New evidence calls into question NICE's endocarditis prevention guidance.

In 2008, National Institute for Health and Care Excellence (NICE) guidelines recommended against the use of antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) to prevent infective endocarditis (IE). They did so because of lack of AP efficacy evidence and adverse reaction concerns. Consequently, NICE concluded AP was not cost-effective and should not be recommended. In 2015, NICE reviewed its guidance and continued to recommend against AP. However, it subsequently changed its wording to 'antibiotic prophylaxis against infective endocarditis is not routinely recommended'. The lack of explanation of what constituted routinely (and not routinely), or how to manage non-routine patients, caused enormous confusion and NICE remained out of step with all major international guideline committees who continued to recommend AP for those at high risk.Since the 2015 guideline review, new data have confirmed an association between IDPs and subsequent IE and demonstrated AP efficacy in reducing IE risk following IDPs in high-risk patients. New evidence also shows that in high-risk patients, the IE risk following IDPs substantially exceeds any adverse reaction risk, and that AP is therefore highly cost-effective. Given the new evidence, a NICE guideline review would seem appropriate so that UK high-risk patients can receive the same protection afforded high-risk patients in the rest of the world.

Prevention of infective endocarditis in at-risk patients: how should dentists proceed in 2024?

National Institute for Health and Care Excellence (NICE) guidelines are ambiguous over the need for patients at increased risk of infective endocarditis (IE) to receive antibiotic prophylaxis (AP) prior to invasive dental procedures (IDPs), and this has caused confusion for patients and dentists alike. Moreover, the current law on consent requires clinicians to ensure that patients are made aware of any material risk they might be exposed to by any proposed dental treatment and what can be done to ameliorate this risk, so that the patient can decide for themselves how they wish to proceed. The aim of this article is to provide dentists with the latest information on the IE-risk posed by IDPs to different patient populations (the general population and those defined as being at moderate or high risk of IE), and data on the effectiveness of AP in reducing the IE risk in these populations. This provides the information dentists need to facilitate the informed consent discussions they are legally required to have with patients at increased risk of IE about the risks posed by IDPs and how this can be minimised. The article also provides practical information and advice for dentists on how to manage patients at increased IE risk who present for dental treatment.

Evaluation of patients labeled with a penicillin allergy to promote antimicrobial stewardship in dental practice.

BACKGROUND: Approximately 10% of the US population self-reports a penicillin allergy history or are labeled as penicillin allergic. However, from 90% through 99% of these patients are not allergic on formal evaluation. CASE DESCRIPTION: Patients labeled as penicillin allergic receive broader-spectrum and sometimes less-effective antibiotics, thereby contributing to increased treatment failures, antibiotic resistance, and adverse drug reactions. Self-reported penicillin allergy can be eliminated or classified as low-, medium-, or high-risk after a careful review of patient history. This allows these patients to be delabeled; that is, having any reference to their penicillin allergy history or of having an allergy to penicillin eliminated from their health records. PRACTICAL IMPLICATIONS: Oral health care professionals are ideally placed to partner in both antibiotic stewardship interventions by means of recognizing pervasive mislabeling and aiding in the process of delabeling.

Antibiotic Prophylaxis and Infective Endocarditis Incidence Following Invasive Dental Procedures: A Systematic Review and Meta-Analysis.

Importance: The association between antibiotic prophylaxis and infective endocarditis after invasive dental procedures is still unclear. Indications for antibiotic prophylaxis were restricted by guidelines beginning in 2007. Objective: To systematically review and analyze existing evidence on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures. Data Sources: PubMed, Cochrane-CENTRAL, Scopus, Web of Science, Proquest, Embase, Dentistry and Oral Sciences Source, and ClinicalTrials.gov were systematically searched from inception to May 2023. Study Selection: Studies on the association between antibiotic prophylaxis and infective endocarditis following invasive dental procedures or time-trend analyses of infective endocarditis incidence before and after current antibiotic prophylaxis guidelines were included. Data Extraction and Synthesis: Study quality was evaluated using structured tools. Data were extracted by independent observers. A pooled relative risk (RR) of developing infective endocarditis following invasive dental procedures in individuals who were receiving antibiotic prophylaxis vs those who were not was computed by random-effects meta-analysis. Main Outcomes and Measures: The outcome of interest was the incidence of infective endocarditis following invasive dental procedures in relation to antibiotic prophylaxis. Results: Of 11 217 records identified, 30 were included (1 152 345 infective endocarditis cases). Of them, 8 (including 12 substudies) were either case-control/crossover or cohort studies or self-controlled case series, while 22 were time-trend studies; all were of good quality. Eight of the 12 substudies with case-control/crossover, cohort, or self-controlled case series designs performed a formal statistical analysis; 5 supported a protective role of antibiotic prophylaxis, especially among individuals at high risk, while 3 did not. By meta-analysis, antibiotic prophylaxis was associated with a significantly lower risk of infective endocarditis after invasive dental procedures in individuals at high risk (pooled RR, 0.41; 95% CI, 0.29-0.57; P for heterogeneity = .51; I2, 0%). Nineteen of the 22 time-trend studies performed a formal pre-post statistical analysis; 9 found no significant changes in infective endocarditis incidence, 7 demonstrated a significant increase for the overall population or subpopulations (individuals at high and moderate risk, streptococcus-infective endocarditis, and viridans group streptococci-infective endocarditis), whereas 3 found a significant decrease for the overall population and among oral streptococcus-infective endocarditis. Conclusions and Relevance: While results from time-trend studies were inconsistent, data from case-control/crossover, cohort, and self-controlled case series studies showed that use of antibiotic prophylaxis is associated with reduced risk of infective endocarditis following invasive dental procedures in individuals at high risk, while no association was proven for those at low/unknown risk, thereby supporting current American Heart Association and European Society of Cardiology recommendations. Currently, there is insufficient data to support any benefit of antibiotic prophylaxis in individuals at moderate risk.

RADseq-based population genomic analysis and environmental adaptation of rare and endangered recretohalophyte Reaumuria trigyna.

Genetic diversity reflects the survival potential, history, and population dynamics of an organism. It underlies the adaptive potential of populations and their response to environmental change. Reaumuria trigyna is an endemic species in the Eastern Alxa and West Ordos desert regions in China. The species has been considered a good candidate to explore the unique survival strategies of plants that inhabit this area. In this study, we performed population genomic analyses based on restriction-site associated DNA sequencing to understand the genetic diversity, population genetic structure, and differentiation of the species. Analyses of 92,719 high-quality single-nucleotide polymorphisms (SNPs) indicated that overall genetic diversity of R. trigyna was low (HO = 0.249 and HE = 0.208). No significant genetic differentiation was observed among the investigated populations. However, a subtle population genetic structure was detected. We suggest that this might be explained by adaptive diversification reinforced by the geographical isolation of populations. Overall, 3513 outlier SNPs were located in 243 gene-coding sequences in the R. trigyna transcriptome. Potential sites under diversifying selection occurred in genes (e.g., AP2/EREBP, E3 ubiquitin-protein ligase, FLS, and 4CL) related to phytohormone regulation and synthesis of secondary metabolites which have roles in adaptation of species. Our genetic analyses provide scientific criteria for evaluating the evolutionary capacity of R. trigyna and the discovery of unique adaptions. Our findings extend knowledge of refugia, environmental adaption, and evolution of germplasm resources that survive in the Ordos area.

Emerging advances in biosecurity to underpin human, animal, plant, and ecosystem health.

One Biosecurity is an interdisciplinary approach to policy and research that builds on the interconnections between human, animal, plant, and ecosystem health to effectively prevent and mitigate the impacts of invasive alien species. To support this approach requires that key cross-sectoral research innovations be identified and prioritized. Following an interdisciplinary horizon scan for emerging research that underpins One Biosecurity, four major interlinked advances were identified: implementation of new surveillance technologies adopting state-of-the-art sensors connected to the Internet of Things, deployable handheld molecular and genomic tracing tools, the incorporation of wellbeing and diverse human values into biosecurity decision-making, and sophisticated socio-environmental models and data capture. The relevance and applicability of these innovations to address threats from pathogens, pests, and weeds in both terrestrial and aquatic ecosystems emphasize the opportunity to build critical mass around interdisciplinary teams at a global scale that can rapidly advance science solutions targeting biosecurity threats.

World Workshop on Oral Medicine VIII: Dentists' compliance with infective endocarditis prophylaxis guidelines for patients with high-risk cardiac conditions: a systematic review.

OBJECTIVE: To determine dentists' awareness and/or adherence to antibiotic prophylaxis (AP) guidelines for preventing infective endocarditis (IE) in patients with high-risk heart conditions. STUDY DESIGN: A systematic literature review was performed on MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library, Proquest, Embase, Dentistry, and Oral Sciences Source databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Nationwide studies based on questionnaires, surveys, and interviews completed by dentists and published since 2007 were included. RESULTS: From 2907 articles screened, 28 studies were selected (across 20 countries). The quality of included studies was poor due to a lack of standard evaluation tools, low response rates, and lack of questionnaire validity and/or reliability. Approximately 75% of surveyed dentists reported being knowledgeable about AP guidelines, but only ∼25% complied. Reported compliance with American Heart Association (AHA) guidelines was 4 times higher than with the National Institute for Health and Care Excellence (NICE) recommendations. Some of the highest adherence rates were reported for other national AP guidelines. Significant geographic differences were observed in the estimated adherence to AHA guidelines and the percentage of dentists who reported seeking advice from physicians and/or cardiologists. CONCLUSION: Rates of compliance and/or adherence were substantially different from rates of knowledge and/or awareness, including relevant geographic dissimilarities. Compliance/adherence was higher for AHA than NICE.

Endocarditis, invasive dental procedures, and antibiotic prophylaxis efficacy in US Medicaid patients.

OBJECTIVE: Antibiotic prophylaxis is recommended before invasive dental procedures to prevent endocarditis in those at high risk, but supporting data are sparse. We therefore investigated any association between invasive dental procedures and endocarditis, and any antibiotic prophylaxis effect on endocarditis incidence. SUBJECTS AND METHODS: Cohort and case-crossover studies were performed on 1,678,190 Medicaid patients with linked medical, dental, and prescription data. RESULTS: The cohort study identified increased endocarditis incidence within 30 days of invasive dental procedures in those at high risk, particularly after extractions (OR 14.17, 95% CI 5.40-52.11, p < 0.0001) or oral surgery (OR 29.98, 95% CI 9.62-119.34, p < 0.0001). Furthermore, antibiotic prophylaxis significantly reduced endocarditis incidence following invasive dental procedures (OR 0.20, 95% CI 0.06-0.53, p < 0.0001). Case-crossover analysis confirmed the association between invasive dental procedures and endocarditis in those at high risk, particularly following extractions (OR 3.74, 95% CI 2.65-5.27, p < 0.005) and oral surgery (OR 10.66, 95% CI 5.18-21.92, p < 0.0001). The number of invasive procedures, extractions, or surgical procedures needing antibiotic prophylaxis to prevent one endocarditis case was 244, 143 and 71, respectively. CONCLUSIONS: Invasive dental procedures (particularly extractions and oral surgery) were significantly associated with endocarditis in high-risk individuals, but AP significantly reduced endocarditis incidence following these procedures, thereby supporting current guideline recommendations.

Oral hygiene and infective endocarditis: a case control study.

OBJECTIVE: To determine if oral hygiene is associated with infective endocarditis (IE) among those at moderate risk for IE. STUDY DESIGN: This is a case control study of oral hygiene among hospitalized patients with IE (cases) and outpatients with heart valve disease but without IE (controls). The primary outcome was the mean dental calculus index. Secondary outcomes included other measures of oral hygiene and periodontal disease (e.g., dental plaque, gingivitis) and categorization of blood culture bacterial species in case participants. RESULTS: The 62 case participants had 53% greater mean dental calculus index than the 119 control participants (0.84, 0.55, respectively; difference = 0.29, 95% CI: 0.11, 0.48; P = .002) and 26% greater mean dental plaque index (0.88, 0.70, respectively; difference = 0.18, 95% CI: 0.01.0.36; P = .043). Overall, cases reported fewer dentist and dental hygiene visits (P = .013) and fewer dental visits in the 12 weeks before enrollment than controls (P = .007). Common oral bacteria were identified from blood cultures in 27 of 62 cases (44%). CONCLUSIONS: These data provide evidence to support and strengthen current American Heart Association guidance that those at risk for IE can reduce potential sources of IE-related bacteremia by maintaining optimal oral health through regular professional dental care and oral hygiene procedures.

Bacteremia following different oral procedures: Systematic review and meta-analysis.

To evaluate the timing, duration and incidence of bacteremia following invasive dental procedures (IDPs) or activities of daily living (ADL). Eight databases were searched for randomized (RCTs) and nonrandomized controlled trials (nRCTs) evaluating bacteremia before and after IDPs or ADL in healthy individuals. The risk of bias was assessed by RoB 2.0 and ROBINS-I. For the meta-analysis, the primary outcomes were the timing and duration of bacteremia. The secondary outcome was the incidence of bacteremia, measuring the proportion of patients with bacteremia within 5 min after the end of the procedure compared with baseline. We included 64 nRCTs and 25 RCTs. Peak bacteremia occurred within 5 min after the procedure and then decreased over time. Dental extractions showed the highest incidence of bacteremia (62%-66%), followed by scaling and root planing (SRP) (44%-36%) and oral health procedures (OHP) (e.g., dental prophylaxis and dental probing without SRP) (27%-28%). Other ADL (flossing and chewing) (16%) and toothbrushing (8%-26%) resulted in bacteremia as well. The majority of studies had some concerns RCTs or moderate risk of bias nRCTs. Dental extractions, SRP and OHP, are associated with the highest frequency of bacteremia. Toothbrushing, flossing, and chewing also caused bacteremia in lower frequency.

Quantifying the risk of prosthetic joint infections after invasive dental procedures and the effect of antibiotic prophylaxis.

BACKGROUND: Dentists face the expectations of orthopedic surgeons and patients with prosthetic joints to provide antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) to reduce the risk of late periprosthetic joint infections (LPJIs), despite the lack of evidence associating IDPs with LPJIs, lack of evidence of AP efficacy, risk of AP-related adverse reactions, and potential for promoting antibiotic resistance. The authors aimed to identify any association between IDPs and LPJIs and whether AP reduces LPJI incidence after IDPs. METHOD: The authors performed a case-crossover analysis comparing IDP incidence in the 3 months immediately before LPJI hospital admission (case period) with the preceding 12-month control period for all LPJI hospital admissions with commercial or Medicare supplemental or Medicaid health care coverage and linked dental and prescription benefits data. RESULTS: Overall, 2,344 LPJI hospital admissions with dental and prescription records (n = 1,160 commercial or Medicare supplemental and n = 1,184 Medicaid) were identified. Patients underwent 4,614 dental procedures in the 15 months before LPJI admission, including 1,821 IDPs (of which 18.3% had AP). Our analysis identified no significant positive association between IDPs and subsequent development of LPJIs and no significant effect of AP in reducing LPJIs. CONCLUSIONS: The authors identified no significant association between IDPs and LPJIs and no effect of AP cover of IDPs in reducing the risk of LPJIs. PRACTICAL IMPLICATIONS: In the absence of benefit, the continued use of AP poses an unnecessary risk to patients from adverse drug reactions and to society from the potential of AP to promote development of antibiotic resistance. Dental AP use to prevent LPJIs should, therefore, cease.

Oral microbiomes of patients with infective endocarditis (IE): a comparative pilot study of IE patients, patients at risk for IE and healthy controls.

Background: Infective endocarditis (IE) is an uncommon disease with high morbidity and mortality rates, which often develops from oral bacterial species entering circulation. Objective: We compared oral microbiome profiles of three groups: IE patients (N  9 patients; n = 27 samples), disease controls at risk for IE (N = 28; n = 84), and healthy controls (N = 37; n = 111). Bacterial species in IE patients' blood cultures were identified for comparison with matched oral samples. Design: Oral microbiome profiles were obtained from buccal mucosa, saliva, and tongue samples for all three groups and from sub- and supra-gingival plaque samples of the IE group (N = 9; n = 16) and disease controls (N = 28; n = 54). Alpha- and beta-diversities were determined based on relative abundance data. Discriminative species were identified by LEfSe, post hoc Mann-Whitney, and ROC analyses. Identity of the bacterial species in IE patients' blood cultures was confirmed by 16S-rRNA gene Sanger sequencing. Results: Alpha- and beta-diversities differed between groups. Discriminative IE-associated species were identified, e.g. Haemophilus parainfluenzae and Streptococcus sanguinis. Two blood isolates were Staphylococcus aureus, also identified in one matched saliva sample. Streptococcus mutans was present in one patient's plaque samples and blood culture. Conclusions: Oral microbiomes of IE, non-IE disease controls, and healthy controls differed significantly. A better understanding of IE-related bacterial-host interactions is warranted.

Temporal association between invasive procedures and infective endocarditis.

OBJECTIVE: Antibiotic prophylaxis has been recommended for patients at increased risk of infective endocarditis (IE) undergoing specific invasive procedures (IPs) despite a lack of data supporting its use. Therefore, antibiotic prophylaxis recommendations ceased in the mid-2000s for all but those at high IE risk undergoing invasive dental procedures. We aimed to quantify any association between IPs and IE. METHODS: All 14 731 IE hospital admissions in England between April 2010 and March 2016 were identified from national admissions data, and medical records were searched for IP performed during the 15-month period before IE admission. We compared the incidence of IP during the 3 months immediately before IE admission (case period) with the incidence during the preceding 12 months (control period) to determine whether the odds of developing IE were increased in the 3 months after certain IP. RESULTS: The odds of IE were increased following permanent pacemaker and defibrillator implantation (OR 1.54, 95% CI 1.27 to 1.85, p<0.001), extractions/surgical tooth removal (OR 2.14, 95% CI 1.22 to 3.76, p=0.047), upper (OR 1.58, 95% CI 1.34 to 1.85, p<0.001) and lower gastrointestinal endoscopy (OR 1.66, 95% CI 1.35 to 2.04, p<0.001) and bone marrow biopsy (OR 1.76, 95% CI 1.16 to 2.69, p=0.039). Using an alternative analysis, bronchoscopy (OR 1.33, 95% CI 1.06 to 1.68, p=0.049) and blood transfusions/red cell/plasma exchange (OR 1.2, 95% CI 1.07 to 1.35, p=0.012) were also associated with IE. CONCLUSIONS: This study identifies a significant association between specific IPs (permanent pacemaker and defibrillator implantation, dental extraction, gastrointestinal endoscopy and bronchoscopy) and subsequent IE that warrants re-evaluation of current antibiotic prophylaxis recommendations to prevent IE in high IE risk individuals.

Assessment of Infectious Diseases Risks From Dental Aerosols in Real-World Settings.

Background: Infectious diseases physicians are leaders in assessing the health risks in a variety of community settings. An understudied area with substantial controversy is the safety of dental aerosols. Previous studies have used in vitro experimental designs and/or indirect measures to evaluate bacteria and viruses from dental surfaces. However, these findings may overestimate the occupational risks of dental aerosols. The purpose of this study was to directly measure dental aerosol composition to assess the health risks for dental healthcare personnel and patients. Methods: We used a variety of aerosol instruments to capture and measure the bacterial, viral, and inorganic composition of aerosols during a variety of common dental procedures and in a variety of dental office layouts. Equipment was placed in close proximity to dentists during each procedure to best approximate the health risk hazards from the perspective of dental healthcare personnel. Devices used to capture aerosols were set at physiologic respiration rates. Oral suction devices were per the discretion of the dentist. Results: We detected very few bacteria and no viruses in dental aerosols-regardless of office layout. The bacteria identified were most consistent with either environmental or oral microbiota, suggesting a low risk of transmission of viable pathogens from patients to dental healthcare personnel. When analyzing restorative procedures involving amalgam removal, we detected inorganic elements consistent with amalgam fillings. Conclusions: Aerosols generating from dental procedures pose a low health risk for bacterial and likely viral pathogens when common aerosol mitigation interventions, such as suction devices, are employed.

Antibiotic Prophylaxis Against Infective Endocarditis Before Invasive Dental Procedures.

BACKGROUND: Antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) is recommended to prevent infective endocarditis (IE) in those at high IE risk, but there are sparse data supporting a link between IDPs and IE or AP efficacy in IE prevention. OBJECTIVES: The purpose of this study was to investigate any association between IDPs and IE, and the effectiveness of AP in reducing this. METHODS: We performed a case-crossover analysis and cohort study of the association between IDPs and IE, and AP efficacy, in 7,951,972 U.S. subjects with employer-provided Commercial/Medicare-Supplemental coverage. RESULTS: Time course studies showed that IE was most likely to occur within 4 weeks of an IDP. For those at high IE risk, case-crossover analysis demonstrated a significant temporal association between IE and IDPs in the preceding 4 weeks (OR: 2.00; 95% CI: 1.59-2.52; P = 0.002). This relationship was strongest for dental extractions (OR: 11.08; 95% CI: 7.34-16.74; P < 0.0001) and oral-surgical procedures (OR: 50.77; 95% CI: 20.79-123.98; P < 0.0001). AP was associated with a significant reduction in IE incidence following IDP (OR: 0.49; 95% CI: 0.29-0.85; P = 0.01). The cohort study confirmed the associations between IE and extractions or oral surgical procedures in those at high IE risk and the effect of AP in reducing these associations (extractions: OR: 0.13; 95% CI: 0.03-0.34; P < 0.0001; oral surgical procedures: OR: 0.09; 95% CI: 0.01-0.35; P = 0.002). CONCLUSIONS: We demonstrated a significant temporal association between IDPs (particularly extractions and oral-surgical procedures) and subsequent IE in high-IE-risk individuals, and a significant association between AP use and reduced IE incidence following these procedures. These data support the American Heart Association, and other, recommendations that those at high IE risk should receive AP before IDP.

Infective endocarditis following invasive dental procedures: IDEA case-crossover study.

BACKGROUND: Infective endocarditis is a heart infection with a first-year mortality rate of ≈ 30%. It has long been thought that infective endocarditis is causally associated with bloodstream seeding with oral bacteria in ≈ 40-45% of cases. This theorem led guideline committees to recommend that individuals at increased risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. However, to the best of our knowledge, there has never been a clinical trial to prove the efficacy of antibiotic prophylaxis and there is no good-quality evidence to link invasive dental procedures with infective endocarditis. Many contend that oral bacteria-related infective endocarditis is more likely to result from daily activities (e.g. tooth brushing, flossing and chewing), particularly in those with poor oral hygiene. OBJECTIVE: The aim of this study was to determine if there is a temporal association between invasive dental procedures and subsequent infective endocarditis, particularly in those at high risk of infective endocarditis. DESIGN: This was a self-controlled, case-crossover design study comparing the number of invasive dental procedures in the 3 months immediately before an infective endocarditis-related hospital admission with that in the preceding 12-month control period. SETTING: The study took place in the English NHS. PARTICIPANTS: All individuals admitted to hospital with infective endocarditis between 1 April 2010 and 31 March 2016 were eligible to participate. INTERVENTIONS: This was an observational study; therefore, there was no intervention. MAIN OUTCOME MEASURE: The outcome measure was the number of invasive and non-invasive dental procedures in the months before infective endocarditis-related hospital admission. DATA SOURCES: NHS Digital provided infective endocarditis-related hospital admissions data and dental procedure data were obtained from the NHS Business Services Authority. RESULTS: The incidence rate of invasive dental procedures decreased in the 3 months before infective endocarditis-related hospital admission (incidence rate ratio 1.34, 95% confidence interval 1.13 to 1.58). Further analysis showed that this was due to loss of dental procedure data in the 2-3 weeks before any infective endocarditis-related hospital admission. LIMITATIONS: We found that urgent hospital admissions were a common cause of incomplete courses of dental treatment and, because there is no requirement to record dental procedure data for incomplete courses, this resulted in a significant loss of dental procedure data in the 2-3 weeks before infective endocarditis-related hospital admissions. The data set was also reduced because of the NHS Business Services Authority's 10-year data destruction policy, reducing the power of the study. The main consequence was a loss of dental procedure data in the critical 3-month case period of the case-crossover analysis (immediately before infective endocarditis-related hospital admission), which did not occur in earlier control periods. Part of the decline in the rate of invasive dental procedures may also be the result of the onset of illness prior to infective endocarditis-related hospital admission, and part may be due to other undefined causes. CONCLUSIONS: The loss of dental procedure data in the critical case period immediately before infective endocarditis-related hospital admission makes interpretation of the data difficult and raises uncertainty over any conclusions that can be drawn from this study. FUTURE WORK: We suggest repeating this study elsewhere using data that are unafflicted by loss of dental procedure data in the critical case period. TRIAL REGISTRATION: This trial is registered as ISRCTN11684416. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 28. See the NIHR Journals Library website for further project information.

Infective endocarditis is a life-threatening infection of the heart valves. Most people are at low risk of infective endocarditis. However, those with certain cardiac conditions are at moderate risk of infective endocarditis, and those with artificial or repaired heart valves, a history of infective endocarditis and certain congenital heart conditions are at high risk of infective endocarditis. In around 40­45% of cases, oral bacteria are the cause of infective endocarditis. For many years, those people at moderate or high risk of infective endocarditis were given antibiotics (antibiotic prophylaxis) before invasive dental procedures such as extractions to reduce the risk of infective endocarditis. There is no good-quality evidence, however, to support the effectiveness of antibiotic prophylaxis, or the link between invasive dental procedures and infective endocarditis. Many believe that the oral bacteria that cause infective endocarditis are more likely to enter the blood during daily activities (e.g. toothbrushing, flossing or chewing), particularly in those with poor oral hygiene, than on the rare occasions when invasive dental procedures are performed. The aim of this study was to link English NHS data on infective endocarditis-related hospital admissions and dental treatments to determine if infective endocarditis is more likely in the weeks immediately after an invasive dental procedure than at any other time. When we linked the data sets and plotted the occurrence of different dental treatments over the year before infective endocarditis-related hospital admission, we detected a problem in the way that dental data were recorded. Unfortunately, there was a failure to collect dental procedure data when courses of treatment were incomplete. As one of the most common reasons for not completing a course of treatment was emergency admission to hospital, this meant that the number of dental procedures recorded decreased in the weeks before any emergency hospital admission. We have attempted to correct for this, but the data loss has affected the data quality. Although the data suggest an association between invasive dental procedures and infective endocarditis in individuals at high risk of infective endocarditis, the certainty of this association has been weakened.