David W. Paquette

The effect of nonsurgical periodontal therapy on hemoglobin a1c levels in persons with type 2 diabetes and chronic periodontitis a randomized clinical trial

IMPORTANCE Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. OBJECTIVE To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. INTERVENTIONS The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. RESULTS Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). CONCLUSIONS AND RELEVANCE Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00997178.

American Academy of Periodontology Task Force report on the update to the 1999 classification of periodontal diseases and conditions

In 2014, the American Academy of Periodontology Board of Trustees charged a Task Force to develop a clinical interpretation of the 1999 Classification of Periodontal Diseases and Conditions to address concerns expressed by the education community, the American Board of Periodontology, and the practicing community that the current Classification presents challenges for the education of dental students and implementation in clinical practice. The Academy announced that an update to the 1999 Classification would commence in 2017. The present focused update addresses three specific areas of concern with the current classification: attachment level, chronic versus aggressive periodontitis, and localized versus generalized periodontitis.

Gingival Transcriptome Patterns During Induction and Resolution of Experimental Gingivitis in Humans

BACKGROUND To our knowledge, changes in the patterns of whole-transcriptome gene expression that occur during the induction and resolution of experimental gingivitis in humans were not previously explored using bioinformatic tools. METHODS Gingival biopsy samples collected from 14 subjects during a 28-day stent-induced experimental gingivitis model, followed by treatment, and resolution at days 28 through 35 were analyzed using gene-expression arrays. Biopsy samples were collected at different sites within each subject at baseline (day 0), at the peak of gingivitis (day 28), and at resolution (day 35) and processed using whole-transcriptome gene-expression arrays. Gene-expression data were analyzed to identify biologic themes and pathways associated with changes in gene-expression profiles that occur during the induction and resolution of experimental gingivitis using bioinformatic tools. RESULTS During disease induction and resolution, the dominant expression pathway was the immune response, with 131 immune response genes significantly up- or downregulated during induction, during resolution, or during both at P <0.05. During induction, there was significant transient increase in the expression of inflammatory and oxidative stress mediators, including interleukin (IL)-1 alpha (IL1A), IL-1 beta (IL1B), IL8, RANTES, colony stimulating factor 3 (CSF3), and superoxide dismutase 2 (SOD2), and a decreased expression of IP10, interferon inducible T-cell alpha chemoattractant (ITAC), matrix metalloproteinase 10 (MMP10), and beta 4 defensin (DEFB4). These genes reversed expression patterns upon resolution in parallel with the reversal of gingival inflammation. CONCLUSIONS A relatively small subset (11.9%) of the immune response genes analyzed by array was transiently activated in response to biofilm overgrowth, suggesting a degree of specificity in the transcriptome-expression response. The fact that this same subset demonstrates a reversal in expression patterns during clinical resolution implicates these genes as being critical for maintaining tissue homeostasis at the biofilm-gingival interface. In addition to the immune response pathway as the dominant response theme, new candidate genes and pathways were identified as being selectively modulated in experimental gingivitis, including neural processes, epithelial defenses, angiogenesis, and wound healing.

Interproximal tissue dimensions in relation to adjacent implants in the anterior maxilla: clinical observations and patient aesthetic evaluation.

OBJECTIVES This clinical study aimed to assess (i) interproximal tissue dimensions between adjacent implants in the anterior maxilla, (ii) factors that may influence interimplant papilla dimensions, and (iii) patient aesthetic satisfaction. MATERIAL AND METHODS Fifteen adults, who had two or more adjacent implants (total of 35) in the anterior maxilla, participated in the study. The study design involved data collection from treatment records, clinical and radiographic assessment, and a questionnaire evaluating aesthetic satisfaction. RESULTS The median vertical dimension of interimplant papillae, i.e., distance from tip of the papilla to the bone crest, was 4.2 mm. Missing papilla height (PH) at interimplant sites was on average 1.8 mm. Median proximal biologic width at interimplant sites was 7 mm. The most coronal bone-to-implant contact at implant-implant sites was located on average 4.6 mm apical to the bone crest at comparable neighbouring implant-tooth sites. The tip of the papilla between adjacent implants was placed on average 2 mm more apically compared with implant-tooth sites. The contact point between adjacent implant restorations extended more apically by 1 mm on average compared with implant-tooth sites. Median missing PH was 1 mm when an immediate provisionalization protocol had been followed, whereas in the case of a removable temporary it was 2 mm. Split group analysis showed that for missing PH<or=1 mm, the median horizontal distance between implants at shoulder level was 3 mm. Patient satisfaction with the appearance of interimplant papillae was on average 87.5%, despite a Papilla Index of 2 in most cases. CONCLUSIONS The apico-coronal proximal biologic width position and dimension appear to determine papilla tip location between adjacent implants. There was a significant association between the provisionalization protocol and missing PH, which was also influenced by the horizontal distance between implants. Patient aesthetic satisfaction was high, despite a less than optimal papilla fill.

Interferon‐gamma promoter hypomethylation and increased expression in chronic periodontitis

AIM The goal of this investigation was to determine whether epigenetic modifications in the IFNG promoter are associated with an increase of IFNG transcription in different stages of periodontal diseases. MATERIALS AND METHODS DNA was extracted from gingival biopsy samples collected from 47 total sites from 47 different subjects: 23 periodontally healthy sites, 12 experimentally induced gingivitis sites and 12 chronic periodontitis sites. Levels of DNA methylation within the IFNG promoter containing six CpG dinucleotides were determined using pyrosequencing technology. Interferon gamma mRNA expression was analysed by quantitative polymerase chain reactions using isolated RNA from part of the biological samples mentioned above. RESULTS The methylation level of all six analysed CpG sites within the IFNG promoter region in the periodontitis biopsies {52% [interquartile range, IQR (43.8%, 63%)]} was significantly lower than periodontally healthy samples {62% [IQR (51.3%, 74%)], p=0.007} and gingivitis biopsies {63% [IQR (55%, 74%)], p=0.02}. The transcriptional level of IFNG in periodontitis biopsies was 1.96-fold and significantly higher than tissues with periodontal health (p=0.04). Although the mRNA level from experimental gingivitis samples exhibited an 8.5-fold increase as compared with periodontally healthy samples, no significant methylation difference was observed in experimental gingivitis sample. CONCLUSIONS A hypomethylation profile within IFNG promoter region is related to an increase of IFNG transcription present in the chronic periodontitis biopsies, while such an increase of IFNG in experimentally induced gingivitis seems independent of promoter methylation alteration.

Factors associated with the clinical response to nonsurgical periodontal therapy in people with type 2 diabetes mellitus

BACKGROUND Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. People with T2DM are at risk of experiencing periodontitis and likely require treatment. Using data from the national multicenter Diabetes and Periodontal Therapy Trial (DPTT), the authors assessed patient-based characteristics associated with the clinical response to nonsurgical therapy. METHODS The DPTT investigators randomly assigned adults with T2DM (hemoglobin A1c [HbA1c] ≥ 7 percent and < 9 percent) and moderate to advanced periodontitis to receive immediate or delayed therapy (scaling and root planing, oral hygiene instruction, chlorhexidine rinse). The investigators assessed probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and medical conditions at baseline, three months and six months. Six-month changes in mean PD, CAL and BOP defined the treatment response. Complete data were available for 473 of 514 DPTT participants. The authors used multiple regression models to evaluate participant-level factors associated with the response. RESULTS More severe baseline PD, CAL and BOP were associated with greater improvements in these same measurements (P < .0001). Hispanic participants experienced greater improvements in PD and CAL than did non-Hispanic participants (P < .0001). Obese participants (those with a body mass index > 30 kilograms per square meter) experienced greater reductions in PD and BOP than did participants who were not obese (P < .001). Age, sex, HbA1c values, diabetes duration, and smoking were not associated with change in any outcome (P > .1). CONCLUSIONS In patients with T2DM, baseline disease severity was associated with the clinical response to nonsurgical periodontal therapy. Body mass index and Hispanic ethnicity-but not glycemic control, diabetes duration or smoking-also may be useful in predicting clinical changes in this population.

In Vivo Assessment of Osseous Wound Healing Using a Novel Bone Putty Containing Lidocaine in the Surgical Management of Tooth Extractions

Objective. This preclinical pilot study evaluated the systemic, radiographic, and histological responses to bone putty containing lidocaine in a canine tooth extraction model. Methods. In five beagle dogs the right mandibular premolars were extracted and sockets grafted with (1) xenograft particulate bone and a collagen sponge plug (control), (2) bone putty alone, (3) bone putty mixed with xenograft (3 : 1), or (4) xenograft sandwiched between bone putty. At 6 weeks post-op, the systemic and local responses were evaluated using a blood chemistry panel, micro-CT, and histological analyses. Results. No significant differences in blood chemistries were noted at 6 weeks postgrafting compared to baseline. Sockets grafted with either bone putty formulation demonstrated comparable radiographic and histologic evidence of bone healing compared to control sockets. Conclusions. Our preclinical results indicate that this bone putty appears to be a safe biocompatible device that may be useful in the postoperative management of tooth extractions.

Comparison of the drug delivery properties of different biocompatible polymer–matrix materials with potential as intra-oral devices

The application of polymers as the drug delivery systems for treating oral infections is a relatively new area of research. The present study was to test and compare the drug release properties of several biocompatible polymeric materials such as EVA copolymer, methacrylate copolymers (poly(EMA-co-HMA)) and polymer blends of poly(ethyl methacrylate) (PEMA) and poly(n-hexyl methacrylate) (PHMA). The effects of polymer composition, drug loading and solubilizing surfactants on the release of the antibacterial drug chlorhexidine diacetate (CHDA), the antifungal drug, nystatin (NYS), and the antiviral drug, acyclovir (ACY), have been studied. Measurements of the in vitro rate of drug release showed a sustained release of drug over extended periods of time. Different polymers showed different drug release rates and EVA copolymer gave the highest rate. Drug release rates increased steadily with increasing drug load and with the addition of surfactants. This study demonstrates that the three therapeutic agents exhibited a sustained rate of drug release from polymers over extended periods of time. By varying polymer compositions as well as the drug concentration (loading), it is possible to control the drug release rates to a desired value. The drug release rate is enhanced by addition of surfactants that solubilize drugs in the polymers. Current treatment of oral infections consists of systemic administration of therapeutic agents at very high concentrations leading to significant toxicity levels and morbidity. In order to avoid serious side effects, an oral drug delivery device based on these polymeric materials has shown significant promise and potential to deliver the drugs directly to the site of infections.