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.

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.

Prevention of Viridans Group Streptococcal Infective Endocarditis: A Scientific Statement From the American Heart Association.

BACKGROUND: In 2007, the American Heart Association published updated evidence-based guidelines on the recommended use of antibiotic prophylaxis to prevent viridans group streptococcal (VGS) infective endocarditis (IE) in cardiac patients undergoing invasive procedures. The 2007 guidelines significantly scaled back the underlying conditions for which antibiotic prophylaxis was recommended, leaving only 4 categories thought to confer the highest risk of adverse outcome. The purpose of this update is to examine interval evidence of the acceptance and impact of the 2007 recommendations on VGS IE and, if needed, to make revisions based on this evidence. METHODS AND RESULTS: A writing group was formed consisting of experts in prevention and treatment of infective endocarditis including members of the American Dental Association, the Infectious Diseases Society of America, and the American Academy of Pediatrics, in addition to the American Heart Association. MEDLINE database searches were done for English language articles on compliance with the recommendations in the 2007 guidelines and the frequency of and morbidity or mortality from VGS IE after publication of the 2007 guidelines. Overall, there was good general awareness of the 2007 guidelines but variable compliance with recommendations. There was no convincing evidence that VGS IE frequency, morbidity, or mortality has increased since 2007. CONCLUSIONS: On the basis of a review of the available evidence, there are no recommended changes to the 2007 VGS IE prevention guidelines. We continue to recommend VGS IE prophylaxis only for categories of patients at highest risk for adverse outcome while emphasizing the critical role of good oral health and regular access to dental care for all. Randomized controlled studies to determine whether antibiotic prophylaxis is effective against VGS IE are needed to further refine recommendations.

Antibiotic Prophylaxis for Prosthetic Joint Patients Undergoing Invasive Dental Procedures: Time for a Rethink?

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.

Genomic Profiling of Mycobacterium tuberculosis Strains, Myanmar.

Multidrug resistance is a major threat to global elimination of tuberculosis (TB). We performed phenotypic drug-susceptibility testing and whole-genome sequencing for 309 isolates from 342 consecutive patients who were given a diagnosis of TB in Yangon, Myanmar, during July 2016‒June 2018. We identified isolates by using the GeneXpert platform to evaluate drug-resistance profiles. A total of 191 (62%) of 309 isolates had rifampin resistance; 168 (88%) of these rifampin-resistant isolates were not genomically related, indicating the repeated emergence of resistance in the population, rather than extensive local transmission. We did not detect resistance mutations to new oral drugs, including bedaquiline and pretomanid. The current GeneXpert MTB/RIF system needs to be modified by using the newly launched Xpert MTB/XDR cartridge or line-probe assay. Introducing new oral drugs to replace those currently used in treatment regimens for multidrug-resistant TB will also be useful for treating TB in Myanmar.

Endosymbiotic origin and differential loss of eukaryotic genes.

Chloroplasts arose from cyanobacteria, mitochondria arose from proteobacteria. Both organelles have conserved their prokaryotic biochemistry, but their genomes are reduced, and most organelle proteins are encoded in the nucleus. Endosymbiotic theory posits that bacterial genes in eukaryotic genomes entered the eukaryotic lineage via organelle ancestors. It predicts episodic influx of prokaryotic genes into the eukaryotic lineage, with acquisition corresponding to endosymbiotic events. Eukaryotic genome sequences, however, increasingly implicate lateral gene transfer, both from prokaryotes to eukaryotes and among eukaryotes, as a source of gene content variation in eukaryotic genomes, which predicts continuous, lineage-specific acquisition of prokaryotic genes in divergent eukaryotic groups. Here we discriminate between these two alternatives by clustering and phylogenetic analysis of eukaryotic gene families having prokaryotic homologues. Our results indicate (1) that gene transfer from bacteria to eukaryotes is episodic, as revealed by gene distributions, and coincides with major evolutionary transitions at the origin of chloroplasts and mitochondria; (2) that gene inheritance in eukaryotes is vertical, as revealed by extensive topological comparison, sparse gene distributions stemming from differential loss; and (3) that continuous, lineage-specific lateral gene transfer, although it sometimes occurs, does not contribute to long-term gene content evolution in eukaryotic genomes.

Transcriptome-Wide Gene Expression Plasticity in Stipa grandis in Response to Grazing Intensity Differences.

Organisms have evolved effective and distinct adaptive strategies to survive. Stipa grandis is a representative species for studying the grazing effect on typical steppe plants in the Inner Mongolia Plateau. Although phenotypic (morphological and physiological) variations in S. grandis in response to long-term grazing have been identified, the molecular mechanisms underlying adaptations and plastic responses remain largely unknown. Here, we performed a transcriptomic analysis to investigate changes in gene expression of S. grandis under four different grazing intensities. As a result, a total of 2357 differentially expressed genes (DEGs) were identified among the tested grazing intensities, suggesting long-term grazing resulted in gene expression plasticity that affected diverse biological processes and metabolic pathways in S. grandis. DEGs were identified in RNA-Seq and qRT-PCR analyses that indicated the modulation of the Calvin-Benson cycle and photorespiration metabolic pathways. The key gene expression profiles encoding various proteins (e.g., ribulose-1,5-bisphosphate carboxylase/oxygenase, fructose-1,6-bisphosphate aldolase, glycolate oxidase, etc.) involved in these pathways suggest that they may synergistically respond to grazing to increase the resilience and stress tolerance of S. grandis. Our findings provide scientific clues for improving grassland use and protection and identifying important questions to address in future transcriptome studies.

Worldwide relationships in the fern genus Pteridium (bracken) based on nuclear genome markers.

PREMISE: Spore-bearing plants are capable of dispersing very long distances. However, it is not known if gene flow can prevent genetic divergence in widely distributed taxa. Here we address this issue, and examine systematic relationships at a global geographic scale for the fern genus Pteridium. METHODS: We sampled plants from 100 localities worldwide, and generated nucleotide data from four nuclear genes and two plastid regions. We also examined 2801 single nucleotide polymorphisms detected by a restriction site-associated DNA approach. RESULTS: We found evidence for two distinct diploid species and two allotetraploids between them. The "northern" species (Pteridium aquilinum) has distinct groups at the continental scale (Europe, Asia, Africa, and North America). The northern European subspecies pinetorum appears to involve admixture among all of these. A sample from the Hawaiian Islands contained elements of both North American and Asian P. aquilinum. The "southern" species, P. esculentum, shows little genetic differentiation between South American and Australian samples. Components of African genotypes are detected on all continents. CONCLUSIONS: We find evidence of distinct continental-scale genetic differentiation in Pteridium. However, on top of this is a clear signal of recent hybridization. Thus, spore-bearing plants are clearly capable of extensive long-distance gene flow; yet appear to have differentiated genetically at the continental scale. Either gene flow in the past was at a reduced level, or vicariance is possible even in the face of long-distance gene flow.

World Workshop on Oral Medicine VII: What participants perceive as important.

Our objective was to identify which aspects of World Workshop on Oral Medicine (WWOM) participation were perceived as significant for participants' professional development. Online survey was sent to previous WWOM participants. Qualitative analysis of participants' responses to an open-ended question was performed. Fifty-two WWOM participants responded. Nearly three quarters of respondents (72.3%) felt that participation in the WWOM helped their career. A high percentage of respondents (67.3%) provided answers that fell under the domains of international collaboration, followed by personal academic benefits (48%). Overall, the results indicate that WWOM participation played an important role in individual's professional development. We identified aspects of WWOM involvement that the participants perceived as important. This information will be used for the development of an objective instrument for measuring impact of WWOM on participant's professional path.

World Workshop on Oral Medicine VII: Platelet count and platelet transfusion for invasive dental procedures in thrombocytopenic patients: A systematic review.

OBJECTIVES: To evaluate the evidence for a 50,000/µl platelet count threshold for platelet transfusion for invasive dental procedures in thrombocytopenic patients. SUBJECTS AND METHODS: We searched in MEDLINE/PubMed, EMBASE, the Cochrane Library (Wiley) and Scopus from 1960 through April 2018 for studies on patients with quantitative platelet disorders not related to medical co-morbidities or medications and undergoing invasive dental procedures. Two reviewers conducted assessments independently. RESULTS: We found a total of 176 non-duplicate articles, of which 9 cohort studies met our inclusion criteria. The incidence of postoperative bleeding in thrombocytopenic patients was low (4.9%), and we found no difference in bleeding incidence between patients who had platelet transfusion and those who did not. There was no difference in the mean platelet count for patients with and without bleeding. Different modalities are now available to prevent and control bleeding, which may reduce the need for platelet transfusion. CONCLUSIONS: There is no evidence to support the long-standing dogma of a need for a platelet count ≥ 50,000/µl for safe invasive dental procedures. Platelet transfusion effectiveness for haemostasis support could not be determined based on available data. Local measures and antifibrinolytics are the mainstay for the prevention and management of bleeding.

World Workshop on Oral Medicine VII: Non-opioid pain management of head and neck chemo/radiation-induced mucositis: A systematic review.

OBJECTIVE: To evaluate the current evidence regarding the effectiveness of non-opioid interventions for the therapeutic management of pain in head and neck cancer patients with oral mucositis resulting from radiotherapy only or chemoradiotherapy. MATERIALS AND METHODS: A literature search was conducted which included randomised controlled trials that assessed patient-related outcome of pain in patients with oral mucositis associated with radiation therapy only or chemoradiotherapy. Literature searches were conducted in MEDLINE via Pubmed, Embase, Scopus and CINAHL. RESULTS: The electronic searches identified 846 articles. Screening revealed that six articles met all eligibility inclusion criteria. Interventions showing statistically significant benefits to reduce oral mucositis associated pain compared to placebo included doxepin (p < 0.001, 95% CI -6.7 to -2.1), amitriptyline (p = 0.04), diclofenac (p < 0.01) and benzydamine (p = 0.014). CONCLUSIONS: Non-opioid interventions, including topical doxepin, amitriptyline, diclofenac and benzydamine, were found to provide relief of pain due to mucositis, and when effective may allow for reduction in the use of opioids in pain management.

World workshop on oral medicine VII: Direct anticoagulant agents management for invasive oral procedures: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to evaluate the current literature regarding the importance of discontinuing or not discontinuing direct oral anticoagulants (DOACs) before invasive oral procedures, and to establish the frequency and type of postoperative bleeding events in patients. MATERIAL AND METHODS: We searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library up until November 5, 2018. Selection of the studies, extraction of data, qualitative, and bias assessment was performed independently by two authors. RESULTS: Twenty-one studies were included. No randomized controlled studies were identified. Six studies reported a direct comparison between patients taking DOACs and those who discontinued DOACs. The meta-analysis of these studies resulted in an OR of 0.92 (95% CI = 0.37-2.27, I2  = 9%) for postoperative bleeding events for patients taking DOACs. We found that 59/497 (11.8%) postoperative bleeding events occurred in patients who continued DOACs, while 27/200 (13.5%) events were reported for patients who discontinued treatment. All postoperative bleeding events were controlled with local measures. CONCLUSION: Results from the included studies did not discern any important differences in postoperative bleeding events in patients who continued versus patients who discontinued DOACs. Furthermore, no thromboembolic events were recorded. However, the low quality of the studies must be considered.

Quantifying infective endocarditis risk in patients with predisposing cardiac conditions.

Aims: There are scant comparative data quantifying the risk of infective endocarditis (IE) and associated mortality in individuals with predisposing cardiac conditions. Methods and results: English hospital admissions for conditions associated with increased IE risk were followed for 5 years to quantify subsequent IE admissions. The 5-year risk of IE or dying during an IE admission was calculated for each condition and compared with the entire English population as a control. Infective endocarditis incidence in the English population was 36.2/million/year. In comparison, patients with a previous history of IE had the highest risk of recurrence or dying during an IE admission [odds ratio (OR) 266 and 215, respectively]. These risks were also high in patients with prosthetic valves (OR 70 and 62) and previous valve repair (OR 77 and 60). Patients with congenital valve anomalies (currently considered 'moderate risk') had similar levels of risk (OR 66 and 57) and risks in other 'moderate-risk' conditions were not much lower. Congenital heart conditions (CHCs) repaired with prosthetic material (currently considered 'high risk' for 6 months following surgery) had lower risk than all 'moderate-risk' conditions-even in the first 6 months. Infective endocarditis risk was also significant in patients with cardiovascular implantable electronic devices. Conclusion: These data confirm the high IE risk of patients with a history of previous IE, valve replacement, or repair. However, IE risk in some 'moderate-risk' patients was similar to that of several 'high-risk' conditions and higher than repaired CHC. Guidelines for the risk stratification of conditions predisposing to IE may require re-evaluation.

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.

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association.

BACKGROUND: Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today's myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. METHODS AND RESULTS: This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. CONCLUSIONS: Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.

Incidence of infective endocarditis in England, 2000-13: a secular trend, interrupted time-series analysis.

BACKGROUND: Antibiotic prophylaxis given before invasive dental procedures in patients at risk of developing infective endocarditis has historically been the focus of infective endocarditis prevention. Recent changes in antibiotic prophylaxis guidelines in the USA and Europe have substantially reduced the number of patients for whom antibiotic prophylaxis is recommended. In the UK, guidelines from the National Institute for Health and Clinical Excellence (NICE) recommended complete cessation of antibiotic prophylaxis for prevention of infective endocarditis in March, 2008. We aimed to investigate changes in the prescribing of antibiotic prophylaxis and the incidence of infective endocarditis since the introduction of these guidelines. METHODS: We did a retrospective secular trend study, analysed as an interrupted time series, to investigate the effect of antibiotic prophylaxis versus no prophylaxis on the incidence of infective endocarditis in England. We analysed data for the prescription of antibiotic prophylaxis from Jan 1, 2004, to March 31, 2013, and hospital discharge episode statistics for patients with a primary diagnosis of infective endocarditis from Jan 1, 2000, to March 31, 2013. We compared the incidence of infective endocarditis before and after the introduction of the NICE guidelines using segmented regression analysis of the interrupted time series. FINDINGS: Prescriptions of antibiotic prophylaxis for the prevention of infective endocarditis fell substantially after introduction of the NICE guidance (mean 10,900 prescriptions per month [Jan 1, 2004, to March 31, 2008] vs 2236 prescriptions per month [April 1, 2008, to March 31, 2013], p<0·0001). Starting in March, 2008, the number of cases of infective endocarditis increased significantly above the projected historical trend, by 0·11 cases per 10 million people per month (95% CI 0·05-0·16, p<0·0001). By March, 2013, 35 more cases per month were reported than would have been expected had the previous trend continued. This increase in the incidence of infective endocarditis was significant for both individuals at high risk of infective endocarditis and those at lower risk. INTERPRETATION: Although our data do not establish a causal association, prescriptions of antibiotic prophylaxis have fallen substantially and the incidence of infective endocarditis has increased significantly in England since introduction of the 2008 NICE guidelines. FUNDING: Heart Research UK, Simplyhealth, and US National Institutes of Health.

The Root of Flowering Plants and Total Evidence.

Support for Amborella as the sole survivor of an evolutionary lineage that is sister to all other angiosperms comes from positions in DNA multiple-sequence alignments that have a poor fit to time-reversible substitution models. These sites exhibit significant levels of homoplasy, compositional heterogeneity, and strong heterotachy. We report phylogenetic analyses with observed, randomized, and simulated data which show there is little or no expectation that these sites provide useful information for understanding relationships among basal angiosperms. Their inclusion in phylogenetic analyses leads to a long-branch attraction artifact that favors Amborella as sister to other angiosperms in reconstructed phylogenies. Using parametric simulations, we show that sites in chloroplast sequences that exhibit less homoplasy between angiosperms and gymnosperms provide more reliable information for inferring basal angiosperm relationships. We confirm our earlier findings that the basal angiosperm Amborella is most closely related to aquatic herbs. Our current and previously reported (Goremykin et al. 2013) analyses highlight an essential aspect of the total evidence approach to phylogenetic inference. They suggest that data partitioning aimed at identifying components of the data that better fit evolutionary models is a more reliable approach to phylogeny reconstruction at deep taxonomic levels.