Evaluating Modeling and Validation Strategies for Tooth Loss

Prediction models learn patterns from available data (training) and are then validated on new data (testing). Prediction modeling is increasingly common in dental research. We aimed to evaluate how different model development and validation steps affect the predictive performance of tooth loss prediction models of patients with periodontitis. Two independent cohorts (627 patients, 11,651 teeth) were followed over a mean ± SD 18.2 ± 5.6 y (Kiel cohort) and 6.6 ± 2.9 y (Greifswald cohort). Tooth loss and 10 patient- and tooth-level predictors were recorded. The impact of different model development and validation steps was evaluated: 1) model complexity (logistic regression, recursive partitioning, random forest, extreme gradient boosting), 2) sample size (full data set or 10%, 25%, or 75% of cases dropped at random), 3) prediction periods (maximum 10, 15, or 20 y or uncensored), and 4) validation schemes (internal or external by centers/time). Tooth loss was generally a rare event (880 teeth were lost). All models showed limited sensitivity but high specificity. Patients' age and tooth loss at baseline as well as probing pocket depths showed high variable importance. More complex models (random forest, extreme gradient boosting) had no consistent advantages over simpler ones (logistic regression, recursive partitioning). Internal validation (in sample) overestimated the predictive power (area under the curve up to 0.90), while external validation (out of sample) found lower areas under the curve (range 0.62 to 0.82). Reducing the sample size decreased the predictive power, particularly for more complex models. Censoring the prediction period had only limited impact. When the model was trained in one period and tested in another, model outcomes were similar to the base case, indicating temporal validation as a valid option. No model showed higher accuracy than the no-information rate. In conclusion, none of the developed models would be useful in a clinical setting, despite high accuracy. During modeling, rigorous development and external validation should be applied and reported accordingly

Antibody responses in furunculosis patients vaccinated with autologous formalin-killed Staphylococcus aureus

Autologous vaccines (short: autovaccines) have been used since the beginning of the 20th century to treat chronic staphylococcal infections, but their mechanisms of action are still obscure. This prospective pilot study involved four patients with furunculosis who were vaccinated with autologous formalin-killed Staphylococcus aureus cells. Vaccines were individually prepared from the infecting S. aureus strain and repeatedly injected subcutaneously in increasing doses over several months. We characterized the virulence gene repertoire and spa genotype of the infecting and colonising S. aureus strains. Serum antibody responses to secreted and surface-bound bacterial antigens were determined by two-dimensional immunoblotting and flow-cytometry based assays (Luminex®). All patients reported clinical improvement. Molecular characterization showed that all strains isolated from one patient over time belonged to the same S. aureus clone. Already before treatment, there was robust antibody binding to a broad range of staphylococcal antigens. Autovaccination moderately boosted the IgG response to extracellular antigens in two patients, while the antibody response of the other two patients was not affected. Similarly, vaccination moderately enhanced the antibody response against some staphylococcal surface proteins, e.g. ClfA, ClfB, SdrD and SdrE. In summary, autovaccination only slightly boosted the pre-existing serum antibody response, predominantly to bacterial surface antigens

Treatment of Candida albicans biofilms with low-temperature plasma induced by dielectric barrier discharge and atmospheric pressure plasma jet

Because of some disadvantages of chemical disinfection in dental practice (especially denture cleaning), we investigated the effects of physical methods on Candida albicans biofilms. For this purpose, the antifungal efficacy of three different low-temperature plasma devices (an atmospheric pressure plasma jet and two different dielectric barrier discharges (DBDs)) on Candida albicans biofilms grown on titanium discs in vitro was investigated. As positive treatment controls, we used 0.1% Chlorhexidine digluconate (CHX) and 0.6% sodium hypochlorite (NaOCl). The corresponding gas streams without plasma ignition served as negative treatment controls. The efficacy of the plasma treatment was determined evaluating the number of colony-forming units (CFU) recovered from titanium discs. The plasma treatment reduced the CFU significantly compared to chemical disinfectants. While 10 min CHX or NaOCl exposure led to a CFU log 10 reduction factor of 1.5, the log10 reduction factor of DBD plasma was up to 5. In conclusion, the use of low-temperature plasma is a promising physical alternative to chemical antiseptics for dental practice. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft

Effect of Periodontal Treatment on HbA1c among Patients with Prediabetes

Evidence is limited regarding whether periodontal treatment improves hemoglobin A1c (HbA1c) among people with prediabetes and periodontal disease, and it is unknown whether improvement of metabolic status persists >3 mo. In an exploratory post hoc analysis of the multicenter randomized controlled trial “Antibiotika und Parodontitis” (Antibiotics and Periodontitis)—a prospective, stratified, double-blind study—we assessed whether nonsurgical periodontal treatment with or without an adjunctive systemic antibiotic treatment affects HbA1c and high-sensitivity C-reactive protein (hsCRP) levels among periodontitis patients with normal HbA1c (≤5.7%, n = 218), prediabetes (5.7% 1 mm in both groups. In the normal HbA1c group, HbA1c values remained unchanged at 5.0% (95% CI, 4.9% to 6.1%) during the observation period. Among periodontitis patients with prediabetes, HbA1c decreased from 5.9% (95% CI, 5.9% to 6.0%) to 5.4% (95% CI, 5.3% to 5.5%) at 15.5 mo and increased to 5.6% (95% CI, 5.4% to 5.7%) after 27.5 mo. At 27.5 mo, 46% of periodontitis patients with prediabetes had normal HbA1c levels, whereas 47.9% remained unchanged and 6.3% progressed to diabetes. Median hsCRP values were reduced in the normal HbA1c and prediabetes groups from 1.2 and 1.4 mg/L to 0.7 and 0.7 mg/L, respectively. Nonsurgical periodontal treatment may improve blood glucose values among periodontitis patients with prediabetes (ClinicalTrials.gov NCT00707369)

Confocal Laser Scanning Microscopy, a New In Vivo Diagnostic Tool for Schistosomiasis

BACKGROUND: The gold standard for the diagnosis of schistosomiasis is the detection of the parasite's characteristic eggs in urine, stool, or rectal and bladder biopsy specimens. Direct detection of eggs is difficult and not always possible in patients with low egg-shedding rates. Confocal laser scanning microscopy (CLSM) permits non-invasive cell imaging in vivo and is an established way of obtaining high-resolution images and 3-dimensional reconstructions. Recently, CLSM was shown to be a suitable method to visualize Schistosoma mansoni eggs within the mucosa of dissected mouse gut. In this case, we evaluated the suitability of CLSM to detect eggs of Schistosoma haematobium in a patient with urinary schistosomiasis and low egg-shedding rates. METHODOLOGY/PRINCIPAL FINDINGS: The confocal laser scanning microscope used in this study was based on a scanning laser system for imaging the retina of a living eye, the Heidelberg Retina Tomograph II, in combination with a lens system (image modality). Standard light cystoscopy was performed using a rigid cystoscope under general anaesthesia. The CLSM endoscope was then passed through the working channel of the rigid cystoscope. The mucosal tissue of the bladder was scanned using CLSM. Schistoma haematobium eggs appeared as bright structures, with the characteristic egg shape and typical terminal spine. CONCLUSION/SIGNIFICANCE: We were able to detect schistosomal eggs in the urothelium of a patient with urinary schistosomiasis. Thus, CLSM may be a suitable tool for the diagnosis of schistosomiasis in humans, especially in cases where standard diagnostic tools are not suitable

Do Genetic Markers of Inflammation Modify the Relationship between Periodontitis and Nonalcoholic Fatty Liver Disease? Findings from the SHIP Study

An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, 3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels

Confocal Laser Scanning Microscopy for Detection of Schistosoma mansoni Eggs in the Gut of Mice

Background: The gold standard for diagnosing Schistosoma mansoni infections is the detection of eggs from stool or biopsy specimens. The viability of collected eggs can be tested by the miracidium hatching procedure. Direct detection methods are often limited in patients with light or early infections, whereas serological tests and PCR methods fail to differentiate between an inactive and persistent infection and between schistosomal species. Recently, confocal laser scanning microscopy (CLSM) has been introduced as a diagnostic tool in several fields of medicine. In this study we evaluated CLSM for the detection of viable eggs of S. mansoni directly within the gut of infected mice. Methodology/Principal Findings: The confocal laser scanning microscope used in this study is based on the Heidelberg Retina Tomograph II scanning laser system in combination with the Rostock Cornea Module (image modality 1) or a rigid endoscope (image modality 2). Colon sections of five infected mice were examined with image modalities 1 and 2 for schistosomal eggs. Afterwards a biopsy specimen was taken from each colon section and examined by bright-field microscopy. Visualised eggs were counted and classified in terms of viability status. Conclusions/Significance: We were able to show that CLSM visualises eggs directly within the gut and permits discrimination of schistosomal species and determination of egg viability. Thus, CLSM may be a suitable non-invasive too

Access to Interdental Brushing in Periodontal Healthy Young Adults: A Cross-Sectional Study

Purpose: Interdental diameter space is largely undefined in adults, which compromises the decision support for daily interdental cleaning during routine practice in individual oral prophylaxis. This study assesses the distribution of diameter access of interdental spaces in an 18- to 25-year-old adult population free of periodontal disease. Methods: In March-April 2015, a cross-sectional study using random sampling was performed at the University Lyon 1, France. The interproximal dental spaces of 99 individuals were examined using a colorimetric calibrated probe associated with the corresponding calibrated interdental brush (IDB). Results: Of the 2,408 out of 2,608 sites, the overall accessibility prevalence of any interdental brushing was 92.3%. In total, 80.6% of the sites required interdental brushes with smaller diameters (0.6–0.7 mm). In anterior sites, the diameter of the interdental brushes used was smaller (55.8% of IDB with 0.6 mm) than the diameter of the interdental brushes used in posterior sites (26.1% of IDB with 0.6 mm) (p < 0.01). The adjusted ORs indicate a significant association with the location of the sites (approximately doubling the risk of bleeding, i.e., OR = 1.9, in posterior sites). Conclusions: Most interdental sites can be cleaned using interdental brushes. Even in healthy people, interdental hygiene requirements are very high. Strengthening the oral hygiene capacity by specifically using interdental brushes can have an effect on the health of the entire population. Screening of the accessibility of the interdental space should be a component of a routine examination for all patients.The study was financially supported by Curaden International AG, Kriens, Switzerlan