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Craig Murdoch,1 Brian H Brown,6 Vanessa Hearnden,1 Paul M Speight,3 Katy D’Apice,1,2 Anne M Hegarty,2 John A Tidy,4 T Jamie Healey,5 Peter E Highfield,7 Martin H Thornhill1,2 1Unit of Oral and Maxillofacial Medicine and Surgery, University of Sheffield School of Clinical Dentistry, Sheffield, United Kingdom; 2Unit of Oral Medicine, Charles Clifford Dental Hospital, Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, United Kingdom; 3Unit of Oral and Maxillofacial Pathology, University of Sheffield School of Clinical Dentistry, Sheffield, United Kingdom; 4Department of Gynaecological Oncology, 5Department of Medical Physics, Royal Hallamshire Hospital, Sheffield, United Kingdom; 6University of Sheffield Medical School, Beech Hill Road, Sheffield, United Kingdom; 7Zilico Ltd., The MedTECH Centre, Rutherford House, Manchester Science Park, Manchester, United Kingdom Abstract: The electrical properties of tissues depend on their architecture and cellular composition. We have previously shown that changes in electrical impedance can be used to differentiate between different degrees of cervical dysplasia and cancer of the cervix. In this proof-of-concept study, we aimed to determine whether electrical impedance spectroscopy (EIS) could distinguish between normal oral mucosa; benign, potentially malignant lesions (PML); and oral cancer. EIS data were collected from oral cancer (n=10), PML (n=27), and benign (n=10) lesions. EIS from lesions was compared with the EIS reading from the normal mucosa on the contralateral side of the mouth or with reference spectra from mucosal sites of control subjects (n=51). Healthy controls displayed significant differences in the EIS obtained from different oral sites. In addition, there were significant differences in the EIS of cancer and high-risk PML versus low-risk PML and controls. There was no significant difference between benign lesions and normal controls. Study subjects also deemed the EIS procedure considerably less painful and more convenient than the scalpel biopsy procedure. EIS shows promise at distinguishing among malignant, PML, and normal oral mucosa and has the potential to be developed into a clinical diagnostic tool. Keywords: oral cancer, head and neck cancer, potentially malignant lesions, dysplasia, impedance spectroscopy

Objectives Recurrent aphthous stomatitis ( RAS) is a common oral inflammatory disease induced by genetic and environmental factors. Gelatinases ( MMP-2 and MMP-9) and their natural inhibitor TIMP-1 are active players in the inflammatory process. We aimed to determine whether inheritance of specific MMP-2, MMP-9, or TIMP-1 gene polymorphisms is associated with RAS susceptibility. Subjects and methods Ninety-six RAS patients and 153 healthy controls were studied. Five polymorphisms were genotyped: rs17576, rs3918242, and rs11697325 in MMP-9, MMP-2 rs2285053, and TIMP-1 rs6609533. Association was assessed by logistic regression analysis after adjustment for confounding factors. Linkage disequilibrium ( LD) was assessed using the Haploview program. Results MMP-9 rs11697325 was significantly associated with RAS, with an increase in the AA genotype in patients, determined using χ2 analysis ( OR = 2.3, P = 0.006) and adjusted regression analysis ( OR = 3.1, P = 0.009). MMP-9 rs11697325 and rs17576 showed strong LD ( D' = 0.95), with an increase in the AA haplotype ( P = 0.023) and a decrease in the GA haplotype ( P = 0.015) in patients. Conclusions This is the first study to investigate the association of MMPs or TIMP-1 with RAS. We found a significant association between MMP-9 rs11697325 polymorphisms and RAS. Confirmatory studies in other populations and functional investigations are needed to determine the role of these genes in RAS. [ABSTRACT FROM AUTHOR]

Some cancer cells can induce apoptosis in tumour infiltrating cytotoxic T cells as a means of escaping immune destruction. This study examined the expression of the apoptosis-inducing ligands, Fas-L, TRAIL and TNF-alpha, on three representative oral squamous cell carcinoma (OSCC) cell lines, TR146, SCC25 and CAL27 and investigates the contribution of these ligands to tumour cell killing of Jurkat T cells in vitro. All three cell lines were able to induce apoptosis in Jurkat T cells to varying degrees. The TR146 cell line predominantly killed Jurkats via the well known Fas-L/Fas mediated pathway. Although TR146 also expressed low levels of TRAIL and TNF-alpha, these did not contribute significantly to TR146 killing of Jurkats. In contrast, the CAL27 cell line expressed little if any Fas-L but was still able to kill Jurkats effectively via an almost exclusively TRAIL mediated mechanism. The SCC25 cell line expressed significant levels of all three ligands but we were unable to significantly inhibit killing of Jurkats by blocking any one pathway with antibodies. SCC25 may use a combination of mechanisms to kill Jurkats and switch between them to compensate when one mechanism is blocked. We found that stimulation with interferon-gamma (IFN-gamma) induced or increased the expression of apoptosis-inducing ligands on OSCC as well as the killing of Jurkat T cells. Not only did IFN-gamma increase killing of Jurkats, but it changed the contribution of the Fas-L, TRAIL and TNF-alpha mediated mechanisms to the killing of Jurkat T cells by the different cell lines. These mechanisms if reproduced in vivo, could confer survival advantage on OSCC by enabling them to kill tumour invading cytotoxic lymphocytes and evade immune destruction. [ABSTRACT FROM AUTHOR]

Objectives: To identify histological features that distinguish amalgam-associated oral lichenoid reactions (AAOLR) from oral lichen planus (OLP).Methods: Oral pathologists provided their opinion as to the possibility of distinguishing AAOLR and OLP histologically, the features important in distinguishing AAOLR from OLP and the diagnosis of 12 AAOLR and 12 OLP cases including the features that drew them to their conclusion.Results: There was considerable variation between pathologists in their ability to distinguish the AAOLR and OLP cases. The sensitivity and specificity for histological diagnosis were 40% and 32% respectively. There were four features that were used most commonly to discriminate between AAOLR and OLP: an inflammatory infiltrate located deep to superficial infiltrate in some or all areas; a focal perivascular infiltrate; plasma cells in the connective tissue and neutrophils in the connective tissue. Each was independently predictive of AAOLR or OLP (P < 0.028).Conclusions: This study confirms the uncertainty of the diagnostic histological differences between AAOLR and OLP. Distinguishing these conditions should not rely on histology alone, but should be based on a synthesis of all available information including history, examination, histopathology and skin patch testing. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis (RAS) is a common, painful, ulcerative condition of the mouth. Although there is no clear genetic mode of inheritance, there is evidence that inheritance of specific gene polymorphisms may predispose individuals to RAS. AlsoTh1 cell mediated immune responses under the control of IL-10/IL-12 are thought to play an important role inits pathogenesis. The objective of this study was to investigate the possibility that susceptibility to RAS is associated with the inheritance of specific gene polymorphisms for the T cell regulatory cytokines interleukin-10 (IL-10) and interleukin-12 (IL-12). One hundred RAS patients and 91 ethnically matched controls were genotyped for the IL-10-592, and -1082 polymorphisms, and the IL-12 1188 polymorphism. Chi-square analysis was used to compare the allele frequencies and genotypes of cases and controls. No significant association was identified between inheritance of specific alleles or genotypes of the IL-10-592 and -1082 polymorphisms or IL-12 1188 polymorphism and susceptibility to RAS. We were unable to demonstrate an association between the inheritance of specific IL-10 or IL-12 gene polymorphisms and RAS susceptibility. [ABSTRACT FROM AUTHOR]

This focused review highlights the latest issues in native valve infective endocarditis. Native valve disease moderately increases the risk of developing infective endocarditis. In 2023, new diagnostic criteria were published by the Duke-International Society of Cardiovascular Infectious Diseases group. New pathogens were designated as typical, and findings on computed tomography imaging were included as diagnostic criteria. It is now recognized that a multidisciplinary approach to care is vital, and the role of an "endocarditis team" is highlighted. Recent studies have suggested that a transition from intravenous to oral antibiotics in selected patients may be reasonable, and the role of long-acting antibiotics is discussed. It is also now clear that an aggressive surgical approach can be life-saving in some patients. Finally, results of several recent studies have suggested there is an association between dental and other invasive procedures and an increased risk of developing infective endocarditis. Moreover, data indicate that antibiotic prophylaxis may be effective in some scenarios., Competing Interests: Funding Support and Author Disclosures Dr Dayer has received payment for expert testimony from Bevan Brittan. Dr Thornhill has received grant support from the National Institutes for Health, Delta Dental of Michigan Research and Data Institute’s Research Committee, and Renaissance Health Service Corporation. Dr Baddour has received consulting fees from Boston Scientific and Roivant Sciences; and has received royalty payments from UpToDate, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

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., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

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., (© 2023 Wiley Periodicals LLC.)

There have been no published prospective randomized clinical trials that have: (1) established an association between invasive dental and nondental invasive procedures and risk of infective endocarditis; or (2) defined the efficacy and safety of antibiotic prophylaxis administered in the setting of invasive procedures in the prevention of infective endocarditis in high-risk patients. Moreover, previous observational studies that examined the association of nondental invasive procedures with the risk of infective endocarditis have been limited by inadequate sample size. They have typically focused on a few potential at-risk surgical and nonsurgical invasive procedures. However, recent investigations from Sweden and England that used nationwide databases and demonstrated an association between nondental invasive procedures, and the subsequent development of infective endocarditis (in particular, in high-risk patients with infective endocarditis) prompted the development of the current science advisory.

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Oral lichen planus (OLP) is a T cell-mediated inflammatory disease of the oral mucosa that has been extensively researched over many years but as yet the mechanisms of pathogenesis are still not fully understood. Whilst the specific aetiological factors driving OLP remain ambiguous, evidence points to the development of a chronic, dysregulated immune response to OLP-mediating antigens presented by innate immune cells and oral keratinocytes leading to increased cytokine, chemokine and adhesion molecule expression. These molecules recruit T cells and mast cells to the diseased site and orchestrate a complex interplay between cells that culminates in keratinocyte cell death, mucosal basement membrane destruction and long-term chronicity of the disease. The main lymphocytes involved are thought to be CD8+ cytotoxic and CD4+ Th1 polarised T cells although recent evidence indicates the involvement of other Th subsets such as Th9, Th17 and Tregs, suggesting that a more complex immune cell relationship exists during the disease process. This review provides an overview of the immune mechanisms at play in OLP pathogenesis with particular emphasis on the role of the different Th subsets and how these recent discoveries may guide research towards identifying potential therapeutic targets., (© 2022 Wiley Periodicals LLC.)

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., Competing Interests: Competing interests: MHT, AC, RC, TS, ECL, MB, VF and JN all received salary support from the British Heart Foundation (Project Grant PG/20/10410) for this study. MHT, PL and JN report other grant support from the National Institutes for Health (USA) or the National Institute for Health Research (UK). BDP reports unrestricted educational and research grants from Edwards Lifesciences, and personal speaker/consultancy fees from Medtronic, Abbott, Microport, Anteris and Edwards Lifesciences. LB reports consulting for Boston Scientific and Roivant Sciences, and royalty payments from UpToDate, Inc. MD reports payment for expert testimony from Bevan Brittan, honoraria for presentations and support for attending meetings from Biotronik. JN reports being chair of the REPHILL trial data monitoring committee from (National Institute for Health and Care Research (NIHR)), chair of research commissioning panels for COVID research (CSO Scotland), member of the UKRI-DHSC COVID-19 Vaccine trial commissioning panel and member of the NIHR commissioning panel for emergency care procedures research., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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., (Copyright © 2023 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the impact of various aerosol mitigation interventions and to establish duration of aerosol persistence in a variety of dental clinic configurations., Methods: We performed aerosol measurement studies in endodontic, orthodontic, periodontic, pediatric, and general dentistry clinics. We used an optical aerosol spectrometer and wearable particulate matter sensors to measure real-time aerosol concentration from the vantage point of the dentist during routine care in a variety of clinic configurations (eg, open bay, single room, partitioned operatories). We compared the impact of aerosol mitigation strategies (eg, ventilation and high-volume evacuation (HVE), and prevalence of particulate matter) in the dental clinic environment before, during, and after high-speed drilling, slow-speed drilling, and ultrasonic scaling procedures., Results: Conical and ISOVAC HVE were superior to standard-tip evacuation for aerosol-generating procedures. When aerosols were detected in the environment, they were rapidly dispersed within minutes of completing the aerosol-generating procedure. Few aerosols were detected in dental clinics, regardless of configuration, when conical and ISOVAC HVE were used., Conclusions: Dentists should consider using conical or ISOVAC HVE rather than standard-tip evacuators to reduce aerosols generated during routine clinical practice. Furthermore, when such effective aerosol mitigation strategies are employed, dentists need not leave dental chairs fallow between patients because aerosols are rapidly dispersed.

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., Competing Interests: Potential conflicts of interest. All authors report no potential conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., Competing Interests: Funding Support and Author Disclosures This study was funded by a research grant from the Delta Dental of Michigan Research Committee and Renaissance Health Service Corporation. The views expressed in this publication are those of the authors and do not necessarily represent those of the funders. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review or approval of the manuscript; or the decision to submit the manuscript for publication. Profs Thornhill, Lockhart, and O’Gara have received support from the Delta Dental Research and Data Institute for this work. Dr Dayer has received support in the last 3 years from Biotronik that was unconnected to the submitted work; and was a consultant to the review committee that produced the 2015 update to NICE clinical guideline 64 on prophylaxis against infective endocarditis. Prof Prendergast has received unrestricted research and educational grants from Edwards Lifesciences; has received lecture fees from Abbott, Anteris, and Edwards Lifesciences; and has received consultancy fees from and serves on the Scientific Advisory Board for Anteris and Microport (all unconnected to the submitted work); was a member of the Task Force on the Prevention, Diagnosis and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC) that produced the 2009 ESC guidelines; and acted as an external advisor to the committee that produced NICE clinical guideline 64 on Prophylaxis Against Infective Endocarditis in March 2008. Dr Lockhart is a member of the writing committee reviewing the current AHA guidelines on antibiotic prophylaxis to prevent infective endocarditis. Drs Lockhart and Baddour were members of the AHA Committee on Rheumatic Fever, Endocarditis and Kawasaki Disease, and were involved in producing both the 2007 and 2021 AHA guidelines on prevention of infective endocarditis. Dr O’Gara has received support in the last 3 years from Medtronic, Edwards Scientific, and the National Heart, Lung, and Blood Institute that was unconnected to the submitted work. Dr Baddour has received royalty payments (authorship duties) from UpToDate, Inc; and has received consulting fees from Boston Scientific, Botanix Pharmaceuticals, and Roivant Sciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In the United States, it has been common practice to recommend that dentists provide antibiotic prophylaxis (AP) before invasive dental procedures (IDPs) to prevent late periprosthetic joint infections (LPJIs) in patients who have prosthetic arthroplasties despite lack of evidence for a causal relationship between IDP and LPJI and a lack of evidence for AP efficacy., Methods: A recent study quantified the IDP incidence over the 15-month period prior to LPJI hospital admissions in the United Kingdom for which dental records were available. A case-crossover analysis compared IDP incidence in the 3 months before LPJI admission with the preceding 12 months. The English population was used because guidelines do not recommend AP and any relationship between IDPs and LPJI should be fully exposed., Results: No significant positive association was identified between IDPs and LPJI. Indeed, the incidence of IDPs was lower in the 3 months before LPJI hospital admission than that in the preceding 12 months., Conclusion: In the absence of a significant positive association between IDPs and LPJI, there is no rationale to administer AP before IDPs in patients with prosthetic joints, particularly given the cost and inconvenience of AP, the risk of adverse drug reactions, and the potential for unnecessary AP use that promotes antibiotic resistance. These results should reassure orthopedic surgeons and their patients that dental care of patients who have prosthetic joints should focus on maintaining good oral hygiene rather than on recommending AP for IDPs. Moreover, it should also reassure those in other countries where AP is not recommended that such guidance is sufficient., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Little is known about factors that influence dentists' decision making concerning antibiotic prophylaxis (AP) prescribing. The objective of this study was to determine factors that influence dentists' AP prescribing habits in patients at risk of developing infective endocarditis and prosthetic joint infections., Methods: A questionnaire was administered to 3,584 dentist members of The National Dental Practice-Based Research Network. In addition to descriptive statistics, ordinal regression models were used to determine the factors most likely to impact dentists' decisions to prescribe AP., Results: Overall, 2,169 (61%) dentists in The National Dental Practice-Based Resesarch Network responded. Responders' decisions to prescribe antibiotics were influenced primarily by official guidelines, scientific literature, and physician or medical specialist opinion. Regarding potential risks, the greatest level of concern was for the development of infective endocarditis or prosthetic joint infections. Although litigation was deemed problematic, more than 90% of responders indicated a strong concern for the best course of action for the patient's health. Dentists also indicated a high level of concern about the potential for generating antibiotic-resistant bacteria with AP use and increased risk of adverse drug reactions., Conclusions: Dentists' AP decision making seems most influenced by official guidelines, scientific literature, and advice from a physician or medical specialist., Practical Implications: These results suggest that one of the most effective means for promoting concordance of dentists clinical practice with the scientific basis for AP is to emphasize the importance and clarity of American Heart Association and American Dental Association recommendations and antimicrobial stewardship regarding prevention of infective endocarditis and prosthetic joint infections., (Copyright © 2022 American Dental Association. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To define the incidence and risk factors for infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI)., Methods: All patients who underwent first SAVR or TAVI in England between 2007 and 2016 were identified from the NICOR databases. Hospital admissions with a primary diagnosis of IE were identified by linkage with the NHS Hospital Episode Statistics database. Approval was obtained from the NHS Research Ethics Committee., Results: 2057 of 91 962 patients undergoing SAVR developed IE over a median follow-up of 53.9 months-an overall incidence of 4.81 [95% CI 4.61 to 5.03] per 1000 person-years. Correspondingly, 140 of 14 195 patients undergoing TAVI developed IE over a median follow-up of 24.5 months-an overall incidence of 3.57 [95% CI 3.00 to 4.21] per 1000 person-years. The cumulative incidence of IE at 60 months was higher after SAVR than after TAVI (2.4% [95% CI 2.3 to 2.5] vs 1.5% [95% CI 1.3 to 1.8], HR 1.60, p<0.001). Across the entire cohort, SAVR remained an independent predictor of IE after multivariable adjustment. Risk factors for IE included younger age, male sex, atrial fibrillation, and dialysis., Conclusions: IE is a rare complication of SAVR and TAVI. In our population, the incidence of IE was higher after SAVR than after TAVI., Competing Interests: Competing interests: BDP has received unrestricted education and research grants from Edwards Lifesciences and speaker fees from Edwards Lifesciences. SRR has served as a proctor for and received speaker fees from Edwards Lifesciences, and has served on the advisory board for Medtronic. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Dentists in the United States are under pressure from orthopedic surgeons and their patients with prosthetic joints to provide antibiotic prophylaxis before invasive dental procedures (IDP) to reduce the risk of late prosthetic joint infection (LPJI). This has been a common practice for decades, despite a lack of evidence for an association between IDP and LPJI, a lack of evidence of antibiotic prophylaxis efficacy, cost of providing antibiotic prophylaxis, and risk of both adverse drug reactions and the potential for promoting antibiotic resistance., Objective: To quantify any temporal association between IDP and subsequent LPJI., Design, Setting, and Participants: This cohort study used a case-crossover and time trend design to examine any potential association between IDP and LPJI. The population of England (55 million) was chosen because antibiotic prophylaxis has never been recommended to prevent LPJI in England, and any association between IDP and LPJI would therefore be fully exposed. All patients admitted to hospitals in England for LPJI from December 25, 2011, through March 31, 2017, and for whom dental records were available were included. Analyses were performed between May 2018 and June 2021., Exposures: Exposure to IDP., Main Outcomes and Measures: The main outcome was the incidence of IDP in the 3 months before LPJI hospital admission (case period) compared with the incidence in the 12 months before that (control period)., Results: A total of 9427 LPJI hospital admissions with dental records (mean [SD] patient age, 67.8 [13.1] years) were identified, including 4897 (52.0%) men and 4529 (48.0%) women. Of these, 2385 (25.3%) had hip prosthetic joints, 3168 (33.6%) had knee prosthetic joints, 259 (2.8%) had other prosthetic joints, and 3615 (38.4%) had unknown prosthetic joint types. There was no significant temporal association between IDP and subsequent LPJI. Indeed, there was a lower incidence of IDP in the 3 months prior to LPJI (incidence rate ratio, 0.89; 95% CI, 0.82-0.96; P = .002)., Conclusions and Relevance: These findings suggest that there is no rationale to administer antibiotic prophylaxis before IDP in patients with prosthetic joints.

Aim: To provide a contemporary analysis of incidence trends of infective endocarditis (IE) with its changing epidemiology over the past two decades in Europe., Methods: A systematic review was conducted at the Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus and Web of Science were searched for studies published between 1 January 2000 and 30 November 2020. All studies were independently reviewed by four referees and those that included a population-based incidence of IE in patients, irrespective of age, in Europe were included. Least squares regression was used to estimate pooled temporal trends in IE incidence., Results: Of 9138 articles screened, 18 studies were included in the review. Elderly men predominated in all studies. IE incidence increased 4.1% per year (95% CI 1.8% to 6.4%) in the pooled regression analysis of eight studies that included comprehensive and consistent trends data. When trends data were weighted according to population size of individual countries, an increase in yearly incidence of 0.27 cases per 100 000 people was observed. Staphylococci and streptococci were the most common pathogens identified. The rate of surgical intervention ranged from 10.2% to 60.0%, and the rate of inpatient mortality ranged from 14.3% to 17.5%. In six studies that examined the rate of injection drug use, five of them reported a rate of less than 10%., Conclusion: Based on findings from our systematic review, IE incidence in Europe has doubled over the past two decades in Europe. Multiple factors are likely responsible for this striking increase., Trial Registeration Number: CRD42020191196., Competing Interests: Competing interests: LMB, M.D. reports Boston Scientific, consultant duties; UpToDate, royalty payments (authorship duties); Botanix Pharmaceuticals, consulting duties; Roivant Sciences, consultant duties. MRS, M.D. reports receiving funds from TYRX and Medtronic for prior research unrelated to this study administered according to a sponsored research agreement between Mayo Clinic and study sponsor that prospectively defined the scope of the research effort and corresponding budget; and honoraria/consulting fees from Medtronic, Philips and Aziyo Biologics. Research Grant: Medtronic. MJD, M.B.B.S. reports payments from Biotronik unrelated to this study. IMT, M.D. reports UpToDate, royalty payments (authorship duties). The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The objective of this paper was to examine temporal changes of infective endocarditis (IE) incidence and epidemiology in North America., Methods: A systematic review was conducted at Mayo Clinic, Rochester. Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science were searched for studies published between January 1, 2000, and May 31, 2020. Four referees independently reviewed all studies, and those that reported a population-based incidence of IE in patients aged 18 years and older in North America were included., Results: Of 8588 articles screened, 14 were included. Overall, IE incidence remained largely unchanged throughout the study period, except for 2 studies that demonstrated a rise in incidence after 2014. Five studies reported temporal trends of injection drug use (IDU) prevalence among IE patients with a notable increase in prevalence observed. Staphylococcus aureus was the most common pathogen in 7 of 9 studies that included microbiologic findings. In-patient mortality ranged from 3.7% to 14.4%, while the percentage of patients who underwent surgery ranged from 6.4% to 16.0%., Conclusions: The overall incidence of IE has remained stable among the 14 population-based investigations in North America identified in our systematic review. Standardization of study design for future population-based investigations has been highlighted for use in subsequent systematic reviews of IE., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Oral cavity cancer has a low 5-y survival rate, but outcomes improve when the disease is detected early. Cytology is a less invasive method to assess oral potentially malignant disorders relative to the gold-standard scalpel biopsy and histopathology. In this report, we aimed to determine the utility of cytological signatures, including nuclear F-actin cell phenotypes, for classifying the entire spectrum of oral epithelial dysplasia and oral squamous cell carcinoma. We enrolled subjects with oral potentially malignant disorders, subjects with previously diagnosed malignant lesions, and healthy volunteers without lesions and obtained brush cytology specimens and matched scalpel biopsies from 486 subjects. Histopathological assessment of the scalpel biopsy specimens classified lesions into 6 categories. Brush cytology specimens were analyzed by machine learning classifiers trained to identify relevant cytological features. Multimodal diagnostic models were developed using cytology results, lesion characteristics, and risk factors. Squamous cells with nuclear F-actin staining were associated with early disease (i.e., lower proportions in benign lesions than in more severe lesions), whereas small round parabasal-like cells and leukocytes were associated with late disease (i.e., higher proportions in severe dysplasia and carcinoma than in less severe lesions). Lesions with the impression of oral lichen planus were unlikely to be either dysplastic or malignant. Cytological features substantially improved upon lesion appearance and risk factors in predicting squamous cell carcinoma. Diagnostic models accurately discriminated early and late disease with AUCs (95% CI) of 0.82 (0.77 to 0.87) and 0.93 (0.88 to 0.97), respectively. The cytological features identified here have the potential to improve screening and surveillance of the entire spectrum of oral potentially malignant disorders in multiple care settings.

Background: In 2007, the American Heart Association recommended that antibiotic prophylaxis (AP) be restricted to those at high risk of developing complications due to infective endocarditis (IE) undergoing invasive dental procedures. The authors aimed to estimate the appropriateness of AP prescribing according to type of dental procedure performed in patients at high risk, moderate risk, or low or unknown risk of developing IE complications., Methods: Eighty patients at high risk, 40 patients at moderate risk, and 40 patients at low or unknown risk of developing IE complications were randomly selected from patients with linked dental care, health care, and prescription benefits data in the IBM MarketScan Databases, one of the largest US health care convenience data samples. Two clinicians independently analyzed prescription and dental procedure data to determine whether AP prescribing was likely, possible, or unlikely for each dental visit., Results: In patients at high risk of developing IE complications, 64% were unlikely to have received AP for invasive dental procedures, and in 32 of 80 high-risk patients (40%) there was no evidence of AP for any dental visit. When AP was prescribed, several different strategies were used to provide coverage for multiple dental visits, including multiday courses, multidose prescriptions, and refills, which sometimes led to an oversupply of antibiotics., Conclusions: AP prescribing practices were inconsistent, did not always meet the highest antibiotic stewardship standards, and made retrospective evaluation difficult. For those at high risk of developing IE complications, there appears to be a concerning level of underprescribing of AP for invasive dental procedures., Practical Implications: Some dentists might be failing to fully comply with American Heart Association recommendations to provide AP cover for all invasive dental procedures in those at high risk of developing IE complications., (Copyright © 2020 American Dental Association. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about antibiotic prescribing practices of dentists. The objective of this study was to gain a better understanding of dentists' beliefs and behaviors regarding the use of antibiotic prophylaxis (AP) before invasive dental procedures., Methods: A multidisciplinary team developed and disseminated a questionnaire to 3,584 dentist members of the National Dental Practice-Based Research Network., Results: Overall, 2,169 network dentists (61%) responded. Respondents saw patients at risk of developing infective endocarditis (IE) and prosthetic joint infection (PJI) at least once per week (35% and 65%, respectively). Although 78% of dentists agreed that the 2007 American Heart Association guidelines for the prevention of IE are well-defined and clear, only 49% agreed concerning PJI guidelines. Differences for the IE and PJI patient populations also existed for questions regarding dentists' understanding of the specific patient groups at risk, the recommended antibiotic regimens, and the need to consult with a patient's cardiologist or orthopedic surgeon., Conclusions: The survey results indicate that decision making regarding the use of AP occurs frequently among dentists. Moreover, dentists reported uncertainty about the appropriate use of AP as defined by both IE and PJI guidelines, which may have resulted in a lack of concordance between dentists' beliefs and their practice behaviors., Practical Implications: The results reported by the authors highlight the need to develop better educational programs that address antimicrobial stewardship in AP for patients at risk of developing IE and PJI and target the dental profession., (Copyright © 2020 American Dental Association. Published by Elsevier Inc. All rights reserved.)

The increasing incidence of infective endocarditis in England is real, and education is critical to ensure swift diagnosis and best clinical outcomes. Factors responsible remain speculative, but multiple explanations are likely.

Background: Dentists are high prescribers of antibiotics for both treatment and prevention of infection, although there are few guidelines to aid clinicians. Given the worldwide concerns about unnecessary use of antibiotics, there is a need for a better understanding of dentists' use of these drugs for antibiotic prophylaxis (AP) to prevent distant site infections (i.e., infective endocarditis and prosthetic joint infection)., Objective: The aim of this study was to develop and implement an effective, self-reporting, cross-sectional, survey instrument that optimized the response rate and maximized reliability and validity for determining the beliefs and behaviors of a large and nationally representative group of generalist and specialist dentists concerning their use of AP., Study Design: A 15-question survey (58 items) was developed in a structured process by a multidisciplinary team and configured for automated online dissemination to 3584 national Dental Practice-Based Research Network (DPBRN; hitherto referred to as "Network") practitioners. The implementation phase consisted of 3 waves of greater than 1000 Network members. Additionally, 47 randomly selected dentists were surveyed twice to assess test-retest reliability., Results: Of 3584 eligible Network members, 2169 (60.5%) completed the survey. The age and geographic distributions of responders was similar to those of dentists in the 2019 American Dental Association census. Furthermore, test-retest weighted kappa values for the survey were acceptable (median 0.56; interquartile range 0.42-0.64)., Conclusions: We developed a highly structured survey with a high response rate and good reliability that will allow us to obtain unique data on dentists' beliefs and practices regarding AP prescribing., (Copyright © 2020 Elsevier Inc. All rights reserved.)