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使用直接作用抗病毒药物实现持续病毒学应答后的新发肝细胞癌的发生率和预测因素:来自吉利德Svr和肝硬化登记处的结果

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使用直接作用抗病毒药物实现持续病毒学应答后的新发肝细胞癌的发...

What is the best biological treatment for rheumatoid arthritis? A systematic review of effectiveness

第十届全国疑难及重症肝病大会

作者： K.Rajender REDDY Ira M.Jacobson Armand Abergel Barbara A.Leggett Charles S.Landis Robert Hyland Frances Chen Liyun Ni Anu O.Osinusi Diana Brainard Jose Luis Calleja Eric J.Lawitz Andrew Joseph Muir alessandra Mangia UniversityofPennsylvania QIMRBerghoferMedicalResearchInstitute UniversityofWashington CentroDeInvestigacionBiomedicaEnRedDeEnfermedadesHepaticasyDigestivas(CIBERehd) Irccs-OspedaleCasaSollievoDellaSofferenza CHUClermontFerrand GileadSciencesInc. DukeClinicalResearchInstitute NewYorkUniversity GileadSciences Inc. TexasLiverInstitute UniversityofTexasHealthSanAntonio

背景一些研究表明,使用直接作用抗病毒药物(DAA)实现持续病毒学应答(SVR)与肝细胞癌(HCC)发生的减少相关。本研究评估了在吉利德登记处的一支包括6700余名患者的特征良好的队列中的SVR后新发HCC的发生率和预测因素。方法本研究进行了一...

背景一些研究表明,使用直接作用抗病毒药物(DAA)实现持续病毒学应答(SVR)与肝细胞癌(HCC)发生的减少相关。本研究评估了在吉利德登记处的一支包括6700余名患者的特征良好的队列中的SVR后新发HCC的发生率和预测因素。方法本研究进行了一项汇总分析,评估了吉利德SVR和肝硬化登记处的患者中的新发HCC的

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World Journal of Rheumatology 2015年第2期5卷 108-126页

作者： Jéssica Barreto dos Santos Juliana de Oliveira Costa Haliton Alves de Oliveira Junior Lívia Lovato Pires Lemos Vnia Eloisa de Araújo Marina Amaral de Avila Machado alessandra Maciel Almeida Francisco de Assis Acurcio Juliana Alvares Postgraduate Programme in Medicines and Pharmaceutical Assistance College of PharmacyFederal University of Minas GeraisAv.Presidente Antonio Carlos College of Pharmacy Federal University of Minas GeraisAv.Presidente Antonio Carlos Department of Social Pharmacy College of PharmacySUS Collaborating Centre-CCATESFederal University of Minas GeraisAv.Presidente Antonio Carlos College of Medicine Federal University of Minas GeraisAv.Prof.Alfredo Balena

AIM:To evaluate the effectiveness of the biological disease-modifying antirheumatic drugs(b DMARD) in the treatment of rheumatoid arthritis through a systematic review of observational ***:The studies were searched in the Pub Med,EMBASE,Cochrane Controlled Trials Register and LILACS databases(until August 2014),in the grey literature and conducted a manual *** assessed criteria of effectiveness included the EULAR,the disease activity score(DAS),the Clinical Disease Activity Index,the Simplified Disease Activity Index,the American College of Rheumatology and the Health Assessment *** meta-analysis was performed with Review Manager 5.2 software using a random effects model.A total of 35 studies were included in this ***:The participants anti-tumor necrosis factor inhibitors(TNF) nave,who used adalimumab(P = 0.0002) and etanercept(P = 0.0006) exhibited greater good EULAR response compared to the participants who used *** difference was detected between adalimumab and etanercept(P = 0.05).The participants who used etanercept exhibited greater remission according to DAS28 compared to the participants who used infliximab(P = 0.01).No differences were detected between adalimumab and infliximab(P = 0.12) or etanercept(P = 0.79).Better results were obtained with b DMARD associated with methotrexate than with b DMARD *** good EULAR response and DAS 28 was better for combination with methotrexate than b DMARD monotherapy(P = 0.03 e P < 0.00001).In cases of therapeutic failure,the participants who used rituximab exhibited greater DAS28 reduction compared to those who used anti-TNF agents(P = 0.0002).The participants who used etanercept achieved greater good EULAR response compared to those who did not use that drug(P = 0.007).Studies that assessed reduction of the CDAI score indicated the superiority of abatacept over rituximab(12.4 vs +1.7) and anti-TNF agents(7.6 vs 8.3).The present systematic review with meta-analys

关键词： Systematic review Meta-analysis Effecti-veness Biological disease-modifying antirheumatic drugs Rheumatoid arthritis

Liver transplantation in patients with SARS-CoV-2:Two case reports

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World Journal of Clinical Infectious Diseases 2021年第1期11卷 27-34页

作者： Camilla Bezerra Bastos Limeira Camila Monteiro Veras JoséHicaro Hellano Gonçalves Lima Paiva Marina Seixas Studart e Neves Themístocles Mesquita Teles de Carvalho Natália Stefani de Assunção Ferreira alessandra Maria Mont`Alverne Pierre Ivelise Regina Canito Brasil Transplantation Division Hospital Geral de FortalezaFORTALEZA 60175742CEBrazil UECE UeceFORTALEZA 60175742CearaBrazil

BACKGROUND Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)causes coronavirus disease 2019(COVID-19).This disease was declared a worldwide health problem with the characteristics of a *** patients have mild symptoms and a good *** on the evolution and prognosis of COVID-19 in solid organ recipients is *** SUMMARY We describe two patients who underwent liver transplantation with a positive test result for detection of the viral sequence for COVID-19,using reversetranscription polymerase chain reaction(RT-PCR),immediately before *** patients showed good evolution in the postoperative period,without signs of graft *** immunosuppressive therapy was not *** patients were discharged for subsequent outpatient *** In conclusion,it is expected that the experience at this center can be used as an example,aimed at the continuation of transplantations by other services and,thus,the morbidity and mortality of patients with liver disease on the transplantation waiting list can be *** centers must be able to readjust daily to the evolution of the COVID-19 pandemic.

关键词： COVID-19 Liver transplantation Coronavirus Pneumonia Immunosuppressed patients Case report Infection diseases

奥拉帕利维持治疗BRCA 1/2突变铂敏感复发性卵巢癌患者(SOLO2/ENGOT-Ov21):一项双盲随机对照Ⅲ期试验的最终分析

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肿瘤药学 2021年第3期11卷 275-279页

作者： Andrés Poveda Anne Floquet Jonathan A Ledermann Rebecca Asher Richard T Penson Amit M Oza Jacob Korach Tomasz Huzarski Sandro Pignata Michael Friedlander alessandra Baldoni Tjoung-Won Park-Simon Kenji Tamura Gabe S Sonke Alla Lisyanskaya Jae-Hoon Kim Elias Abdo Filho Tsveta Milenkova Elizabeth S Lowe Phil Rowe Ignace Vergote Eric Pujade-Lauraine the SOLO/ENGOT-Ovinvestigators 王娟(校) 李征(校) 不详

背景既往发表的SOLO2/ENGOT-Ov21试验的第一部分研究结果表明,作为BRCA1或BRCA2(BRCA1/2)突变铂敏感型的高级别浆液性或子宫内膜样卵巢癌复发患者使用奥拉帕利可延长无进展生存期。因此,本研究的最终分析目的是研究奥拉帕利对这类患者... 详细信息

背景既往发表的SOLO2/ENGOT-Ov21试验的第一部分研究结果表明,作为BRCA1或BRCA2(BRCA1/2)突变铂敏感型的高级别浆液性或子宫内膜样卵巢癌复发患者使用奥拉帕利可延长无进展生存期。因此,本研究的最终分析目的是研究奥拉帕利对这类患者总生存期的影响。方法本研究是一项在16个国家123个医疗中心进行的双盲、随机、安慰剂对照、Ⅲ期临床试验。纳入标准包括:年龄≥18岁;ECOG体能状态评分基线水平为0~1分;组织学检查确诊为复发性、高级别浆液性或高级别子宫内膜样卵巢癌,包括原发性腹膜癌或输卵管癌;以及既往接受过2种或2种以上铂类药物的治疗方案。入选患者按2∶1分配到奥拉帕利组(150 mg片剂,每日2次口服,共300 mg)或安慰剂组;根据既往化疗后是否缓解以及无铂治疗间隔时长进行分层;受试者、治疗提供者和数据分析人员在治疗分配时均设盲。主要终点是既往已报道过的无进展生存期;总生存期作为重要的次要终点之一,在所有随机分配的患者中进行分析;安全性评估在至少接受过1次给药的所有患者中进行。结果2013年9月3日—2014年11月21日,共295例患者参与了试验并被随机分到奥拉帕利组(196例,66%)或安慰剂组(99例,34%)治疗。奥拉帕利组患者中位随访时间为65.7个月(IQR:63.6~69.3),安慰剂组为64.5个月(IQR:63.4~68.7)。奥拉帕利组中位总生存期为51.7个月(95%CI:41.5~59.1),安慰剂组为38.8个月(95%CI:31.4~48.6)(HR=0.74,95%CI:0.54~1.00,P=0.054)。安慰剂组38%接受PARP抑制剂治疗的患者未作调整。治疗引发的最常见的Ⅲ级以上不良事件为贫血,奥拉帕利组发生率为21%(41/195),安慰剂组为2%(2/99)。

关键词：安慰剂 Ⅲ期临床试验输卵管癌铂类药物患者参与组织学检查 BRCA SOLO

复合型遗产的管理——预防性和计划性保护在意大利蒙扎皇家别墅和公园项目中的运用

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中国文化遗产 2020年第2期 47-58页

作者：罗塞拉·莫伊欧利克里斯提娜·伯尼欧迪安卓拉·康斯塔亚历桑德拉皮里吴丽君(译) 意大利米兰理工大学建筑、建成环境和建造工程学院意大利米兰

关于预防性和计划性保护在蒙扎皇家别墅和公园中运用的案例,是基于蒙扎和布里安扎文化区(MonzaandBrianzaCultural District)总体框架下的一个试点项目。蒙扎皇家别墅和公园项目是近年来由公共机构和私人团体共同推进下的计划性保护和... 详细信息

关于预防性和计划性保护在蒙扎皇家别墅和公园中运用的案例,是基于蒙扎和布里安扎文化区(MonzaandBrianzaCultural District)总体框架下的一个试点项目。蒙扎皇家别墅和公园项目是近年来由公共机构和私人团体共同推进下的计划性保护和适度利用⑥活动中的典型代表。该试点项目在蒙扎皇家别墅和公园保护活动所开展的案例分析基础上,对前期相关数据和信息进行收集,通过建立建成文化遗产保护的信息系统,对保护计划的各个组成部分(包括技术手册、保护方案、经济预算以及用户手册)进行设计和后期有效管理。同时也对蒙扎皇家别墅和公园的建成环境进行了分析,尤其关注位于蒙扎公园的每栋特定历史建筑。该项目实施的评估工作是在"上游投资"⑦理论框架内进行的。该研究强调了整合方法的重要性、为建立以事实为基础的政策而对所收集数据实施共享的必要性以及提升相关专业人士和决策者技能的必要性。该研究项目的价值体现在保护方法的进步、将保护和适度利用理解为预防性活动、私有经济模式下维护工作的有效性、优秀案例的宣传以及当地利益相关者间关系网的创建等方面。

关键词：文化遗产管理当地发展政府和社会资本合作模式(PPP模式) 复合型遗产预防性和计划性保护

有 CT 冠的 angiography 的匾成像: 匾类型分类上的 intra 脉管的变细的效果

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World Journal of Radiology 2012年第6期4卷 265-272页

作者： Erica Maffei Chiara Martini Teresa Arcadi Alberto Clemente Sara Seitun alessandra Zuccarelli Tito Torri Nico R Mollet Alexia Rossi Onofrio Catalano Giancarlo Messalli Filippo Cademartiri Cardiovascular Imaging Unit Giovanni XXIII Hospital31050 Monastier di TrevisoTrevisoItaly Department of Radiology Academic Hospital of Parma43100 ParmaItaly Department of Radiology Ospedale di Carrara54033 CarraraItaly Department of Radiology Erasmus Medical Center University3015 CE RotterdamThe Netherlands Filippo Cademartiri Department of Radiology SDN FoundationIRCCS80143 NaplesItaly Department of Radiology Erasmus Medical Center University3015 CE RotterdamThe Netherlands

AIM:To assess the attenuation of non-calcified atherosclerotic coronary artery plaques with computed tomography coronary angiography(CTCA).METHODS:Four hundred consecutive patients underwent CTCA(Group 1:200 patients,Sensation 64 Cardiac,Siemens;Group 2:200 patients,VCT GE Healthcare,with either Iomeprol 400 or Iodixanol 320,respectively) for suspected coronary artery disease(CAD).CTCA was performed using standard *** quality(score 0-3),plaque(within the accessible non-calcified component of each non-calcified/mixed plaque) and coronary lumen attenuation were *** were compared on a per-segment/perplaque *** were classified as fibrous vs lipid rich based on different attenuation thresholds.A P < 0.05 was considered ***:In 468 atherosclerotic plaques in Group 1 and 644 in Group 2,average image quality was 2.96 ± 0.19 in Group 1 and 2.93 ± 0.25 in Group 2(P ≥ 0.05).Coronary lumen attenuation was 367 ± 85 Hounsfield units(HU) in Group 1 and 327 ± 73 HU in Group 2(P < 0.05);non-calcified plaque attenuation was 48 ± 23 HU in Group 1 and 39 ± 21 HU in Group 2(P < 0.05).Overall signal to noise ratio was 15.6 ± 4.7 in Group 1 and 21.2 ± 7.7 in Group 2(P < 0.01).CONCLUSION:Higher intra-vascular attenuation modifies significantly the attenuation of non-calcified coronary *** results in a more difficult characterization between lipid rich vs fibrous type.

关键词： Computed tomography coronary angiography Coronary artery plaque Plaque characterization Contrast material Lumen enhancement

Accretion in strong field gravity with eXTP

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Science China(Physics,Mechanics & Astronomy) 2019年第2期62卷 45-73页

作者： alessandra De Rosa Phil Uttley LiJun Gou Yuan Liu Cosimo Bambi Didier Barret Tomaso Belloni Emanuele Berti Stefano Bianchi Ilaria Caiazzo Piergiorgio Casella Marco Feroci Valeria Ferrari Leonardo Gualtieri Jeremy Heyl Adam Ingram Vladimir Karas FangJun Lu Bin Luo Giorgio Matt Sara Motta Joseph Neilsen Paolo Pani Andrea Santangelo XinWen Shu JunFeng Wang Jian-Min Wang YongQuan Xue YuPeng Xu WeiMin Yuan YeFei Yuan Shuang-Nan Zhang Shu Zhang Ivan Agudo Lorenzo Amati Nils Andersson Cristina Baglio Pavel Bakala Altan Baykal Sudip Bhattacharyya Ignazio Bombaci NiccolóBucciantini Fiamma Capitanio Riccardo Ciolfi Wei K.Cui Filippo D'Ammando Thomas Dauser Melania Del Santo Barbara De Marco Tiziana Di Salvo Chris Done Michal Dovciak Andrew C.Fabian Maurizio Falanga Angelo Francesco Gambino Bruce Gendre Victoria Grinberg Alexander Heger Jeroen Homan Rosario Iaria JiaChen Jiang ChiChuan Jin Elmar Koerding Manu Linares Zhu Liu Thomas J.Maccarone Julien Malzac Antonios Manousakis Frédéric Marin Andea Marinucci Missagh Mehdipour Mariano Méndez Simone Migliari Cole Miller Giovanni Miniutti Emanuele Nardini Paul T.O'Brien Julian P.Osborne Pierre Olivier Petrucci Andrea Possenti Alessandro Riggio Jerome Rodriguez Andrea Sanna LiJing Shao Malgosia Sobolewska Eva Sramkova Abigail L.Stevens Holger Stiele Giulia Stratta Zdenek Stuchlik Jiri Svoboda Fabrizio Tamburini Thomas M.Tauris Francesco Tombesi Gabriel Torok Martin Urbanec Frederic Vincent QingWen Wu Feng Yuan Jean J.M.in't Zand Andrzej A.Zdziarski XinLin Zhou INAF-Istituto di Astrofisica e Planetologie Spaziali Via Fosso del Cavaliere Anton Pannekoek Institute for Astronomy University of Amsterdam National Astronomical Observatories Chinese Academy of Science Institute of High Energy Physics Chinese Academy of Science Center for Field Theory and Particle Physics and Department of Physics Fudan University IRAP Universitéde ToulouseCNRSUPSCNES INAF-Osservatorio Astronomico di Brera Department of Physics and Astronomy The University of MississippiUniversity Dipartimento di Matematica e Fisica Universitàdegli studi Roma Tre University of British Columbia INAF-Osservatorio Astronomico di Roma INFN-Roma 2 c/o Dipartimento di Fisica II Universit?di Roma"Tor Vergata" Dipartimento di Fisica Universitàdegli Studi di Roma"La Sapienza"&Sezione INFN Roma1 Department of Physics University of OxfordClarendon Laboratory Astronomical Institute Academy of Sciences School of Astronomy and Space Science Nanjing University MIT Kavli Institute for Astrophysics and Space Research Institut für Astronomie und Astrophysik Eberhard Karls Universität Department of Physics Anhui Normal University Department of Astronomy and Institute of Theoretical Physics and Astrophysics Xiamen University CAS Key Laboratory for Research in Galaxies and Cosmology Department of AstronomyUniversity of Science and Technology of China Instituto de Astrofísica de Andalucia(CSIC) Glorieta de la Astronomía s/n INAF-Istituto di Astrofisica Spaziale e Fisica cosmica di Bologna Mathematical Sciences and STAG Research Centre University of Southampton New York University Abu Dhabi Institute of Physics and Research Centre for Computational Physics and Data Processing Faculty of Philosophy&ScienceSilesian University in OpavaíBezru?ovo nám. Department of Physics Middle East Technical University Department of Astronomy and Astrophysics Tata Institute of Fundamental Research Dipartimento di Fisica Universit?di Pisa&INFN INAF-Osservatorio Astrofisico di Arcetri INAF-Osservatorio Astronomico di Padova INFN-TIFPA Trento Ins

In this paper we describe the potential of the enhanced X-ray Timing and Polarimetry(eXTP) mission for studies related to accretion flows in the strong field gravity regime around both stellar-mass and supermassive black-holes. eXTP has the unique capability of using advanced "spectral-timing-polarimetry" techniques to analyze the rapid variations with three orthogonal diagnostics of the flow and its geometry, yielding unprecedented insight into the inner accreting regions, the effects of strong field gravity on the material within them and the powerful outflows which are driven by the accretion process.

关键词： X-ray black holes physics accretion

Resolutive Results with Oral Corticosteroids for Patients with COVID-19 in Pulmonary Inflammatory Phase. Successful Outpatient Experience during the Collapse of Belem Do Para Health System—Brazil

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Health 2021年第8期13卷 830-838页

作者： Roberto S. Zeballos Luciana N. L. Cruz Vânia C. R. Brilhante Adriana V. Lima Carlliane L. L. P. Martins Karla N. A. Lima Michele C. G. L. Leão Belinete L. Cruz alessandra B. Dysarz Paulo C. B. Lobato Erika S. Almeida Rute A. P. Costa Klevison C. Araújo Augusto C. C. Almeida Leônidas B. D. Junior Kathia O. Harada Rita H. V. S. Araújo Elaine X. Prestes Ivete M. S. Souza Avany M. P. Pereira Antônio B. M. A. Rocha Iracema A. Estevão Fagnei I. C. Carvalho Paulo M. P. Melo Clinical Care Sao Paulo Brazil Instituto de Ciencias da Saude Faculdade de Medicina Universidade Federal do Para Belem Brazil Fundacao Publica Estadual Hospital de Clinicas Gaspar Vianna Belem Brazil Hospital da Policia Militar do Para Belem Brazil Imunoclinic Belem Brazil Universidade Estadual do Para Fundacao Santa Casa de Misericordia do Para Belem Brazil Clinica Barros Cirurgia Plastica Belem Brazil Secretaria de Estado de Saude Publica Castanhal Brazil Centro de Tratamento Oncologico Belem Brazil Sociedade Brasileira de Valorizaç ã o das Sociedades Medicas—SOBEMED S&#227 o Paulo Brazil Clinica de Nutrologia Sao Luiz Brazil Hospital Nipo Brasileiro de Olhos Belem Brazil Centro de Ciencias Biologicas e da Saude Universidade do Estado do Para Belem Brazil Hospital Regional do Baixo Amazonas Santarem Brazil Clinica Vallinoto Secretaria de Saude de Barcarena Barcarena Brazil Estrategia Saude da Familia Secretaria Municipal de Saude de Ananindeua Centro Universitario do Estado do Para Belem Brazil A. M. P. Endocrinologia Belem Brazil Instituto Avertano Rocha Belem Brazil Departamento de Neurocirurgia Hospital Militar de Area De Sao Paulo Sao Paulo Brazil

In the face of new diseases, medicine needs to reinvent itself in order to contain and control epidemics, such as the one we have recently faced, COVID-19, a disease with a wide spectrum of clinical severity. A new moment has been established, since the application of well-known, effective and safe medications for other diseases, has shown high success rates in the treatment of COVID-19. Thereunto, studies with early intervention are needed, which can change the unfavorable outcome of patients. In this article, we report the successful experience using an oral strategy during the collapse of Belem (Para, Brazil) Health System. Two hundred and ten patients were diagnosed with respiratory failure due to COVID-19, with no option of hospital treatment due to lack of beds and resources. These patients were then started on therapeutic regimen consisting of 40 mg prednisolone, 40 mg enoxaparin and macrolides (500 mg clarithromycin, 500 mg axetylcefuroxime) associated and followed in outpatient facilities. Two hundred and eight patients had an excellent therapeutic response and there were only two fatalities. These results push research boundaries, valuing outpatient treatment with early use of prednisolone in the initial pulmonary phase, preventing severe COVID-19 pneumonitis. Adoption of the proposed treatment intends to reduce the need for hospitalization, as well as lethality, with social robust benefits and incalculable economic savings since involves the use of accessible, safe and not expensive medications.

关键词： COVID-19 Corticosteroids Pulmonary Inflammatory Phase Collapse Brazil

更年期医学:欧洲男女更年期协会2004/2005关于围绝经期和绝经后激素补充治疗的立场声明

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国外医学（妇幼保健分册） 2005年第5期16卷 319-322页

作者： Sven O.Skouby Farook Al-Azzawi David Barlow Joaquin Calaf-Alsina Erdogan Ert ungealp Anne Gompel alessandra Graziottin Decebal Hudita Amos ines Serge Rozenberg Gran Samsioe John C.Stevenson 陈瑛

目前从大量的随机对照临床试验(RCT)中已得出结论性的证据:对于经历令人痛苦的更年期症状的围绝经期和绝经后妇女,任何形式的全身HRT均可以缓解症状,没有其它治疗手段能产生相似效果。尽管这种证据与日俱增,但如何提供最好的临床医疗以... 详细信息

目前从大量的随机对照临床试验(RCT)中已得出结论性的证据:对于经历令人痛苦的更年期症状的围绝经期和绝经后妇女,任何形式的全身HRT均可以缓解症状,没有其它治疗手段能产生相似效果。尽管这种证据与日俱增,但如何提供最好的临床医疗以减轻绝经症状和预防较远期的绝经后退化性疾病,仍在争论之中。当提供更年期医药时,HRT的剂量和方案的个体化是基于与症状的严重程度和绝经时间相关的最低有效剂量的原则。然而,在有症状的妇女中,尚没有多少关于长期应用不同HRT方案的资料,同时赖以说明心血管疾病、乳腺癌和骨质疏松症的基线风险的影响。在大多数病例中,个体化的处方联同生活方式的调整就可能对更年期症状、生活质量、性问题和骨质疏松症产生最终有益的作用,罕见严重副反应。基于最近的流行病学研究,不少是来自WHI中单用雌激素组的结果,欧洲男女更年期协会(EMAS)支持在有症状的妇女中进行新的HRT方案的研究,以提高临床中受益和风险之间的平衡,包括生活质量方面特有的信息;并解释美国和欧洲之间在治疗模式上的传统差异,以及在BMI、生活方式和饮食习惯方面的不同所产生的影响。对于早绝经(<45岁)的妇女,现有的资料支持HRT所特有的总体益处。目前,具有骨质疏松性骨折高危险性的妇女可考虑应用较长期的全身HRT,尤其是当其它治疗措施既不恰当又疗效不佳时,因为此时收益大于风险。而对于泌尿生殖道症状,已认为长期的局部雌激素治疗可能安全和有效。

关键词：男女更年期协会立场声明更年期医药围绝经期绝经后激素补充治疗更年期症状绝经后妇女围绝经期激素补充治疗欧洲协会随机对照临床试验 HRT方案最低有效剂量