Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, the Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3508 GA Utrecht, the Netherlands; evidENT, Ear Institute, University College London, London, United Kingdom; NIHR UCLH Biomedical Research Centre, London W1T 7DN, United Kingdom.
Vaccine. 2019 Mar 7;37(11):1528-1532. doi: 10.1016/j.vaccine.2019.01.064. Epub 2019 Feb 6.
It has been hypothesized that widespread implementation of pneumococcal conjugate vaccination (PCV) in infancy reduces early AOM and thereby prevents further AOM episodes and associated health care resource use.
We tested this hypothesis by applying an extension of the original Cox proportional hazards model (Prentice, Williams and Petersons' total time) to individual AOM episodes recorded in pseudonymised primary care electronic health records of 18,237 Dutch children born between 2004 and 2015. Children were assigned to three groups: no-PCV (January 2004-March 2006), PCV7 (April 2006-February 2011) and PCV10 (March 2011-February 2015).
Of the 18,237 newborns, 6967 (38%) experienced at least one GP-diagnosed AOM episode up to the age of four years (median age at first AOM: 12 months, interquartile range: 12; total number of AOM episodes: 14,689). Time-to-first AOM was longest in the PCV10 group compared with the PCV7 and no-PCV groups (log rank test: P < 0.001); in these groups 30% had experienced a first AOM at 20, 17 and 15 months, respectively. Children in the PCV10 group had a 21% lower risk of experiencing a first AOM episode than those in the no-PCV group (hazard ratio (HR): 0.79, 95% confidence interval (CI): 0.72-0.86), while the effect was less pronounced for the PCV7 group (HR: 0.94, 95% CI: 0.87-1.02). Neither PCV7 nor PCV10 reduced the risk of AOM recurrences. Compared to no-PCV, HRs for overall AOM were 1.00 (95% CI: 0.95-1.06) and 0.89 (95% CI: 0.84-0.95) for PCV7 and PCV10, respectively.
Our cohort study suggests that PCV postpones the onset and reduces the risk of first AOM without affecting recurrences. The impact of PCV on overall AOM in children up to the age of four years seems therefore largely attributable to the prevention of a first AOM episode.
有人假设，在婴儿期广泛实施肺炎球菌结合疫苗（PCV）接种可减少早期中耳炎（AOM）的发生，从而预防进一步的 AOM 发作和相关的医疗资源使用。
我们通过将原始 Cox 比例风险模型（Prentice、Williams 和 Petersons 的总时间）应用于 2004 年至 2015 年间出生的 18237 名荷兰儿童的假名化初级保健电子健康记录中记录的单个 AOM 发作，检验了这一假设。儿童分为三组：无 PCV 组（2004 年 1 月至 2006 年 3 月）、PCV7 组（2006 年 4 月至 2011 年 2 月）和 PCV10 组（2011 年 3 月至 2015 年 2 月）。
在 18237 名新生儿中，6967 名（38%）在 4 岁前至少经历过一次由全科医生诊断的 AOM 发作（首次 AOM 的中位年龄：12 个月，四分位间距：12；AOM 发作总数：14689）。与 PCV7 组和无 PCV 组相比，PCV10 组的首次 AOM 时间最长（对数秩检验：P<0.001）；在这些组中，30%的儿童在 20、17 和 15 个月时首次发生 AOM。与无 PCV 组相比，PCV10 组首次发生 AOM 的风险降低了 21%（风险比（HR）：0.79，95%置信区间（CI）：0.72-0.86），而 PCV7 组的效果则不那么明显（HR：0.94，95% CI：0.87-1.02）。PCV7 和 PCV10 均未降低 AOM 复发的风险。与无 PCV 组相比，PCV7 和 PCV10 组的总体 AOM 风险比（HR）分别为 1.00（95%CI：0.95-1.06）和 0.89（95%CI：0.84-0.95）。
我们的队列研究表明，PCV 可延迟 AOM 的发作并降低首次 AOM 的风险，但不影响复发。因此，PCV 对 4 岁以下儿童整体 AOM 的影响在很大程度上归因于预防首次 AOM 发作。
