Department of Medicine, Brown University, Providence, RI, USA; Department of Health Services, Policy and Practice, Brown University, Providence, RI, USA; Center for Gerontology and Healthcare Research, Brown University, Providence, RI, USA; Departments of Medicine and Family Medicine, Center for Geriatrics and Palliative Care, University Hospitals Cleveland Medical Center and Case Western Reserve University, Cleveland, OH, USA; Providence Veterans Administration Medical Center, Providence, RI, USA.
Insight Therapeutics LLC, Norfolk, VA, USA.
Lancet Respir Med. 2017 Sep;5(9):738-746. doi: 10.1016/S2213-2600(17)30235-7. Epub 2017 Jul 20.
Immune responses to influenza vaccines decline with age, reducing clinical effectiveness. We compared the effect of the more immunogenic high-dose trivalent influenza vaccine with a standard-dose vaccine to identify the effect on reducing hospital admissions of nursing home residents in the USA.
We did a single-blind, pragmatic, comparative effectiveness, cluster-randomised trial with a 2 × 2 factorial design. Medicare-certified nursing homes in the USA located within 50 miles of a Centers for Disease Control and Prevention influenza reporting city were recruited, so long as the facilities were not located in a hospital, had more than 50 long-stay residents, had less than 20% of the population aged under 65 years, and were not already planning to administer the high-dose influenza vaccine to residents. Enrolled nursing homes were randomised to a facility-wide standard of care for the residents of either high dose or standard dose as the vaccine for the 2013-14 influenza season and half of each group were randomly allocated to free vaccines for staff. Individual residents were included in the analysis group if they were aged 65 years or older and were long-stay residents (ie, had been in the facility 90 days or more before commencing the influenza vaccination programme). The analysts and investigators with access to the raw data were masked to study group by coding the groups until after the analyses were complete. The primary outcome was hospital admissions related to pulmonary and influenza-like illness between Nov 1, 2013, and May 31, 2014, identified from Medicare hospital claims available for residents who were without private health insurance (ie, those who were considered Medicare fee-for-service). We obtained data from the Centers for Medicare & Medicaid Services (CMS) and enrolled facilities. The analyses used marginal Poisson and Cox proportional hazards regression, accounting for clustering of residents within homes, on an intention-to-treat basis, adjusting for facility clustering and prespecified covariates. Safety data were voluntarily reported according to the standard of care. This trial is registered with ClinicalTrials.gov, number NCT01815268.
823 facilities were recruited to the study between March and August, 2013, to participate in the trial, of which 409 facilities were randomised for residents to receive high-dose vaccine, and 414 facilities for residents to receive standard-dose vaccine. The facilities housed 92 269, of whom 75 917 were aged 65 years or older and 53 008 were also long-stay residents, and 38 256 were matched to Medicare hospital claims as of Nov 1, 2013. Staff vaccination rates did not differ between groups, so analyses focused on the high-dose versus standard-dose vaccine comparison. On the basis of Medicare fee-for-service claims, the incidence of respiratory-related hospital admissions was significantly lower in facilities where residents received high-dose influenza vaccines than in those that received standard-dose influenza vaccines (0·185 per 1000 resident-days or 3·4% over 6 months vs 0·211 per 1000 resident-days or 3·9% over 6 months; unadjusted relative risk of 0·888, 95% CI 0·785-1·005, 0=0·061, and adjusted relative risk 0·873, 0·776-0·982, p=0·023).
When compared with standard-dose vaccine, high-dose influenza vaccine can reduce risk of respiratory-related hospital admissions from nursing home residents aged 65 years and older.
Sanofi Pasteur, Swiftwater, PA, USA.
流感疫苗引发的免疫应答会随年龄增长而减弱，从而降低临床效果。我们比较了免疫原性更强的高剂量三价流感疫苗与标准剂量疫苗的效果，以确定其对降低美国养老院居民住院的影响。
我们进行了一项单盲、实用、比较效果、集群随机试验，采用 2×2 析因设计。美国疾病控制与预防中心流感报告城市 50 英里内的经认证的医疗保险养老院符合条件，只要这些设施不在医院内，有 50 名以上的长期居民，居民中年龄在 65 岁以下的比例低于 20%，并且不打算向居民接种高剂量流感疫苗。入组的养老院随机分配给居民接受标准剂量或高剂量的标准护理，作为 2013-14 流感季节的疫苗，每组的一半随机分配免费的员工疫苗。如果居民年龄在 65 岁或以上且为长期居民（即在开始流感疫苗接种计划前在设施中居住 90 天或以上），则将其纳入分析组。分析人员和调查人员通过对组进行编码，直到分析完成后才能访问原始数据，从而对研究组进行了盲法。主要结局是在 2013 年 11 月 1 日至 2014 年 5 月 31 日期间，通过医疗保险医院索赔确定与肺部和流感样疾病相关的住院治疗，这些索赔适用于没有私人医疗保险的居民（即，被认为是医疗保险按服务收费的居民）。我们从医疗保险和医疗补助服务中心（CMS）和入组设施获取数据。分析采用边缘泊松和 Cox 比例风险回归，根据居民在养老院的聚类进行分析，采用意向治疗，调整设施聚类和预设协变量。根据标准护理，自愿报告安全性数据。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT01815268。
2013 年 3 月至 8 月期间，有 823 家养老院参与了这项研究，以参与试验，其中 409 家养老院随机分配给居民接种高剂量疫苗，414 家养老院随机分配给居民接种标准剂量疫苗。这些设施共容纳了 92269 名居民，其中 75917 名居民年龄在 65 岁或以上，53008 名居民也是长期居民，截至 2013 年 11 月 1 日，有 38256 名居民与医疗保险医院索赔相匹配。两组的员工疫苗接种率没有差异，因此分析集中在高剂量与标准剂量疫苗的比较上。根据医疗保险按服务收费的索赔，接受高剂量流感疫苗的居民的呼吸道相关住院治疗发生率明显低于接受标准剂量流感疫苗的居民（每 1000 名居民-日 0.185 或 6 个月 3.4%，与每 1000 名居民-日 0.211 或 6 个月 3.9%；未调整的相对风险 0.888，95%CI 0.785-1.005，p=0.061，调整后的相对风险 0.873，0.776-0.982，p=0.023）。
与标准剂量疫苗相比，高剂量流感疫苗可降低 65 岁及以上养老院居民呼吸道相关住院治疗的风险。
赛诺菲巴斯德，美国宾夕法尼亚州斯威沃特。
