Khazeni Nayer, Bravata Dena M, Holty Jon-Erik C, Uyeki Timothy M, Stave Christopher D, Gould Michael K
Stanford University Medical Center, Center for Health Policy and Center for Primary Care and Outcomes Research, Stanford Sleep Disorders Center, and Lane Medical Library, Stanford, California 94305, USA.
Ann Intern Med. 2009 Oct 6;151(7):464-73. doi: 10.7326/0003-4819-151-7-200910060-00143. Epub 2009 Aug 3.
Neuraminidase inhibitors (NAIs) are stockpiled internationally for extended use in an influenza pandemic.
To evaluate the safety and efficacy of extended-duration (>4 weeks) NAI chemoprophylaxis against influenza.
Studies published in any language through 11 June 2009 identified by searching 10 electronic databases and 3 trial registries.
Randomized, placebo-controlled, double-blind human trials of extended-duration NAI chemoprophylaxis that reported outcomes of laboratory-confirmed influenza or adverse events.
2 reviewers independently assessed study quality and abstracted information from eligible studies.
Of 1876 potentially relevant citations, 7 trials involving 7021 unique participants met inclusion criteria. Data were pooled by using random-effects models. Chemoprophylaxis with NAIs decreased the frequency of symptomatic influenza (relative risk [RR], 0.26 [95% CI, 0.18 to 0.37]; risk difference [RD], -3.9 percentage points [CI, -5.8 to -1.9 percentage points]) but not asymptomatic influenza (RR, 1.03 [CI, 0.81 to 1.30]; RD, -0.4 percentage point [CI, -1.6 to 0.9 percentage point]). Adverse effects were not increased overall among NAI recipients (RR, 1.01 [CI, 0.94 to 1.08]; RD, 0.1 percentage point [CI, -0.2 to 0.4 percentage point]), but nausea and vomiting were more common among those who took oseltamivir (RR, 1.48 [CI, 1.86 to 2.33]; RD, 1.7 percentage points [CI, 0.6 to 2.9 percentage points]). Prevention of influenza did not statistically significantly differ between zanamivir and oseltamivir.
All trials were industry-sponsored. No study was powered to detect rare adverse events, and none included diverse racial groups, children, immunocompromised patients, or individuals who received live attenuated influenza virus vaccine.
Extended-duration zanamivir and oseltamivir chemoprophylaxis seems to be highly efficacious for preventing symptomatic influenza among immunocompetent white and Japanese adults. Extended-duration oseltamivir is associated with increased nausea and vomiting. Safety and efficacy in several subpopulations that might receive extended-duration influenza chemoprophylaxis are unknown.
神经氨酸酶抑制剂（NAIs）在国际上被储备起来以备在流感大流行时长期使用。
评估长期（>4周）使用NAIs进行流感化学预防的安全性和有效性。
通过检索10个电子数据库和3个试验注册库，确定截至2009年6月11日以任何语言发表的研究。
长期使用NAIs进行化学预防的随机、安慰剂对照、双盲人体试验，这些试验报告了实验室确诊流感或不良事件的结果。
2名审阅者独立评估研究质量，并从符合条件的研究中提取信息。
在1876条潜在相关引文中，7项试验涉及7021名独特参与者，符合纳入标准。使用随机效应模型汇总数据。使用NAIs进行化学预防可降低有症状流感的发生率（相对风险[RR]，0.26[95%可信区间，0.18至0.37]；风险差值[RD]，-3.9个百分点[可信区间，-5.8至-1.9个百分点]），但对无症状流感无效（RR，1.03[可信区间，0.81至1.30]；RD，-0.4个百分点[可信区间，-1.6至0.9个百分点]）。NAIs接受者总体上不良反应未增加（RR，1.01[可信区间，0.94至1.08]；RD，0.1个百分点[可信区间，-0.2至0.4个百分点]），但服用奥司他韦的人恶心和呕吐更为常见（RR，1.48[可信区间，1.86至2.33]；RD，1.7个百分点[可信区间，0.6至2.9个百分点]）。扎那米韦和奥司他韦在预防流感方面无统计学显著差异。
所有试验均由行业资助。没有研究有足够的效力检测罕见不良事件，且没有一项研究纳入不同种族群体、儿童、免疫功能低下患者或接受减毒活流感病毒疫苗的个体。
长期使用扎那米韦和奥司他韦进行化学预防似乎对预防免疫功能正常的白人和日本成年人的有症状流感非常有效。长期使用奥司他韦与恶心和呕吐增加有关。在可能接受长期流感化学预防的几个亚人群中的安全性和有效性尚不清楚。
