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.

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.

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.

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.

Point-of-care oral cytology tool for the screening and assessment of potentially malignant oral lesions.

BACKGROUND: The effective detection and monitoring of potentially malignant oral lesions (PMOL) are critical to identifying early-stage cancer and improving outcomes. In the current study, the authors described cytopathology tools, including machine learning algorithms, clinical algorithms, and test reports developed to assist pathologists and clinicians with PMOL evaluation. METHODS: Data were acquired from a multisite clinical validation study of 999 subjects with PMOLs and oral squamous cell carcinoma (OSCC) using a cytology-on-a-chip approach. A machine learning model was trained to recognize and quantify the distributions of 4 cell phenotypes. A least absolute shrinkage and selection operator (lasso) logistic regression model was trained to distinguish PMOLs and cancer across a spectrum of histopathologic diagnoses ranging from benign, to increasing grades of oral epithelial dysplasia (OED), to OSCC using demographics, lesion characteristics, and cell phenotypes. Cytopathology software was developed to assist pathologists in reviewing brush cytology test results, including high-content cell analyses, data visualization tools, and results reporting. RESULTS: Cell phenotypes were determined accurately through an automated cytological assay and machine learning approach (99.3% accuracy). Significant differences in cell phenotype distributions across diagnostic categories were found in 3 phenotypes (type 1 ["mature squamous"], type 2 ["small round"], and type 3 ["leukocytes"]). The clinical algorithms resulted in acceptable performance characteristics (area under the curve of 0.81 for benign vs mild dysplasia and 0.95 for benign vs malignancy). CONCLUSIONS: These new cytopathology tools represent a practical solution for rapid PMOL assessment, with the potential to facilitate screening and longitudinal monitoring in primary, secondary, and tertiary clinical care settings.

Adverse drug reactions due to oral antibiotics prescribed in the community setting - England.

Background: Prescribing of oral antibiotics in the community setting is commonplace with ongoing efforts to optimize this practice. There are several concerns related to such prescriptions including antibiotic cost, development of bacterial resistance, and associated adverse drug reactions. We therefore performed an analysis of adverse drug reactions associated with oral antibiotics prescribed in community care (non-hospital) in England to determine adverse drug reaction reporting rates and severity of adverse reactions. Methods: Data for all oral antibiotic use in the primary care settings in England and the National Yellow Card Interactive Drug Analysis Profile was extracted for 2010 through 2017. Results: There were 320,599,292 prescriptions issued for oral antibiotics during the eight-year survey. Although the overall adverse drug reaction rate was relatively low at 58/1,000,000 prescriptions, the reported rates of serious (63.6%) and fatal (1.21%) reactions were striking and probably due to reporting bias as minor adverse drug reactions are less likely to be reported. Conclusions: Continued monitoring of adverse drug reactions rates for oral antibiotics prescribed in the community is warranted, considering the prevalence of serious and fatal reactions identified during the eight-year study period in the Yellow Card profile. These data should be useful in developing strategies to secure optimal prescribing practices.

Antibiotic Prophylaxis and Incidence of Endocarditis Before and After the 2007 AHA Recommendations.

BACKGROUND: The American Heart Association updated its recommendations for antibiotic prophylaxis (AP) to prevent infective endocarditis (IE) in 2007, advising that AP cease for those at moderate risk of IE, but continue for those at high risk. OBJECTIVES: The authors sought to quantify any change in AP prescribing and IE incidence. METHODS: High-risk, moderate-risk, and unknown/low-risk individuals with linked prescription and Medicare or commercial health care data were identified in the Truven Health MarketScan databases from May 2003 through August 2015 (198,522,665 enrollee-years of data). AP prescribing and IE incidence were evaluated by Poisson model analysis. RESULTS: By August 2015, the 2007 recommendation change was associated with a significant 64% (95% confidence interval [CI]: 59% to 68%) estimated fall in AP prescribing for moderate-risk individuals and a 20% (95% CI: 4% to 32%) estimated fall for those at high risk. Over the same period, there was a barely significant 75% (95% CI: 3% to 200%) estimated increase in IE incidence among moderate-risk individuals and a significant 177% estimated increase (95% CI: 66% to 361%) among those at high risk. In unknown/low-risk individuals, there was a significant 52% (95% CI: 46% to 58%) estimated fall in AP prescribing, but no significant increase in IE incidence. CONCLUSIONS: AP prescribing fell among all IE risk groups, particularly those at moderate risk. Concurrently, there was a significant increase in IE incidence among high-risk individuals, a borderline significant increase in moderate-risk individuals, and no change for those at low/unknown risk. Although these data do not establish a cause-effect relationship between AP reduction and IE increase, the fall in AP prescribing in those at high risk is of concern and, coupled with the borderline increase in IE incidence among those at moderate risk, warrants further investigation.

Assessment of inappropriate antibiotic prescribing among a large cohort of general dentists in the United States.

BACKGROUND: The purpose of this study was to assess dental antibiotic prescribing trends over time, to quantify the number and types of antibiotics dentists prescribe inappropriately, and to estimate the excess health care costs of inappropriate antibiotic prescribing with the use of a large cohort of general dentists in the United States. METHODS: We used a quasi-Poisson regression model to analyze antibiotic prescriptions trends by general dentists between January 1, 2013, and December 31, 2015, with the use of data from Express Scripts Holding Company, a large pharmacy benefits manager. We evaluated antibiotic duration and appropriateness for general dentists. Appropriateness was evaluated by reviewing the antibiotic prescribed and the duration of the prescription. RESULTS: Overall, the number and rate of antibiotic prescriptions prescribed by general dentists remained stable in our cohort. During the 3-year study period, approximately 14% of antibiotic prescriptions were deemed inappropriate, based on the antibiotic prescribed, antibiotic treatment duration, or both indicators. The quasi-Poisson regression model, which adjusted for number of beneficiaries covered, revealed a small but statistically significant decrease in the monthly rate of inappropriate antibiotic prescriptions by 0.32% (95% confidence interval, 0.14% to 0.50%; P = .001). CONCLUSIONS: Overall antibiotic prescribing practices among general dentists in this cohort remained stable over time. The rate of inappropriate antibiotic prescriptions by general dentists decreased slightly over time. PRACTICAL IMPLICATIONS: From these authors' definition of appropriate antibiotic prescription choice and duration, inappropriate antibiotic prescriptions are common (14% of all antibiotic prescriptions) among general dentists. Further analyses with the use of chart review, administrative data sets, or other approaches are needed to better evaluate antibiotic prescribing practices among dentists.

Is antibiotic prophylaxis to prevent infective endocarditis worthwhile?

Infective endocarditis (IE) is a rare condition which is associated with considerable morbidity and mortality. Almost 100 years ago, the links between endocarditis and procedures, particularly dental procedures, were postulated. Over 50 years ago the first guidelines recommending antibiotic prophylaxis (AP), with the aim of preventing IE developing after procedures, were proposed. However, there has only ever been circumstantial evidence in humans that AP prevents IE. The rarity of IE has made a randomised controlled clinical trial impractical to date. This article outlines the history of AP and reviews the evidence base for the use of AP to prevent IE.

The Cost-Effectiveness of Antibiotic Prophylaxis for Patients at Risk of Infective Endocarditis.

BACKGROUND: In March 2008, the National Institute for Health and Care Excellence recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the United Kingdom, citing a lack of evidence of efficacy and cost-effectiveness. We have performed a new economic evaluation of AP on the basis of contemporary estimates of efficacy, adverse events, and resource implications. METHODS: A decision analytic cost-effectiveness model was used. Health service costs and benefits (measured as quality-adjusted life-years) were estimated. Rates of IE before and after the National Institute for Health and Care Excellence guidance were available to estimate prophylactic efficacy. AP adverse event rates were derived from recent UK data, and resource implications were based on English Hospital Episode Statistics. RESULTS: AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high risk of IE. Only a marginal reduction in annual IE rates (1.44 cases in high-risk and 33 cases in all at-risk patients) would be required for AP to be considered cost-effective at £20 000 ($26 600) per quality-adjusted life-year. Annual cost savings of £5.5 to £8.2 million ($7.3-$10.9 million) and health gains >2600 quality-adjusted life-years could be achieved from reinstating AP in England. CONCLUSIONS: AP is cost-effective for preventing IE, particularly in those at high risk. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals.