Assessment of the Quality of Current American Dental Association Clinical Practice Guidelines.

INTRODUCTION: The American Dental Association (ADA) defines evidence-based dentistry (EBD) as "an approach to oral healthcare that requires the judicious integration of systematic assessments of clinically relevant scientific evidence, relating to the oral and medical condition and history, with the dentist's clinical expertise and the patient's treatment needs and preferences." Clinical practice guidelines (CPGs) are statements that include recommendations intended to optimize patient care that are informed by a systematic review of evidence and an assessment of the benefits and harms of alternative care options. Therefore, ADA CPGs are the most rigorous examples of EBD to inform clinical practice. CPGs should be of the highest level of quality to ensure the appropriateness and timeliness of clinical recommendations. OBJECTIVES: The aim of this study was to measure the methodological rigor and transparency of the ADA CPGs. METHODS: Each ADA CPG was appraised by 4 independent assessors using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Quantitative quality scores were obtained for 6 domains and overall quality. In addition, assessors provided a qualitative analysis by providing comments for each item and an appraisal of the full recommendation. RESULTS: A quality score of 75% was used as the threshold for high-quality guidelines. Using this metric, 6 of the current 10 current ADA CPGs were considered to be of high quality, 1 was slightly below the quality threshold, and 3 were considered marginal. Even among those evaluated to be high quality in overall assessment, certain domains did not reach the quality threshold of 75%. CONCLUSION: Overall, the ADA CPGs collectively provide high-quality guidance for the clinician. While the AGREE appraisal guidelines have been used in CPG development since 2016, there is still room for improvement in certain domains (i.e., stakeholder involvement, rigor of development, applicability, and editorial independence). KNOWLEDGE TRANSFER STATEMENT: The results of this study summarize the methodological rigor and transparency of the 10 current ADA clinical practice guidelines. Since adoption of AGREE standards (2016), CPGs have been uniformly of high quality. The quality of older CPGs was somewhat lower but overall deemed acceptable. Thus, ADA CPGs may be used with confidence to inform practitioners of treatment options supported by rigorous evidence-based dentistry standards. However, there is still room for improvement in methodological quality.

Global, Regional, and National Levels and Trends in Burden of Oral Conditions from 1990 to 2017: A Systematic Analysis for the Global Burden of Disease 2017 Study.

Government and nongovernmental organizations need national and global estimates on the descriptive epidemiology of common oral conditions for policy planning and evaluation. The aim of this component of the Global Burden of Disease study was to produce estimates on prevalence, incidence, and years lived with disability for oral conditions from 1990 to 2017 by sex, age, and countries. In addition, this study reports the global socioeconomic pattern in burden of oral conditions by the standard World Bank classification of economies as well as the Global Burden of Disease Socio-demographic Index. The findings show that oral conditions remain a substantial population health challenge. Globally, there were 3.5 billion cases (95% uncertainty interval [95% UI], 3.2 to 3.7 billion) of oral conditions, of which 2.3 billion (95% UI, 2.1 to 2.5 billion) had untreated caries in permanent teeth, 796 million (95% UI, 671 to 930 million) had severe periodontitis, 532 million (95% UI, 443 to 622 million) had untreated caries in deciduous teeth, 267 million (95% UI, 235 to 300 million) had total tooth loss, and 139 million (95% UI, 133 to 146 million) had other oral conditions in 2017. Several patterns emerged when the World Bank's classification of economies and the Socio-demographic Index were used as indicators of economic development. In general, more economically developed countries have the lowest burden of untreated dental caries and severe periodontitis and the highest burden of total tooth loss. The findings offer an opportunity for policy makers to identify successful oral health strategies and strengthen them; introduce and monitor different approaches where oral diseases are increasing; plan integration of oral health in the agenda for prevention of noncommunicable diseases; and estimate the cost of providing universal coverage for dental care.

A mouse model linking viral hepatitis and salivary gland dysfunction.

OBJECTIVE: Viral hepatitis is known to cause xerostomia in humans, but this has not been reported in an animal model. We report a severe, acute, highly reproducible saliva deficiency occurring in BALB/c mice as a result of experimental viral hepatitis. MATERIALS AND METHODS: BALB/c mice, splenectomized or carrying genetic mutations to detect immunological contributions to the saliva deficiency syndrome, were infected intraperitoneally with a non-lethal dose of murine cytomegalovirus. Pilocarpine-stimulated saliva volumes were determined between 0 and 15 days after infection. Salivary gland, liver, spleen, and sera were analyzed for the presence of virus, cytokines, inflammatory infiltrates, and tissue damage. RESULTS: Saliva deficiency was detectable 2 days after cytomegalovirus infection, peaked at 88% below normal by day 7, and resolved partially in all mice by 15 days postinfection as sialoadenitis increased. Neither salivary gland viral titers, sialoadenitis, splenectomy, nor systemic inflammatory markers correlated with hyposalivation severity. Elevated liver enzymes did correlate with hyposalivation, and mice genetically resistant to murine cytomegalovirus-induced hepatitis were significantly protected. CONCLUSIONS: Murine cytomegalovirus-induced salivary gland dysfunction is biphasic, with an acute hepatitis-associated phase and a later sialoadenitis-associated phase. Acute murine cytomegalovirus infection of BALB/c mice may provide a model for investigation of hepatitis-associated xerostomia.

High glucose-boosted inflammatory responses to lipopolysaccharide are suppressed by statin.

BACKGROUND AND OBJECTIVE: It has been established that periodontal diseases are more prevalent and of greater severity in diabetic patients than in nondiabetic patients. Recent studies have underscored the role of monocytes and macrophages in periodontal tissue inflammation and destruction in diabetic patients. Although it has been shown that monocytes isolated from diabetic patients produce more inflammatory cytokines and that gingival crevicular fluid collected from diabetic patients contains higher levels of inflammatory cytokines than that obtained from nondiabetic patients, the underlying mechanisms are not well understood. MATERIAL AND METHODS: U937 histiocytes cultured in medium containing either normal (5 mM) or high (25 mM) glucose were treated with 100 ng/ml of lipopolysaccharide for 24h. After the treatment, cytokines in the medium and cytokine mRNA in the cells were quantified using enzyme-linked immunosorbet assay and real-time polymerase chain reaction, respectively. RESULTS: In this study, we demonstrated that the pre-exposure of U937 histiocytes to high glucose concentrations markedly increased the lipopolysaccharide-induced secretion of pro-inflammatory cytokines and chemokines and the cellular inducible nitric oxide level compared with pre-exposure to normal glucose. Our data also showed that the increased secretion of cytokines was a result of increased mRNA expression. Furthermore, the effects of statin and peroxisome proliferators-activated receptor agonists on high glucose-enhanced secretion of cytokines were determined. The results showed that simvastatin, but not fenofibrate or pioglitazone, inhibited high glucose-enhanced cytokine release. CONCLUSION: This study has shown that high glucose concentrations and lipopolysaccharide act synergistically to stimulate the secretion of inflammatory mediators, and that statin is capable of suppressing the high glucose-boosted proinflammatory response. This study therefore delineates a novel mechanism by which hyperglycemia enhances the inflammatory responses of macrophages and suggests that statin may be useful in the treatment of periodontal disease in diabetic patients.

Microbiology of chronic frontal sinusitis.

OBJECTIVES: To determine bacterial and fungal organisms that are present in patients undergoing surgery for chronic frontal sinusitis. STUDY DESIGN: Retrospective, nonrandomized study. METHODS: Retrospective, nonrandomized bacterial and fungal cultures were performed on 46 sinus aspirates obtained by frontal sinus trephination performed on 30 consecutive patients with chronic frontal sinusitis. RESULTS: Six patients were having sinus surgery for the first time, 19 patients had undergone prior functional endoscopic sinus surgery without instrumentation of the frontal sinus/recess, and the third group included 5 patients who had undergone prior frontal sinus/recess surgery. Preoperative computed tomography scan of the frontal sinuses revealed complete opacification in 63% (29/46 frontal sinuses) and partial opacification in 22% (10/46), and no data were available for 15% (7/46). Aerobic cultures revealed that 38% (13/35 cultures) had no growth, 21% (7/35) grew Staphylococcus aureus, 21% (7/35) grew coagulase-negative Staphylococcus, 9% (3/35) grew Haemophilus influenzae, and 26% (9/35) grew a variety of other organisms. Anaerobic cultures were positive in 3% (1/32) of sinuses, and fungal cultures were positive in 4% (1/24). Haemophilus influenzae was most common in primary cases, whereas coagulase-negative Staphylococcus was most common in patients undergoing revision frontal sinus surgery. There were no other significant differences between cultures from patients undergoing revision frontal sinus surgery, revision functional endoscopic sinus surgery without prior frontal surgery, and primary surgery. CONCLUSIONS: This study suggests that organisms involved in chronic inflammatory disease of the frontal sinus may change after previous sinus surgery. The study failed to support a significant role for anaerobes. The role for coagulase-negative Staphylococcus as a potential pathogen or a contaminating agent remains unclear.

Reovirus triggers cell type-specific proinflammatory responses dependent on the autocrine action of IFN-beta.

Resident cells of the respiratory and gastrointestinal tracts, including epithelial and fibroblast cells, are the initial sites of entry for many viral pathogens. We investigated the role that these cells play in the inflammatory process in response to infection with reovirus 1/L. In A549 human bronchial or HT-29 human colonic epithelial cells, interferon (IFN)-beta, regulated on activation T cell expressed and secreted (RANTES), IFN-gamma-inducible protein (IP)-10, and interleukin-8 were upregulated regardless of whether cells were infected with replication-competent or replication-deficient reovirus 1/L. However, in CCD-34Lu human lung fibroblast cells, IFN-beta, IP-10, and RANTES were expressed only after infection with replication-competent reovirus 1/L. Expression of interleukin-8 in CCD-34Lu fibroblast cells was viral replication independent. This differential expression of IFN-beta, RANTES, and IP-10 was shown to be due to the lack of induction of IFN regulatory factor-1 and -2 in CCD-34Lu fibroblast cells treated with replication-deficient reovirus 1/L. We have shown that cytokine and/or chemokine expression may not be dependent on viral replication. Therefore, treatment of viral infections with inhibitors of replication may not effectively alleviate inflammatory mediators because most viral infections result in the generation of replication-competent and replication-deficient virions in vivo.

The use of bone morphogenetic protein gene therapy in craniofacial bone repair.

Bone morphogenetic proteins (BMPs) are capable of inducing endochondral bone formation when applied on biologic carriers in numerous mammalian in vivo assay systems. Bone morphogenetic protein gene therapy is also currently being developed to promote osteogenesis for clinical indications such as spinal fusions, craniofacial bone loss, and osteoporosis. In this study, critical-sized mandibular defects were treated with a control adenoviral vector (Ad-beta-gal), a BMP-2 adenoviral vector (Ad-BMP-2), or a BMP-9 adenoviral vector (Ad-BMP-9). Gross tissue examination, radiographic analysis, and histologic analysis demonstrated significant bony healing in the BMP treated groups compared to controls. Osteogenesis was limited to the bony defect, without extension into the surrounding soft tissues. The study suggests that with further development, BMP gene therapy may be potentially useful for repair of bony defects in the craniofacial region.

Polychlorinated biphenyl mixtures (Aroclors) inhibit LPS-induced murine splenocyte proliferation in vitro.

The immune system is believed to be a sensitive indicator for adverse polychlorinated biphenyl (PCB)-induced health effects. Four commercial PCB mixtures (Aroclors) or six individual PCB congeners were evaluated for their effect on splenocyte viability and lipopolysaccharide (LPS)-induced splenocyte proliferation in vitro in two strains of mice, C57B1/6 (high affinity aromatic hydrocarbon receptor (AhR) complex) and DBA/J (low affinity AhR complex). All four Aroclors, the selected individual noncoplanar congeners, or two tertiary mixtures containing one congener from each class significantly decreased the in vitro LPS-induced proliferation of murine splenocytes in either strain of mice without inducing a significant decrease in viability. In contrast, selected individual coplanar or mono-ortho-coplanar congeners did not inhibit splenocyte proliferation or viability at any concentration. These results suggest that mixtures of PCBs and/or congener class (specifically, noncoplanar congeners) may be more highly immunotoxic than individual planar and mono-ortho-coplanar congeners alone. Thus, this in vitro assay has revealed a more complex pattern of immunotoxicity of Aroclors versus individual congeners than has previously been reported or anticipated based on both in vivo derived immunotoxic data and standard comparisons to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These results have important practical significance since mixtures of PCB congeners were used industrially and now contaminate the environment.

Prolonged induction of IL-8 gene expression in a human fibroblast cell line infected with reovirus serotype 1 strain Lang.

Viruses which infect mucosal surfaces commonly infect these particular anatomical sites based on both the virion structure and the interaction of the virus with a particular microenvironment. We infected a human lung epithelial cell line, a human gut epithelial cell line, and a human lung fibroblast cell line with reovirus 1/L to explore how this natural isolate of both the lung and the gut may interact with mucosal surfaces. While reovirus infection of the gut and lung epithelial cell lines was lytic, a chronic infection was established in the human lung fibroblast cell line. All three cell lines also produced interleukin-8 (IL-8) after infection with reovirus 1/L, and IL-8 production was not dependent upon viral replication. A prolonged production of IL-8 was observed in the chronically infected lung fibroblast cell line, suggesting that this mucosal population may be involved in the generation of inflammatory responses after the resolution of the initial lytic infection of the epithelium. These studies provide an in vitro model system for analyzing the interaction of reovirus 1/L with resident mucosal cell populations.

Optimal induction of upper respiratory tract immunity to reovirus 1/L by combined upper and lower respiratory tract inoculation.

There has been an increasing interest in developing vaccines which are both easy to administer and which elicit functionally protective immune responses at mucosal and/or systemic sites. Intranasally administered vaccines meet the criteria of ease of administration and are thought to stimulate respiratory-mucosal immunity via interaction with nasal associated lymphoid tissues (NALT). The aim of this study was to gain a better understanding of how best to stimulate respiratory-mucosal immunity using a murine model of respiratory reovirus infection. Either a predominantly upper respiratory tract infection or a combination upper and lower respiratory tract infection was established by administering the same virus dose in either a small or large inoculum volume. These studies demonstrate that stimulation of NALT alone by an upper respiratory tract infection does not induce an optimal primary antibody response even in the nasal cavity. Effective immunity of both the upper and lower respiratory tract was obtained when a combination upper and lower respiratory tract infection was established. These results have important clinical implications since they suggest that effective respiratory mucosal immunity will be best achieved by the combined stimulation of both the upper and lower respiratory tract and will likely require both intranasal as well as inhaled aerosol delivery of antigen to the lower respiratory tract in humans.

Heterogeneous cytokine production by acutely stimulated bronchoalveolar T lymphocytes in reovirus 1/Lang-infected mice.

While the in vitro properties of CD4(+) and CD8(+) cytokine-producing lymphocytes have been well studied, the in vivo cytokine production patterns and relative roles of CD4(+) and CD8(+) T lymphocytes during a primary in vivo immune response remain unclear. In this study, mice were inoculated intranasally with reovirus 1/L, and respiratory T lymphocyte populations were analyzed using multicolor flow cytometric analysis for the production of cytokine within and between classical type 1/type 2 patterns. Cytokine production observed in vivo following infection did not correlate with classical T cell cytokine expression patterns; instead, multiple types of lymphocyte populations that produced one of several possible cytokine combinations were present. Cytokine production by CD4(+) lymphocytes appears in the early and middle stages of the immune response, while CD8(+) lymphocytes produce more cytokine in the later stages. Early cytokine responses occurred predominantly in the whole lung and lung-associated lymph node populations. The complex patterns of cytokine expression seen in this study likely influence local cell-mediated immunity as well as the complex interaction of T cell subsets and the interaction of T cells with B cells which are necessary for the generation of cell-mediated and humoral immune responses required for effective broad-spectrum immunity.

Hyperbaric oxygen for the management of radionecrosis of bone and cartilage.

OBJECTIVES: To review the use of hyperbaric oxygen in the management of radionecrosis of the head and neck. STUDY DESIGN: A retrospective analysis of patients utilizing chart review and telephone interviews. All patients diagnosed with osteoradionecrosis and chondroradionecrosis of the head and neck and treated with hyperbaric oxygen at the University of Virginia are included. METHODS: Demographics, pretreatment data, and precipitating events were recorded. Outcomes were evaluated using a grading scale of symptomatology and physical examination as determined by the patient and physician. RESULTS: Sixteen patients with osteoradionecrosis and five with chondroradionecrosis were reviewed. All patients showed clinical improvement with decreased pain following HBO therapy. None of the patients with chondroradionecrosis required laryngectomies, and two of the four who were tracheotomy dependent were successfully decannulated. The patient and physician grading scores demonstrated moderate to significant improvement in both groups following therapy. CONCLUSION: The successful use of hyperbaric oxygen for the management of radionecrosis of the head and neck is supported. The unusual prevalence of chondroradionecrosis may be an early reflection of changes in treatment protocols for patients with head and neck cancer.

A nasal critical-size defect: an experimental model for the evaluation of facial osseous repair techniques.

OBJECTIVE: To create a standardized nonhealing defect of craniofacial, minimal load-bearing, endochondral type bone with geometric properties that are amenable to quantitative and biomechanical testing that can be used to develop new osteoconductive and osteoinductive engineering repair techniques. DESIGN: Before-and-after randomized trial of an anatomical description. SUBJECTS: Twenty-four retired male breeder Sprague-Dawley rats. METHODS: A standardized osseous defect was created by removing the nasal bones with a cutting burr to the level of the nasal mucosal membranes. The defects were not repaired, and groups of 8 animals were examined using planimetry, computed tomographic scanning, and histological analysis at 1, 3, and 6 months following surgery to quantify defect repair. RESULTS: Mean repair rate by surface area measurements at 1, 3, and 6 months was 5.75%, 4.89%, and 7.09%, respectively. Results from histological analysis revealed that the defects were filled with fibrous tissue. Computed tomographic scans showed the bone defect without repair. CONCLUSION: This nasal osseous defect fulfills criteria to be considered as a critical-size defect that can be used to investigate new techniques for bone reconstruction.

Biomechanical performance of cutting edge surgical needles.

The purpose of this study was to compare the biomechanical performance of cutting edge needles made of S45500 stainless steel alloy to Surgalloy stainless steel. The new high-nickel stainless steel alloy, Surgalloy, has superior performance characteristics over that of the other high-nickel stainless steel alloy, S45500. The Surgalloy needle is produced from a stronger stainless steel alloy than the S45500 needle. The Surgalloy needle has considerably greater resistance to bending than the needle produced from S45500 alloy. In addition, Surgalloy stainless steel has almost a twofold greater resistance to fracture than the S45500 stainless steel alloy.

Respiratory reovirus 1/L induction of intraluminal fibrosis. A model for the study of bronchiolitis obliterans organizing pneumonia.

Bronchiolitis obliterans organizing pneumonia (BOOP) is a term that was first applied in 1985 to describe a long-observed but unclassified pattern of acute lung injury. BOOP lesions are characterized by fibrous extensions into the alveolar spaces in association with a peribronchiolar organizing pneumonia. Since 1985, an increasing number of reports of BOOP have appeared in the clinical literature, and it is now accepted that BOOP is a significant pulmonary syndrome. Although BOOP can be associated with a number of documented pulmonary insults, many cases are not associated with known causes and are thus classified as idiopathic. The lack of an appropriate small animal model that closely mimics the generation of BOOP lesions has been an impediment to basic studies of the pathogenic mechanisms responsible for the generation of BOOP in humans. In this report, we describe an animal model for BOOP in which CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions. These lesions closely resemble those seen in humans and occur in a well defined temporal sequence that proceeds from initial peribronchiolar inflammatory lesions to characteristic, fibrotic cellular BOOP lesions over a 3-week time course.

Respiratory-mucosal lymphocyte populations induced by reovirus serotype 1 infection.

Respiratory virus infections are a serious health challenge. While models exist to study immune mechanisms of the respiratory tract, they have not allowed analysis of the interaction of the lower respiratory tract with other components of the mucosal immune system. This study demonstrates that reovirus 1/Lang, an effective gut mucosal immunogen, also provides a useful model of respiratory mucosal infection. Intra-nasal infection of Balb/c mice resulted in severe viral bronchopneumonia. Major components of the cellular inflammatory response in the lung interstitium and alveolar spaces were CD8 lymphocytes. Lung lymphocyte populations exhibited lysis of reovirus-infected, but not uninfected target cells after in vitro culture. The GCT antigen, a germinal center B-cell and CD8 T-cell marker, was present on 21-60% of the inflammatory lymphocytes. A novel population of GCT-expressing CD4+ lymphocytes unique to reovirus-stimulated lung alveolar and interstitial lymphocyte populations was identified.

Experimental reovirus serotype 1/strain Lang infection of the lung: a model for the study of the lung in the context of mucosal immunity.

A number of studies have examined the nature of the respiratory immune response to particular pathogens. Although many pathogens stimulate specific immunity in the lung, they frequently are not effective immunogens at other mucosal sites. Because the gastrointestinal tract is a major inductive site for mucosal immunity, a pathogen that is an effective respiratory and gut immunogen would allow studies of the interaction of the lung with gut mucosal immune system. Reovirus, a respiratory isolate that previously has been shown to be an effective gut mucosal immunogen, provides a potential model of the relationship of the lung to the gut mucosal immune system. In this report, we demonstrate that intranasal application of reovirus serotype 1/strain Lang (1/L) to CD-1 mice elicits an acute lymphocytic inflammatory infiltration of the lung and hyperplasia of the lung-associated lymph nodes. The initial inflammatory response occurs in the airspaces and interstitium of the lung. As the infection progresses, the initially diffuse cellular infiltrate becomes more focused around small bronchioles. Viral replication occurs predominantly during the first week of the infection, and infectious virions are eliminated during the second week. After the elimination of infectious virions, a secondary response consisting of the appearance of plasma cells adjacent to pulmonary arteries develops as the primary infiltrate organizes into peribronchiolar follicles, resembling the human inflammatory lung condition termed follicular bronchiolitis. These two infiltration patterns were also observed by immunohistochemical analysis of the the infected lung. Whereas CD4+ and CD8+ lymphocytes and Mac-1+ cells were found to be more closely associated with the primary infiltration process, B220+ lymphocytes were observed adjacent to pulmonary arteries. These results establish respiratory reovirus 1/L infection as a viable model for future investigations of the mucosal immune response in the lung and its relationship to the common mucosal immune system.

Studies of determinants of glove hole puncture during electrosurgery.

Holes in surgical gloves are considered to be an important source of transmission of pathogens between patient and surgeon. The purpose of this study was to determine if electrosurgery could alter the integrity of latex surgical gloves. The effects of electrosurgery on 11 brands of commercially available latex surgical gloves were tested through an in vitro study that simulated the conditions in the operating room. Glove hole puncture was encountered only with coagulation current operating at the highest setting. In addition, maximal surface area contact with the hemostat to the glove surface was required to produce glove puncture. The presence of powder and glove hydration were not significant determinants of glove hole puncture. On the basis of our study, we believe that all surgical gloves tested offered the surgeon adequate protection at commonly used levels of cutting and coagulation current, as long as no breach existed prior to the donning of gloves.