20 / 10 / 16
关于“利福平耐药结核的短疗程方案试验”一文医学翻译摘要学习情况，记录于此。
A Trial of a Shorter Regimen for Rifampin-Resistant Tuberculosis
背景
世界卫生组织（WHO）2011年对耐多药结核的治疗方案提出了建议，而孟加拉国队列研究表明，耐多药结核患者以比上述方案时间短的治疗方案接受现有药物治疗后，达到了很有前景的治愈率。
BACKGROUND
Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011.
本段笔记：
方法
METHODS
我们在对氟喹诺酮类药物和氨基糖苷类药物敏感的利福平耐药结核患者中开展了一项3期非劣效性试验。
We conducted a phase 3 noninferiority trial in participants with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides.
笔记：
noninferiority trial 非劣效性试验
A that be susceptible to xxx 对xxx敏感的A
以2∶1的比例将参与者随机分组，分别接受包含大剂量莫西沙星的短疗程方案（9～11个月）或遵循2011年WHO指南的长疗程方案（20个月）治疗。
Participants were randomly assigned, in a 2:1 ratio, to receive a short regimen (9 to 11 months) that included high-dose moxifloxacin or a long regimen (20 months) that followed the 2011 WHO guidelines.
笔记：
主要疗效结局是132周时的良好状态，良好状态的定义为132周及之前一次检测中结核分枝杆菌培养结果呈阴性，并且两次检测之间无阳性培养结果，之前也无不良结局。
The primary efficacy outcome was a favorable status at 132 weeks, defined by cultures negative for Mycobacterium tuberculosis at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome.
笔记：
利用良好状态组间差异的95%置信区间上限≤10个百分点确定非劣效性。
An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority.
笔记：
结果
RESULTS
在被随机分组的424例参与者中，383例被纳入改良意向治疗人群。
Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population.
笔记：
长疗程方案组79.8%的参与者和短疗程方案组78.8%的参与者报告了良好状态，根据人类免疫缺陷病毒状态校正后的差异为1.0个百分点（95%置信区间[CI]，－7.5～9.5）（对于非劣效性，P=0.02）。
Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group — a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], −7.5 to 9.5) (P=0.02 for noninferiority).
在符合方案人群的321例参与者中，非劣效性结果一致（校正的差异，－0.7个百分点；95% CI，－10.5～9.1）。
The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, –0.7 percentage points; 95% CI, −10.5 to 9.1).
长疗程方案组45.4%的参与者和短疗程方案组48.2%的参与者发生了3级或更高级别的不良事件。
An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group.
短疗程方案组11.0%参与者和长疗程方案组6.4%参与者的QT间期或校正QT间期（利用Fridericia公式计算）延长至500 ms（P=0.14）；由于短疗程方案组的发生率较高，因此我们对参与者进行了密切监测，并对一些参与者的用药进行了调整。
Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia’s formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P=0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments.
笔记：
QT interval QT间期
corrected QT interval 校正QT间期
msec ms
个人看法：关于冒号后面的译文，中文增补主语（即，我们），似乎与原文被动体现客观性相悖。
短疗程方案组8.5%的参与者和长疗程方案组6.4%的参与者死亡，两组分别有3.3%和2.3%的参与者对氟喹诺酮类药物或氨基糖苷类药物产生了获得性耐药。
Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively.
结论
CONCLUSIONS
在对氟喹诺酮类药物和氨基糖苷类药物敏感的利福平耐药性结核患者中，短疗程方案的主要疗效结局不劣于长疗程方案，安全性与长疗程方案相似（由美国国际开发署[U.S. Agency for International Development]等资助；在Current Controlled Trials注册号为ISRCTN78372190；在ClinicalTrials.gov注册号为NCT02409290）。
In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190 ; ClinicalTrials.gov number, NCT02409290 .)
笔记：
耐多药结核对结核的关键治疗药物异烟肼和利福平耐药1 。
Multidrug-resistant tuberculosis is resistant to isoniazid and rifampin (also called rifampicin), key drugs used in the treatment of tuberculosis.1
笔记：
isoniazid 异烟肼
全世界每年有近500,000例耐多药结核新患者，而耐多药结核远比药物敏感性结核难以治疗。
The condition affects almost 500,000 new persons worldwide each year and is considerably more difficult to treat than drug-susceptible tuberculosis.
有不到1/4的患者开始接受治疗，2012年2 和2017年1 的报告治疗成功率分别为48%和54%。
Less than a quarter of patients start treatment, and the reported success rates were 48% in 20122 and 54% in 2017.1
虽然这一问题严重，但目前却缺乏耐多药结核联合用药方案的3期随机试验数据。
Despite the magnitude of the problem, data from phase 3 randomized trials of combination drug regimens for multidrug-resistant tuberculosis are lacking.
WHO的耐多药结核治疗建议（2011年发布）是基于质量极低的证据，被称作有条件的建议（即“遵循建议带来的合意效果很可能超过不合意效果”）3 。
Recommendations from the World Health Organization (WHO) for the treatment of multidrug-resistant tuberculosis (published in 2011) are based on evidence that was classified as very low quality and were described as conditional (i.e., “the desirable effects of adherence to a recommendation probably outweigh the undesirable effects”).3
2011年WHO指南建议8个月的强化治疗期和20个月的总治疗期3 。
The 2011 WHO guidelines recommended an intensive treatment phase of 8 months and a total treatment duration of 20 months.3
由于缺乏适用于资源匮乏环境的有效标准化治疗方案，Van Deun和同事在孟加拉国开展了观察性队列研究，在既往未接受过二线药物治疗的患者中评估耐多药结核的数种治疗方案。
In view of the lack of an effective standardized regimen that is appropriate for resource-poor settings, Van Deun and colleagues conducted observational cohort studies in Bangladesh to evaluate several regimens for multidrug-resistant tuberculosis in patients who had not received previous treatment with second-line drugs.
笔记：
对206例患者用药9～11个月的第六种治疗方案获得了令人鼓舞的结果，无复发治愈率为87.9%（95% CI，82.7～91.6）4 。
The sixth regimen, administered to 206 participants for 9 to 11 months, yielded encouraging results, with relapse-free cure occurring in 87.9% (95% confidence interval [CI], 82.7 to 91.6).4
笔记：
虽然这一方案与WHO建议的长疗程方案相比有相当大的优势，但我们认为需要随机试验来证明结果的再现性和普遍适用性，特别是因为在孟加拉国研究的参与者中，合并感染人类免疫缺陷病毒（HIV）和二线药物耐药的情况罕见。
Although such a regimen could have considerable advantages over the much longer WHO-recommended regimen, we considered that a randomized trial would be necessary for reproducibility and generalizability of results, particularly because human immunodeficiency virus (HIV) coinfection and second-line drug resistance were rare among the participants in the Bangladesh study.