type2diabetes.Clinical presenta- tion and disease progression vary consider- ably in both types of diabetes.Occasionally, patients who otherwise have type2diabetes may present with ketoacidosis.Similarly, patients with type1may have a late onset and slow(but relentlessprogression of dis- ease despite having features of autoimmune disease.Such difficulties in diagnosis may occur in children,adolescents,and adults. The true diagnosis may become more obvi- ous over time.B.Diagnosis of diabetesCurrent criteria for the diagnosis of diabetes in nonpregnant adults are shown in Table2.Three ways to diagnose diabetes are recom- mended at the time of this statement,and each must be confirmed on a subsequent day unless unequivocal symptoms of hy- perglycemia are present.Although the75-g oral glucose tolerance test(OGTTis more sensitive and modestly more specific than the fasting plasma glucose(FPGto diag- nose diabetes,it is poorly reproducible and difficult to perform in practice.Because of ease of use,acceptability to patients,and lower cost,the FPG has been the preferred diagnostic test.Though FPG is less sensitive than the OGTT,the vast majority of people who do not meet diagnostic criteria for dia- betes by FPG but would by OGTT will have an A1C value well under7.0%(6.Though the OGTT is not recom-mended for routine clinical use,it may beuseful for further evaluation of patients in whom diabetes is still strongly suspected but who have normal FPG or IFG(see Section I.C.The use of the A1C for the diagnosisof diabetes has previously not been rec- ommended due to lack of global stan- dardization and uncertainty about diagnostic thresholds.However,with a world-wide move toward a standardized assay and with increasing observational evidence about the prognostic signifi- cance of A1C,an Expert Committee on the Diagnosis of Diabetes was convened in2008.This joint committee of ADA,the European Association for the Study of Di- abetes,and the International Diabetes Federation will likely recommend that the A1C become the preferred diagnostic testfor diabetes.Diagnostic cut-points are be-ing discussed at the time of publication ofthis statement.Updated recommenda-tions will be published in Diabetes Careand will be available at .C.Diagnosis of pre-diabetesHyperglycemia not sufficient to meet thediagnostic criteria for diabetes is catego-●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●The recommendations in this article are based on the evidence reviewed in the following publication: Standards of Care for Diabetes(Technical Review.Diabetes Care17:1514–1522,1994.Originally approved1988.Most recent review/revision October2008.DOI:10.2337/dc09-S013©2009by the American Diabetes Association.Readers may use this article as long as the work is properly cited,the use is educational and not for profit,and the work is not altered.See http://creativecommons.org/licenses/by-nc-nd/3.0/for details.P O S I T I O N S T A T E M E N Trized as either impaired fasting glucose (IFGor impaired glucose tolerance (IGT,depending on whether it is identi-fied through the FPG or the OGTT:●IFGϭFPG100mg/dl(5.6mmol/lto 125mg/dl(6.9mmol/l●IGTϭ2-h plasma glucose140mg/dl(7.8mmol/lto199mg/dl(11.0 mmol/lIFG and IGT have been officially termed “pre-diabetes.”Both categories of pre-diabetes are risk factors for future diabetes and for cardiovascular disease(CVD(7.II.TESTING FOR PRE-DIABETES AND DIABETESIN ASYMPTOMATIC PATIENTSRecommendations●Testing to detect pre-diabetes and type 2diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese(BMI Ն25kg/m2and who have one or more additional risk factors for diabetes(Ta-ble3.In those without these risk fac-tors,testing should begin at age45 years.(B●If tests are normal,repeat testing shouldbe carried out at least at3-year inter-vals.(E●To test for pre-diabetes or diabetes,anFPG test or2-h OGTT(75-g glucoseloador both are appropriate.(B●An OGTT may be considered in pa-tients with IFG to better define the riskof diabetes.(E●In those identified with pre-diabetes, identify and,if appropriate,treat other CVD risk factors.(BFor many illnesses,there is a major dis- tinction between screening and diagnos- tic testing.However,for diabetes,the same tests would be used for“screening”as for diagnosis.Type2diabetes has a long asymptomatic phase and significant clinical risk markers.Diabetes may be identified anywhere along a spectrum of clinical scenarios ranging from a seem- ingly low-risk individual who happens to have glucose testing,to a higher-risk in- dividual whom the provider tests because of high suspicion of diabetes,to the symp- tomatic patient.The discussion herein is primarily framed as testing for diabetes inthose without symptoms.Testing for dia- betes will also detect individuals with pre- diabetes.A.Testing for pre-diabetes and type2diabetes in adultsType2diabetes is frequently not diag- nosed until complications appear,and approximately one-third of all people with diabetes may be undiagnosed.Al- though the effectiveness of early identifi- cation of pre-diabetes and diabetes through mass testing of asymptomatic in- dividuals has not been definitively proven (and rigorous trials to provide such proof are unlikely to occur,pre-diabetes and diabetes meet established criteria for con- ditions in which early detection is appro- priate.Both conditions are common, increasing in prevalence,and impose sig-nificant public health burdens.There is along presymptomatic phase before the di-agnosis of type2diabetes is usually made.Relatively simple tests are available to de-tect preclinical disease(8.Additionally,the duration of glycemic burden is astrong predictor of adverse outcomes,and effective interventions exist to pre-vent progression of pre-diabetes to diabe-tes(see Section IVand to reduce risk ofcomplications of diabetes(see SectionVI.Recommendations for testing for pre-Table1—ADA evidence grading system for clinical practice recommendations Level ofevidence DescriptionA Clear evidence from well-conducted,generalizable,randomized controlled trials that are adequately powered,including:●Evidence from a well-conducted multicenter trial●Evidence from a meta-analysis that incorporated quality ratings in the analysisCompelling nonexperimental evidence,i.e.,“all or none”rule developed by the Centre for Evidence-Based Medicine at OxfordSupportive evidence from well-conducted randomized controlled trials that are adequately powered,including:●Evidence from a well-conducted trial at one or more institutions●Evidence from a meta-analysis that incorporated quality ratings in the analysisB Supportive evidence from well-conducted cohort studies,including:●Evidence from a well-conducted prospective cohort study or registry ●Evidence from a well-conducted meta-analysis of cohort studies Supportive evidence from a well-conducted case-control studyC Supportive evidence from poorly controlled or uncontrolled studies●Evidence from randomized clinical trials with one or more major or three or more minor methodologicalflaws that could invalidate the results●Evidence from observational studies with high potential for bias(such as case series with comparison to historical controls●Evidence from case serie s or case reportsConflicting evidence with the weight of evidence supporting therecommendationE Expert consensus or clinical experienceTable2—Criteria for the diagnosis of diabetes1.FPGՆ126mg/dl(7.0mmol/l.Fasting is defined as no caloric intake for atleast8h.*OR2.Symptoms of hyperglycemia and a casual(randomplasma glucoseՆ200mg/dl(11.1mmol/l.Casual(randomis defined as any time of day withoutregard to time since last meal.The classic symptoms of hyperglycemiainclude polyuria,polydipsia,and unexplained weight loss.OR3.2-h plasma glucoseՆ200mg/dl(11.1mmol/lduring an OGTT.The testshould be performed as described by the World Health Organization usinga glucose load containing the equivalent of75-g anhydrous glucosedissolved in water.**In the absence of unequivocal hyperglycemia,these criteria should be confirmed by repeat testing on adifferent day(5.Standards of Medical Carediabetes and diabetes in asymptomatic, undiagnosed adults are listed in Table3. Testing should be considered in adults of any age with BMIՆ25kg/m2and one or more risk factors for diabetes.Because age is a major risk factor for diabetes,testing of those without other risk factors should begin no later than age45years.Either FPG testing or the2-h OGTT is appropriate for testing.The2-h OGTTidentifies people with either IFG or IGT, and thus,more pre-diabetic people at in-creased risk for the development of dia-betes and CVD.It should be noted that the two tests do not necessarily detect the same pre-diabetic individuals(9.The ef-ficacy of interventions for primary pre-vention of type2diabetes(10–16has primarily been demonstrated among in-dividuals with IGT,not individuals with IFG(who do not also have IGT.As noted in the diagnosis section(Section I.B,the FPG test is more convenient,more repro-ducible,less costly,and easier to admin-ister than the2-h OGTT(4,5.An OGTT may be useful in patients with IFG to bet-ter define the risk of diabetes.The appropriate interval between tests is not known(17.The rationale for the3-year interval is that false-negatives will be repeated before substantial time elapses,and there is little likelihood that an individual will develop significant complications of diabetes within3years of a negative test result.Because of the need for follow-up and discussion of abnormal results,testing should be carried out within the health care munity screening out-side a health care setting is not recom-mended because people with positive tests may not seek,or have access to,ap-propriate follow-up testing and care.Conversely,there may be failure to ensureappropriate repeat testing for individuals who test munity screening may also be poorly targeted,i.e.,it may fail to reach the groups most at risk and inappropriately test those at low risk(the worried wellor even those already diag- nosed(18,19.B.Testing for type2diabetes inchildrenThe incidence of type2diabetes in ado- lescents has increased dramatically in the last decade,especially in minority popu- lations(20,although the disease remains rare in the general adolescent population (21.Consistent with recommendations for adults,children and youth at in- creased risk for the presence or the devel- opment of type2diabetes should be tested within the health care setting(22.The recommendations of the ADA con- sensus statement on type2diabetes in children and youth,with some modifica- tions,are summarized in Table4.C.Screening for type1diabetes Generally,people with type1diabetes present with acute symptoms of diabetes and markedly elevated blood glucose lev- els,and most cases are diagnosed soon after the onset of hyperglycemia.How- ever,evidence from type1prevention studies suggests that measurement of islet autoantibodies identifies individuals who are at risk for developing type1diabetes. Such testing may be appropriate in high- risk individuals,such as those with prior transient hyperglycemia or those who have relatives with type1diabetes,in the context of clinical research studies(see,for exam-ple,. Widespread clinical testing of asymptom- atic low-risk individuals cannot currently be recommended,as it would identify very few individuals in the general population who are at risk.Individuals who screen pos- itive should be counseled about their risk of developing diabetes.Clinical studies are be- ing conducted to test various methods of preventing type1diabetes,or reversing early type1diabetes,in those with evidence of autoimmunity.III.DETECTION ANDDIAGNOSIS OF GDM Recommendations●Screen for GDM using risk factor ana l- ysis and,if appropriate,use of anOGTT.(C●Women with GDM should be screenedfor diabetes6–12weeks postpartumand should be followed up with subse-quent screening for the development ofdiabetes or pre-diabetes.(EGDM is defined as any degree of glucoseintolerance with onset orfirst recognitionduring pregnancy(4.Although mostcases resolve with delivery,the definitionapplies whether or not the condition per-sists after pregnancy and does not excludethe possibility that unrecognized glucoseintolerance may have antedated or begunconcomitantly with the pregnancy.Ap-Table3—Criteria for testing for pre-diabetes and diabetes in asymptomatic adult individuals1.Testing should be considered in all adults who areoverweight(BMIՆ25kg/m2*andhave additional risk factors:●physical inactivity●first-degree relative with diabetes●members of a high-risk ethnic population(e.g.,African American,Latino,NativeAmerican,Asian American,Pacific Islander●women who delivered a baby weighingϾ9lb or were diagnosed with GDM●hypertension(Ն140/90mmHg or on therapy for hypertension●HDL cholesterol levelϽ35mg/dl(0.90mmol/land/or a triglyceride levelϾ250mg/dl(2.82mmol/l●women with polycystic ovarian syndrome(PCOS●IGT or IFG on previous testing●other clinical conditions associ ated with insulin resistance(e.g.,severe obesity,acanthosis nigricans●history of CVD2.In the absence of the above criteria,testing for pre-diabetes and diabetes should beginat age45years3.If results are normal,testing should be repeated at least at3-year intervals,withconsideration of more frequent testing depending on initial results and risk status.*At-risk BMI may be lower in some ethnic groups.Table4—Testing for type2diabetes inasymptomatic childrenCriteria:●Overweight(BMIϾ85th percentile for age and sex,weight for heightϾ85th percentile,or weightϾ120%of ideal for heightPlus any two of the following risk factors: ●Family history of type2diabetes infirst- or second-degree relative●Race/ethnicity(Native American,African American,Latino,Asian Am erican,Pacific Islander●Signs of insulin resistance or conditions associated with insulin resistance (acanthosis nigricans,hypertension, dyslipidemia,PCOS,or small-for- gestational-age birthweight●Maternal history of diabetes or GDM during the child’s ges tationAge of initiation:age10years or at onset ofpuberty,if puberty occurs at a youngerageFrequency:every3yearsTest:FPG preferredPosition Statementproximately7%of all pregnancies(rang-ing from1to14%depending on the population studied and the diagnostic tests employedare complicated by GDM, resulting in more than200,000cases annually.Because of the risks of GDM to the mother and neonate,screening and di-agnosis are warranted.The screening and diagnostic strategies,based on the 2004ADA position statement on gesta-tional diabetes mellitus(23,are outlined in Table5.Results of the Hyperglycemia and Ad-verse Pregnancy Outcomes study(24,a large-scale(includingϳ25,000pregnant womenmultinational epidemiologic study,demonstrated that risk of adverse maternal,fetal,and neonatal outcomes continuously increased as a function of maternal glycemia at24–28weeks,even within ranges previously considered nor-mal for pregnancy.For most complica-tions,there was no threshold for risk.These results have led to careful reconsid-eration of the diagnostic criteria for GDM.An international group representing mul-tiple obstetrical and diabetes organiza-tions,including ADA,is currentlyworking on consensus toward1a world- wide standard for which diagnostic test to use for GDM and2rational diagnosticcut points.Because women with a history ofGDM have a greatly increased subse- quent risk for diabetes(25,they shouldbe screened for diabetes6–12weeks postpartum,using nonpregnant OGTT criteria,and should be followed up with subsequent screening for the develop- ment of diabetes or pre-diabetes,as out- lined in Section II.For information on the National Diabetes Education Pro- gram(NDEPcampaign to prevent type2diabetes in women with GDM,go to /diabetes/pubs/ NeverTooEarly_Tipsheet.pdf.IV.PREVENTION/DELAYOF TYPE2DIABETES Recommendations●Patients with IGT(Aor IFG(Eshouldbe referred to an effective ongoing sup- port program for weight loss of5–10%of body weight and for increasing phys- ical activity to at least150min per week of moderate activity such as walking.●Follow-up counseling appears to be im- portant for success.(B●Based on potential cost savings of dia- betes prevention,such counseling should be covered by third-party pay- ors.(E●In addition to lifest yle counseling,met- formin may be considered in those who are at very high risk for developing di- abetes(combined IFG and IGT plus other risk factors such as A1CϾ6%,hypertension,low HDL cholesterol,el- evated triglycerides,or family history of diabetes i n afirst-degree relativeandwho are obese and under60years of age.(E●Monitoring for the development of di- abetes in those with pre-diabetesshould be performed every year.(E Randomized controlled trials have shown that individuals at high risk for develop- ing diabetes(those with IFG,IGT,or bothcan be given interventions that sig-nificantly decrease the rate of onset of di- abetes(10–16.These interventions include intensive lifestyle modification programs that have been shown to be very effective(Ն58%reduction after3years and use of the pharmacologic agents met- formin,acarbose,orlistat,and thiazo-lidinediones(TZDs,each of which has been shown to decrease incident diabetes to various degrees.A summary of major diabetes prevention trials is shown in Ta- ble6.Two studies of lifestyle interventionhave shown persistent reduction in the rate of conversion to type2diabetes with3(26to14years(27of postintervention follow-up.Based on the results of clinical trialsand the known risks of progression ofpre-diabetes to diabetes,an ADA Consen- sus Development Panel(7concludedthat persons with pre-diabetes(IGTand/or IFGshould be counseled on life- style changes with goals similar to those of the Diabetes Prevention Program(DPP (5–10%weight loss and moderate physi-cal activity ofϳ30min per day.Regard-ing the more difficult issue of drugTable5—Screening for and diagnosis of GDMCarry out GDM risk assessment at thefirst prenatal visit.Women at very high risk for GDM should be screened for diabetes as soon as possible after the confirmation of pregnancy.Criteria for very high risk are:●severe obesity●prior history of GDM or delivery of large-for-gestational-age infant●presence of glycosuria●diagnosis of PCOS●strong family history of type2diabetesScreening/diagnosis at this stage of pregnancy should use standard diagnostic testing(Table2. All women of greater than low risk of GDM,including those above not found to havediabetes early in pregnancy,should undergo GDM testing at24–28weeks of gestation.Low risk status,w hich does not require GDM screening,is defined as women with ALL of the following characteristics:●ageϽ25years●weight normal before pregnancy●member of an ethnic group with a low prevalence of diabetes●no known diabetes infirst-degree relatives●no histo ry of abnormal glucose tolerance●no history of poor obstetrical outcomeTwo approaches may be followed for GDM screening at24–28weeks:1.Two-step approach:A.Perform initial screening by measuring plasma or serum glucose1h after a50-g oralglucose load.A glucose threshold after50-g load ofՆ140mg/dl identifiesϳ80%ofwomen with GDM,while the sensitivity is further increased toϳ90%by a threshold of Ն130mg/dl.B.Perform a diagnostic100-g OGTT on a separate day in women who exceed thechosen threshold on50-g screening.2.One-step approach(may be preferred in clinics with high prevalence ofGDM:Performa diagnostic100-g OGTT in all women to be tested at24–28weeks.The100-g OGTT should be performed in the morning after an overnight fast of at least8h. To make a diagnosis of GDM,at least two of the following plasma glucose values must be found: Fasting:Ն95mg/dl1h:Ն180mg/dl2h:Ն155mg/dl3h:Ն140mg/dlStandards of Medical Caretherapy for diabetes prevention,the con-sensus panel felt that metformin should be the only drug considered for use in diabetes prevention.For other drugs,the issues of cost,side effects,and lack of per-sistence of effect in some studies led the panel to not recommend their use for di-abetes prevention.Metformin use was recommended only for very-high-risk in-dividuals(those with combined IGT and IFG who are obese and under60years of age with at least one other risk factor for diabetes.In addition,the panel high-lighted the evidence that in the DPP,met-formin was most effective compared to lifestyle in those with BMI of at least35 kg/m2and those under age60years.V.DIABETES CAREA.Initial evaluationA complete medical evaluation should be performed to classify the diabetes,detect the presence of diabetes complications, review previous treatment and glycemic control in patients with established diabe-tes,assist in formulating a management plan,and provide a basis for continuing boratory tests appropriate to the evaluation of each patient’s medical con-dition should be performed.A focus on the components of comprehensive care (Table7will assist the health care team to ensure optimal management of the pa-tient with diabetes.B.ManagementPeople with diabetes should receive med-ical care from a physician-coordinatedteam.Such teams may include,but are not limited to,physicians,nurse practitio- ners,physician’s assistants,nurses,dieti- tians,pharmacists,and mental health professionals with expertise and a special interest in diabetes.It is essential in this collaborative and integrated team ap- proach that individuals with diabetes as- sume an active role in their care.The management plan should be for- mulated as an individualized therapeutic alliance among the patient and family,the physician,and other members of the health care team.A variety of strategies and techniques should be used to provide adequate education and development of problem-solving skills in the various as- pects of diabetes management.Imple- mentation of the management planrequires that each aspect is understood and agreed on by the patient and the care providers and that the goals and treat- ment plan are reasonable.Any plan should recognize diabetes self-manage- ment education(DSMEas an integral component of care.In developing the plan,consideration should be given to the pati ent’s age,school or work schedule and conditions,physical activity,eating patterns,social situation and personality, cultural factors,and presence of compli- cations of diabetes or other medical con- ditions.C.Glycemic control1.Assessment of glycemic controlTwo primary techniques are available for health providers and patients to assess the effectiveness of the management plan onglycemic control:patient self-monitoringof blood glucose(SMBGor of interstitialglucose and measurement of A1C.a.Glucose monitoringRecommendations●SMBG should be carried out three ormore times daily for patients using mul-tiple insulin injections or insulin pumptherapy.(A●For patients using less frequent insulininjections,noninsulin therapies,ormedical nutrition therapy(MNTandphysical activity alone,SMBG may beuseful as a guide to the success of ther-apy.(E●To achieve postprandial glucose tar-gets,postprandial SMBG may be appro-priate.(ETable6—Therapies proven effective in diabetes prevention trialsStudy(ref.n Population Meanage(yearsDuration(yearsIntervention(daily doseConversion incontrol subjects(%/yearRelative riskLifestyleFinnish DPS(11522IGT,BMIՆ25kg/m255 3.2Individual diet/exercise60.42(0.30–0.70DPP(102,161*IGT,BMIՆ24kg/m2,FPGϾ5.3mmol/l 513Individualdiet/exercise100.42(0.34–0.52Da Qing(12259*IGT(randomizedgroups456Group diet/exercise160.62(0.44–0.86Toranomon study(28458IGT(men,BMIϭ24kg/m2554Individualdiet/exercise20.33(0.10–1.0†Indian DPP(16269*IGT46 2.5Individualdiet/exercise220.71(0.63–0.79MedicationsDPP(102,155*IGT,BMIϾ24kg/m2,FPGϾ5.3mmol/l51 2.8Metformin(1,700mg100.69(0.57–0.83 Indian DPP(16269*IGT462.5Metformin(500mg220.74(0.65–0.81 STOP NIDDM(141,419IGT,FPGϾ5.6mmol/l543.2Acarbose(300mg130.75(0.63–0.90XENDOS(293,277BMIϾ30kg/m2434Orlistat(360mg20.63(0.46–0.86DREAM(155,269IGT or IFG55 3.0Rosiglitazone(8mg90.40(0.35–0.46 *Number of participants in the indicated comparisons,not necessarily in the entire study.†Calculated from information in the article.DPP,Diabetes Prevention Program;DREAM,Diabetes REduction Assessment with ramipril and rosiglitazone Medication;DPS,Diabetes Prevention Study;STOP NIDDM,Study to Prevent Non-Insulin DependentDiabetes;XENDOS,Xenical in the prevention of Diabetes in Obese Subjects.This table has b een reprinted with permission(30with some modification.Position Statement解析：此题原创性比较好，这样才能有很好的区分度。
卡达尔健康2023盲吸营养编码指南说明书
Cardinal Health™ Nutritional Delivery2023 Enteral Nutrition Coding GuideReference: 1. Alpha-Numeric HCPCS. Centers for Medicare & Medicaid Services. https:///Medicare/Coding/HCPCSReleaseCodeSets/Alpha-Numeric-HCPCS. Last modified November 28, 2022. Accessed November 28, 2022.* CMS 2023 Alpha-Numeric HCPCS File; https:///Medicare/Coding/HCPCSReleaseCodeSets/Alpha-Numeric-HCPCS † CMS Coverage Limits in LCD L33783Note for Medicare patients: Enteral feeding supply kits (B4034-B4036) have a one-unit daily allowance; therefore, refill requirements are not applicable to these HCPCS codes. These codes must also correspond with the method of administration indicated in question 5 of the Medicare DME Information Form (CMS-10126) at https:///Medicare/CMS-Forms/CMS-Forms/downloads/cms10126.pdf.The codes contained in this guide are for informational purposes only and are not intended to serve as reimbursement advice. The information is taken from materials published by the Centers for Medicare and Medicaid Services and the American Medical Association and may be helpful to providers in staying up to date on reimbursement codes. This information is current at the time of publication of this document and subject to change. This information cannot guarantee coverage or reimbursement. Cardinal Health makes no other representations as to selecting codes for products or services or compliance with any other billing protocols or requirements. Providers should consult with each patient’s health plan directly for appropriate coverage, medical necessity, coding and billing requirements for products and services provided.© 2023 Cardinal Health. All Rights Reserved. CARDINAL HEALTH, the Cardinal Health LOGO, KANGAROO, ARGYLE, MONOJECT and DOBBHOFF are trademarks of Cardinal Health and may be registered in the US and/or in other countries. All other marks are the property of their respective owners. Patent /patents. Lit. No. 2GM20-1308734 (01/2023)Supplies and kits (continued)B4034Enteral feeding supply kit; syringe fed, per day,includes but not limited to feeding/day, includes but not limited to feeding/flushing syringe, administration set tubing, dressings, tape KANGAROO™ I.V. Pole Pouch and Kit MONOJECT™ Enteral Syringe with Tip Cap (all sizes) MONOJECT™ Medicine Syringe Straw (all sizes) KANGAROO™ Milk Straw KANGAROO™ Feeding Tube Extension Set with ENFit® Connection KANGAROO™ Bifurcated Extension Set with ENFit® Connection B4035Enteral feeding supply kit; pump fed, per day,includes but not limited to feeding/flushing syringe, administration set tubing, dressings, tape tubing, dressings, tapeKANGAROO™ ePump 500 mL or 1,000 mL SetKANGAROO™ ePump 1,000 mL Set with 1,000 mL Flush Bag KANGAROO™ ePump ENPlus Spike Set KANGAROO™ ePump ENPlus Spike Set with 1,000 mL Flush Bag KANGAROO™ ePump Burette 100 mL SetKANGAROO™ Joey Pump 500 mL or 1,000 mL Set KANGAROO™ Joey ENPlus Spike SetKANGAROO™ Joey 1,000 mL Set with 1,000 mL Flush Bag KANGAROO™ Joey ENPlus Spike Set with 1,000 mL Flush Bag KANGAROO™ Connect ENPlus Spike Set Non-Sterile KANGAROO™ Connect Feeding Set 500 mL or 1,000 mL KANGAROO™ Irrigation Piston Syringe 60 mLKANGAROO™ Irrigation Syringe with 500 mL Container 60 mL Piston SyringeKANGAROO™ Irrigation Syringe with 500 mL Container 60 mL Piston Syringe, Basin KANGAROO™ Y-Port/PEG Adapter (all colors/sizes)KANGAROO™ Y-Site Extension 6 in. (15.2 cm)B4036Enteral feeding supply kit; gravity fed, per day,includes but not limited to per day, includes but not limited to feeding/flushing syringe, administration set tubing, dressings, tape KANGAROO™ Gravity Feeding Bag Large Bore 1,000 mL KANGAROO™ Gravity Feeding Bag 1,000 mLB9998Not for enteral suppliesKANGAROO™ Bolus Feeding Kit Bulb Syringe KANGAROO™ CO Detector with Bellows †KANGAROO™ ePump Backpack KANGAROO™ ePump Pole ClampKANGAROO™ ePump Power Adapter Plug KANGAROO™ Connect Backpack KANGAROO™ Joey Power Cord KANGAROO™ Joey Pole ClampKANGAROO™ Joey Mini and Super Mini Backpacks (all colors)KANGAROO™ Skin Level Stoma Measuring Device Tube Access KANGAROO™ Skin Level Tube Access Bolus Feeding SetKANGAROO™ Skin Level Tube Access Continuous Right Angle Feeding Set KANGAROO™ Connect Enteral Feeding Pole Clamp********************************。
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The Definition and Purpose of Organisational Communication
Organisational communication is:
the process of creating and exchanging messages among communication units Understanding how the context of the organisation influences communication processes
Organisational communication has a number of purposes
– Control – Motivate – Inform – Direct – Balance needs and goals – Evaluate
Organisational Structure
Shortens lines of communication within units, but lengthens it between units Less “noise” within unit Increased employee participation in communication
Formal = slow, deliberate, largely written, on the record, oriented towards things, mgt controlled Informal = fast, spontaneous, largely verbal, off the record, oriented towards people, employee controlled
Managers may ignore or discourage employee feedback Managers may blame employees for unpleasant news Culture may not encourage employee participation
What do staff need to know?
Aims of downward communication include:
Instructions and rationale Organisational procedure and practice Feedback Indoctrination to organisational culture
Downward communication
Benefits Prevention/solving of emplosfaction Improved morale People know what is expected of them and what is happening around them Problems Unclear messages – unable to understand, poor channels etc Message overload Distorted messages – too many levels Can often be negative
Aims of horizontal communication
Co-ordinate tasks Solve problems Share information Manage conflict Build rapport
Horizontal communication
Benefits
Upward communication
Benefits
Solve old problems and prevent new ones Increased acceptance of management decisions Employee participation and involvement
Communication Concept
Introduction to communication (1)
Challenges
Diversity (11) Conflict (10)
Contexts
Listening and Perception(5) Organisational Communication (6&7)
Organisational Communication
Relates to:
Structures (flat, tall, centralised, decentralised) Flows (Formal: upward, downward, horizontal) Networking (group processes) Informal v formal communication Knowledge management
Problems
Horizontal communication
Between co-workers with different areas of responsibility
For example, heads of different departments within an organisation All have to fit into overall aims of organisation while managing different groups of staff
Tall
More layers, narrow span of control, and centralised decision making
Organisational Structure
Organisations may be
Impact on communication
Centralised
Formal communication networks
Systems designed by management to dictate who should talk to whom to get a job done
From the organisational charts
MCD2030 Managerial Communication
Week 6: Organisational Communication -Informal versus formal
Types
Oral Communication: Informative and Persuasive Speaking(3) Intra and Interpersonal Communication (4) Verbal and Non-Verbal Communication(2)
Upward communication
Employee to manager
What do managers need to know?
Aims of upward communication
Communicate what staff are doing Unsolved work problems – seek advice Suggestions for improvement Feedback about job and co-workers Vehicle to raise concerns from lower sections of the organisation
An organisation’s structure can determine how people communicate within a workplace Organisations may be
Flat
Few middle layers, decision making by teams/groups, workers have increased power
Downward Upward Horizontal
Consider these communication networks using the example of large-scale organisational change
Downward communication
Manager to employee
Increased co-operation between staff Greater understanding of organisation’s missions and values and of what others do Rivalry between employees and sections Lack of understanding between different areas Information overload Physical location of different staff Lack of need or motivation
Organisational Structure
Organisations may be Decentralised
Impact on communication
More flexible response to environment Increase in self-control and autonomy Minimal supervision and maximum empowerment Top management focus on managing