2012级住院医师吴玲 - westicu.cn · Lower versus Higher Hemoglobin Threshold for Transfusion...

2012级住院医师吴玲

Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD

BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored.

长效支气管扩张剂联合应用吸入糖皮质激素被推荐用于重度COPD频繁发作。然而，在吸入糖皮质激素是否能增加两种长效支气管扩张剂的益处还未得到验证。

METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored.

这是一项为期12个月双盲，平行对照试验，共招募2485位慢性COPD急性发作史患者，接受三联治疗，包括tiotropium（噻托溴铵）（18 μg，每天一次)，salmeterol（沙美特罗，50μg，每日两次），同时配合吸入糖皮质激素丙酸氟替卡松（每日两次500μg）。研究设置6周的导入期。患者随机分为两组，采用随机撤药试验，观察继续采用三联治疗还是在超过12周后撤退氟替卡松。主要终点是到中重度COPD首次急性发作的时间。同时还监测了肺功能，健康状况，以及呼吸困难。（ WISDOM 试验）

Helgo Magnussen, M.D., Bernd Disse, M.D., Ph.D., Roberto Rodriguez-Roisin, M.D，etc.

Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD

RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group.

这是一项非劣效研究，非劣效界值为1.20。研究结果表明，与连续使用糖皮质激素相比，糖皮质激素撤退并不劣于连续使用糖皮质激素（HR：1.06， 95%CI：0.94 to 1.19）。在第18周，当糖皮质激素撤退完成后，与连续使用糖皮质激素相比，1秒钟用力呼气容积（FEV1）平均减少38ml(P<0.001)，在52周两组相差43 ml(P=0.001).糖皮质激素撤退组在呼吸困难以及健康状况方面没有显著性改变。

CONCLUSIONS: In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.)

最终结果显示，对重度COPD患者接受噻托溴铵以及沙美特罗后，是否撤退吸入糖皮质激素对中重度急性发作的风险

是相似的。然而，在糖皮质激素撤退组的肺功能有更大的下降。

Helgo Magnussen, M.D., Bernd Disse, M.D., Ph.D., Roberto Rodriguez-Roisin, M.D，etc.

Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

BACKGROUND: Blood transfusions are frequently given to patients with septic shock. However, the benefits and harms of different hemoglobin thresholds for transfusion have not been established.

在感染性休克的病人，输血是很常见的。然而，对于输血，不同的血红蛋白阈值的利弊尚未确定。

METHODS: In this multicenter, parallel-group trial, we randomly assigned patients in the intensive care unit (ICU) who had septic shock and a hemoglobin concentration of 9 g per deciliter or less to receive 1 unit of leukoreduced red cells when the hemoglobin level was 7 g per deciliter or less (lower threshold) or when the level was 9 g per deciliter or less (higher threshold) during the ICU stay. The primary outcome measure was death by 90 days after randomization.

在这项多中心、平行组试验中，纳入对象ICU感染性休克且血红蛋白浓度为9g/L或以下的患者，随机分配为2组：当血红蛋白水平为升7g/L或以下（较低阈值）或者当血红蛋白水平为9g/L或以下（较高的阈值）接受1个单位去白红细胞。研究的主要终点是随机分组后90天的死亡率。

JLars B. Holst, M.D., Nicolai Haase, M.D., Ph.D., Jørn Wetterslev, M.D., Ph.D., etc.


RESULTS: We analyzed data from 998 of 1005 patients (99.3%) who underwent randomization. The two intervention groups had similar baseline characteristics. In the ICU, the lower-threshold group received a median of 1 unit of blood (interquartile range, 0 to 3) and the higher-threshold group received a median of 4 units (interquartile range, 2 to 7). At 90 days after randomization, 216 of 502 patients (43.0%) assigned to the lower-threshold group, as compared with 223 of 496 (45.0%) assigned to the higher-threshold group, had died (relative risk, 0.94; 95% confidence interval, 0.78 to 1.09; P=0.44). The results were similar in analyses adjusted for risk factors at baseline and in analyses of the per-protocol populations. The numbers of patients who had ischemic events, who had severe adverse reactions, and who required life support were similar in the two intervention groups.

我们分析了1005例接受随机分组中998例（99.3％）的数据。这两个干预组有相似的基线特征。在ICU，低阈值组接受中位数为1个单位血（四分位距，0～3）和高阈值组接受中位数为4个单位血（四分位距为2～7）。在随机化后90天，502名低阈值组中的216名患者（43.0％），对比496名高阈值组中的223名患者（45.0％）死亡（相对风险0.94，95％置信区间为0.78～1.09，P=0.44）。在这两个干预组中，发生缺血事件、有严重不良反应以及需要生命维持的患者数量均是相似的。



CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions.

对于感染性休克患者，高低阈值组的90天死亡率、缺血性事件发生率和需要生命维持比率是相似的；低阈值组接受较少的输血量。


Goal-Directed Resuscitation for Patients with Early Septic Shock

BACKGROUND : Early goal-directed therapy (EGDT) has been endorsed in the guidelines of the Surviving Sepsis Campaign as a key strategy to decrease mortality among patients presenting to the emergency department with septic shock. However, its effectiveness is uncertain.EGDT已作为治疗脓毒症休克的指南，同时可以降低急诊脓毒症休克患者的死亡率。但是它的有效性存在争议。

METHODS: In this trial conducted at 51 centers (mostly in Australia or New Zealand), we randomly assigned patients presenting to the emergency department with early septic shock to receive either EGDT or usual care. The primary outcome was all-cause mortality within 90 days after randomization.多中心、RCT，纳入对象为急诊早期脓毒症休克患者，随机分为EGDT和常规治疗组，主要结局为90天死亡率。

The ARISE Investigators and the ANZICS Clinical Trials Group


RESULTS: Of the 1600 enrolled patients, 796 were assigned to the EGDT group and 804 to the usual-care group. Primary outcome data were available for more than 99% of the patients. Patients in the EGDT group received a larger mean (±SD) volume of intravenous fluids in the first 6 hours after randomization than did those in the usual-care group (1964±1415 ml vs. 1713±1401 ml) and were more likely to receive vasopressor infusions (66.6% vs. 57.8%), red-cell transfusions (13.6% vs. 7.0%), and dobutamine (15.4% vs. 2.6%) (P<0.001 for all comparisons). At 90 days after randomization, 147 deaths had occurred in the EGDT group and 150 had occurred in the usual-care group, for rates of death of 18.6% and 18.8%, respectively (absolute risk difference with EGDT vs. usual care, −0.3 percentage points; 95% confidence interval, −4.1 to 3.6; P=0.90). There was no significant difference in survival time, in-hospital mortality, duration of organ support, or length of hospital stay.

该研究最终纳入了1600例患者，EGDT组796 例，常规治疗组804例. EGDT组患者在前6h内接受的液体量显著高于常规治疗组 (1964±1415 ml vs.1713±1401 ml) 而且使用血管收缩药物和输血更多 (66.6% vs. 57.8%),(13.6% vs.7.0%), 以及使用更多多巴酚丁胺 (15.4% vs. 2.6%)(P<0.001). 90天EGDT组147例患者死亡，常规治疗组150例患者死亡，死亡率分别为18.6% 以及18.8%(绝对风险减低 EGDT vs.常规治疗,为−0.3%; 95% CI, −4.1 - 3.6; P = 0.90).在生存时间，院内死亡率，器官功能支持时间，住院时间两组均没有显著的区别。



CONCLUSIONS

In critically ill patients presenting to the emergency department with early septic shock, EGDT did not reduce all-cause mortality at 90 days. (Funded by the National Health and Medical Research Council of Australia and the Alfred Foundation; ARISE ClinicalTrials.gov number, NCT00975793.)

作者最终得出急诊室诊断为脓毒症休克患者，使用EGDT不能改善90天死亡率的结论。


Trial of the Route of Early Nutritional Support in Critically Ill Adults

BACKGROUND: Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route.在重症患者中早期营养支持最有效的途径仍有争议。

METHODS:

We conducted a pragmatic, randomized trial involving adults with an unplanned admission to one of 33 English intensive care units. We randomly assigned patients who could be fed through either the parenteral or the enteral route to a delivery route, with nutritional support initiated within 36 hours after admission and continued for up to 5 days. The primary outcome was all-cause mortality at 30 days.

研究以非预期进入33个ICU的患者为研究对象，之后将这类患者随机分为肠内营养组及肠外营养组，在患者进入ICU的36小时内开始营养支持，持续至5天的时间。研究终点定义为30天内全因死亡率。

Sheila E. Harvey, Ph.D., Francesca Parrott, M.Sci., David A. Harrison, Ph.D., etc.


RESULTS: We enrolled 2400 patients; 2388 (99.5%) were included in the analysis (1191 in the parenteral group and 1197 in the enteral group). By 30 days, 393 of 1188 patients (33.1%) in the parenteral group and 409 of 1195 patients (34.2%) in the enteral group had died (relative risk in parenteral group, 0.97; 95% confidence interval, 0.86 to 1.08; P=0.57). There were significant reductions in the parenteral group, as compared with the enteral group, in rates of hypoglycemia (44 patients [3.7%] vs. 74 patients [6.2%]; P=0.006) and vomiting (100 patients [8.4%] vs. 194 patients [16.2%]; P<0.001). There were no significant differences between the parenteral group and the enteral group in the mean number of treated infectious complications (0.22 vs. 0.21; P=0.72), 90-day mortality (442 of 1184 patients [37.3%] vs. 464 of 1188 patients [39.1%], P=0.40), in rates of 14 other secondary outcomes, or in rates of adverse events. Caloric intake was similar in the two groups, with the target intake not achieved in most patients.

研究纳入了2400个患者，其中2388例（99.5%）患者进入随访（肠外营养组1191例；肠内营养组1197例）。在30天内，1188个肠外营养组的患者中393例（33.1%）死亡，而1195个肠内营养组的患者中409例发生死亡（34.2%），统计学并未发现显著差异（P=0.57）。而在肠外营养组中，低血糖及呕吐的发生率明显低于肠内营养组（44例[3.7%]比74例[6.2%]，P=0.006；100例[8.4%]比194例[16.2%]，P＜0.001），而感染发生率（0.22vs.0.21 =0.72）、90天死亡率（442of1184patients[37.3%]vs.464of1188patients[39.1%],P=0.40）、并发症及总能量摄入方面两组间并无显著差异。



CONCLUSIONS

We found no significant difference in 30-day mortality associated with the route of delivery of early nutritional support in critically ill adults. (Funded by the United Kingdom National Institute for Health Research; CALORIES Current Controlled Trials number, ISRCTN17386141.)

研究表明，肠内营养及肠外营养对预后的影响并无显著差异，而肠内营养组患者发生肠道反应及低血糖的几率要高于肠外营养组。


Four-Month Moxifloxacin-Based Regimens for Drug-Sensitive Tuberculosis

BACKGROUND: Early-phase and preclinical studies suggest that moxifloxacin-containing regimens could allow for effective 4-month treatment of uncomplicated, smear-positive pulmonary tuberculosis.

既往早期的研究以及临床前期的研究均提示，对于非复杂性的、痰涂片阳性的结核病患者，采用含有莫西沙星的 4 个月短疗程的治疗方案是有效的。

METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial to test the noninferiority of two moxifloxacin-containing regimens as compared with a control regimen. One group of patients received isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by 18 weeks of isoniazid and rifampin (control group). In the second group, we replaced ethambutol with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (isoniazid group), and in the third group, we replaced isoniazid with moxifloxacin for 17 weeks, followed by 9 weeks of placebo (ethambutol group). The primary end point was treatment failure or relapse within 18 months after randomization.

该研究为随机、双盲、安慰剂对照的 3 期临床研究，来比较两个含莫西沙星的方案和对照组之间的非劣效性，共纳入了 1931 例结核患者。所有受试者被随机分入 3 个治疗组。治疗时间都为26周。

第 1 组（对照组）：口服异烟肼+利福平+吡嗪酰胺+乙胺丁醇（前8 个星期），异烟肼和利福平治疗（后18 个星期）。

第 2 组（异烟肼组）：异烟肼+利福平+吡嗪酰胺+莫西沙星（前17个星期），异烟肼和利福平治疗（后9 个星期）。

第 3 组（乙胺丁醇组）莫西沙星+利福平+吡嗪酰胺+莫西沙星（前17个星期），异烟肼和利福平治疗（后9 个星期）。

主要研究终点是随机分组后的 18 个月内出现治疗失败或者结核复发。

Stephen H. Gillespie, M.D., D.Sc., Angela M. Crook, Ph.D., Timothy D. McHugh, Ph.D., etc.


RESULTS: Of the 1931 patients who underwent randomization, in the per-protocol analysis, a favorable outcome was reported in fewer patients in the isoniazid group (85%) and the ethambutol group (80%) than in the control group (92%), for a difference favoring the control group of 6.1 percentage points (97.5% confidence interval [CI], 1.7 to 10.5) versus the isoniazid group and 11.4 percentage points (97.5% CI, 6.7 to 16.1) versus the ethambutol group. Results were consistent in the modified intention-to-treat analysis and all sensitivity analyses. The hazard ratios for the time to culture negativity in both solid and liquid mediums for the isoniazid and ethambutol groups, as compared with the control group, ranged from 1.17 to 1.25, indicating a shorter duration, with the lower bounds of the 95% confidence intervals exceeding 1.00 in all cases. There was no significant difference in the incidence of grade 3 or 4 adverse events, with events reported in 127 patients (19%) in the isoniazid group, 111 (17%) in the ethambutol group, and 123 (19%) in the control group.在进入随机分组的1931名患者中，异烟肼组和乙胺丁醇组有利结果（85% 和 80%）要少于对照组（92%）；对照组有利结果要高出异烟肼组6.1 个百分点；对照组有利结果则高出乙胺丁醇组11.4 个百分点。与对照组相比，异烟肼组和乙胺丁醇组从接种到培养结果阴性（固体和液体培养基）的时间风险比为 1.17 到 1.25。在发生 3 级或者 4 级的不良反应方面，各组之间没有明显的差异。



CONCLUSIONS The two moxifloxacin-containing regimens produced a more rapid initial decline in bacterial load, as compared with the control group. However, noninferiority for these regimens was not shown, which indicates that shortening treatment to 4 months was not effective in this setting.

研究发现，与对照组比较，两组包含有莫西沙星的方案可以在初始治疗中更快的降低结核菌的负荷。然而却没有显示出在非劣效性方面的优势。


High-Dose Rifapentine with Moxifloxacin for Pulmonary Tuberculosis

BACKGROUND：Tuberculosis regimens that are shorter and simpler than the current 6-month daily regimen are needed.对于现有的6个月的常规治疗结核方案，时间更短更简单的方案是需要的。

METHODS：We randomly assigned patients with newly diagnosed, smear-positive, drug-sensitive tuberculosis to one of three regimens: a control regimen that included 2 months of ethambutol, isoniazid, rifampicin, and pyrazinamide administered daily followed by 4 months of daily isoniazid and rifampicin; a 4-month regimen in which the isoniazid in the control regimen was replaced by moxifloxacin administered daily for 2 months followed by moxifloxacin and 900 mg of rifapentine administered twice weekly for 2 months; or a 6-month regimen in which isoniazid was replaced by daily moxifloxacin for 2 months followed by one weekly dose of both moxifloxacin and 1200 mg of rifapentine for 4 months. Sputum specimens were examined on microscopy and after culture at regular intervals. The primary end point was a composite treatment failure and relapse, with noninferiority based on a margin of 6 percentage points and 90% confidence intervals.

研究对象为初诊病人、涂阳和药敏的肺结核患者，随机分为3组。

对照组：每天服用乙胺丁醇片+异烟肼+利福平+吡嗪酰胺（前2个月），后每天服用异烟肼和利福平（后4个月）；

4个月方案：每天服用乙胺丁醇片+莫西沙星+利福平+吡嗪酰胺（前2个月），后每周两次服用莫西沙星+利福喷汀900 mg （后2个月）；

6个月方案为每天服用乙胺丁醇片+莫西沙星+利福平+吡嗪酰胺(前2个月)，后每周一次服用莫西沙星+利福喷汀1200 mg （4 个月）。

定期检查痰涂片培养。主要终点是治疗失败和复发，非劣性临界点为6%。

Amina Jindani, F.R.C.P., Thomas S. Harrison, F.R.C.P., Andrew J. Nunn, M.Sc., Patrick P.J. Phillips, Ph.D., etc.


RESULTS：We enrolled a total of 827 patients from South Africa, Zimbabwe, Botswana, and Zambia; 28% of patients were coinfected with the human immunodefiency virus. In the per-protocol analysis, the proportion of patients with an unfavorable response was 4.9% in the control group, 3.2% in the 6-month group (adjusted difference from control, −1.8 percentage points; 90% confidence interval [CI], −6.1 to 2.4), and 18.2% in the 4-month group (adjusted difference from control, 13.6 percentage points; 90% CI, 8.1 to 19.1). In the modified intention-to-treat analysis these proportions were 14.4% in the control group, 13.7% in the 6-month group (adjusted difference from control, 0.4 percentage points; 90% CI, −4.7 to 5.6), and 26.9% in the 4-month group (adjusted difference from control, 13.1 percentage points; 90% CI, 6.8 to 19.4).

该研究从南非、津巴布韦、博茨瓦纳和赞比亚招募827名患者，其中28%合并感染HIV。不良反应：对照组：4.9%，6个月方案组中：3.2%，4个月方案组：18.2%。按改良的意向性治疗分析，对照组中有不利反应的患者占14.4%，新的6个月的治疗方案中有13.7%患者有不利的反应，新的4个月的治疗方案中有26.9%患者有不利反应。



CONCLUSIONS

The 6-month regimen that included weekly administration of high-dose rifapentine and moxifloxacin was as effective as the control regimen. The 4-month regimen was not noninferior to the control regimen. (Funded by the European and Developing Countries Clinical Trials Partnership and the Wellcome Trust; RIFAQUIN Current Controlled Trials number, ISRCTN44153044.)

新的6个月的治疗方案（即每天服用乙胺丁醇片+莫西沙星+利福平+吡嗪酰胺(前2个月)，后每周一次服用莫西沙星+

利福喷汀1200 mg （后4个月）），与对照治疗方案同样有效。4个月的治疗方案与对照组相比，治疗效果差。


Provision of No-Cost, Long-Acting Contraception and Teenage Pregnancy 为美国十多岁青少年提供免费、长效避孕措施的前瞻性研究(避孕手段免费，青少年意外怀孕减少)

Follow-up of Blood-Pressure Lowering and Glucose Control in Type 2 Diabetes 降压治疗可更有效降低2型糖尿病患者死亡率(该研究提示，在ADVANCE研究试验后随访第6年期间，降压治疗仍与2型糖尿病患者死亡率下降有关，但是，没有证据表明强化血糖控制能降低患者死亡风险。)

A Four-Month Gatifloxacin-Containing Regimen for Treating Tuberculosis 四个月短程使用加替沙星治疗药物敏感性结核（不适于）

Initial Therapy with FOLFOXIRI and Bevacizumab for Metastatic Colorectal Cancer FOLFOXIRI+贝伐珠单抗治疗转移性结直肠癌的初始治疗（FOLFOXIRI：氟尿嘧啶，亚叶酸钙，奥沙利铂，和伊立替康，可以延长转移性结直肠癌患者的生存期）

Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia 嵌合抗原受体T细胞可有效治疗白血病(嵌合抗原受体修饰T细胞免疫疗法（CART）)(嵌合抗原受体——抗CD19修饰的T细胞疗法对治疗复发和难治型ALL是有效的。CTL019和高缓解率有关，即使是干细胞移植失败的患者和缓解耐受24个月的患者也有效。)

Response and Acquired Resistance to Everolimus in Anaplastic Thyroid Cancer 肿瘤重复测序结果大不同

One-Unit versus Two-Unit Cord-Blood Transplantation for Hematologic Cancers

单单位与双单位脐血移植在干细胞移植治疗中的比较（我们的研究发现，血液肿瘤患者（包括儿童和成人）接受单单位和双单位的脐血移植后的生存率相近。然而，接受单单位脐血移植的患者能获得较高的血小板恢复能力以及较低的移植物抗宿主病发生率）

Survival and Long-term Outcomes Following Bioprosthetic vs Mechanical Aortic Valve Replacement in Patients Aged 50 to 69 Years

Importance The choice between bioprosthetic and mechanical aortic valve replacement in younger patients is controversial because long-term survival and major morbidity are poorly characterized.

主动脉瓣置换术中，选择生物瓣膜还是机械瓣膜，一直存在争议。

Objective To quantify survival and major morbidity in patients aged 50 to 69 years undergoing aortic valve replacement.量化的患者年龄在50到69年间接受主动脉瓣置换术的生存和发病率。

Design, Setting, and Participants Retrospective cohort analysis of 4253 patients aged 50 to 69 years who underwent primary isolated aortic valve replacement using bioprosthetic vs mechanical valves in New York State from 1997 through 2004, identified using the Statewide Planning and Research Cooperative System. Median follow-up time was 10.8 years (range, 0 to 16.9 years); the last follow-up date for mortality was November 30, 2013. Propensity matching yielded 1001 patient pairs.本队列共收集从1997年到2004年4253位50-69岁之间的首次接受主动脉瓣置换术患者。随访时间为10.8年（平均0-16.9年），随访到2013年11月。

Main Outcomes and Measures Primary outcome was all-cause mortality; secondary outcomes were stroke, reoperation, and major bleeding.

主要结局指标为全因死亡，次要结局指标为卒中，再手术和大出血状况。

Yuting P. Chiang, BA1; Joanna Chikwe, MD1; Alan J. Moskowitz, MD2;etc.


Results No differences in survival or stroke rates were observed in patients with bioprosthetic compared with mechanical valves. Actuarial 15-year survival was 60.6% (95% CI, 56.3%-64.9%) in the bioprosthesis group compared with 62.1% (95% CI, 58.2%-66.0%) in the mechanical prosthesis group (hazard ratio, 0.97 [95% CI, 0.83-1.14]). The 15-year cumulative incidence of stroke was 7.7% (95% CI, 5.7%-9.7%) in the bioprosthesis group and 8.6% (95% CI, 6.2%-11.0%) in the mechanical prosthesis group (hazard ratio, 1.04 [95% CI, 0.75-1.43). The 15-year cumulative incidence of reoperation was higher in the bioprosthesis group (12.1% [95% CI, 8.8%-15.4%] vs 6.9% [95% CI, 4.2%-9.6%]; hazard ratio, 0.52 [95% CI, 0.36-0.75]). The 15-year cumulative incidence of major bleeding was higher in the mechanical prosthesis group (13.0% [95% CI, 9.9%-16.1%] vs 6.6% [95% CI, 4.8%-8.4%]; hazard ratio, 1.75 [95% CI, 1.27-2.43]). The 30-day mortality rate was 18.7% after stroke, 9.0% after reoperation, and 13.2% after major bleeding.

结果发现，两组患者在生存或卒中发生率方面没有显著性差异。

15年随访中，存活率：生物瓣膜组60.6%，而机械瓣膜组为 62.1% 。

卒中发生率：生物瓣膜组为7.7%，在机械瓣膜组为8.6% 。

再手术在生物瓣膜组为12.1%，机械械瓣组为6.9%。

大出血事件在机械瓣膜组为13.0%，生物瓣组为6.6%。

卒中后30天内致死率为18.7%，再手术为9.0%，大出血为13.2%。



Conclusions and Relevance Among propensity-matched patients aged 50 to 69 years who underwent aortic valve replacement with bioprosthetic compared with mechanical valves, there was no significant difference in 15-year survival or stroke. Patients in the bioprosthetic valve group had a greater likelihood of reoperation but a lower likelihood of major bleeding. These findings suggest that bioprosthetic valves may be a reasonable choice in patients aged 50 to 69 years.

结论：两组在15年生存状况和卒中状况方面均没有显著性差异。但是生物瓣膜组再手术率更高，大出血风险可能更低。因此，从整体来说，在50-69岁人群中，主动脉置换术中，更推荐使用生物瓣膜。


Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D DeficiencyThe VITdAL-ICU Randomized Clinical Trial

Importance Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal.低VitD状态可能会增加急诊患者的致死率和死亡率，但是它们的原因并不清楚。

Objective To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs.本研究旨在在急诊ICU人群的VitD缺乏人群中给予VitD3，恢复到正常VitD3水平持续6个月，对健康的影响。

Design, Setting, and Participants A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243).研究采用随机双盲，安慰剂对照的单中心试验，从2010年5月到2012年9月492例VitD缺乏患者(血清VitD≤20 ng/mL)，患者随机分配接受VitD3组(n = 249)和安慰剂组(n = 243)。

Karin Amrein, MD, MSc1; Christian Schnedl, MD1; Alexander Holl, MD2; etc.


Interventions Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540 000 IU followed by monthly maintenance doses of 90 000 IU for 5 months. VitD3和安慰剂都是通过口服或鼻饲管给予首次540000 IU/月，维持剂量为90000IU 5个月。

Main Outcomes and Measures The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis.主要终点为住院的时间，次要终点包括ICU和其它住院的时间，患者血清VitD3在第7天高于30ng/mL的百分比，院内死亡率，6个月内死亡率。以及对严重VitD缺乏者(≤12 ng/mL) 进行亚组分析。



Results A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = 0.18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = 0.09).

最终475位患者进入最终分析，VitD3组237人，安慰剂组238人。住院时间中位长度并无显著性差异，在VitD3组为20.1 days ，安慰剂组为19.3 days 。院内死亡率与6个月死亡率也没有显著性差异。院内死亡率在VitD3组为 28.3% ，安慰剂组为 35.3% 。6个月死亡率在VitD3组为35.0% ，安慰剂组为42.9% 。



For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction =0.04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction =0.12).

对于严重VitD缺乏的亚组(n = 200)分析显示，两组住院长度没有显著性差异。在VitD3组为20.1 days ，安慰剂组为19.0 days 。院内死亡率在VitD3组显著性降低，为 28/98(28.6% [95% CI, 19.9%-38.6%])死亡，安慰剂组为 47/102 (46.1% [95% CI, 36.2%-56.2%])死亡，HR： 0.56 [95% CI, 0.35-0.90], P for interaction = 0.04)。但6个月死亡率并没有显著差异，在VitD3组为(34.7% [95% CI, 25.4%-45.0%]，安慰剂组为 50.0% [95% CI, 39.9%-60.1%]，HR： 0.60 [95% CI, 0.39-0.93], P for interaction = 0.12。



Conclusions and Relevance Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study.

上述结果显示，在VitD缺乏人群中，补充高剂量VitD，在住院时间，院内死亡率和6个月死亡率方面，并没有看到明显的获益状况。虽然在严重缺乏VitD的亚组中看到明显获益，但需要更大的样本量和后续研究进一步证实。


Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients With Staphylococcus aureus Bloodstream Infections A Systematic Review and Meta-analysis

Importance Staphylococcus aureus bacteremia (SAB) is a worldwide problem. It is unclear whether higher-vancomycin minimum inhibitory concentration (MIC) is associated with mortality. This potential association has direct consequences for patients and public health.金黄色葡萄球菌菌血症（SAB）是一个世界性难题。尚不清楚较高的万古霉素最低抑菌浓度（MIC）是否与死亡率相关。这种潜在相关性对患者和公共卫生具有直接影响。

Data Sources PubMed, Embase, the Cochrane Library, Evidence-based Medicine BMJ, and the American College of Physicians Journal Club were searched from inception through April 2014.研究人员检索PubMed、Embase、Cochrane图书馆、英国医学杂志（BMJ）循证医学以及美国医师学会杂志俱乐部中从创建到2014年4月的资料。

Study Selection Studies reporting mortality and vancomycin MIC in patients with SAB were included.本研究纳入报告SAB患者死亡率和万古霉素MIC的研究。

Data Extraction and Synthesis Two authors performed the literature search and the study selection separately. Random-effects modeling was used for all analyses.两位作者进行文献检索和独立选择研究。随机效应模型被用于所有的分析。

Main Outcomes and Measures All-cause mortality.全因死亡率。

Andre C. Kalil, MD, MPH1; Trevor C. Van Schooneveld, MD1; Paul D. Fey, PhD2; etc.

Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients With Staphylococcus aureus Bloodstream Infections A Systematic Review and Meta-analysis

Findings Among 38 included studies that involved 8291 episodes of SAB, overall mortality was 26.1%. The estimated mortality was 26.8% among SAB episodes (n = 2740) in patients with high-vancomycin MIC (≥1.5 mg/L) compared with 25.8% mortality among SAB episodes (n = 5551) in patients with low-vancomycin MIC (<1.5 mg/L) (adjusted risk difference [RD], 1.6% [95% CI, −2.3% to 5.6%]; P = .43). For the highest-quality studies, the estimated mortality was 26.2% among SAB episodes (n = 2318) in patients with high-vancomycin MIC compared with 27.8% mortality among SAB episodes (n = 4168) in patients with low-vancomycin MIC (RD, 0.9% [95% CI, −2.9% to 4.6%]; P = 0.65)..

研究结果显示：在所纳入涉及8291例次SAB的38项研究中，整体死亡率为26.1%。高万古霉素MIC（≥1.5mg/L）患者SAB（n＝2740）的估计死亡率为26.8%，相比之下，低万古霉素MIC（＜1.5mg/L）患者SAB（n＝5551）的死亡率为25.8%[校正危险差（RD）为1.6%，95%可信区间（CI）为-2.3%～5.6%，P＝0.43]。对于质量最高的研究，高万古霉素MIC患者SAB（n＝2318）的估计死亡率为26.2%，相比之下，低万古霉素MIC患者SAB（n＝4168）的死亡率为27.8%[RD为0.9%（95%CI为-2.9%～4.6%），P＝0.65]。


Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients With Staphylococcus aureus Bloodstream InfectionsA Systematic Review and Meta-analysis

In studies that included only methicillin-resistant S aureus infections (n = 7232), the mortality among SAB episodes (n = 2384) in patients with high-vancomycin MIC was 27.6% compared with mortality of 27.4% among SAB episodes (n = 4848) in patients with low-vancomycin MIC (adjusted RD, 1.6% [95% CI, −2.3% to 5.5%]; P = 0.41). No significant differences in risk of death were observed in subgroups with high-vancomycin MIC vs low-vancomycin MIC values across different study designs, microbiological susceptibility assays, MIC cutoffs, clinical outcomes, duration of bacteremia, previous vancomycin exposure, and treatment with vancomycin .在只纳入耐甲氧西林金黄色葡萄球菌感染（n＝7232）的研究中，高万古霉素MIC患者SAB（n＝2384）的死亡率为27.6%，相比之下，低万古霉素MIC患者SAB（n＝4848）的死亡率为27.4%[校正RD为1.6%，95%CI为-2.3%～5.5%），P＝0.41]。在不同的研究设计、微生物敏感性测试方法、MIC界值、临床转归、菌血症持续时间、前期万古霉素暴露以及应用万古霉素治疗方面，未观察到高万古霉素MIC值和低万古霉素MIC值亚组之间，死亡危险存在显著差异。


Association Between Vancomycin Minimum Inhibitory Concentration and Mortality Among Patients With Staphylococcus aureus Bloodstream InfectionsA Systematic Review and Meta-analysis

Conclusions and Relevance In this meta-analysis of SAB episodes, there were no statistically significant differences in the risk of death when comparing patients with S aureus exhibiting high-vancomycin MIC (≥1.5 mg/L) to those with low-vancomycin MIC (<1.5 mg/L), although the findings cannot definitely exclude an increased mortality risk. These findings should be considered when interpreting vancomycin susceptibility and in determining whether alternative antistaphylococcal agents are necessary for patients with SAB with elevated but susceptible vancomycin MIC values.

本研究结果表明：高万古霉素MIC（≥1.5mg/L）和低万古霉素MIC（<1.5mg/L）的金黄色葡萄球菌感染患

者的死亡危险无统计学显著差异，尽管该结果不能明确排除死亡危险增加。当对万古霉素敏感性进行解读时，以及对于万古霉素MIC值升高但仍然敏感的SAB患者，在确定是否有必要应用备选的抗葡萄球菌药物时，应该考虑到这些结果。


Effect of a Postdischarge Virtual Ward on Readmission or Death for High-Risk Patients: A Randomized Clinical Trial. 虚拟病房可能并不能减少高风险人群的再住院或死亡。

Serological Responses to an Avian Influenza A/H7N9 Vaccine Mixed at the Point-of-Use With MF59 AdjuvantA Randomized Clinical Trial. A/H7N9型禽流感疫苗与MF59佐剂混合使用安全有效（2期临床试验）。

Acupuncture for Chronic Knee Pain: A Randomized Clinical Trial. 临床对照试验再次证实针灸不能改善慢性膝关节炎疼痛。

Association Between Hospital-Level Obstetric Quality Indicators and Maternal and Neonatal Morbidity

医院产科质量水平指标和母婴患病率。（认为目前质量评估指标不足以综合性指导并改善产科管理质量。）

Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUs: A Randomized Clinical Trial 口咽部和肠道去污染能够降低抗生素耐药率(全病房使用SDD和SOD伴随较低的抗生素耐药率，但28天病死率无差异。与SOD相比，SDD组直肠携带抗生素耐药革兰阴性杆菌比例以及ICU获得性菌血症比例更低，但是耐氨基糖甙革兰阴性杆菌增加更为明显。)

Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial

Background

Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise).很多长病程2型糖尿病患者的 HbA1c没有达标，

既往比较胰岛素泵和每日多次注射胰岛素有效性的随机对照研究都没有得出确定性结果。研究者进行了这项随机对照研究(OpT2mise研究)，旨在解决这一问题。

Dr Yves Reznik MD a, Ohad Cohen MD b, Ronnie Aronson MD,etc.

Insulin pump treatment compared with multiple daily injections for treatment of type 2 diabetes (OpT2mise): a randomised open-label controlled trial Methods

We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8·0—12·0% (64—108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0·75 and size 4 with probability 0·25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01182493.

OpT2mise研究在全球36家医院招募每日多次注射胰岛素类似物但血糖控制仍较差的2型糖尿病患者，导入期为2个月。此后HbA1c水平为(8.0%~12.0%)的患者被随机分入胰岛素泵治疗组(n=168)或继续每日多次注射胰岛素组(n=163)。主要终点为意向治疗人群研究结束时平均HbA1c水平较基线的变化。


Findings 495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1·1% (SD 1·2; 12 mmol/mol, SD 13) in the pump treatment group and 0·4% (SD 1·1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of −0·7% (95% CI −0·9 to −0·4; −8 mmol/mol, 95% CI −10 to −4, p<0·0001). At the end of the study, the mean total daily insulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (p<0·0001), with no significant difference in bodyweight change between the two groups (1·5 kg [SD 3·5] vs 1·1 kg [3·6], p=0·322). Two diabetes-related serious adverse events (hyperglycaemia or ketosis without acidosis) resulting in hospital admission occurred in the pump treatment group compared with one in the multiple daily injection group. No ketoacidosis occurred in either group and one episode of severe hypoglycaemia occurred in the multiple daily injection group.

主要结果为，基线时两组平均HbA1c水平均为9%。6个月时，胰岛素泵治疗组平均HbA1c水平降低了1.1%，每日多次注射胰岛素组降低了0.4%(P<0.0001)。研究结束时，胰岛素泵治疗组和每日多次注射胰岛素组的每日平均总胰岛素剂量分别为97单位和122单位(P<0.0001)，两组患者的体重变化无明显差异(胰岛素泵治疗组1.5 kg对每日多次注射胰岛素组1.1 kg，P=0.322)。胰岛素泵治疗组和每日多次注射胰岛素组分别发生了2例和1例需要住院的糖尿病相关严重不良事件[高血糖和酮症(无酸中毒 )]。两组均没有发生酮症酸中毒，每日多次注射胰岛素组发生了1例重度低血糖发作。



Interpretation

In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option. 研究提示在增加胰岛素剂量但仍无法控制血糖的患者中，胰岛素泵有助于改善血糖控制。



Adverse outcomes after total and unicompartmental knee replacement in 101 330 matched patients: a study of data from the National Joint Registry for England and Wales.部分膝关节置换比全膝关节置换更安全。（本项研究评估了相应风险，结果提示，部分膝关节置换术的并发症和死亡例数更少，但该术式的确导致了更多的二次手术。但与二次手术相比，患者更需要注意的是避免死亡和心脏病发作或卒中等重大并发症的发生。）

The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.笑气用於非心脏外科大手术患者的全麻，安全有效（ENIGMA-II研究).(在非心脏外科大手术患者中，笑气并不增加死亡和心血管并发症，以及手术部位感染的风险。一氧化二氮的致吐作用可予止吐预防控制。)

Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: an open-label, randomised controlled trial 额外接种一剂灭活脊灰疫苗可增强儿童免疫力。

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Transcript of 2012级住院医师 吴玲 - westicu.cn · Lower versus Higher Hemoglobin Threshold for Transfusion...

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