Microbiota signature of oral chronic graft-versus-host disease 6+ years after transplantation.

Not available.

Estimating the Impact of Verification Bias on Celiac Disease Testing.

GOAL: The goal of this study was to estimate the impact of verification bias on the diagnostic accuracy of immunoglobulin A tissue transglutaminase (IgA tTG) in detecting celiac disease as reported by an authoritative meta-analysis, the 2016 Comparative Effectiveness Review (CER). BACKGROUND: Verification bias is introduced to diagnostic accuracy studies when screening test results impact the decision to verify disease status. MATERIALS AND METHODS: We adjusted the sensitivity and specificity of IgA tTG reported by the 2016 CER with the proportion of IgA tTG positive and negative individuals who are referred for confirmatory small bowel biopsy. We performed a systematic review from January 1, 2007, to July 19, 2017, to determine these referral rates. RESULTS: The systematic review identified 793 articles of which 9 met inclusion criteria (n=36,477). Overall, 3.6% [95% confidence interval (CI): 1.1%-10.9%] of IgA tTG negative and 79.2.2% (95% CI: 65.0%-88.7%) of IgA tTG positive individuals were referred for biopsy. Adjusting for these referral rates the 2016 CER reported sensitivity of IgA tTG dropped from 92.6% (95% CI: 90.2%-94.5%) to 57.1% (95% CI: 35.4%-76.4%) and the specificity increased from 97.6% (95% CI: 96.3%-98.5%) to 99.6% (95% CI: 98.4%-99.9%). CONCLUSIONS: The CER may have largely overestimated the sensitivity of IgA tTG due to a failure to account for verification bias. These findings suggest caution in the interpretation of a negative IgA tTG to rule out celiac disease in clinical practice. More broadly, they highlight the impact of verification bias on diagnostic accuracy estimates and suggest that studies at risk for this bias be excluded from systematic reviews.

Effect of birth season on anthropometrics and diseases of bone mineralization in the US population.

OBJECTIVES: Birth season has been inconsistently associated with anthropometrics, bone fractures, and malocclusion. Our aim was to assess the association between birth season and anthropometrics (height, weight, birth weight), bone fractures and dental malocclusion in the United States. METHODS: US surveys conducted between 1963-1973 assessed 16 152 6-to-21-year-old participants. Prevalence ratios and mean differences were estimated using linear models using fall as reference. RESULTS: Participants born in spring, when compared to fall, were of similar height (mean difference (MD) in height-adjusted Z score 0.03, 95% Confidence Interval (CI): -0.01 to 0.08; P-value = .17), weight (MD for weight-adjusted Z-score 0.00, 95% CI: -0.05 to 0.04; P-value =0.83), had similar rates of bone fractures (Prevalence Rate [PR] 1.07; 95% CI: 0.94 to 1.22; P-value = .28) and similar rates of dental malocclusion (MD of malocclusion index HLD -0.16; 95% confidence interval - 0.39 to 0.07; P = .18). CONCLUSION: We did not find an impact of birth season on anthropometrics, bone fractures, and dental malocclusions.

NO EVIDENCE THAT PERIODONTAL DISEASES CAUSE LUNG CANCER.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Relationship between periodontal disease and lung cancer: A systematic review and meta-analysis. Wang J, Yang X, Zou X, Zhang Y, Wang J, Wang Y. J Periodontal Res. 2020 Oct;55(5):581-593. doi:10.1111/jre.12772. Epub 2020 Jun 25. PMID: 32,583,879. SOURCE OF FUNDING: National Natural Science Foundation of China and Scientific Research foundation of the Health Planning Committee of Sichuan. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis of cohort and case-control studies.

Breastfeeding and handedness: a systematic review and meta-analysis of individual participant data.

This study aims to determine whether breastfeeding duration affects the prevalence of nonrighthandedness in later life. A systematic search for studies on this topic was completed in 2018, and risk of bias was assessed by means of the Newcastle-Ottawa scale. Seven national surveys in five countries with Individual Participant Data (IPD) were identified (n = 62,129 mother-child dyads). These surveys had low risk of bias. An IPD meta-analysis showed that breastfeeding for < 1 month, 1 to 6 months, and > 6 months, when compared to bottle feeding, was associated with a 9%, 15% and 22% decreased prevalence of nonrighthandedness, respectively (Prevalence Ratio (PR) = 0.91, 95% confidence interval (ci): 0.83, 1.00; p-value = 0.05, PR = 0.85, 95% CI: 0.79, 0.92; p-value < 0.0001 and PR = 0.78; 95% CI: 0.71, 0.85; p-value < 0.0001). This dose-response relationship was significant (p < 0.001). No significant heterogeneity across surveys was detected (p-value > 0.54). Breastfeeding for longer than 9 months was not associated with further reductions in the prevalence for nonrighthandedness (p > 0.58). It is concluded that the critical age window for establishing hemispheric dominance in handedness includes the first 9 months of infancy and is in part determined by nurture.

Historical perspectives on advertising and the meme that personal oral hygiene prevents dental caries.

The consensus of a leading scientific panel in 1930 was that oral hygiene products could not prevent dental caries. Their view was that dental caries prevention required the proper mineralisation of teeth and that vitamin D could achieve this goal. Over a hundred subsequent controlled trials, conducted over seven decades, largely confirmed that this scientific panel had made the right decisions. They had, in 1930, when it comes to dental caries, correctly endorsed vitamin D products as dental caries prophylactics and oral hygiene products as cosmetics. And yet, despite this consistent scientific evidence for close to a century, an opposing conventional wisdom emerged which thrives to this day: oral hygiene habits (without fluoride) protect the teeth from dental caries, and vitamin D plays no role in dental caries prevention. This historical analysis explores whether persistent advertising can deeply engrain memes on dental caries prevention which conflict with controlled trial results. The question is raised whether professional organisations, with a dependence on advertising revenues, can become complicit in amplifying advertised health claims which are inconsistent with the principles of evidence-based medicine.

Dental enamel defects predict adolescent health indicators: A cohort study among the Tsimane' of Bolivia.

OBJECTIVES: Bioarchaeological findings have linked defective enamel formation in preadulthood with adult mortality. We investigated how defective enamel formation in infancy and childhood is associated with risk factors for adult morbidity and mortality in adolescents. METHODS: This cohort study of 349 Amerindian adolescents (10-17 years of age) related extent of enamel defects on the central maxillary incisors (none, less than 1/3, 1/3 to 2/3, more than 2/3) to adolescent anthropometrics (height, weight) and biomarkers (hemoglobin, glycated hemoglobin, white blood cell count, and blood pressure). Risk differences and 95% confidence intervals were estimated using multiple linear regression. Enamel defects and stunted growth were compared in their ability to predict adolescent health indicators using log-binomial regression and receiver operating characteristics (ROCs). RESULTS: Greater extent of defective enamel formation on the tooth surface was associated with shorter height (-1.35 cm, 95% CI: -2.17, -0.53), lower weight (-0.98 kg, 95% CI: -1.70, -0.26), lower hemoglobin (-0.36 g/dL, 95% CI: -0.59, -0.13), lower glycated hemoglobin (-0.04 %A1c , 95% CI: -0.08, -0.00008), and higher white blood cell count (0.74 109 /L, 95% CI: 0.35, 1.14) in adolescence. Extent of enamel defects and stunted growth independently performed similarly as risk factors for adverse adolescent outcomes, including anemia, prediabetes/type II diabetes, elevated WBC count, prehypertension/hypertension, and metabolic health. CONCLUSIONS: Defective enamel formation in infancy and childhood predicted adolescent health outcomes and may be primarily associated with infection. Extent of enamel defects and stunted growth may be equally predictive of adverse adolescent health outcomes.

Handedness and lower face variability: Findings in three national surveys.

Lower face variability in modern humans has been associated with a series of phenotypic characteristics including body architecture and handedness. The aim of this study was to provide a systematic review of lower face variability and handedness in national health surveys conducted in the United States. Three informative surveys with a total of 13,663 participants were identified. Lower face variability was described as one of six facial phenotypes and related to handedness using logistic regression models while adjusting for sex, ancestry, geography, and income. The results on 13,536 participants with complete information showed that bilateral retrognathism-a marker for a lower face phenotype characterized by a convex facial profile and slender jaws-was associated with a 25% increased odds for non-right-handedness (odds ratio, 1.250; 95% confidence interval: 1.076-1.453, p-value < .004). This association between non-right-handedness and a convex facial profile may unexpectedly find its origin in the genetic polymorphisms which determine tuberculosis susceptibility.

Nutrition, dental caries and periodontal disease: a narrative review.

AIM: To provide a narrative review of the role of macro- and micronutrients in relation to dental caries, gingival bleeding and destructive periodontal disease. MATERIALS & METHODS: This review is based on systematic reviews (when available) and comparative human studies. RESULTS: Dental caries cannot develop without the presence of dietary fermentable carbohydrates, in particular sugar. The susceptibility to develop caries in the presence of carbohydrates may be influenced by genetics and micronutrients such as vitamin D. Gingival bleeding and destructive periodontal disease are sensitive markers to both abnormalities in macronutrient content (excessive carbohydrates or poly-unsaturated fat intake, deficient protein intake) and micronutrient intake (e.g. vitamin C and B12). CONCLUSION: Dental caries and periodontal diseases are a sensitive alarm bell for an unhealthy diet, which predicts the future onset of the diseases of civilizations.

Malnutrition-related early childhood exposures and enamel defects in the permanent dentition: A longitudinal study from the Bolivian Amazon.

OBJECTIVES: We investigated the relationship between early childhood malnutrition-related measures and subsequent enamel defects in the permanent dentition. MATERIALS AND METHODS: This cohort study included 349 Amerindian adolescents (10-17 years, 52% male) from the Bolivian Amazon. Exposures included: stunted growth (height-for-age z-scores), underweight (weight-for-age z-scores), anemia (hemoglobin), acute inflammation (C-reactive protein) and parasitic infection (hookworm). We measured the occurrence (no/yes) and extent (<1/3, 1/3-2/3, >2/3) of enamel defects. We estimated associations between childhood exposures and enamel defect measures using log-binomial and multinomial logistic regression. RESULTS: The prevalence of an enamel defect characterized by an orange peel texture on a large central depression on the labial surface of the central maxillary incisors was 92.3%. During childhood (1-4 years), participants had a high prevalence of stunted growth (75.2%), anemia (56.9%), acute inflammation (39.1%), and hookworm infection (49.6%). We observed associations between childhood height-for-age (OR = 0.65; P = 0.028 for >2/3 extent vs. no EH) and gastrointestinal hookworm infection (OR = 3.43; P = 0.035 for >2/3 extent vs. no defects or <1/3 extent) with enamel defects. DISCUSSION: The study describes a possibly novel form of enamel hypoplasia and provides evidence for associations of malnutrition-related measures in early childhood, including stunted growth and parasitic helminth infection, with the observed enamel defects.

Lower face asymmetry as a marker for developmental instability.

OBJECTIVES: Fluctuating asymmetries in the craniofacial skeleton have been shown to be predictive for mortality from degenerative diseases. We investigate whether lower face asymmetries are a potential marker for the developmental origins of health and disease. METHODS: The lower face of a representative sample of 6654 12- to 17-year old United States (US) adolescents (1966-1970, National Health Examination Survey III) was classified as asymmetric when the mandibular teeth occluded prognathically (forward) or retrognathically (backward) on one side of the face only. It was investigated whether these lower face asymmetries were directional (preferentially to the left or the right) or fluctuating (random left-right distribution) in the US population. RESULTS: Lower face asymmetries affected 1 in 4 of the US adolescents. Unilateral retrognathic dental occlusions were fluctuating asymmetries, had a US prevalence of 17.0% (95% confidence interval: 15.5-18.4) and were associated with race/ethnicity (P < .0001), not with handedness (P < .7607). Unilateral prognathic dental occlusions were directional asymmetries (P < .0001), had a US prevalence of 7.6% (95% confidence interval: 6.4-8.7) and were associated with large household size (P < .001) and handedness (P < .0223). Lower face asymmetries were not associated with distinct heritable traits such as color blindness. CONCLUSIONS: The findings suggest that lower face asymmetries are a marker for environmental stress and cerebral lateralization during early development.

Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas.

BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.

Private Interests and the Start of Fluoride-Supplemented High-Carbohydrate Nutritional Guidelines.

Fluoride has no tangible health benefits other than preventing dental caries and there is a small difference between its minimum effective dose and its minimum toxic dose. Leading global organizations currently recommend fluoride supplementation because they recommend high-carbohydrate diets which can cause dental caries. Low-carbohydrate diets prevent dental caries making such fluoride recommendations largely unnecessary. A dental organization was among the first to initiate the public health recommendations which started fluoride-supplemented high-carbohydrate nutritional guidelines. This start required expert panels at this dental organization to reverse on three key scientific points between 1942 and 1949: (1) that topical fluoride had potential harms, (2) that dental caries was a marker for micronutrient deficiencies, and (3) that low-carbohydrate diets are to be recommended for dental caries prevention. Internal documents show that private interests motivated the events which led these expert panels to engage in pivotal scientific reversals. These private interests biased scientific processes and these reversals occurred largely in an absence of supporting evidence. It is concluded that private interests played a significant role in the start of public health endorsements of fluoride-supplemented high-carbohydrate nutritional guidelines.

Vitamin C and scar strength: analysis of a historical trial and implications for collagen-related pathologies.

A double-blind controlled trial initiated in 1944 has led to the common narrative that a 10-mg daily vitamin C intake is adequate to prevent and treat impaired wound healing, and by inference, other collagen-related diseases such as heart disease or stroke. The WHO relies on this narrative to set the recommended nutrient intake for vitamin C. This narrative, however, is based on what is known as the eyeball method of data assessment. The 1944 trial published individual participant data on scar strength providing an opportunity to statistically probe the validity of the 10-mg narrative, something which has not yet been done. The findings show that a vitamin C intake that averages to 10 mg/d over a mean follow-up of 11.5 mo was associated with a 42% weakened scar strength when compared with 80 mg vitamin C intake/d (P < 0.001). The observed dose-response curve between scar strength and vitamin C intake suggests that the daily vitamin C intake needed to prevent collagen-related pathologies is in the range recommended by the National Academy of Medicine and the European Food Safety Authority (75 to 110 mg/d), not the WHO recommendation (45 mg/d). The findings also show that a vitamin C intake that averages to 65 mg/d over a mean follow-up of 6.5 mo failed to restore the normal wound-healing capacity of vitamin C-depleted tissues; such tissues had a 49% weaker scar strength when compared with nondepleted tissues (P < 0.05). Thus, average daily vitamin C intakes ∼50% higher than the WHO recommends may fail to treat existing collagen-related pathologies. It is concluded that the prior lack of statistical analyses of a landmark trial may have led to a misleading narrative on the vitamin C needs for the prevention and treatment of collagen-related pathologies.

How a Nutritional Deficiency Became Treated with Fluoride.

Ignoring evidence on causes of disease such as smoking can harm public health. This report explores how public health experts started to ignore evidence that pediatric vitamin D deficiencies are associated with dental caries. Historical analyses show that an organization of clinical specialists, the American Dental Association (ADA), initiated this view. The ADA was a world-leading organization and its governing bodies worked through political channels to make fluoride a global standard of care for a disease which at the time was viewed as an indicator of vitamin D deficiencies. The ADA scientific council was enlisted in this endeavor and authorized the statement saying that "claims for vitamin D as a factor in tooth decay are not acceptable". This statement was ghost-written, the opposite of what the ADA scientific council had endorsed for 15 years, and the opposite of what the National Academy of Sciences concluded. Internal ADA documents are informative on the origin of this scientific conundrum; the ADA scientific council had ignored their scientific rules and was assisting ADA governing bodies in conflicts with the medical profession on advertising policies. The evidence presented here suggests that professional organizations of clinical specialists have the power to create standards of care which ignore key evidence and consequently can harm public health.

Bleeding tendency and ascorbic acid requirements: systematic review and meta-analysis of clinical trials.

CONTEXT: The World Health Organization set the recommended daily vitamin C intake, henceforth referred to as ascorbic acid (AA), on the basis of scurvy prevention. Double-blind AA depletion-repletion studies suggest that this recommended AA dose may be too low to prevent microvascular fragility. OBJECTIVES: (1) To conduct a systematic review and meta-analysis of controlled clinical trials on whether AA supplementation leads to a reduced gingival bleeding tendency, a manifestation of microvascular fragility; and (2) to relate AA plasma levels to retinal hemorrhaging, another manifestation of microvascular fragility. DATA SOURCES: Data were reviewed from 15 trials conducted in 6 countries with 1140 predominantly healthy participants with measures of gingival bleeding tendency, and from the National Health and Nutrition Examination Survey (NHANES) III of 8210 US residents with measures of retinal hemorrhaging. RESULTS: In clinical trials, AA supplementation reduced gingival bleeding tendency when estimated baseline AA plasma levels were < 28 µmol/L (standardized mean difference [SMD], -0.83; 95%CI, -1.16 to -0.49; P < 0.002). Supplementation with AA did not unequivocally reduce gingival bleeding tendency when baseline estimated AA plasma levels were >48 µmol/L or unknown (respective standardized mean differences: -0.23, 95%CI, -0.45 to -0.01, P < 0.05; and -0.56; 95%CI: -1.19 to 0.06, P < 0.08). In NHANES III, prevalence of both retinal hemorrhaging and gingival bleeding tendency increased when AA plasma levels were within the range that protects against scurvy (11-28 µmol/L; respective prevalence ratios adjusted for age and sex: 1.47; 95%CI: 1.22-1.77; and 1.64; 95%CI: 1.32-2.03; P < 0.001 for both). CONCLUSION: Consistent evidence from controlled clinical trials indicates that setting human AA requirements based on scurvy prevention leads to AA plasma levels that may be too low to prevent an increased gingival bleeding tendency. Gingival bleeding tendency and retinal hemorrhaging coincide with low AA plasma levels and thus may be reflective of a systemic microvascular pathology that is reversible with an increased daily AA intake.

Long-term use of medications and destructive periodontal disease.

BACKGROUND: Knowledge of typical medication use among patients with chronic periodontitis or destructive periodontal disease is limited. The aim of this study was to associate periodontitis severity with the use of different classes of medications. METHODS: Patients (N=12,631) who had medical, dental, and pharmaceutical coverage with a health maintenance organization and whose severity of destructive periodontal disease was diagnosed by a dentist or specialist were included in the study. The rate of drug use over 7 years was related to the severity of destructive periodontal disease by means of Poisson regression models. RESULTS: Individuals with moderate to advanced periodontitis had significantly lower fill rates for the respiratory agents (antihistamines: -23%, 95% confidence interval [CI]: -10% to -34%; decongestants: -24%, 95% CI: -13% to -34%; and cough/cold medications: -12%, 95% CI: -3% to -21%) and anti-infective agents (antibiotics: -12%, 95% confidence interval: -6% to -18%; urinary anti-infectives: -36%, 95% CI: -6% to -56%; and topical antibiotics: -18%, 95% CI: -5% to -29%). CONCLUSIONS: More severe periodontitis was a marker for reduced medication use for allergies and infections. The associations between destructive periodontal disease, infections, allergies, and the hygiene hypothesis need further exploration.

The effects of orthodontic therapy on periodontal health: a systematic review of controlled evidence.

BACKGROUND: Orthodontic therapy has been suggested to lead to an improved periodontal status through mechanisms such as increased ease of plaque removal and reduced occlusal trauma. The objective of the authors' systematic review was to compare contemporary orthodontic treatment with no intervention, by means of evaluating periodontal outcomes measured after end of treatment. METHODS: The authors completed electronic searches in eight databases (1980-2006) and hand searches in six dental journals (1980-2006). They extracted data using standardized forms and calculated weighted mean differences. RESULTS: Weak evidence from one randomized study and 11 nonrandomized studies suggested that orthodontic therapy was associated with 0.03 millimeters of gingival recession (95 percent confidence interval [CI], 0.01-0.04), 0.13 mm of alveolar bone loss (95 percent CI, 0.07-0.20) and 0.23 mm of increased pocket depth (95 percent CI, 0.15-0.30) when compared with no treatment. The effects of orthodontic therapy on gingivitis and attachment loss were inconsistent across studies. CONCLUSIONS: This systematic review identified an absence of reliable evidence describing positive effects of orthodontic treatment on periodontal health. The existing evidence suggests that orthodontic therapy results in small detrimental effects to the periodontium.