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英文药理学考卷样题
英文药理学考卷样题一、选择题（每题2分，共40分）1. Which of the following is NOT a route of drug administration?A. OralB. IntravenousC. TransdermalD. InhalationE. Intramuscular2. The process which a drug enters the bloodstream is known as:A. AbsorptionB. DistributionC. MetabolismD. ExcretionE. Bioavailability3. Which of the following is an example of a prodrug?A. PenicillinB. CodeineC. AspirinD. AcetaminophenE. Morphine4. The drug concentration in the blood at a specific time is known as:A. Peak concentrationB. HalflifeC. Steadystate concentrationD. BioavailabilityE. Therapeutic index5. Which of the following is a phase I reaction in drug metabolism?A. HydrolysisB. OxidationC. ReductionD. ConjugationE. Glucuronidation6. The drug digoxin is used to treat:A. HypertensionB. ArrhythmiasC. DiabetesD. AsthmaE. Gout7. Which of the following is a selective serotonin reuptake inhibitor (SSRI)?A. FluoxetineB. AmitriptylineC. ClonidineD. MorphineE. Risperidone8. The primary mechanism of action of ACE inhibitors is:A. Inhibition of angiotensin II productionB. Blockade of betaadrenergic receptorsC. Inhibition of sodium channelsD. Increase in nitric oxide productionE. Blockade of calcium channels9. Which of the following is a benzodiazepine?A. AlprazolamB. LithiumC. FluoxetineD. ClonidineE. Methadone10. The drug warfarin is an example of:A. An anticoagulantB. An antiplatelet agentC. A thrombolytic agentD. A diureticE. A betablocker11. Which of the following is a potassiumsparing diuretic?A. FurosemideB. SpironolactoneC. HydrochlorothiazideD. AmilorideE. Bumetanide12. The drug albuterol is used to treat:A. HypertensionB. AsthmaC. DiabetesD. GoutE. Peptic ulcer disease13. Which of the following is a muscarinic antagonist?A. AtropineB. PilocarpineC. AcetylcholineD. BethanecholE. Carbachol14. The drug metformin is used to treat:A. HypertensionB. DiabetesC. AsthmaD. GoutE. Peptic ulcer disease15. Which of the following is a cephalosporin antibiotic?A. PenicillinB. CiprofloxacinC. ErythromycinE. Ceftriaxone16. The drug morphine is used to treat:A. HypertensionB. ArrhythmiasC. PainD. AsthmaE. Gout17. Which of the following is a local anesthetic?A. LidocaineB. MorphineC. AspirinD. AcetaminophenE. Codeine18. The drug amoxicillin is used to treat:A. HypertensionB. DiabetesC. Bacterial infectionsD. AsthmaE. Gout19. Which of the following is a betalactamase inhibitor?A. Clavulanic acidB. SulbactamC. TazobactamD. All of the aboveE. None of the above20. The drug heparin is an example of:A. An anticoagulantB. An antiplatelet agentC. A thrombolytic agentD. A diureticE. A betablocker二、填空题（每题2分，共40分）21. The process which a drug is released from its dosage form is known as ____________.22. The drug concentration in the blood at a specific time is known as ____________.23. The primary site of drug metabolism is the____________.24. The drug concentration that produces a therapeutic effect is known as the ____________.25. The process which a drug is excret一、选择题答案1. E2. A3. D4. C5. B6. B7. A8. A9. A10. A11. B12. B13. A14. B15. E16. C17. A18. C19. D20. A二、填空题答案21. Drug release22. Drug concentration23. Liver24. Therapeutic concentration25. Drug excretion1. 药物代谢动力学药物吸收（Absorption）药物分布（Distribution）药物代谢（Metabolism）药物排泄（Excretion）药物浓度时间曲线（Concentrationtime curve）2. 药物效应动力学药物作用机制（Mechanism of action）药物效应（Pharmacological effects）药物副作用（Side effects）药物相互作用（Drug interactions）3. 药物剂型与给药途径药物剂型（Dosage forms）给药途径（Routes of administration）药物释放（Drug release）4. 药物分类与代表性药物抗生素（Antibiotics）抗高血压药（Antihypertensive drugs）抗糖尿病药（Antidiabetic drugs）抗心律失常药（Antiarrhythmic drugs）镇痛药（Analgesics）各题型知识点详解及示例：1. 选择题考察学生对药物基本概念、药物分类、药物作用机制、药物代谢途径等方面的掌握。
总生存期及无进展生存期偏倚产生的原因
总生存期及无进展生存期偏倚产生的原因常树建【摘要】总生存期是评价临床疗效的"金标准",但使用总生存期作为疗效判定标准可能存在偏倚.总生存期产生偏倚的可能原因包括:患者从发病到生命终止治疗的非单一性,不同组间治疗存在交叉;肿瘤患者合并慢性病对生存可能产生影响;病程中合并使用了非试验药物,如中药等.作为总生存期的替代指标,无进展生存期偏倚的主要来源为随访时间间隔的长短不同.%Overall survival is the gold standard for measuring clinical efficacy. However,there is bias in using overall survival as endpoint in clinical trial. The bias may be resulted from multiple-line treatments before patient's death,crossover of active treatment arms,the concomitant chronic diseases of the tumor which can affect patient's survival, and the treatment with non-trial active therapies, such as traditional Chinese medicine. Progression free survival( PFS ) can also be considered as a primary end-point. The bias of PFS mainly results from the interval time length of follow-up.【期刊名称】《医学综述》【年(卷),期】2013(019)011【总页数】3页(P1970-1972)【关键词】总生存期;无进展生存期;偏倚【作者】常树建【作者单位】无锡市第四人民医院肿瘤内科,江苏,无锡,214062【正文语种】中文【中图分类】R730.7循证医学时代各种各样的临床试验为临床医师的医学实践提供了依据，但由于临床工作的对象是人，人的特殊性使得临床试验结果的本身往往带有偏倚。
1乳腺癌疾病基础知识1
CR（complete response）：完全缓解。所有靶病灶消失，病理性淋巴结的短轴值<10mm
PR（ partial response ）：部分缓解。靶病灶最长径之和与基线状态比较，至少减少30% SD（ stable disease ）：疾病稳定。介于部分缓解和疾病进展之间 PD（ progressive disease ）：疾病进展。靶病灶最长径之和与治疗开始之后所记录到的最小 的靶病灶最长径之和比较，增加20%，另外，半径总和增加的绝对值还必须大于5mm。或 者出现一个或多个新病灶。 ORR （Objective Response Rate） ：客观缓解率。指肿瘤缩小达到一定量并且保持一定时 间的病人的比例，包括CR+PR的病例。 DCR (disease control rate) ：疾病控制率，是指CR+PR+SD.
全球新增乳腺癌病例138万例
GLOBOCAN 2008
中国女性第二位杀手
近17万/年新增病例
7
病因学
• 病因：确切病因仍不清楚 • 高危因素：
– 激素长期刺激 ，主要为雌激素
• 月经初潮早（早于12岁） • 绝经晚（晚于50岁） • 未育
– 家族史
• 母亲或姐妹有乳腺癌病史 • 对侧乳房曾有癌症史
• • M0：无远处转移 M1：有远处转移
常见转移部位
转移 脑 皮肤 对侧乳腺 肺 肝 骨 局部浸润 原发灶 局部浸润或 播散 局部淋巴结
治疗目的和手段
早
期
治愈
局部晚期
降低分期
晚期/转移
姑息治疗
治疗目的和手段
局部治疗
手术 放疗
全身治疗
化疗 内分泌
基础治疗 辅助治疗 新辅助治疗 姑息治疗
双标记延迟时间3D ASL对脑血管狭窄灌注代偿的评估价值
双标记延迟时间3D ASL对脑血管狭窄灌注代偿的评估价值王莉蓉，高志国，鲁金飞湖北省荆门市第二人民医院磁共振室湖北荆门448000【摘要】目的探讨磁共振三维动脉自旋标记(three-dimensional arterial spin labeling,3D ASL)采用双标记延迟时间(postlabeling delayt,PLD)评估脑血管狭窄或闭塞后侧枝循环灌注代偿的价值。
方法以一侧颅内供血动脉严重狭窄或闭塞的患者为观察对象,所有患者均行DWI、MRA、3D ASL及DSA检查,ASL采用两个标记延迟时间进行扫描，评估脑血管狭窄或闭塞后侧枝循环代偿情况。
结果28例中6例DWI提示小面积急性脑梗塞，余22例DWI未见异常，所有患者均可见责任血管供血区域的低灌注改变,缺血侧CBF1.5与对侧CBF1.5比较差异有统计学意义,缺血侧CBF2.5与对侧CBF2.5比较差异有统计学意义,缺血侧CBF1.5与同侧CBF2.5比较差异有统计学意义。
结论双标记延迟时间3D ASL可以有效评估责任血管供血区的灌注情况，以及侧枝循环代偿情况，为临床精细、个体化治疗提供理论依据。
【关键词】动脉自旋标记;双标记延迟时间;脑血管狭窄;磁共振成像中图分类号:R743；R445.2文献标识码:A文章编号:1006-9011(2021)048546-04VaUie of3D ASL with dual postlabeling delays in evaUiation of perfision compensation of ceredrai vascular stenosis WANG Liroog,GAO Zhipuw,LU JiufeiDepaOment of MRI and Intervention,The Second People'o Hosoital o fingmee,Jingmee448000,P.R.China*Abstract]Objective To evaluate the value of three-dimensional arterial spin labeling imaging(3D ASL)with dual postlabeling delays in evaluating perfusion compensation of cerebral vascular stenosis.Methods Patients with severe stenosis oe occlusion of one side cerebral vascular were enrolled in this study.AH patients were performed DWI,MRA,3D ASL(with dual labeled delays)and DSA examination,te evaluate the compensation of collateral circulation.Reselts Only6cases presented with small area of the acute cerebral infarction in28patients,al patients with low perfusion in responsibility blood-supply area.There were significant dmerences of CBF1.5between the Ischemio side and the contralaterai area(P<0.05).There were significanh dmerences of CBF2.5between the Ischemio side and the contralaterai area(P'0.05).There were significant differences of Is-chemio side between C BF1.5and CBF2.5(P'0.05).Conclusion3D ASL with duai postlabeling delays can evaluate the perfusion compensation of circulation,and provide basis for individualized Weatwent.*Key words]Arteriai spin labeling；Duai postlabeling delays；Cerebrai vascular stenosis；Magnetio resonancc irnaaing动脉狭窄或闭塞是脑组织灌注减低的基础，但狭窄程度与脑卒中的发生并无明显相关性,这取决于侧枝循环代偿储备能力。
德曲妥珠单抗对比恩美曲妥珠单抗二线治疗HER2_阳性转移性乳腺癌的成本-效用分析
·药物经济学·德曲妥珠单抗对比恩美曲妥珠单抗二线治疗HER 2阳性转移性乳腺癌的成本-效用分析Δ武亚楠＊，吴方，侯艳红 #（中国药科大学国际医药商学院，南京 211198）中图分类号 R 956；R 979.1 文献标志码 A 文章编号 1001-0408（2024）02-0204-06DOI 10.6039/j.issn.1001-0408.2024.02.14摘要 目的 评估德曲妥珠单抗（T-DXd ）对比恩美曲妥珠单抗（T-DM 1）二线治疗HER 2阳性转移性乳腺癌的经济性，为临床用药方案的选择及医疗卫生决策提供依据。
方法 基于DESTINY-Breast 03试验构建分区生存模型，以3周为循环周期，模拟至患者终身。
以质量调整生命年（QALY ）作为产出指标并计算增量成本-效果比（ICER ），再利用敏感性分析验证基础分析结果的稳健性，以此来比较T-DXd 与T-DM 1二线治疗HER 2阳性转移性乳腺癌的经济性。
结果 在以3倍我国2022年人均国内生产总值（GDP ）为意愿支付阈值（257 094元/QALY ）的前提下，使用T-DXd 方案的患者在获得增量效用（0.69 QALYs ）的同时也需要支付更多成本，ICER 值为1 850 478.40元/QALY 。
单因素敏感性分析结果显示，对ICER 影响较大的因素有无进展生存期状态效用值、T-DXd 价格、成本贴现率等，但这些参数在合理范围内波动均不能使基础分析结果发生翻转。
概率敏感性分析结果显示，当WTP 的阈值上升为1 500 400元/QALY 时，T-DXd 方案具有经济性的概率为50%。
情境分析结果也验证了基础分析结果的稳健性。
结论 在以3倍我国人均GDP 为意愿支付阈值的前提下，与T-DM 1方案相比，T-DXd 二线治疗HER 2阳性转移性乳腺癌不具有经济性。
关键词 德曲妥珠单抗；恩美曲妥珠单抗；HER 2阳性转移性乳腺癌；分区生存模型；成本-效用分析Cost -utility analysis of trastuzumab deruxtecan versus trastuzumab emtansine in the second -line treatment for HER 2-positive metastatic breast cancerWU Yanan ，WU Fang ，HOU Yanhong （School of International Pharmaceutical Business ，China Pharmaceutical University ，Nanjing 211198，China ）ABSTRACTOBJECTIVE To evaluate the cost-effectiveness of trastuzumab deruxtecan （T-DXd ） versus trastuzumab emtansine（T-DM 1） in the second-line treatment of HER 2-positive metastatic breast cancer ， and to provide a basis for the selection of clinical medication regimen and medical and health decisions. METHODS Based on the clinical trial DESTINY-Breast 03， a partitioned survival model was constructed ， with a cycle of 3 weeks as the simulation of patients ’ lifetime. The incremental cost-effectiveness ratio （ICER ） was calculated by using quality-adjusted life years （QALY ） as output indicators ， and sensitivity analysis was used to verify the robustness of the basic analysis results ； the cost-effectiveness of the second-line treatment for HER 2-positive metastatic breast cancer was compared between T-DXd and T-DM 1. RESULTS Under the premise of taking 3 times China ’s per capita gross domestic product （GDP ） in 2022 as the willingness-to-pay threshold （257 094 yuan/QALY ）， the T-DXd group also needed to pay more cost compared with T-DM 1 group while obtaining incremental utility （0.69 QALYs ）， and the ICER value was 1 850 478.40 yuan/QALY . The results of univariate sensitivity analysis showed that progression-free survival state utility value ， T-DXd price ， cost discount rate were factors that had a great influence on ICER value ， but these parameters could not flip the basic analysis results within a reasonable range. In the probability sensitivity analysis ， when the threshold of willingness-to-pay rose to 1 500 400 yuan/QALY ， the probability of economic activity was 50% in the T-DXd regimen. The results of the scenario analysis also verified the robustness of the original research results. CONCLUSIONS Under the premise of 3 times China ’s per capita GDP as the WTP threshold ， compared with T-DM 1， T-DXd is not cost-effective in the second-line treatment of HER 2-positive metastatic breast cancer.KEYWORDStrastuzumab deruxtecan ； trastuzumab emtansine ； HER 2-positive metastatic breast cancer ； partitioned survivalmodel ； cost-utility analysis乳腺癌是女性最常见的恶性肿瘤。
VERSILOK 254 产品说明书
USA SAFETY DATA SHEET1. CHEMICAL PRODUCT AND COMPANY IDENTIFICATIONProduct name:VERSILOK 254Product Use/Class: Acrylic Adhesive, Part 2 of 2LORD Corporation111 LORD DriveCary, NC 27511-7923 USATelephone: 814 868-3180Non-Transportation Emergency: 814 763-2345Chemtrec 24 Hr Transportation Emergency No.800 424-9300 (Outside Continental U.S. 703 527-3887)EFFECTIVE DATE: 11/18/20202. HAZARDS IDENTIFICATIONGHS CLASSIFICATION:Acute toxicity Inhalation - Dust and MistCategory 4 - 63.1% of the mixture consists of ingredient(s) of unknown toxicity.Reproductive toxicity Category 2Specific target organ systemic toxicity (single exposure) Category 1 Nervous systemSpecific target organ systemic toxicity (repeated exposure) Category 1 Nervous systemSpecific target organ systemic toxicity (repeated exposure) Category 2 Adrenal glandHazardous to the aquatic environment - acute hazard Category 1Hazardous to the aquatic environment - chronic hazard Category 1GHS LABEL ELEMENTS:Symbol(s)Signal WordD ANGERHazard StatementsHarmful if inhaled.Suspected of damaging fertility or the unborn child.Causes damage to organs.(Nervous system)Causes damage to organs through prolonged or repeated exposure.(Nervous system)May cause damage to organs through prolonged or repeated exposure.(Adrenal gland)Very toxic to aquatic life.Very toxic to aquatic life with long lasting effects.Precautionary StatementsPreventionObtain special instructions before use.Do not handle until all safety precautions have been read and understood.Use personal protective equipment as required.Do not breathe dust/fume/gas/mist/vapors/spray.Wash thoroughly after handling.Do not eat, drink or smoke when using this product.Use only outdoors or in a well-ventilated area.Avoid release to the environment.300000001064ResponseCall a POISON CENTER or doctor/physician if you feel unwell.IF exposed: Call a POISON CENTER or doctor/physician.Specific treatment (see supplemental first aid instructions on this label).IF INHALED: Remove to fresh air and keep at rest in a position comfortable for breathing.Collect spillage.StorageStore locked up.Disposal:Dispose of contents/container in accordance with waste/disposal laws and regulations of your country or particular locality.Other Hazards:This product contains component(s) which have the following warnings; however based on the GHS classification criteria of your country or locale, the product mixture may be outside the respective category(s).Acute: Dermal absorption possible. May cause eye irritation. May cause respiratory tract irritation. May causeheadache and nausea. See Section 11 for additional information. May be harmful if swallowed. Ingestion is not an expected route of entry in industrial or commercial uses.Chronic: Repeated or prolonged skin contact may cause allergic reactions with susceptible persons. Chronicexposure to the tricresyl phosphate in this product may cause adrenal, reproductive and developmental effects based on animal data. See Section 11 for additional information.withheld.FIRST AID - EYE CONTACT: Flush eyes immediately with large amount of water for at least 15 minutes holding eyelids open while flushing. Get prompt medical attention.FIRST AID - SKIN CONTACT: Flush contaminated skin with large amounts of water while removing contaminated clothing. Wash affected skin areas with soap and water. Get medical attention if symptoms occur.FIRST AID - INHALATION: Move person to fresh air. Restore and support continued breathing. If breathing is difficult, give oxygen. Get immediate medical attention.FIRST AID - INGESTION: If swallowed, do not induce vomiting. Call a physician or poison control center immediately for further instructions. Never give anything by mouth if victim is rapidly losing consciousness, unconscious or convulsing.SUITABLE EXTINGUISHING MEDIA: Carbon Dioxide, Dry Chemical, Foam, Water FogUNSUITABLE EXTINGUISHING MEDIA: Not determined for this product.SPECIFIC HAZARDS POSSIBLY ARISING FROM THE CHEMICAL: Keep containers tightly closed. Closed containers may rupture when exposed to extreme heat. Use water spray to keep fire exposed containers cool. During a fire, irritating and/or toxic gases and particulate may be generated by thermal decomposition or combustion.SPECIAL PROTECTIVE EQUIPMENT AND PRECAUTIONS FOR FIRE-FIGHTERS: Wear full firefighting protective clothing, including self-contained breathing apparatus (SCBA). If water is used, fog nozzles are preferable.PERSONAL PRECAUTIONS, PROTECTIVE EQUIPMENT AND EMERGENCY PROCEDURES: Avoid breathing vapors. Avoid contact. Use appropriate respiratory protection for large spills or spills in confined area.ENVIRONMENTAL PRECAUTIONS: Do not contaminate bodies of water, waterways, or ditches, with chemical or used container.METHODS AND MATERIALS FOR CONTAINMENT AND CLEANUP: Notify appropriate authorities if necessary. Avoid contact. Keep non-essential personnel away from spill area. Scoop spilled material into an appropriate container for proper disposal. (If necessary, use inert absorbent material to aid in containing the spill).HANDLING: Keep closure tight and container upright to prevent leakage. Avoid skin and eye contact. Wash thoroughly after handling. Do not handle until all safety precautions have been read and understood.STORAGE: Store only in well-ventilated areas. Keep container closed when not in use.INCOMPATIBILITY: Amines, acids, water, hydroxyl, or active hydrogen compounds.Engineering controls: Sufficient ventilation in pattern and volume should be provided in order to maintain air contaminant levels below recommended exposure limits.PERSONAL PROTECTION MEASURES/EQUIPMENT:RESPIRATORY PROTECTION: Use a NIOSH approved air-purifying organic vapor respirator if occupational limits are exceeded. For emergency situations, confined space use, or other conditions where exposure limits may be greatly exceeded, use an approved air-supplied respirator. For respirator use observe OSHA regulations (29CFR1910.134) or use in accordance with applicable laws and regulations of your country or particular locality.SKIN PROTECTION: Use neoprene, nitrile, or rubber gloves to prevent skin contact.EYE PROTECTION: Use safety eyewear including safety glasses with side shields and chemical goggles where splashing may occur.OTHER PROTECTIVE EQUIPMENT: Use disposable or impervious clothing if work clothing contamination is likely. Remove and wash contaminated clothing before reuse.HYGIENIC PRACTICES: Wash hands before eating, smoking, or using toilet facility. Food or beverages should not be consumed anywhere this product is handled or stored. Wash thoroughly after handling.Typical values, not to be used for specification purposes.ODOR: Epoxy VAPOR PRESSURE: N.D.APPEARANCE: Gray VAPOR DENSITY: Heavier than AirPHYSICAL STATE: Liquid LOWER EXPLOSIVE LIMIT: Not ApplicableUPPER EXPLOSIVE LIMIT: Not ApplicableFLASH POINT:≥ 201 °F, 93 °CSetaflash Closed CupBOILING RANGE: N.A.EVAPORATION RATE: Not Applicable AUTOIGNITION TEMPERATURE:N.D.DENSITY: 1.44 g/cm3 (11.97 lb/gal) DECOMPOSITION TEMPERATURE:N.D. VISCOSITY, DYNAMIC: N.D.ODOR THRESHOLD: N.D.VISCOSITY, KINEMATIC: N.D.SOLUBILITY IN H2O: Insoluble VOLATILE BY WEIGHT: 0.03 %pH: N.A.VOLATILE BY VOLUME: 0.05 %FREEZE POINT: N.D. VOC CALCULATED: 0 lb/gal, 0 g/l0 g/lN.D. METHOD 24: 0.85 lbs/gal COEFFICIENT OF WATER/OILDISTRIBUTION:LEGEND: N.A. - Not Applicable, N.E. - Not Established, N.D. - Not DeterminedHAZARDOUS POLYMERIZATION: Hazardous polymerization will not occur under normal conditions. STABILITY: Product is stable under normal storage conditions.CONDITIONS TO AVOID: High temperatures.INCOMPATIBILITY: Amines, acids, water, hydroxyl, or active hydrogen compounds.HAZARDOUS DECOMPOSITION PRODUCTS: Carbon monoxide, carbon dioxide, aldehydes, Oxides of phosphorusEXPOSURE PATH: Refer to section 2 of this SDS.SYMPTOMS:Refer to section 2 of this SDS.TOXICITY MEASURES:Germ cell mutagenicity: No classification proposedCarcinogenicity: No classification proposedReproductive toxicity: Category 2 - Suspected of damaging fertility or the unborn child.Components contributing to classification: Tricresyl phosphate.TOXICOLOGICAL INFORMATION:Historical data on Tricresyl phosphate (TCP) has shown neurological effects associated with levels of the ortho isomer within TCP. The manufacturer of the TCP in this product has noted on their SDS that the TCP does not exhibit negative neurological effects based on toxicology and epidemiology studies. This LORD product may contain a very small amount of the ortho isomer. However, LORD analytical testing of the raw material containing TCP indicates no ortho isomer present. Also, based on the TCP manufacturer's information, the LORD product content should not exceed225ppm, if present at all.ECOTOXICITY:PERSISTENCE AND DEGRADABILITY:Not determined for this product.BIOACCUMULATIVE: Not determined for this product.MOBILITY IN SOIL: Not determined for this product.OTHER ADVERSE EFFECTS: Not determined for this product.DISPOSAL METHOD: Disposal should be done in accordance with Federal (40CFR Part 261), state and local environmental control regulations. If waste is determined to be hazardous, use licensed hazardous waste transporter and disposal facility.US DOT RoadProper Shipping Name: Environmentally hazardous substances, liquid, n.o.s.Hazard Class: 9SECONDARY HAZARD: NoneUN/NA Number: 3082Packing Group: IIIEmergency Response Guide Number: 171For US DOT non-bulk road shipments this material may be classified as NOT REGULATED. For the most accurate shipping information, refer to your transportation/compliance department regarding changes inpackage size, mode of shipment or other regulatory descriptors.IATA CargoPROPER SHIPPING NAME: Environmentally hazardous substance, liquid, n.o.s.Hazard Class: 9HAZARD CLASS: NoneUN NUMBER: 3082PACKING GROUP: IIIEMS: 9LIMDGPROPER SHIPPING NAME: Environmentally hazardous substance, liquid, n.o.s.Hazard Class: 9HAZARD CLASS: NoneUN NUMBER: 3082PACKING GROUP: IIIEMS: F-AThe listed transportation classification applies to non-bulk shipments. It does not address regulatory variations due to changes in package size, mode of shipment or other regulatory descriptors. For the most accurate shipping information, refer to your transportation/compliance department.U.S. FEDERAL REGULATIONS: AS FOLLOWS:SARA SECTION 313This product contains the following substances subject to the reporting requirements of Section 313 of Title III of the Superfund Amendment and Reauthorization Act of 1986 and 40 CFR part 372.:Chemical Name CAS Number Weight % Less ThanDibenzoyl peroxide94-36-0 5.0%TOXIC SUBSTANCES CONTROL ACT:INVENTORY STATUSThe chemical substances in this product are on the TSCA Section 8 Inventory.EXPORT NOTIFICATIONThis product contains the following chemical substances subject to the reporting requirements of TSCA 12(B) if exported from the United States:NoneUnder HazCom 2012 it is optional to continue using the HMIS rating system. It is important to ensure employees have been trained to recognize the different numeric ratings associated with the HazCom 2012 and HMIS schemes.HMIS RATINGS - HEALTH: 2* FLAMMABILITY: 1 PHYSICAL HAZARD: 1* - Indicates a chronic hazard; see Section 2Revision: Company LogoEffective Date: 11/18/2020The information contained herein is, to the best of our knowledge and belief, accurate. However, since the conditions of handling and use are beyond our control, we make no guarantee of results, and assume no liability for damages incurred by use of this material. It is the responsibility of the user to comply with all applicable federal, state and local laws and regulations.。
三甲复脉汤加减辨治快速型心房颤动医案
医话医案中国民间疗法 犆犎犐犖犃 犛犖犃犜犝犚犗犘犃犜犎犢，犕犪狉 ２０２４，犞狅犾 ３２犖狅 ５ 参考文献［１］ＮＡＧＨＡＶＩＭ，ＷＡＮＧＨ，ＬＯＺＡＮＯＲ，ｅｔａｌ．Ｇｌｏｂａｌ，ｒｅ ｇｉｏｎａｌ，ａｎｄｎａｔｉｏｎａｌａｇｅ ｓｅｘｓｐｅｃｉｆｉｃａｌｌ ｃａｕｓｅａｎｄｃａｕｓｅ ｓｐｅ ｃｉｆｉｃｍｏｒｔａｌｉｔｙｆｏｒ２４０ｃａｕｓｅｓｏｆｄｅａｔｈ，１９９０—２０１３：ａｓｙｓ ｔｅｍａｔｉｃａｎａｌｙｓｉｓｆｏｒｔｈｅｇｌｏｂａｌｂｕｒｄｅｎｏｆｄｉｓｅａｓｅｓｔｕｄｙ２０１３［Ｊ］．Ｌａｎｃｅｔ，２０１５，３８５（９９６３）：１１７ １７１．［２］ＺＨＡＮＧＬＸ，ＷＡＮＧＦ，ＷＡＮＧＬ，ｅｔａｌ．ＰｒｅｖａｌｅｎｃｅｏｆｃｈｒｏｎｉｃｋｉｄｎｅｙｄｉｓｅａｓｅｉｎＣｈｉｎａ：ａｃｒｏｓｓ：ｓｅｃｔｉｏｎａｌｓｕｒｖｅｙ［Ｊ］．Ｌａｎｃｅｔ，２０１２，３７９（９８１８）：８１５ ８２２．［３］桂志红，黄刚，王华富，等．加味益肾活血方对慢性肾脏病５期患者肠道微生态的影响［Ｊ］．南京中医药大学学报，２０１９，３５（３）：２５８ ２６１．［４］李佳霖，王倩，赵海玲，等．慢性肾脏病临床危险因素研究［Ｊ］．世界中医药，２０２０，１５（１７）：２５３８ ２５４３．［５］ＧＯＮ ＡＬＶＥＳＧＬ，ＣＯＳＴＡ ＰＥＳＳＯＡＪＭ，ＴＨＩＥＭＥＫ，ｅｔａｌ．ＩｎｔｒａｃｅｌｌｕｌａｒａｌｂｕｍｉｎｏｖｅｒｌｏａｄｅｌｉｃｉｔｓｅｎｄｏｐｌａｓｍｉｃｒｅｔｉｃｕｌｕｍｓｔｒｅｓｓａｎｄＰＫＣ ｄｅｌｔａ／ｐ３８ＭＡＰＫｐａｔｈｗａｙａｃｔｉｖａｔｉｏｎｔｏｉｎｄｕｃｅｐｏｄｏｃｙｔｅａｐｏｐｔｏｓｉｓ［Ｊ］．ＳｃｉＲｅｐ，２０１８，８（１）：１８０１２．［６］ＳＧＡＬＨＡＤＯＭ，ＫＥＭＰＪＡ，ＡＺＥＶＥＤＯＲ，ｅｔａｌ．Ｃｏｕｌｄｒｅｓｉｓ ｔａｎｔｓｔａｒｃｈｓｕｐｐｌｅｍｅｎｔａｔｉｏｎｉｍｐｒｏｖｅｉｎｆｌａｍｍａｔｏｒｙａｎｄｏｘｉｄａｔｉｖｅｓｔｒｅｓｓｂｉｏｍａｒｋｅｒｓａｎｄｕｒｅｍｉｃｔｏｘｉｎｓｌｅｖｅｌｓｉｎｈｅｍｏｄｉａｌｙｓｉｓｐａ ｔｉｅｎｔｓＡｐｉｌｏｔｒａｎｄｏｍｉｚｅｄｃｏｎｔｒｏｌｌｅｄｔｒｉａｌ［Ｊ］．ＦｏｏｄＦｕｎｃｔ，２０１８，９（１２）：６５０８ ６５１６．［７］张泽宇，尹良红．缺氧诱导因子调节铁调素在肾性贫血中的研究进展［Ｊ］．中国病理生理杂志，２０２１，３７（３）：５５８ ５６４．［８］钱寒阳，任文凯，王宁宁．重视继发性甲状旁腺功能亢进患者术后甲状旁腺激素持续过低状态［Ｊ］．肾脏病与透析肾移植杂志，２０２１，３０（４）：３６８ ３７３．［９］陈胜男，李宁，申燕．２种风险预测模型在慢性肾脏病患者动脉粥样硬化风险预测中的价值［Ｊ］．中南大学学报（医学版），２０２１，４６（９）：９６６ ９７３．［１０］ＯＲＡＹＭ，ＡＢＵＳＫ，ＥＢＲＡＨＩＭＩＡＤＩＢＮ，ｅｔａｌ．Ｌｏｎｇ ｔｅｒｍｓｉｄｅｅｆｆｅｃｔｓｏｆｇｌｕｃｏｃｏｒｔｉｃｏｉｄｓ［Ｊ］．ＥｘｐｅｒｔＯｐｉｎＤｒｕｇＳａｆ，２０１６，１５（４）：４５７ ４６５．［１１］李燕，胡顺金，孙咏，等．中药内服联合保留灌肠治疗慢性肾脏病系统评价［Ｊ］．中医药临床杂志，２０２１，３３（１）：９８ １０６．［１２］孙蓓蓓，何立群．何立群教授运用中医药治疗慢性肾脏病经验集锦［Ｊ］．世界中医药，２０１９，１４（５）：１１０２ １１０５．［１３］孙鲁英，孙卫卫，周少峰，等．中医药防治慢性肾脏病的临床证据及效应机制［Ｊ］．生物医学转化，２０２２，３（３）：３１ ４４，６３．［１４］田济，范玉强．国医大师张大宁论治慢性肾功能衰竭经验管窥［Ｊ］．中华中医药杂志，２０１９，３４（１０）：４６０７ ４６０９．［１５］窦一田，杨洪涛，林燕，等．名老中医曹式丽治疗慢性肾脏病３期经验概述［Ｊ］．中华中医药杂志，２０１７，３２（１１）：４９７８ ４９８０．［１６］张小娟，蒋珍秀，董娜．基于肠道微生态及“肠 肾轴”理论探讨慢性肾脏病从脾论治机理［Ｊ］．中国中医药信息杂志，２０２０，２７（６）：１４ １７．［１７］李雅纯，刘利飞，陈志强．化瘀及通络中药对糖尿病肾病大鼠肾脏氧化应激和ＴＧＦ β１／ｐ３８ＭＡＰＫ信号转导通路的影响［Ｊ］．时珍国医国药，２０２１，３２（６）：１２８６ １２８９．（收稿日期：２０２２ １０ ２８）［编辑：周荣荣］※基金项目：２０２１年度齐鲁医派中医学术流派传承项目（鲁卫函〔２０２１〕４５号）；齐鲁中医药优势专科集群建设单位（鲁卫函〔２０２１〕２号）通信作者：张蕴慧，Ｅ ｍａｉｌ：１４４４５７５１４８＠ｑｑ．ｃｏｍ第一作者：刘华峥，Ｅ ｍａｉｌ：１５９９６２３４０９＠ｑｑ．ｃｏｍ三甲复脉汤加减辨治快速型心房颤动医案※刘华峥１张蕴慧１，蔡兆明２（１．山东中医药大学，山东济南２５０３５５；２．山东中医药大学附属医院，山东济南２５００１４）【摘要】 心房颤动属中医“心悸”范畴，张蕴慧教授认为“阴虚不能敛阳，阴阳无法续接”是其发病的主要原因，并提出“滋阴潜阳，养血复脉”的治疗原则。
不可手术切除的肝细胞癌的疗效评价标准——改良RECIST标准更可靠
ｓ ｍｅ ａ ｈ ｔｂ ｆ ｒ ｈ ｒ ａ ｍｅ ｔ ｏ ｖ ｎ ｂ ｃ ｍｅ ｎ ａ ｇ ｄ Ｔ ｅ ｅ ｏ ｅ ａ ｓ ｔ ａ ｅ ｏ ｅ ｔ ｅ ｔ ｔ ｎ ， ｒ ｅ ｅ ｅ ｏ ｓ ｅ ｌｒ ｅ ． ｈ ｒ ｆ ｒ ， ｔ ｄ ｔ ｎ ｌｒｓ ｏ ｓ ｖ ｕ ｔ ｎ ｅ ｒ ｉ ｏ ａ ｅ ｐ ｎ ｅ ｅ ａ ａｉ ａ ｉ ｌ ｏ
ｒｌ ｂｅｊｄ ｍ ｎ ｒｈ ｅａｅ ｔ ｅｕｔ ｏ ｔ ｖｎｉ ａ ｔｅａｙａｄｔｒｅ ｎ ｒｇｃｎｂ ｂａｎｄ （ ｅｉ ｌ ｕ ｇ ｅ ｔ ｅｔ ｒｐｕｉ ｒｓｌ ｆｎｅ ｅ ｔｎ ｒｐ ｎ ｇｔ ｇｄ ａ ｅｏ ｔ ｅ ． Ｊ ａ ｏ ｆ ｔ ｈ ｃ ｓ ｉ ｒ ｏｌ ｈ ａ ｉ ｕ ｉ
于 介 人 治 疗 和 靶 向药 物 等 治 疗 ， 良 Ｒ ＣＳ 改 Ｅ ＩＴ标 准 的 评估 结果 更 可 靠 。
【 键 词 】 肝 细 胞 癌 ； 体 瘤 评 估 标 准 ； 效 评 价 关 实 疗
中 图分 类 号 ：７ ５７ 文 献 标 志 码 ： 文章 编 号 ：０ ８７ ４ ２ １ ） ３０７ —３ Ｒ ３． Ａ １ｏ —９ Ｘ（０ ２ － —１７０ ０
实体瘤疗效评价标准 (recist)
实体瘤疗效评价标准 (recist)1. RECIST是实体瘤疗效评价的国际通用标准。
RECIST is the international standard for evaluating the efficacy of solid tumor treatments.2. RECIST标准包括一系列标准化测量方法和评估指标。
The RECIST criteria include a series of standardized measurement methods and evaluation indicators.3.通过RECIST标准，医生可以更准确地评估患者疗效。
With the RECIST criteria, doctors can more accurately evaluate the efficacy of patients.4. RECIST标准主要用于评估化疗、放疗和靶向治疗的疗效。
The RECIST criteria are mainly used to evaluate the efficacy of chemotherapy, radiotherapy, and targeted therapy.5.根据RECIST标准，肿瘤疗效一般分为完全缓解、部分缓解、疾病稳定和疾病进展四个阶段。
According to the RECIST criteria, tumor efficacy is generally classified as complete response, partial response, stable disease, and disease progression.6. RECIST标准要求医生在治疗前后通过影像学检查测量肿瘤的尺寸变化。
The RECIST criteria require doctors to measure the size changes of tumors through radiological examinations before and after treatment.7.通过RECIST标准可以更客观地评估患者的治疗效果。
恶性肿瘤药物治疗相关不良事件健康状态负效用测量研究的系统评价
China Pharmacy 2022V ol.33No.14中国药房2022年第33卷第14期恶性肿瘤药物治疗相关不良事件健康状态负效用测量研究的系统评价Δ卢钰琼＊，代展菁，路云，常峰#（中国药科大学国际医药商学院，南京211198）中图分类号R 956文献标志码A 文章编号1001-0408（2022）14-1748-06DOI 10.6039/j.issn.1001-0408.2022.14.15摘要目的为我国开展健康状态负效用测量研究、计算药物经济学评价中的健康产出提供方法学参考。
方法计算机检索中国知网、万方数据、维普网3个中文数据库和PubMed 、Web of Science 、the Cochrane Library 3个英文数据库中有关恶性肿瘤药物治疗相关不良事件负效用测量的文献，检索时限均为各数据库建库起至2021年7月。
由2名研究者独立筛选文献并提取资料后进行定性分析，采用改良后的英国国家卫生与临床优化研究所决策技术支持文件进行质量评估，总结健康状态负效用测量的实践情况和存在问题并提出建议。
结果共纳入相关文献77篇。
首篇文献发表于1991年，之后发表数量呈波动式上升。
77篇文献共涉及120种不良事件，以效用研究（49篇，63.64％）为主，仅有3篇（3.90％）的调查国家/地区涉及中国。
35篇文献（45.45％）未说明研究设计类型；48篇（62.34％）未说明健康状态开发方法；52篇（67.53％）未说明健康状态验证方法；46篇（59.74％）设定并说明了基础健康状态；20篇（25.97％）进行了健康状态排名；应用的效用测量工具主要为标准博弈法和欧洲五维健康量表（各23篇，各占29.87％）；45篇（58.44％）的调研对象为患者人群；63篇（81.82％）未说明人群代表性检验；效用报告类型包括负值、非负值以及合并基础状态的非负值3种类型；45篇（58.44％）未说明效用统计方法。
E14 Guideline (R3) - questions and answers说明书
30 Churchill Place ● Canary Wharf ● London E14 5EU ● United Kingdom Telephone +44 (0)20 3660 6000 Facsimile +44 (0)20 3660 555525 January 2016EMA/CHMP/ICH/310133/2008Committee for Human Medicinal ProductsICH guideline E14: the clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (R3) - questions and answersStep 5E14 Q&As (R3) Document HistoryICH guideline E14: the clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs (R3) - questions and answersICH guideline E14 (R3) - questions and answersTable of contents1E lectrocardiograms methodology (4)2G ender (9)3P ositive control (10)4S tudy design (12)5U se of concentration response modeling of QTc data (13)6S pecial cases (16)7E lectrocardiograms monitoring in late stage clinical trials (17)ICH guideline E14 (R3) - questions and answers1Electrocardiograms methodologyICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 4/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 5/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 6/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 7/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 8/202GenderICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 9/203Positive controlICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 10/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 11/204Study designICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 12/205Use of concentration response modeling of QTc dataICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 13/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 14/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 15/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 16/20 6 Special cases6.1 March2014 The ICH E14 Guideline states that in certain cases a conventional thoroughQT study might not be feasible. In suchcases what other methods should beused for evaluation of QT/QTc andproarrhythmic potential? In certain cases the conventional “thorough QT/QTc” study design (a crossover study in healthy volunteers with short-term administration of the usual maximum dose and one higher dose with placebo and positive control) might need to be modified for a drug or active metabolite with a long half-life or delayed QT effect, or because of safety, tolerability or practical issues that preclude use in healthy subjects. In most cases alternative designs can be used that may affect power considerations, but do notcompromise study interpretation. For example, multiple doses can be studied in aparallel design trial or can use patients with the disease for which the drug is intendedrather than healthy volunteers.Where a placebo-controlled comparison using appropriate doses is not possible,alternative study d esigns should incorporate as many of the usual “thorough QT/QTc”design features as possible, and the quality and extent of the pre-clinical evaluation (ICHS7B Guideline) is particularly critical. Other useful supplementary data might includeintensive ECG data acquisition in early phase single or multiple ascending dose studies,utilisation of concentration-response analysis, and evaluation of exposures that aregreater than are anticipated with the intended marketed dose.A single dose of a positive control is generally sufficient, even if it precedes theinvestigational drug treatment. In the absence of a positive control, there is reluctanceto draw conclusions of lack of an effect; however, if the upper bound of the two-sided90% confidence interval around the estimated maximal effect on QTc is less than 10 ms,it is unlikely to have an actual mean effect as large as 20 ms.When a thorough QTc study of usual or modified design is not feasible, the intensity oflate phase ECG monitoring will be dependent upon the quality and extent of the non-clinical and clinical evaluation. In situations where it is not possible to study higherexposures than are anticipated with the intended marketed dose, more intensive ECGmonitoring might be necessary during Phase 3 trials. When the non-clinical and early7Electrocardiograms monitoring in late stage clinical trialsICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 17/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 18/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 19/20ICH guideline E14 (R3) - questions and answersEMA/CHMP/ICH/310133/2008 Page 20/20。
血药浓度随时间变化的规律及药动学...
血药浓度随时间变化的规律及药动学参数（The regularity and pharmacokinetic parameters of serum concentration with time）The regularity and pharmacokinetic parameters of serum concentration with time(I) drug time curveAfter administration of drug concentration in vivo by transfer or transformation that is changing with time, effect also changes along with concentration, such as curve representation, the former is called curve relationship (Time-concentration Relationship Curve), the latter for the aging curve(Time-response Relationship Curve).Taking the non intravenous administration for example, the dose duration relationship and the time dependence of the drug pass through the following three stages: incubation period, duration, and residual period.Incubation period: the time after which medication starts to function, reflecting the absorption and distribution of drugs;Duration: the time at which an effective concentration of the drug is maintained;Residual period: the concentration of the drug has been reduced to below the minimum effective concentration, but has not yet been completely eliminated from the body.(three) elimination kinetics of drugs: the dynamic process ofcontinuous attenuation of serum concentration.Elimination of drugs: the process of biotransformation and excretion of drugs that results in the disappearance of pharmacological activity. There are two kinds of the kinetics of the elimination of drugs:1, first-order elimination kinetics: the elimination of drugs at a constant rate per unit time.That is, the rate of elimination of drugs in the blood is directly proportional to the concentration of drugs in the blood, the blood concentration of the body is high, the amount of drugs is eliminated in unit time, and the elimination rate decreases with the decrease of serum concentration. After the decrease in serum concentration, the elimination of the drug is still eliminated at a rate. Therefore, it is also called the constant ratio elimination of drugs. Most drugs are eliminated this way.Such as the elimination of 1/2 per hour.2. Zero elimination kinetics: the elimination of a constant amount of drugs per unit time. That is, regardless of the level of plasma drug concentration, the amount of drugs removed per unit time. It is also known as the quantity of drug elimination. Often too much, more than the maximum elimination capacity caused by the body.Such as the elimination of 100mg/h per hour.(three) elimination kinetics of drugs: the dynamic process of continuous attenuation of serum concentration.Elimination of drugs: the process of biotransformation and excretion of drugs that results in the disappearance of pharmacological activity. There are two kinds of the kinetics of the elimination of drugs:1, first-order elimination kinetics: the elimination of drugs at a constant rate per unit time.That is, the rate of elimination of drugs in the blood is directly proportional to the concentration of drugs in the blood, the blood concentration of the body is high, the amount of drugs is eliminated in unit time, and the elimination rate decreases with the decrease of serum concentration. After the decrease in serum concentration, the elimination of the drug is still eliminated at a rate. Therefore, it is also called the constant ratio elimination of drugs. Most drugs are eliminated this way.Such as the elimination of 1/2 per hour.2. Zero elimination kinetics: the elimination of a constant amount of drugs per unit time. That is, regardless of the level of plasma drug concentration, the amount of drugs removed per unit time. It is also known as the quantity of drug elimination. Often too much, more than the maximum elimination capacity caused by the body.Such as the elimination of 100mg/h per hour.Four 、 pharmacokinetic parameters of commonly used drugs(a) bioavailability (Bioavailability):.The speed and extent of absorption of drugs into the body circulation.Notation: F= (A/D) * 100% (oral: <100%; vein: 100%)Divided into: absolute bioavailability: F= (PO equal amount of drugs, AUC/iv equal amount of drugs AUC) * 100%The relative bioavailability of F= (equivalent to the reagent AUC/ with standard drug AUC * 100%)(two) apparent volume of distributionThe volume of fluid required for the distribution of plasma drug levels in vivo after the distribution of plasma and tissue is balanced. Vd=A/C0, theoretical capacity)Significance:1, the distribution volume of a given drug is measured to produce the desired dosage of the drug concentration: D = C, Vd2. Predict the distribution of drugs:Vd small drugs are mainly distributed in organs with large bloodflow;Vd large, low blood concentration and wide distribution of drugs;(three) half-life: generally refers to the half-life of plasma (T1/2), that is, the time required for the plasma concentration to fall by half. Since most drugs are eliminated in afirst-order kinetic manner, their half-life is a constant, T1/2=0.693/ke.Significance: reflects the rate of drug elimination. T1/2 long to eliminate slow and maintain long time(1) drug classification according to: short effect, medium effect, long effect;(2) determine the interval between dosing(3) the steady-state concentration time was predicted: 4-5 t1/2;(4) predict the basic elimination time of drugs: 4-5 t1/2 after the last dose(four) the steady blood concentration (CSS/ / Ping Ping concentration value): continuous constant drug dosages, gradually accumulated, through 5 half-life, blood concentration reached a stable level. The serum concentration at this time is called steady-state serum concentration, CSS. At this point the amount of drugs removed and the amount of drugsentering the body is equal, drugs are no longer accumulated in the body.Significance: (1) the plateau concentration is directly proportional to the total quantity of the day.(2) the fluctuation range of plateau concentration, high limit and low limit is proportional to each dose.(five) clearance rate:The rate of clearance of the drug is how many liters of blood can be removed per unit time. Each drug has its own fixed CL.CL=ke/Vd.Four 、 the change of serum concentration and the regimen of administrationIn clinical, most drugs need to be repeatedly given in order to achieve the desired level of serum concentration. Therefore, the time curve of the administration is zigzag.(1) continuous constant dose, total dose increases, CSS increases; administration of the same amount, change the number of drug CSS invariant. A total of conventional drugs in children, the same day the total number of drug, the more each use less, smaller fluctuations in safety range of small, multiple service, Ping concentration maintained at the minimum effective dose and minimum dose.(2) dose volume maintenance method: doubling the first dose, then rapidly reaching CSS in a half life, and then using maintenance dose. This method is suitable for emergency treatment, and requires rapid treatment.(3) intermittent administration: according to the needs of clinical treatment, the medication regimen with interval of more than half time can be used to reduce the incidence of adverse reactions. Such as glucocorticoids.(4) the regimen should be individualized, such as liver and kidney dysfunction, the half-life is longer than normal, and the time to CSS is longer. Therefore, the dosage should be reduced and the interval between doses should be extended.。
一次搞懂6大肿瘤临床试验终点
1
定义：肿瘤体积缩小达到预先规定值并能维持最低时限要求的患者比例，为完全缓解和部分缓解比例之和。
3
ORR 是一种直接衡量药物抗肿瘤活性的指标，在单臂试验中进行评价。
2
缓解期通常是指从开始出现疗效直至证实出现肿瘤进展的这段时间。
客观缓解率 Objective Response Rate，ORR
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总生存，Overall Survival，OS
缺点：大型试验随访期较长。 临床试验中常常会用到 5 年生存率，即——某种肿瘤经过各种综合治疗后，生存五年以上的患者比例。 肿瘤患者治疗后，一部分复发转移、一部分死亡，一部分生存。80% 复发转移常发生在根治术后 3 年内，10% 左右发生在 5 年内，5 年后再次复发概率很低。因此以 5 年为节点，这是有一定科学性的。 当然，也有用三年生存率和十年生存率表示疗效的。
无病生存期 Disease-Free Survival，DFS
定义：从随机化开始到肿瘤发生（任何方面）进展或（因任何原因）死亡之间的时间。
01
与 OS 相比，增加了「发生恶化」这一节点，而「发生恶化」往往早于死亡，所以 PFS 常常短于 OS，却也能在 OS 之前被评价，因而随访时间短一些。
02
DFS: Disease-Free Survival, 无病生存期
5
ORR: Objective Response Rate, 客观缓解率
6
TTP: Time To Progress, 疾病进展时间
7
TTF: Time To treatment Failure, 治疗失败时间
8
……
9
不同的终点服务于不同的研究目的。
永恒的时间偏移Immortaltimebias-国家药品不良反应监测中心共71页文档
永恒的时间偏移Immortaltimebias国家药品不良反应监测中心
36、“不可能”这个字(法语是一个字 )，只 在愚人 的字典 中找得 到。--拿 破仑。 37、不要生气要争气，不要看破要突 破，不 要嫉妒 要欣赏 ，不要 托延要 积极， 不要心 动要行 动。 38、勤奋，机会，乐观是成功的三要 素。(注 意：传 统观念 认为勤 奋和机 会是成 功的要 素，但 是经过 统计学 和成功 人士的 分析得 出，乐 观是成 功的第 三要素 。
42、只有在人群中间，才能认识自 己。——德国
43、重复别人所说的话，只需要教育； 而要挑战别人所说的话，则需要头脑。—— 玛丽·佩蒂博恩·普尔
44、卓越的人一大优点是：在不利与艰 难的遭遇里百折不饶。——贝多芬
45、自己的饭量自己知道。——苏联
Macugen (pegaptanib) 商品说明书
Macugen® (pegaptanib)Document Number: IC-0081 Last Review Date: 05/31/2016Date of Origin: 01/01/2012Dates Reviewed: 03/2012, 06/2012, 09/2012, 12/2012, 03/2013, 06/2013, 09/2013, 12/2013, 03/2014, 06/2014, 09/2014, 12/2014, 03/2015, 6/2015, 9/2015, 3/2016, 05/2016I.Length of AuthorizationCoverage will be provided annually and may be renewed.II.Dosing LimitsA.Quantity Limit (max daily dose) [Pharmacy Benefit]:-0.3 mg injection - 2 injections every 42 daysB.Max Units (per dose and over time) [Medical Benefit]:Male 1 unit every 42 days per eyeFemale 1 unit every 42 days per eyeIII.Initial Approval CriteriaCoverage is provided in the following conditions:Patient is free of ocular and/or peri-ocular infections; ANDPatient has a definitive diagnosis of one of the following:∙Neovascular age-related macular degeneration (AMD) †∙Diabetic Macular Edema ‡∙Diabetic Retinopathy ‡†FDA Approved Indication(s)‡ Compendium recommended indication(s)IV.Renewal CriteriaCoverage can be renewed based upon the following criteria:∙Patient continues to meet criteria identified in section III; AND∙Absence of unacceptable toxicity from the drug; AND∙Continued administration is necessary for the maintenance treatment of the conditionV.Dosage/AdministrationVI.Billing Code/Availability InformationJcode:J2503– Macugen (Eyetech) 0.3 mg Injection: 1 billable unit = 0.3 mgNDC:N/AVII.References1.Macugen [package insert]. Cedar Knolls, NJ; Eyetech, Inc; October 2011. Accessed May2016.2.Cunningham ET Jr, Adamis AP, Altaweel M, et al. A phase II randomized double-maskedtrial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabeticmacular edema. Ophthalmology 2005;112:1747-57.3.Gonzalez VH, Giuliari GP, Banda RM, et al. Intravitreal injection of pegaptanib sodium forproliferative diabetic retinopathy. Br J Ophthalmol 2009;93:1474-78.4.Cunningham ET Jr, Adamis AP, Altaweel M, et al. A phase II randomized double-maskedtrial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabeticmacular edema. Ophthalmology 2005;112:1747-57.5.Adamis AP, Altaweel M, Bressler NM, et al. Changes in retinal neovascularization afterpegaptanib (Macugen) therapy in diabetic individuals. Ophthalmology 2006;113:23–8.6.Hornan D, Edmeades N, Krishnan R, et al. Use of pegaptanib for recurrent and non-clearing vitreous haemorrhage in proliferative diabetic retinopathy. Eye (Lond)2010;24(8):1315-19.7.Cahaba Government Benefit Administrators, LLC. Local Coverage Determination (LCD):Drugs and Biologicals: Antiangiogenic Therapy for Ophthalmic Conditions (L34252).Centers for Medicare & Medicaid Services, Inc. Updated on 12/18/2015 with effective date 10/01/2015. Accessed May 20168.Wisconsin Physicians Service Insurance Corporation. Local Coverage Determination (LCD):Drugs and Biologics (Non-chemotherapy) (L34741). Centers for Medicare & MedicaidServices, Inc. Updated on 04/28/2016 with effective date 05/16/2016. Accessed May 2016.9.First Coast Service Options, Inc. Local Coverage Determination (LCD): Macugen(pegaptanib sodium injection) (L33919). Centers for Medicare & Medicaid Services, Inc.Updated on 07/01/2014 with effective date 10/01/2015. Accessed May 2016.Appendix 1 – Covered Diagnosis CodesAppendix 2 – Centers for Medicare and Medicaid Services (CMS)Medicare coverage for outpatient (Part B) drugs is outlined in the Medicare Benefit Policy Manual (Pub. 100-2), Chapter 15, §50 Drugs and Biologicals. In addition, National Coverage Determination (NCD) and Local Coverage Determinations (LCDs) may exist and compliance with these policies is required where applicable. They can be found at: /medicare-coverage-database/search/advanced-search.aspx. Additional indications may be covered at the discretion of the health plan.Medicare Part B Covered Diagnosis Codes (applicable to existing NCD/LCD):。
帕罗西汀联合喹硫平治疗抑郁症的疗效观察
帕罗西汀联合喹硫平治疗抑郁症的疗效观察袁刚;杨通林【摘要】目的：观察帕罗西汀联合喹硫平治疗抑郁症的疗效和安全性。
方法将55例在精神病专科医院接受住院治疗的抑郁症患者随机分配为两组，疗程为4周。
用汉密尔顿抑郁量表（HRSD）进行疗效评定，用副反应量表（TESS）评估患者的药品不良反应，采用重复测量的方差分析比较帕罗西汀联合喹硫平与单用帕罗西丁治疗抑郁症的起效快慢及疗效。
结果在4周的疗程中，分组与时间之间存在交互作用（ F =7.107，P =0.000），两组药品不良反应之间无统计学差异（χ2=0.162，P =0.688﹥0.05）。
两组在第4周末的疗效有统计学差异（ t=5.720，P =0.000﹤0.05）。
结论帕罗西汀合用喹硫平治疗抑郁症起效时间及疗效均优于单用帕罗西汀，联合用药未增加药物的不良反应。
%Objective To observe the efficacy and safety of paroxetine combined with quetiapine in treating depressive disorder. Methods 55 inpatients with depressive disorder in the psychiatric specialist hospital were randomly divided into 2 groups. The course of treatment was 4 weeks. The effects were evaluated by the Hamilton Rating Scale for Depression(HRSD)and the adverse reactions were evaluat-ed by the Treatment Emergent SymptomScale(TESS). The repeated measures analysis of variance(ANOVA)was adopted to compare the initial effect time and effects between paroxetine combined with quetiapine and single paroxetine in treating depressive disor-der. Results Throughout the 4 - week treatment course,the interactions existed between group and time( F = 7. 107 P = 0. 000),while no statistically difference existed among adverse reactions( χ2 = 0. 162 P =0. 688 ﹥ 0. 05). The efficacy at the end of 4 weeks had sta-tistical difference between the two groups( t = 5. 720 P = 0. 000 ﹤ 0. 05). Conclusion The initial effect time and effect of paroxetine combined with quetiapine in treating depressive disorder are superior to single use of paroxetine. The combination medication does not increase the adverse drug reactions.【期刊名称】《中国药业》【年(卷),期】2014(000)014【总页数】3页(P33-34,35)【关键词】抑郁症;帕罗西汀;喹硫平【作者】袁刚;杨通林【作者单位】重庆市精神卫生中心女病区，重庆 401147;重庆市长寿区精神病医院，重庆 401221【正文语种】中文【中图分类】R969.4;R971+.43抑郁症是一种以情绪低落为特征伴有睡眠障碍、焦虑及躯体不适等症状的情感性精神病，可影响患者的工作能力、生活质量，甚至危及生命，严重抑郁症患者有15%自杀，已成为危害人类健康的严重疾病[1]。
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Newest Methods in Pharmacoepidemiology: back to basics and beyond
上海市药品不良反应监测中心 杜文民
Shanghai Center for Adverse Drug Reaction Monitoring Du Wenmin
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
药物流行病学 (Pharmacoepidemiology)
• 药物流行病学是研究大人群中药物利用和 药物作用的研究 • 药物流行病学是应用流行病学的方法研究 临床药理学的问题
• (Pharmacoepidemiology is the study of the use of and the effects of drugs in large numbers of people. Pharmacoepidemiology applies the methods of Epidemiology to the content area of Clinical Pharmacology.) Prof. Brain Strom
病例报告和病例系列
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
--- RCT 设计 ---
--- RWS 设计 ---
患病人群 纳入 / 排除标准 随机化 治疗 对照 暴露
患病人群
治疗的适应症 进行治疗 对照
研究方案的治疗和随访
专门的治疗和随访
结果?
2007年11月29-30日 第一届中国药物警戒研讨会 杜文民
结果?
依那西普研究
• 评价依那西普在真实世界环境下,治疗RA的 疗效、安全性和经济性 • 利用来自RCT的资料观察比较RWS的患者 特点、临床结果和经济学评价
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
RWS vs RCTs: 6个月治疗患者的ACR
80 70 60 50 40 30 20 10 0 ACR 20
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
药物流行病学研究方法
真实世界研究 (RWS)
队列和病例对照研究
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
我们所看到的是 “冰山的一角”
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
各种指南是理想的临床环境下写出的
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
基于社区的临床实践遇到的是“真实世 界”(real world)的条件
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
评价的原则
理想状态
暴露
因果联系
事件
实际情况
Exposure Statistical association Event estimate estimate Biases Confounding factors
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
2007年11月29-30日
%
Cost RCT C
Other
第一届中国药物警戒研讨会 杜文民
局限性
• 样本的选择偏移 • 电话收集资料 • 没有随机分配治疗
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
结论
• 基础特征(预后指标)临床试验和社区实际依 那西普治疗的患者是不同的 • 依那西普在社区治疗中，临床反应可以不 同，并且治疗时间可以是重要的 • 依那西普的费用-效益在临床试验和社区治 疗可以不同
2007年11月29-30日
* * *
RWS RCT A RCT B RCT C
*
ACR 50
ACR 70
* P < 0.01 compared to RWS 第一届中国药物警戒研讨会
杜文民
12个月的停止治疗
10 9 8 7 6 5 4 3 2 1 0 Advese Events Ineffective RWS
医生的靶人群
概括化?
亚组患者的冲突 合格的人群 概括化? 研究人群 推荐? 治疗潜在的冲突
治疗的靶人群
依从性?
第一届中国药物警戒研讨会 杜文民
治疗真实的冲突
2007年11月29-30日
治疗涉及的人群
23rd International Conference on Pharmacoepidemiology & Therapeutic Risk Management Quebec City, Canada August 19-22, 2007
必要性的发展
2007年11月29-30日 第一届中国药物警戒研讨会 杜文民
患病人群 医生的靶人群
药物相关人群
每个研究方案 准备治疗
合格的人群
研究队列
治疗的靶人群
结果
?
治疗涉及的人群 2007年11月29-30日 第一届中国药物警戒研讨会 = 治疗过的人群 杜文民
?
药物相关的问题
观点 患病人群 治疗期望的冲突 问题 可得到治疗 的比率?
Bayesian 方法
选择的人群 霍索恩效应 时间短 样本量少 观察范围窄
局限性
临床试 验
内在的 真实性
2007年11月29-30日
实效性研究 第一届中国药物警戒研讨会
杜文民
哪些方面需要实效性研究?
医疗付费者水平的决策 效果、效能
疾病管理: 医院和社区
人群健康管理: - 健康促进 - 健康监管& 政策
评价: 双重的挑战
观察性研究 局限性
选择偏移 观察偏移 混杂
内在的 真实性
?
外在的 真实性
选择的人群 霍索恩效应） 时间短 样本量少 观察范围窄
局限性
临床 试验
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
评价: 双重的挑战
观察性研究
局限性
选择偏移 观察偏移 混杂
内在 的真 实性
敏感性 分析 模型 外在的 真实性
2007年11月29-30日
第一届中国药物警戒研讨会 杜文民
关于真实世界研究的结论
• RCT应该用于评价功效（efficacy ），而 RWS用于决定有效性（effectiveness ） • RWS 提供RCT没有的补充资料 • RWS 能够作为属于药物流行病学重要的工 具用于决定临床实践中真实的效益、风险 和治疗价值