A Before and After Study of the Effect of Ceasing to Give Antibiotic Prophylaxis

描述（由申请人提供）：感染性心内膜炎（IE）是心脏瓣膜的感染，最常见的原因是循环细菌（菌血症）。美国每年约有27，000例病例，并且与高死亡率（第一年内约30%）和严重的长期并发症相关。35-45%的IE病例涉及口腔细菌。有充分的证据表明，菌血症发生在进食、刷牙和侵入性牙科手术期间。正因为如此，美国心脏协会（AHA）指南委员会建议，在侵入性牙科手术之前，应给予患IE风险最高的患者抗生素预防（AP），目的是杀死进入循环的细菌。大多数心血管 世界各地的指南委员会都推荐AP给这些人。然而，从未有过AP的临床试验，也缺乏科学证据支持给予AP的做法。在英国，AP是“护理标准”，直到2008年3月，国家健康与临床卓越研究所（NICE）推出了新的指南，建议在英国完全停止AP处方。从那时起，“护理标准”一直是在牙科手术前不开AP。目的：通过进行一项前后研究，比较AP为英国“标准治疗”（2008年3月之前）时IE的发生率与“标准治疗”为不给予AP（2008年3月之后）时IE的发生率，确定AP预防IE的有效性。具体目标：进行一项关于在英国建议在侵入性牙科手术前停止给予AP对IE发生率的影响的前后研究。研究方法：我们将：（1）分析国家处方数据，以确定在NICE指南引入之前和之后4年内AP处方的水平。(2)分析国家医院事件统计（HES）数据，以确定NICE指南引入前后4年内IE的发病率。(3)分析HES数据与国家统计局数据之间的联系，以确定IE相关死亡率的发生率，在住院治疗IE期间和90 在NICE指南引入之前和之后的住院天数。(5)此外，我们将对IE发病率和死亡率数据进行以下子分析：（a）为了更直接地评估AP在预防由口腔细菌引起的IE方面的益处，我们将确定那些致病微生物被记录为口腔来源的患者的IE发病率和IE相关死亡率。(b)为了更直接地评价现行AHA指南的潜在受益，我们还将确定既存人工心脏瓣膜或既往有IE病史的患者中IE和IE相关死亡率，因此这些患者属于现行AHA指南下适用于接受AP的AHA“高风险”类别。

DESCRIPTION (provided by applicant): Infective endocarditis (IE) is an infection of the heart valves, most often caused by circulating bacteria (bacteremia). There are ~27,000 cases a year in the USA and it is associated with high mortality (~30% within the first year) and serious long-term complications. Oral bacteria are implicated in 35-45% of IE cases. It is well documented that bacteremia occur during eating, tooth-brushing and invasive dental procedures. Because of this, the American Heart Association (AHA) guideline committee recommends that patients at highest risk from developing IE should be given antibiotic prophylaxis (AP) before invasive dental procedures, with the aim of killing bacteria that enter the circulation. Most cardiovascular guidelines committees around the world recommend AP for these people. However, there has never been a clinical trial of AP and there is a lack of scientific evidence to support the practic of giving AP. In the UK, AP was the 'standard of care' until March 2008 when the National Institute for Health and Clinical Excellence (NICE) introduced new guidelines recommending the complete cessation of AP prescribing in the UK. Since then the 'standard of care' has been NOT to prescribe AP prior to dental procedures. Objectives: To determine the efficacy of AP in preventing IE by performing a before and after study comparing the incidence of IE when AP was the 'standard of care' in the UK (before March 2008) with the incidence of IE when the 'standard of care' was NOT to give AP (after March 2008). Specific Aims: To perform a before and after study of the impact of the recommendation in the UK to stop giving AP, prior to invasive dental procedures, on the incidence of IE. Methods: We will: (1) Analyze National Prescribing data to determine the level of AP prescribing prior to and in the 4 years after the introduction of the NICE guidelines. (2) Analyze national Hospital Episode Statistics (HES) data to determine the incidence of IE prior to and in the 4 years after the introduction of the NICE guidelines. (3) Analyze links between HES data and Office of National Statistics data to determine the incidence of IE related mortality, during the hospital stay to treat IE and within 90 days of hospital admission, before and after the introduction of the NICE guidelines. (5) In addition, we will do the following sub-analysis of the IE incidence and mortality data: (a) In orde to more directly assess the benefit of AP in preventing IE caused by oral bacteria, we will determine the incidence of IE and IE related mortality for those patients where the causal organism was recorded as being of oral origin. (b) To more directly evaluate the potential benefit of the current AHA guidelines, we will also determine the incidence of IE and IE related mortality in those patients with a pre-existing prosthetic heart valve or previous history of IE, and who therefore fall into the AHA 'High-Risk' category indicated to receive AP under the current AHA guidelines.