Do Invasive Dental Procedures Cause Prosthetic Joint Infections (PJI)? - The PJI Study

项目总结/摘要 背景：患病和受损关节的假体置换是现代医学的重大进展之一。 药人工关节感染（PJI）是一种严重的并发症。改进手术技术 降低了术后不久PJI的风险，但晚期PJI（LPJI）对> 700万人来说是一种持续的风险 在美国做了一个人工关节为了减少这种风险，鼓励牙医给患者提供人工关节。 患者在侵入性牙科手术（IDP）前使用抗生素，以减少细菌进入循环的风险 感染关节这被称为抗生素预防（AP）。然而，从来没有一个审判， 证明AP疗效，并且几乎没有证据支持IDP和LPJI之间的关联。因此，在本发明中， AP指南在世界各地都很混乱和不同。在美国，AP被广泛使用，尽管AP指南 对于临床医生和他们的病人来说都是不清楚和令人困惑的。相比之下，AP从未在英国使用过。到 解决这一困惑，指导临床医生，数据证明或反驳IDP和LPJI之间的任何关联是 迫切需要。如果存在关联，那么AP的广泛采用可能有助于减少约20，000 例和~ 5.66亿美元的LPJI在美国的年度成本。如果不是，那么AP是不必要的，可以停止保存 每年约6000万美元，避免了AP抗生素不良反应的风险和AP可能对社会造成的风险。 促进抗生素耐药性细菌的发展。 目的：确定IDP是否与LPJI的发生有因果关系。 具体目的：（i）进行病例交叉研究，以确定3个月内IDP的频率是否 紧接在LPJI之前的时间显著大于前3个月的匹配对照期，即3-6、6-9 LPJI前9-12个月。(ii)我们还将进行一项病例对照研究， 在LPJI前3个月内涉及和不涉及IDP的治疗。 方法：我们将使用国家医院事件统计（HES）数据来确定英国的LPJI患者， 2010-2017.我们将使用英文数据，因为（i）AP，可以隐藏IDP和LPJI之间的任何关联， 从未在英格兰使用，（ii）英国国家卫生服务（NHS）数据系统允许我们链接课程 牙科治疗（CoT）的病例LPJI。使用每个LPJI患者的NHS号码，我们可以将LPJI数据链接到 每个人的牙齿数据。这将使我们能够确定发生LPJI的患者是否有CoT， 上一年，是否涉及国内流离失所者，以及何时发生与入院有关的事件。我们将使用 强有力的病例交叉分析方法，以确定在LPJI前3个月内IDP的发病率 (case期）的发生率显著高于或不高于前3个月期（3-6，6-9 LPJI前9-12个月）。还将进行更传统的病例对照分析，以确定CoT 在之前的3个月内，涉及IDP的CoT的发生频率显著高于不涉及IDP的CoT 国内流离失所者这些方法将提供统计功效以确定IDP是否与LPJI相关。

Project Summary/Abstract Background: Prosthetic replacement of diseased and damaged joints is one of the great advances of modern medicine. Prosthetic joint infections (PJI) however are a serious complication. Improved operative techniques have reduced the risk of PJI soon after surgery but late PJI (LPJI) are an ongoing risk for the >7 million individuals with a prosthetic joint in the US. In an attempt to reduce this risk dentists are encouraged to give prosthetic joint patients antibiotics before invasive dental procedures (IDP) to reduce the risk of bacteria entering the circulation and infecting the joint. This is called antibiotic prophylaxis (AP). However, there has never been a trial to demonstrate AP efficacy and there is little evidence to support an association between IDP and LPJI. As a result, AP guidelines are confused and differ around the world. In the US, AP is widely used although the AP guidelines are unclear and baffling for both clinicians and their patients. In contrast, AP has never been used in the UK. To resolve this confusion and guide clinicians, data proving or disproving any association between IDP and LPJI is urgently needed. If an association exists, then the widespread adoption of AP could help reduce the ~20,000 cases and ~$566 million annual cost of LPJI in the US. If not, then AP is unnecessary and could be stopped saving ~$60 million annually, avoiding the risk of adverse reactions to AP antibiotics and the risk to society that AP may promote the development of antibiotic resistant bacteria. Objectives: To determine if IDP are causally associated with the development of LPJI or not. Specific Aims: (i) To perform a case-crossover study to determine if the frequency of IDP in the 3 months immediately preceding LPJI is significantly greater than in earlier 3 month matched control periods i.e. 3-6, 6-9 and 9-12 months before the LPJI. (ii) We will also perform a case control study comparing the incidence of dental treatment involving and not involving an IDP in the 3 months preceding an LPJI. Methods: We will use national Hospital Episode Statistics (HES) data to identify LPJI patients in England from 2010-2017. We will use English data because (i) AP, that could hide any association between IDP and LPJI, has never been used in England and (ii) the UK National Health Service (NHS) data systems allows us to link courses of dental treatment (CoT) to cases of LPJI. Using each LPJI patient’s NHS number we can link the LPJI data to each individual’s dental data. This will allow us to determine if patients who develop LPJI had a CoT in the preceding year, if it involved an IDP or not and when it occurred in relation to the hospital admission. We will use the powerful case-crossover analysis method to determine if the incidence of IDP in the 3 months preceding LPJI (case periods) was significantly higher, or not, than the incidence in each of the earlier 3 month periods (3-6, 6-9 and 9-12 months before LPJI). A more traditional case-control analysis will also be performed to see if CoT involving an IDP occurred significantly more frequently than CoT not involving an IDP in the 3 months preceding an IDP. These methods will provide the statistical power to determine if IDP are associated with LPJI or not.