McGrath Leah J, Kshirsagar Abhijit V, Cole Stephen R, Wang Lily, Weber David J, Stürmer Til, Brookhart M Alan
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7435, USA.
Arch Intern Med. 2012 Apr 9;172(7):548-54. doi: 10.1001/archinternmed.2011.2238.
Although the influenza vaccine is recommended for patients with end-stage renal disease, little is known about its effectiveness. Observational studies of vaccine effectiveness (VE) are challenging because vaccinated subjects may be healthier than unvaccinated subjects.
Using US Renal Data System data, we estimated VE for influenza-like illness, influenza/pneumonia hospitalization, and mortality in adult patients undergoing hemodialysis by using a natural experiment created by the year-to-year variation in the match of the influenza vaccine to the circulating virus. We compared vaccinated patients in matched years (1998, 1999, and 2001) with a mismatched year (1997) using Cox proportional hazards models. Ratios of hazard ratios compared vaccinated patients between 2 years and unvaccinated patients between 2 years. We calculated VE as 1 - effect measure.
Vaccination rates were less than 50% each year. Conventional analysis comparing vaccinated with unvaccinated patients produced average VE estimates of 13%, 16%, and 30% for influenza-like illness, influenza/pneumonia hospitalization, and mortality, respectively. When restricted to the preinfluenza period, results were even stronger, indicating bias. The pooled ratio of hazard ratios comparing matched seasons with a placebo season resulted in a VE of 0% (95% CI, -3% to 2%) for influenza-like illness, 2% (-2% to 5%) for hospitalization, and 0% (-3% to 3%) for death.
Relative to a mismatched year, we found little evidence of increased VE in subsequent well-matched years, suggesting that the current influenza vaccine strategy may have a smaller effect on morbidity and mortality in the end-stage renal disease population than previously thought. Alternate strategies (eg, high-dose vaccine, adjuvanted vaccine, and multiple doses) should be investigated.
尽管推荐终末期肾病患者接种流感疫苗，但其有效性却鲜为人知。疫苗有效性（VE）的观察性研究颇具挑战性，因为接种疫苗的受试者可能比未接种疫苗的受试者更健康。
利用美国肾脏数据系统的数据，我们通过流感疫苗与流行病毒匹配度逐年变化所产生的自然实验，估算了接受血液透析的成年患者患流感样疾病、因流感/肺炎住院以及死亡的疫苗有效性。我们使用Cox比例风险模型，将匹配年份（1998年、1999年和2001年）的接种患者与不匹配年份（1997年）的患者进行比较。风险比的比率比较了两年间接种疫苗的患者与两年间未接种疫苗的患者。我们将疫苗有效性计算为1减去效应量。
每年的接种率均低于50%。对接种患者与未接种患者进行的传统分析得出，流感样疾病、流感/肺炎住院和死亡的平均疫苗有效性估计值分别为13%、16%和30%。当仅限于流感前期时，结果更为显著，表明存在偏差。将匹配季节与安慰剂季节的风险比汇总后得出，流感样疾病的疫苗有效性为0%（95%CI，-3%至2%），住院为2%（-2%至5%），死亡为0%（-3%至3%）。
相对于不匹配年份，我们几乎没有发现后续匹配良好年份疫苗有效性增加的证据，这表明当前的流感疫苗策略对终末期肾病患者发病率和死亡率的影响可能比之前认为的要小。应研究替代策略（如高剂量疫苗、佐剂疫苗和多剂疫苗）。
