The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Manuscript Checklist.

Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the OHStat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials (CONSORT), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and CONSORT harms guidelines and incorporate the SAMPL guidelines for reporting statistics, the CLIP principles for documenting images, and the GRADE indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on P values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental research into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research.

The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Explanation and Elaboration.

Adequate and transparent reporting is necessary for critically appraising research. Yet, evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-empaneled a group of authors to develop methodological and statistical reporting guidelines identifying the minimum information needed to document and evaluate observational studies and clinical trials in oral health: the OHstat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The final version was subsequently approved by the Task Force in September 2021, submitted for journal review in 2022, and revised in 2023. The checklist consists of 48 guidelines: 5 for introductory information, 17 for methods, 13 for statistical analysis, 6 for results, and 7 for interpretation; 7 are specific to clinical trials. Each of these guidelines identifies relevant information, explains its importance, and often describes best practices. The checklist was published in multiple journals. The article was published simultaneously in JDR Clinical and Translational Research, the Journal of the American Dental Association, and the Journal of Oral and Maxillofacial Surgery. Completed checklists should accompany manuscripts submitted for publication to these and other oral health journals to help authors, journal editors, and reviewers verify that the manuscript provides the information necessary to adequately document and evaluate the research.

The OHStat Guidelines for Reporting Observational Studies and Clinical Trials in Oral Health Research: Manuscript Checklist.

Adequate and transparent reporting is necessary for critically appraising published research. Yet, ample evidence suggests that the design, conduct, analysis, interpretation, and reporting of oral health research could be greatly improved. Accordingly, the Task Force on Design and Analysis in Oral Health Research-statisticians and trialists from academia and industry-identified the minimum information needed to report and evaluate observational studies and clinical trials in oral health: the OHStat Guidelines. Drafts were circulated to the editors of 85 oral health journals and to Task Force members and sponsors and discussed at a December 2020 workshop attended by 49 researchers. The guidelines were subsequently revised by the Task Force's writing group. The guidelines draw heavily from the Consolidated Standards for Reporting Trials (CONSORT), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE), and CONSORT harms guidelines and incorporate the SAMPL guidelines for reporting statistics, the CLIP principles for documenting images, and the GRADE indicating the quality of evidence. The guidelines also recommend reporting estimates in clinically meaningful units using confidence intervals, rather than relying on P values. In addition, OHStat introduces 7 new guidelines that concern the text itself, such as checking the congruence between abstract and text, structuring the discussion, and listing conclusions to make them more specific. OHStat does not replace other reporting guidelines; it incorporates those most relevant to dental research into a single document. Manuscripts using the OHStat guidelines will provide more information specific to oral health research.

Periodontal Effects of the Reversible Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Bronchiectasis.

AIMS: Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1 (cathepsin C), in development to treat chronic non-cystic fibrosis bronchiectasis. The phase 2, randomized, placebo-controlled WILLOW trial (NCT03218917) was conducted to examine whether brensocatib reduced the incidence of pulmonary exacerbations. Brensocatib prolonged the time to the first exacerbation and led to fewer exacerbations than placebo. Because brensocatib potentially affects oral tissues due to its action on neutrophil-mediated inflammation, we analyzed periodontal outcomes in the trial participants. MATERIALS AND METHODS: Patients with bronchiectasis were randomized 1:1:1 to receive once-daily oral brensocatib 10 or 25 mg or placebo. Periodontal status was monitored throughout the 24-week trial in a prespecified safety analysis. Periodontal pocket depth (PPD) at screening, week 8, and week 24 was evaluated. Gingival inflammation was evaluated by a combination of assessing bleeding upon probing and monitoring the Löe-Silness Gingival Index on 3 facial surfaces and the mid-lingual surface. RESULTS: At week 24, mean ± SE PPD reductions were similar across treatment groups: -0.07 ± 0.007, -0.06 ± 0.007, and -0.15 ± 0.007 mm with brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. The distribution of changes in PPD and the number of patients with multiple increased PPD sites were similar across treatment groups at weeks 8 and 24. The frequencies of gingival index values were generally similar across treatment groups at each assessment. An increase in index values 0-1 and a decrease in index values 2-3 over time and at the end of the study were observed in all groups, indicating improved oral health. CONCLUSIONS: In patients with non-cystic fibrosis bronchiectasis, brensocatib 10 or 25 mg had an acceptable safety profile after 6 months' treatment, with no changes in periodontal status noted. Improvement in oral health at end of the study may be due to regular dental care during the trial and independent of brensocatib treatment. KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that 24 weeks of treatment with brensocatib does not affect periodontal disease progression. This information can be used by clinicians when considering treatment approaches for bronchiectasis and suggests that the use of brensocatib will not be limited by periodontal disease risks. Nevertheless, routine dental/periodontal care should be provided to patients irrespective of brensocatib treatment.

Unusual Findings in Trials Evaluating Adjuncts to Scaling and Root Planing: Reporting Quality (Part 2).

INTRODUCTION: On the topic of adjuncts to scaling and root planing (SRP), numerous randomized clinical trials (RCTs) were published by a single group of authors and frequently reported unusually large effect sizes. A meta-analysis in part 1 of this project failed to explain the causes for these unusual findings. We assessed the reporting quality and trial registration discrepancies to examine the possibility of replicating the work of this research group as well as the overall rigor of the research methodology. METHODS: This study was preregistered at the Open Science Framework (https://osf.io/4meyd/). The Scopus platform was utilized for the RCT search on SRP adjuncts in intrabony defects in patients with periodontitis as compared with SRP alone. The search analysis was limited from 2010 to 2017, and RCTs on SRP adjuncts published by a single research group were selected for screening and inclusion. RCT registration records were assessed for consistency. RESULTS: Out of 92 studies that were retrieved from Scopus and PubMed, 32 were included for quality assessment per the CONSORT guidelines (Consolidated Standards of Reporting Trials). Results showed that all RCTs were characterized by a low reporting quality. The majority of CONSORT items scored <50%, including critical items (randomization, registration, and blinding). When registration records were compared with published RCTs, several discrepancies were found. The per-protocol follow-up duration was compared against the study's initiation and termination dates. Only 38% of the RCTs presented a follow-up period within the initiation and termination dates. The remaining RCTs showed inconsistent follow-up in comparison with the initiation and termination dates. CONCLUSION: RCTs by this group were characterized by poor adherence to reporting quality guidelines. Crucial RCT elements, such as randomization, blinding, and primary outcomes, were not reported properly. RCT registration records revealed systematic inconsistencies when compared with RCT publication. Therefore, the unusually large effects reported by this group should be viewed with extreme caution. KNOWLEDGE TRANSFER STATEMENT: The included randomized clinical trials were characterized by poor adherence to reporting quality guidelines, missing information about important trial items, and discrepancies between the reports and trial registrations. This quality assessment should guide clinical research and show clinicians that they should be cautious when applying evidence in their clinical practice.

Unusual Findings in Trials Evaluating Adjuncts to Scaling and Root Planing: Meta-analysis (Part 1).

BACKGROUND: A number of studies in patients with periodontitis have compared scaling and root planning (SRP) combined with an adjunctive treatment to SRP alone. Within that literature, an array of studies with overlapping investigators has consistently yielded substantially greater effects of adjunctive treatments than had been previously noted. This report investigates discrepancies between that cluster of research and the most recent American Dental Association (ADA) systematic review. METHODS: This review was preregistered at https://osf.io/4meyd/. A search using the Scopus platform identified 32 articles published from 2010 to 2017 by investigators affiliated with the Government Dental College and Research Institute (GDCRI) in Bangalore, India. The primary outcome used in this meta-analysis was the change in clinical attachment level (CAL) after 6 mo. Effect sizes were estimated using Comprehensive Meta-Analysis software after categorizing agents into groups based on pharmacologic similarity. RESULTS: The search identified 32 studies encompassing 5 sets of adjunctive agents. Across the GDCRI studies, the CAL averaged 1.67 mm (95% confidence interval [CI]: 1.43-1.91 mm), substantially exceeding values reported in the ADA review (mean: 0.39 mm, 95% CI: 0.27-0.51 mm). For categories of studies in which comparable subgroup estimates were available, the evaluations yielded overlapping estimates of SRP alone, but CAL estimates were discrepant for both locally delivered antimicrobials (GDCRI studies: mean: 1.45 mm, 95% CI: 0.63-2.27 mm; ADA review: mean: 0.38 mm, 95% CI: 0.16 -0.60 mm) and systemic antibiotics (GDCRI studies: mean: 1.35 mm, 95% CI: 0.97-1.73 mm; ADA review: mean: 0.39 mm, 95% CI: 0.21-0.57 mm). CONCLUSION: In the literature on adjunctive agents supplementing SRP, findings from investigators linked to GDCRI stand out as having significantly more favorable estimated effects. Meanwhile, some agents studied by GDCRI-linked investigators have not been investigated by other researchers. In the absence of a clear explanation for discrepant results, it is recommended that unusually favorable reported effects of adjunctive agents be viewed with caution. KNOWLEDGE TRANSFER STATEMENT: The present meta-analysis observed an unusually large effect size of adjunctive agents to scaling and root planning in studies conducted by the same research group. These results were not consistent with trials on adjunctive agents and previous reports. As this research group has exclusively tested most of the agents, their results must be viewed with caution until other independent groups replicate the studies and reproduce the effect size.

Prevalence of white spot lesions during orthodontic treatment with fixed appliances.

OBJECTIVE: To determine the prevalence of white spot lesions (WSLs) in orthodontic patients at 6 and 12 months into treatment using the visual examination method. MATERIALS AND METHODS: Patients 6 and 12 months into treatment were examined for the presence of WSLs. The control group consisted of patients who were examined for WSLs immediately after bonding. Upon clinical evaluation, teeth were given a visual score based on the extent of demineralization. RESULTS: The percentages of individuals having at least one WSL were 38%, 46%, and 11% for the 6-month, 12-month, and control groups, respectively. The 6-month (P  =  .021) and 12-month groups (P  =  .005) were significantly different from the control group but were not significantly different from each other (P  =  .50). Of subjects in the study who had at least one visible WSL, 76% were males and 24% were females (P  =  .009). CONCLUSIONS: This clinical study showed a sharp increase in the number of WSLs during the first 6 months of treatment that continued to rise at a slower rate to 12 months. Clinicians should evaluate the oral hygiene status of patients during the initial months of treatment and, if necessary, should implement extra measures to prevent demineralization.

Single nucleotide polymorphisms of pattern recognition receptors and chronic periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial disease influenced partly by genetics. Activation of pattern recognition receptors (PRRs) can lead to the up-regulation of inflammatory pathways, resulting in periodontal tissue destruction. Hence, functional polymorphisms located in PRRs can explain differences in host susceptibility to periodontitis. This study investigated single nucleotide polymorphisms of PRRs including toll-like receptor (TLR)2 (G2408A), TLR4 (A896G), TLR9 (T1486C), TLR9 (T1237C) and CD14 (C260T) in patients with chronic periodontitis and in periodontally healthy subjects. METHODS: One-hundred and fourteen patients with chronic periodontitis and 77 periodontally healthy subjects were genotyped using TaqMan® allelic discrimination assays. Fisher's exact test and chi-square analyses were performed to compare genotype and allele frequencies. RESULTS: The frequency of subjects with the CC genotype of CD14 (C260T) (24.6% in the chronic periodontitis group vs. 13% in the periodontally healthy group) and those expressing the T allele of CD14 (C260T) (CT and TT) (75.4% in the chronic periodontitis group vs. 87% in the periodontally healthy group) was statistically different among groups (p = 0.04). Homozygocity for the C allele of the CD14 (C260T) polymorphism (CC) was associated with a two--fold increased susceptibility to periodontitis (p = 0.04; odds ratio, 2.49; 95% confidence interval, 1.06-6.26). Individuals with the CC genotype of TLR9 (T1486C) (14.9% in the chronic periodontitis group vs. 28.6% in the periodontally healthy group) and those expressing the T allele of TLR9 (T1486C) (CT and TT) (85.1% in the chronic periodontitis group vs. 71.4% in the periodontally healthy group) were also significantly differently distributed between groups without adjustment (p = 0.03). Further analysis of nonsmokers revealed a significant difference in the distribution of genotypes between groups for TLR9 (T1486C; p = 0.017) and CD14 (C260T; p = 0.03), polymorphisms again without adjustment. CONCLUSION: The CC genotype of CD14 (C260T) is related to susceptibility to chronic periodontitis in Caucasians. In addition, differences observed in the distribution of TLR9 (T1486C) genotypes between groups warrant further investigation.

Differential gender effects of a reduced-calorie diet on systemic inflammatory and immune parameters in nonhuman primates.

BACKGROUND AND OBJECTIVE: Dietary manipulation, including caloric restriction, has been shown to impact host response capabilities significantly, particularly in association with aging. This investigation compared systemic inflammatory and immune-response molecules in rhesus monkeys (Macaca mulatta). MATERIAL AND METHODS: Monkeys on continuous long-term calorie-restricted diets and a matched group of animals on a control ad libitum diet, were examined for systemic response profiles including the effects of both gender and aging. RESULTS: The results demonstrated that haptoglobin and alpha1-antiglycoprotein levels were elevated in the serum of male monkeys. Serum IgG responses to Campylobacter rectus, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis were significantly elevated in female monkeys. While only the antibody to Fusobacterium nucleatum was significantly affected by the calorie-restricted diet in female monkeys, antibody levels to Prevotella intermedia, C. rectus and Treponema denticola demonstrated a similar trend. CONCLUSION: In this investigation, only certain serum antibody levels were influenced by the age of male animals, which was seemingly related to increasing clinical disease in this gender. More generally, analytes were modulated by gender and/or diet in this oral model system of mucosal microbial challenge.

A multi-center study comparing dual acid-etched and machined-surfaced implants in various bone qualities.

BACKGROUND: A major reason for the success of modern dental implant systems has been the development of implant designs that enhance direct bone-implant interface. Surface roughness has been a factor in this success and different systems have utilized very different implant surface roughness. The major purpose of this study was to evaluate 2 similar implants with different surface roughness characteristics. METHODS: Two similarly designed, screw-type, commercially pure titanium implants, one dual acid-etched (DAE) and the other machined-surfaced (MS), were compared in this prospective, randomized-controlled, multi-center study, in which a total of 97 patients were enrolled at a private dental practice or a university dental clinic. Both implant types were placed in each patient using a 2-stage approach with a conventional 4- to 6-month healing period. Implants supported fixed prostheses, hybrid prostheses, and overdentures as dictated by the individual patient's need. All of the cases were followed using clinical and radiographic examinations. Criteria of success were the absence of peri-implant radiolucency, mobility, and persistent signs or symptoms of pain or infection. RESULTS: Of the 432 implants (247 dual acid-etched, 185 machined-surfaced), 36 implants (12 dual acid-etched and 24 machined-surfaced) have failed. The pre-loading integration success rate of the dual acid-etched implants (95.0%) was statistically higher (P < 0.01) than the success rate of the machined-surfaced implants (86.7%). At 36 months, the cumulative success rates (CSR) are 95.0% for the dual acid-etched implants and 86.7% for the machined-surfaced implants. CONCLUSIONS: The difference in success rates is most likely attributed to the acid-etched surface characteristics. The greatest performance difference is observed in the conditions of poor quality or soft bone where the 3-year post-loading CSR are 96.8% (dual acid-etched) and 84.8% (machined-surfaced).

Is loss of attachment due to root planning and scaling in sites with minimal probing depths a statistical or real occurrence?

BACKGROUND: Following root planing and scaling many studies have implied an association between a loss of clinical attachment at sites with initially shallow pockets (1 to 3 mm) and gains in attachment level for deeper probing depths. However, these effects are also consistent with a statistical phenomenon referred to as regression towards the mean. This principle suggests that extreme values will moderate the next time they are recorded. The purpose of this report was to estimate the effect that regression towards the mean has on perceived changes in attachment level after root planing and scaling. METHODS: During the initial examination, 2 different investigators conducted 2 full-mouth probings. Two quadrants were randomly selected to be root planed and scaled until the root surfaces were smooth by tactile touch of an explorer. The 2 remaining quadrants were not treated. At 4 to 6 weeks after treatment, another full mouth probing was done. An examiner who was blind to the quadrants that had been scaled measured attachment level and probing depth after therapy. This study design provided periodontal measurements before and after root planing and scaling, measurements before and after a period of 4 to 6 weeks of no therapy, and duplicate measurements at the beginning of the study. RESULTS: Using the repeat examination when no true change could occur, shallow sites (< or =3 mm of probing depth) showed average negative differences between repeat attachment level measurements (-0.23 mm), which mimicked loss of periodontal attachment. Deep sites, (>6 mm) showed average positive values (0.40) mimicking gain in attachment level. These results suggest that regression towards the mean is a significant effect in this data set. Both shallow non-scaled and scaled sites had similar differences in repeat measures (-0.28 mm, -0.25 mm) which were also similar to and not statistically different from changes after therapy for both non-scaled (-0.21 mm) and scaled sites (-0.08 mm). Thus not only does this data set exhibit regression towards the mean, but it explains the majority of perceived loss of periodontal attachment after scaling at sites that have minimal probing depth. CONCLUSIONS: These results suggest that the majority of perceived loss of attachment due to scaling at sites of minimal probing depth that have been reported in many studies may be due a statistical phenomenon called regression towards the mean.

Treatment of human mucogingival defects utilizing a bioabsorbable membrane with and without a demineralized freeze-dried bone allograft.

BACKGROUND: The use of guided tissue regeneration (GTR) has become an effective procedure for the treatment of gingival recession. No reports exist on the use of a bioabsorbable membrane in combination with a demineralized freeze-dried bone allograft (DFDBA) for the treatment of these defects. METHODS: Fourteen (14) patients with 17 recession defects were included in this clinical study. Each patient had at least 1 tooth with 3 mm or greater marginal tissue recession on the facial surface as measured from the cemento-enamel junction (CEJ). Each patient was treated by GTR using a bioabsorbable membrane. When the first patient presented for inclusion in the study, a coin was flipped to determine if the tooth being treated would be a test tooth (DFDBA) or a control tooth (no DFDBA). Each subsequent patient was alternated between test and control. Immediately prior to the surgical procedure, measurements were made which included recession depth, recession width at the widest point, probing depth, amount of keratinized tissue, and marginal tissue thickness. Local anesthesia was administered, and a measurement from the CEJ to the bone crest was made by sounding through the attachment. RESULTS: The mean initial recession for all defects was 3.35 mm (SD +/- 0.49) and at 6 months postsurgery, mean recession was 0.47 mm (SD +/0.62). This correlated to 86% root coverage for both treatments. For all defects treated, there was a statistically significant increase in keratinized tissue (mean 0.88 mm) and tissue thickness (mean 0.47 mm) and a significant decrease in probing bone level (mean 0.76 mm). No statistically significant differences were observed between groups for any parameter. CONCLUSIONS: Although only 14 subjects with 17 defects were included in this study, the results suggest that the treatment of human gingival recession with a bioabsorbable membrane with or without the use of DFDBA results in significant root coverage, and slight, but significant improvements in keratinized tissue, tissue thickness, and bone level. The greatest limitation of the study was its lack of statistical power. Twenty-two (22) subjects would have been required for the results of the study to show equivalence between groups.

Evidence of a substantial genetic basis for risk of adult periodontitis.

BACKGROUND: A few previous studies have suggested that risk for adult periodontitis (AP) has a genetic (heritable) component. We estimated genetic and environmental variances and heritability for gingivitis and adult periodontitis using data from twins reared together. METHODS: One hundred seventeen (117) pairs of adult twins (64 monozygotic [MZ] and 53 dizygotic [DZ] pairs) were recruited. Probing depth (PD), attachment loss (AL), plaque, and gingivitis (GI) were assessed on all teeth by two examiners. Measurements were averaged over all sites, teeth, and examiners. Extent of disease in subjects was defined at four thresholds: the percentage of teeth with AL > or = 2, AL > or = 3, PD > or = 4, or PD > or = 5 mm. Genetic and environmental variances and heritability were estimated using path models with maximum likelihood estimation techniques. RESULTS: MZ twins were more similar than DZ twins for all clinical measures. Statistically significant genetic variance was found for both the severity and extent of disease. AP was estimated to have approximately 50% heritability, which was unaltered following adjustments for behavioral variables including smoking. In contrast, while MZ twins were also more similar than DZ twins for gingivitis scores, there was no evidence of heritability for gingivitis after behavioral covariates such as utilization of dental care and smoking were incorporated into the analyses. CONCLUSIONS: These results confirm previous studies and indicate that approximately half of the variance in disease in the population is attributed to genetic variance. The basis for the heritability of periodontitis appears to be biological and not behavioral in nature.

Comparison of angled and standard abutments and their effect on clinical outcomes: a preliminary report.

This study was conducted to compare the success of implants restored with angled abutments to implants restored with standard abutments. Eighty-one implants in 24 patients were evaluated for up to 36 months. Measurements included probing depths, gingival level, gingival index, and mobility. No significant difference could be found for any of the parameters examined between implants restored with angled and standard abutments. This suggests that the angled abutment may be considered a suitable restorative option when implants are not placed in ideal axial positions.

Antiphosphorylcholine antibody levels are elevated in humans with periodontal diseases.

Human immunoglobulin G2 (IgG2) serum concentrations and the IgG2 antibody response to Actinobacillus actinomycetemcomitans can be influenced by genes, by environmental factors such as smoking, and by periodontal disease status. Examination of the IgG2 response to phosphorylcholine (PC), a response thought to be mainly induced by the C polysaccharide of Streptococcus pneumoniae, suggested that periodontal disease status was also associated with this response. This prompted the hypothesis that PC is an important oral antigen associated with organisms in the periodontal flora and that anti-PC antibody is elevated as a consequence of periodontal disease. Subjects in various periodontal disease diagnostic categories in which attachment loss is exhibited were tested for anti-PC in serum. Those with adult periodontitis, localized juvenile periodontitis, generalized early-onset periodontitis, and gingival recession all had similar levels of anti-PC IgG2 serum antibody which were significantly greater than in the group of subjects with no attachment loss. Analysis of plaque samples from subgingival and supragingival sites in all diseases categories for reactivity with the anti-PC specific monoclonal antibody TEPC-15 revealed that a substantial proportion of the bacteria in dental plaque (30 to 40%) bear PC antigen; this antigen was not restricted to morphotypes resembling only cocci but was also present on rods and branched filamentous organisms. We found that S. mitis, S. oralis, and S. sanguis, as well as oral actinomycetes, including A. viscosus, A. odontolyticus, and A. israelii, incorporated substantial amounts of [(3)H]choline from culture media. Further analysis of antigens derived from these organisms by Western blot indicated that S. oralis, S. sanguis, A. viscosus, A. odontolyticus, and A. israelii contained TEPC-15-reactive antigens. The data show that many commonly occurring bacterial species found in dental plaque contain PC antigen and that immunization with plaque-derived PC antigens as a consequence of inflammation and periodontal attachment loss may influence systemic anti-PC antibody concentrations.

Antibody reactive with Porphyromonas gingivalis serotypes K1-6 in adult and generalized early-onset periodontitis.

BACKGROUND: Six serotypes of Porphyromonas gingivalis have recently been described. We sought to test the hypothesis that serotype specific carbohydrates from these strains are important antigens that elicit potent immune responses. METHODS: Serum concentrations of IgG reactive with P. gingivalis serotypes K1-K6 were determined for 28 adult (AP) and 28 generalized early-onset (G-EOP) periodontitis patients previously determined to be seropositive for a broken cell preparation of P. gingivalis. To confirm relationships suggested for K1, K2, and K6 in the analysis of initial data, the study population was increased to 133. RESULTS: Frequency of seropositivity for the 6 serotypes ranged from 26 to 54% of subjects. IgG concentrations ranged from 0 to 453 microg/ml with many subjects seropositive to more than one serotype. Concentrations for the subset of patients who was seropositive were high (mean responses ranged from 20 to 105 microg/ml for the 6 serotypes). Significant correlations between seropositivity to serotypes K1 and K5 as well as between K5 and K6 were found. CONCLUSIONS: We examined the relationship of diagnosis, race, gender, smoking, probing depth, attachment loss, and antibody reaction with the P. gingivalis serotypes by analysis of variance. Initial findings suggested potential relationships between diagnosis, smoking, race, gender, and antibody reactive with serotypes K1, K2, and K6. A significant relationship did exist between smoking and decreased antibody reactive with P. gingivalis serotype K2. No other relationships were substantiated. We also examined the IgG subclass distribution and found that responses were almost exclusively IgG2. These data support the concept that antibody responses to all 6 serotypes are common in both AP and G-EOP and that these K serotype carbohydrates elicit potent IgG2 responses.

Adjunctive use of a subgingival controlled-release chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone.

The present studies evaluated the efficacy of a controlled-release biodegradable chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root planing on reducing probing depth (PD) and improving clinical attachment level (CAL) in adult periodontitis. Two double-blind, randomized, placebo-controlled multi-center clinical trials (5 centers each) were conducted; pooled data are reported from all 10 centers (447 patients). At baseline, following 1 hour of scaling and root planing (SRP) in patients free of supragingival calculus, the chip was placed in target sites with PD 5 to 8 mm which bled on probing. Chip placement was repeated at 3 and/or 6 months if PD remained > or = 5 mm. Study sites in active chip subjects received either CHX chip plus SRP or SRP alone (to maintain study blind). Sites in placebo chip subjects received either placebo chip plus SRP or SRP alone. Examinations were performed at baseline; 7 days; 6 weeks; and 3, 6, and 9 months. At 9 months significant reductions from baseline favoring the chlorhexidine chip compared with both control treatments were observed with respect to PD (chlorhexidine chip plus SRP, 0.95 +/- 0.05 mm; SRP alone, 0.65 +/- 0.05 mm, P < 0.001; placebo chip plus SRP, 0.69 +/- 0.05 mm, P < 0.001) and CAL (chlorhexidine chip plus SRP, 0.75 +/- 0.06 mm; SRP alone, 0.58 +/- 0.06 mm, P < 0.05; placebo chip plus SRP, 0.55 +/- 0.06 mm, P < 0.05). The proportion of patients who evidenced a PD reduction from baseline of 2 mm or more at 9 months was significantly greater in the chlorhexidine chip group (19%) compared with SRP controls (8%) (P < 0.05). Adverse effects were minor and transient toothache, including pain, tenderness, aching, throbbing, soreness, discomfort, or sensitivity was the only adverse effect that was higher in the chlorhexidine group as compared to placebo (P = 0.042). These data demonstrate that the adjunctive use of the chlorhexidine chip results in a significant reduction of PD when compared with both SRP alone or the adjunctive use of a placebo chip. These multi-center randomized control trials suggest that the chlorhexidine chip is a safe and effective adjunctive chemotherapy for the treatment of adult periodontitis.

Equivalence and superiority testing in regeneration clinical trials.

The purpose of this report is to investigate sample size requirements for both equivalence and superiority studies investigating products used in regeneration. The goal of a superiority clinical trial is to determine if a new therapy is superior to an established therapy or placebo. In contrast to superiority trials, equivalence trials are used to determine if a new product has similar therapeutic properties to an established product. The sample sizes for the two different types of clinical trials were based on the following assumptions: an alpha of 0.05, a power of 0.80, a 2 group parallel arm study, and equal variances and sample sizes for both groups. Separate sample size calculations were done for both intrabony defects and Class II furcation defects. Sample sizes for the equivalence and superiority trials using the same criteria were the same. However, criteria for estimating sample sizes for equivalence clinical trials require much smaller differences between groups, resulting in much larger sample sizes. A criterion of a 20% difference between groups of the total therapeutic effect resulted in sample sizes which ranged from 64 to 127 in equivalence clinical trials. These samples sizes are much larger than have been generally used in clinical trials investigating periodontal regeneration.

The influence of smoking and race on adult periodontitis and serum IgG2 levels.

Smoking is a known risk factor for developing periodontal diseases, but the risk appears to be greater for white smokers than black smokers. Furthermore, it has been reported that young white subjects have significantly lower levels of serum IgG2 than their non-smoking counterparts while young black adult subjects are generally not affected by smoking. These relationships prompted the hypothesis that adult white subjects, including periodontitis subjects, who smoked would have more attachment loss than adult black subjects and that smoking would be associated with lower serum IgG2 levels in adult white subjects but not in adult black subjects. Smoking status was established from serum cotinine levels determined by radioimmunoassay. Serum IgG subclass levels were determined using radial immunodiffusion. White adult periodontitis (AP) and non-periodontitis (NP) subjects who smoked had greater mean attachment loss per site than their non-smoking counterparts. Furthermore, smoking white AP subjects and their age-matched NP controls had substantially less IgG2 in their serum. In marked contrast, we were unable to detect any increase in periodontal destruction or a significant decrease in serum IgG2 levels in smoking black AP subjects or their age-matched controls. However, IgG1 and IgG4 levels were reduced in smoking black AP subjects. IgG3 was the only subclass in adults that was unaffected by smoking. IgG2 can be a good opsonin and may help control periodontitis-associated bacteria in adults. Even though a cause-and-effect relationship has not been established, the association between a smoking-related decrease in serum IgG2 and an increase in periodontal destruction in white subjects is striking.