Postmenopausal hormone replacement therapy: scientific review

Context  Although postmenopausal hormone replacement therapy (HRT) is widely used in the United States, new evidence about its benefits and harms requires reconsideration of its use for the primary prevention of chronic conditions. Objective  To assess the benefits and harms of HRT for the primary prevention of cardiovascular disease, thromboembolism, osteoporosis, cancer, dementia, and cholecystitis by reviewing the literature, conducting meta-analyses, and calculating outcome rates. Data Sources  All relevant English-language studies were identified in MEDLINE (1966-2001), HealthSTAR (1975-2001), Cochrane Library databases, and reference lists of key articles. Recent results of the Women's Health Initiative (WHI) and the Heart and Estrogen/progestin Replacement Study (HERS) are included for reported outcomes. Study Selection and Data Extraction  We used all published studies of HRT if they contained a comparison group of HRT nonusers and reported data relating to HRT use and clinical outcomes of interest. Studies were excluded if the population was selected according to prior events or presence of conditions associated with higher risks for targeted outcomes. Data Synthesis  Meta-analyses of observational studies indicated summary relative risks (RRs) for coronary heart disease (CHD) incidence and mortality that were significantly reduced among current HRT users only, although risk for incidence was not reduced when only studies that controlled for socioeconomic status were included. The WHI reported increased CHD events (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.02-1.63). Stroke incidence but not mortality was significantly increased among HRT users in the meta-analysis and the WHI. The meta-analysis indicated that risk was significantly elevated for thromboembolic stroke (RR, 1.20; 95% CI, 1.01-1.40) but not subarachnoid or intracerebral stroke. Risk of venous thromboembolism among current HRT users was increased overall (RR, 2.14; 95% CI, 1.64-2.81) and was highest during the first year of use (RR, 3.49; 95% CI, 2.33-5.59) according to a meta-analysis of 12 studies. Protection against osteoporotic fractures is supported by a meta-analysis of 22 estrogen trials, cohort studies, results of the WHI, and trials with bone density outcomes. Current estrogen users have an increased risk of breast cancer that increases with duration of use. Endometrial cancer incidence, but not mortality, is increased with unopposed estrogen use but not with estrogen with progestin. A meta-analysis of 18 observational studies showed a 20% reduction in colon cancer incidence among women who had ever used HRT (RR, 0.80; 95% CI, 0.74-0.86), a finding supported by the WHI. Women symptomatic from menopause had improvement in certain aspects of cognition. Current studies of estrogen and dementia are not definitive. In a cohort study, current HRT users had an age-adjusted RR for cholecystitis of 1.8 (95% CI, 1.6-2.0), increasing to 2.5 (95% CI, 2.0-2.9) after 5 years of use. Conclusions  Benefits of HRT include prevention of osteoporotic fractures and colorectal cancer, while prevention of dementia is uncertain. Harms include CHD, stroke, thromboembolic events, breast cancer with 5 or more years of use, and cholecystitis.      

心力衰竭的起搏治疗

充血性心力衰竭 (congestiveheartfailure ,CHF)是常见而难治的心脏疾病 ,是各种心脏疾病的主要死亡原因。尽管药物治疗 ,尤其是ACEI和 β受体阻滞剂的应用已使CHF患者的生存期和生活质量得到明显改善 ,但对心功能NYHAⅢ～Ⅳ级患者预后仍差 ;心脏移植由于供体的缺乏和排斥反应限制了它的应用 ;人工心脏仍处于实验和计划阶段 ;近年来双心室起搏的应用 ,为治疗CHF提供了新的途径 ,取得了初步成果。CHF患者的左心房功能常常不正常 ,充盈受限很常见。在彩色多普勒检查时可见二尖瓣E峰增高而A峰降低。在一些严重的患者 ,当心房收缩时 ,…     

从禁忌证到标准治疗——β阻滞剂治疗慢性心力衰竭的循证历程

慢性充血性左心力衰竭已成为全球严重的公共卫生问题。β受体阻滞剂从心力衰竭的禁忌证到心力衰竭的标准治疗，反映了β阻滞剂治疗慢性心力衰竭的循证历程。多项多中心大规模临床试验的结果证明，β受体阻滞剂可以改善慢性充血性左心力衰竭患者的预后。     

Drug therapy in chronic heart failure

Chronic heart failure is widely recognised as a common and escalating problem that causes major disability and often shortens life. Diuretics and digoxin have formed the mainstay of treatment for many years. Clinical trials have demonstrated that angiotensin converting enzymes and beta-blockers, in selected patients, improve symptoms and reduce mortality. Angiotensin-II antagonists and spironolactone may also have a role in certain individuals. Newer pharmacological approaches to the management of this complex disease are being developed, but await full evaluation.     

心力衰竭的临床进展

第一节心力衰竭治疗的回顾及现状(上) 1 基本概念 1.1 心力衰竭的概念 心力衰竭定义为:由于任何原因的初始心肌损伤,引起心肌结构和功能的变化,最后导致心室泵血功能低下,即为心力衰竭.本文所指的心力衰竭是指慢性收缩性心衰.     

线粒体在心力衰竭发展过程中的作用

作为心肌细胞的主要能量来源,线粒体与心功能密切相关。在心脏代偿性肥大以及失代偿期间线粒体功能发生变化,受损的线粒体反过来通过异常的能量代谢、氧化应激以及介导细胞死亡加重心力衰竭的进程。本研究就心力衰竭发展过程中线粒体功能的改变及其交互作用做一综述。     

Oral antihyperglycemic therapy for type 2 diabetes: scientific review

Context  Care of patients with type 2 diabetes has been revolutionized throughout the past several years—first, by the realization of the importance of tight glycemic control in forestalling complications, and second, by the availability of several unique classes of oral antidiabetic agents. Deciphering which agent to use in certain clinical situations is a new dilemma facing the primary care physician. Objective  To systematically review available data from the literature regarding the efficacy of oral antidiabetic agents, both as monotherapy and in combination. Data Sources  A MEDLINE search was performed to identify all English-language reports of unique, randomized controlled clinical trials involving recently available oral agents for type 2 diabetes. Bibliographies were also reviewed to find additional reports not otherwise identified. Study Selection and Data Extraction  Studies (63) were included in the analysis if they had a study period of at least 3 months; if each group contained at least 10 subjects at the study's conclusion; and if hemoglobin A_1c was reported. When multiple dosages of a drug were tested, the results of the highest approved dosage were used. In placebo-controlled trials, hemoglobin A_1c data are presented as the difference between the change in treated vs placebo subjects. Data Synthesis  Five distinct oral drug classes are now available for the treatment of type 2 diabetes. Compared with placebo treatment, most of these agents lower hemoglobin A_1c levels approximately 1% to 2%. Equivalent efficacy is usually demonstrated when different agents are compared with one another in the same study population. When they are used in combination, there are additional glycemic benefits. Long-term vascular risk reduction has been demonstrated only with sulfonylureas and metformin. Conclusions  With few exceptions, the available oral antidiabetic agents are equally effective at lowering glucose concentrations. Their mechanisms of action are different, however, and as a result they appear to have distinct metabolic effects. These are reflected in their adverse effect profiles and their effect on cardiovascular risk, which may influence drug choice.      

充血性心力衰竭患者双室起搏治疗的临床观察

目的观察心室同步起搏对顽固性伴有室内传导或室间隔运动异常的充血性心衰的治疗效果.方法选择21例,其中男18例,女3例,年龄(64±11)岁,合并左束支阻滞的顽固性心衰患者给予双心室同步起搏治疗(16例安装三腔起搏器,5例安装三腔心脏自动交律除颤器).观察术中、术后3、6月左室电极的起搏参数,同时观察术前、术后3个月的QRS波时限、LVEF、LVDD、二尖瓣返流量、VO2max以及临床症状的变化.结果随访3～20个月,左室电极的起搏阀值、阻抗及感知各参数值稳定(P＞0.05),起搏功能良好.与术前相比,术后3个月LVEF等心功能指标均明显改善(P<0.05).随访期间猝死1例,接受心脏移植1例.结论心室再同步治疗是治疗存在室间传导异常的充血性心衰的有效的新方法.三腔起搏器可改善患者血流动力学、心功能和心衰的临床症状.左室电极的植入成功率高,性能稳定,安全可靠.三腔ICD不仅可治疗心衰,同时具有良好的抗室性心律失常预防猝死的作用.     

慢性心力衰竭的现代治疗

心力衰竭是由各种心脏疾病导致心功能不全的一种复杂的临床症候群,主要是指心室充盈和射血能力受损,为各种心脏病的严重阶段.目前,心力衰竭已成为一个主要的公共卫生问题,由于人口老龄化,高血压的高发病率和低控制率,急性心肌梗死存活率升高,各种心肌病的增多,使心力衰竭的发病率日益增高.     

心肌纤维化--心力衰竭治疗的新靶标

20世纪90年代以来的研究充分证明,在慢性充血性心力衰竭（congestive heart failure,CHF）的患者中,神经-内分泌异常所致的左室重构是导致心功能减退和临床不良预后的主要原因。左室重构的病理改变包括两个方面：一是心肌细胞的肥大、坏死和凋亡,二是成纤维细胞的增生和心肌间质纤维化。以往研究的焦点主要集中于心肌细胞结构和功能异常的预防和逆转,但近年来人们逐渐认识到,心肌纤维化在心力衰竭的发生和发展中起有十分重要的作用,因而已成为心力衰竭治疗的一个新靶标。     

Nitrate therapy for congestive heart failure.

A randomized double-blind crossover trial included 16 patients with severe congestive heart failure who received isosorbide dinitrate or placebo for eight weeks, and then the opposite treatment for eight more weeks. All patients received their usual maintenance therapy with digitalis and diuretics. Seven morbid events occurred during 85 patient-weeks of isosorbide dinitrate therapy compared with 17 during 76 patient-weeks of placebo. Severity of congestive heart failure improved in all eight patients who received isosorbide dinitrate compared with two patients who showed improvement and five whose symptoms became worse with placebo. No significant differences in physical findings, cardiac dimensions, or resting hemodynamics were observed. Maximal exercise duration increased significantly by 2.54 minutes with isosorbide dinitrate therapy, and rose insignificantly by 1.24 minutes with placebo. This preliminary trial suggests that long-term vasodilator therapy may be clinically beneficial in congestive heart failure.     

心力衰竭治疗药物新进展

目的对传统心力衰竭的药物治疗有新的转变和新的认识。方法参阅相关文献,对之综合、分析和归纳。结果洋地黄类、血管紧张素转换酶抑制剂、β受体阻滞剂、血管紧张素受体拮抗剂和醛固酮拮抗剂（螺内酯）等是治疗心力衰竭中较为理想的药物。结论心力衰竭治疗应从最新模式———神经内分泌综合调控模式进行。     

心力衰竭基因治疗的研究进展

心力衰竭是多种心血管疾病的终末阶段。在过去二三十年里,虽然广泛采用药物和尖端仪器治疗心力衰竭,但患者数量仍不断增加。近年来,一些学者提出基因治疗方法,并进行了大量实验研究。本文就心力衰竭基因治疗的研究进行综述。     

Outpatient insulin therapy in type 1 and type 2 diabetes mellitus: scientific review

CONTEXT: Newer insulin therapies, including the concept of physiologic basal-prandial insulin and the availability of insulin analogues, are changing clinical diabetes care. The key to effective insulin therapy is an understanding of principles that, when implemented, can result in improved diabetes control. OBJECTIVE: To systematically review the literature regarding insulin use in patients with type 1 and type 2 diabetes mellitus (DM). DATA SOURCES: A MEDLINE search was performed to identify all English-language articles of randomized controlled trials involving insulin use in adults with type 1 or type 2 DM from January 1, 1980, to January 8, 2003. Bibliographies and experts were used to identify additional studies. STUDY SELECTION AND DATA EXTRACTION: Studies were included (199 for type 1 DM and 144 for type 2 DM, and 38 from other sources) if they involved human insulins or insulin analogues, were at least 4 weeks long with at least 10 patients in each group, and glycemic control and hypoglycemia were reported. Studies of insulin-oral combination were similarly selected. DATA SYNTHESIS: Twenty-eight studies for type 1 DM, 18 for type 2 DM, and 48 for insulin-oral combination met the selection criteria. In patients with type 1 DM, physiologic replacement, with bedtime basal insulin and a mealtime rapid-acting insulin analogue, results in fewer episodes of hypoglycemia than conventional regimens. Rapid-acting insulin analogues are preferred over regular insulin in patients with type 1 DM since they improve HbA1C and reduce episodes of hypoglycemia. In patients with type 2 DM, adding bedtime neutral protamine Hagedorn (isophane) insulin to oral therapy significantly improves glycemic control, especially when started early in the course of disease. Bedtime use of insulin glargine results in fewer episodes of nighttime hypoglycemia than neutral protamine Hagedorn regimens. For patients with more severe insulin deficiency, a physiologic insulin regimen should allow lower glycemic targets in the majority of patients. Adverse events associated with insulin therapy include hypoglycemia, weight gain, and worsening diabetic retinopathy if hemoglobin A1C levels decrease rapidly. CONCLUSIONS: Many options for insulin therapy are now available. Physiologic insulin therapy with insulin analogues is now relatively simple to use and is associated with fewer episodes of hypoglycemia.