Considerations in establishing an oral disease clinical research center.

Oral Diseases (2010) 16, 586-591 High quality clinical research is necessary to improve oral health and translate research findings to the practice of dentistry. This has led many academic institutions to consider establishing a formal clinical research center. This is not a trivial undertaking and requires that the center have an appropriate physical infrastructure, trained investigators with recognized expertise in the planning and conduct of high quality clinical research, and very importantly, a financial plan to assure its long-term sustainability. The purpose of this paper is to provide some guidance and practical advice with respect to factors that should be considered in developing and maintaining a successful oral disease clinical research center.

Methods for enhancing the efficiency of dental/oral health clinical trials: current status, future possibilities.

In recent years, there has been an increasing demand for clinical trials to study oral, dental, and craniofacial diseases and conditions. This has resulted from such factors as the increasing pace of discoveries requiring translational research to develop them for clinical use, FDA requirements for product approval, a need for additional data to support evidence-based dental practice, and the expansion of the NIDCR's clinical research programs. The complexity, size, and duration of clinical trials often make them quite costly to conduct, and may impede the development of novel diagnostic, preventive, and therapeutic methods that could have a significant impact on clinical practice and inform public health policy. Recent advances in such areas as genomics and proteomics, coupled with the development of new technologies, have expanded our knowledge of the etiology and pathogenesis of disease and, from this, have provided new insights into the design and conduct of clinical trials. The workshop, "Methods for Enhancing the Efficiency of Dental/Oral Health Clinical Trials: Current Status, Future Possibilities", held on May 6-7, 2004, considered a variety of ways in which these insights are being, or have the potential to be, applied to clinical trials so as to enhance their efficiency and, hence, their cost-effectiveness, without diminishing the quality of information produced. The focus of this workshop was to assess the state of the science and identify research needs for the use of biomarkers, surrogate endpoints, and new technologies in oral disease clinical trials. Examples of ways in which clinical trials of other diseases have benefited from the use of new methods and technologies and FDA considerations were also discussed.

No heritability of temporomandibular joint signs and symptoms.

The causes of temporomandibular joint (TMJ)-related signs and symptoms are largely unknown. We tested the hypotheses that these signs and symptoms, as well as oral parafunctional habits, are substantially heritable. Questionnaire and clinical data were collected from 494 twins, including pairs of reared-apart and reared-together monozygotic (MZ) and dizygotic (DZ) twins. A history of joint-area pain, joint noises, and clenching and grinding habits was scored as present or absent. Twenty-nine percent of the population experienced at least one sign or symptom. Nearly one-quarter of subjects clenched or ground their teeth, and 8.7% reported a history of joint-area pain. Pain was associated with clenching, grinding, and joint noises. MZ twins were no more similar than DZ twins for any outcome, suggesting that genetic factors do not influence these traits in the population. Reared-together MZ twins were no more similar than reared-apart MZ twins, suggesting a negligible effect of the family environment on these outcomes. Environmental factors unique to each twin appeared to be the major determinants of variation in this population.

Multiple-outcomes meta-analysis of treatments for periodontal disease.

The results of periodontal therapy vary by disease severity, outcome measure, and method of data analysis. Several clinical trials and a subsequent meta-analysis have demonstrated that, for teeth with severe disease, surgery decreases probing depth (PD) and increases attachment level (AL) more than non-surgical treatment. For other disease levels, the choice of therapy depends on the outcome measure. When clinical trials use two or more outcome measures (such as PD and AL), investigators ordinarily analyze each outcome separately. When the correlations are incorporated among the outcomes, a meta-analysis can use generalized-least-squares (GLS) regression to analyze multiple outcomes jointly. We applied the GLS multiple-outcomes model in a meta-analysis of 5 trials comparing surgical and non-surgical periodontal treatments, each assessing the outcomes PD and AL one year after treatment. The clinical conclusions are similar to those reported earlier, but our estimates of the relative benefits of surgical and non-surgical treatment should be more accurate, because the GLS method takes into account correlation between AL and PD. When correlations between the two outcomes rise, as they do with increasing severity of disease, the GLS estimates depart from those derived from separate analyses of PD and AL.

A twin study of genetic variation in proportional radiographic alveolar bone height.

The purpose of this study was to estimate the genetic variance for alveolar bone height by means of the classic twin method and the study of monozygous twins reared apart. Panoramic radiographs were obtained from 120 pairs of adult twins (mean age = 40.4 years, S.D. = 10.4 years), for comparison of 62 pairs of monozygous twins reared together (MZT), 25 pairs of like-sexed dizygous twins reared together (DZT), and 33 pairs of monozygous twins reared apart (MZA). Mesial and distal bone heights were determined as a proportion of tooth length. A full-mouth bone score was computed for each twin by averaging these proportions from all measurable teeth. Between-pair (B) and within-pair (W) variances were computed for each twin group. The population variances (B + W) of the MZT and DZT twin groups were similar, which validated a basic assumption of the twin model. Intraclass correlations and heritability estimates were also computed for the reared-together and reared-apart twin groups. Boot-strap sampling was used to provide estimates and confidence limits for these values. The intraclass correlations for the twin groups were: MZT = 0.70, DZT = 0.52, and MZA = 0.55. The results of this study suggest that there is significant genetic variance in the population for proportional alveolar bone height.

Measurement of attachment level in clinical trials: probing methods.

Measurement of clinical attachment level has become a standard for judging clinical response in periodontal therapy. A number of probing methods and instruments have been developed in an attempt to address limitations in obtaining this measurement. First generation instruments include conventional periodontal probes; second generation probes utilize controlled forces; and third generation probes incorporate automated measurement, controlled forces, and computerized data capture. Various types of stents have been used and repeated measurement techniques have been proposed to reduce examiner error. Controlled force probes appear to have their greatest advantage in increasing inter-examiner repeatability. The use of measurement stents increases inter- and intra-examiner reliability. However, use of such stents may be limited to small sample studies of limited duration. Third generation instruments offer advantages in terms of automated measurement and data capture, increased resolution, and a more continuous measurement scale, but do not necessarily result in increased intra- or inter-examiner reliability. Examiner training and calibration are essential for any measurement instrument. Decisions for or against use of a particular instrument must be made on the basis of the needs of each clinical trial. At the present time, no commercially available instrument resolves all of the inherent limitations of clinical measurement of attachment.

Treatment of gingivitis and periodontitis. Research, Science and Therapy Committee of the American Academy of Periodontology.

This paper is one of three in a series prepared by the Research, Science and Therapy Committee of The American Academy of Periodontology and is intended for the information of the dental profession. It represents the position of the Academy regarding the current state of knowledge about treatment of gingivitis and periodontitis. The other papers are entitled The Etiology and Pathogenesis of Periodontal Diseases and Diagnosis of Periodontal Diseases.

Granulomatous gingivitis in Anderson-Fabry disease.

The patient is suffering from Anderson-Fabry disease. This was documented by family history, clinical findings, histochemical and electronmicroscopic demonstration of ceramide in the blood vessels, and enzyme studies. The patient, at age 17, developed a unique gingival enlargement, gingivitis granulomatosa, a cobbled tongue, glossitis granulomatosa, and a lip enlargement, cheilitis granulomatosa. This was not found in other members of the family. The clinical, histological, and electronmicroscopic findings were analogous to Melkersson-Rosenthal syndrome. The patient did not have sarcoidosis or other specific granulomatous diseases. These were ruled out by skin examination, chest films, histology, and skin sensitivity testing, nor did he have Dilantin associated gingival enlargement. The patient had only taken the drug for a brief period at age 11 when he had a generalized granulomatous lymphadenopathy which was not categorized with certainty. This could have been secondary to Anderson-Fabry disease aggravated by a minor infection, an idiosyncratic reaction to Dilantin, or the lymph node equivalent of the granulomatous response that later affected the gingiva. Although the gingival enlargement appeared to be a manifestation of an unusual syndrome, local therapy in the form of oral hygiene instruction, dental prophylaxis, gingivectomy, and regular maintenance therapy was successful in treatment and prevention of recurrence.

Association between signs of trauma from occlusion and periodontitis.

The purpose of this study was to evaluate the association between signs of trauma from occlusion, severity of periodontitis and radiographic record of bone support. The maxillary first molars of 300 individuals were independently evaluated by two examiners for signs of trauma from occlusion, pattern or occlusal contacts and severity of periodontitis. Each site was also evaluated radiographically by an independent third examiner. The results indicated that: teeth with either bidigital mobility, functional mobility, a widened periodontal ligament space or the presence of radiographically visible calculus had a deeper probing depth, more loss of clinical attachment and less radiographic osseous support than teeth without these findings, teeth with occlusal contacts in centric relation, working, nonworking or protrusive positions did not exhibit any greater severity of periodontitis than teeth without these contacts, teeth with both functional mobility and radiographically widened periodontal ligament space had deeper probing depth, more clinical attachment loss and less radiographic osseous support than teeth without these findings and given equal clinical attachment levels, teeth with evidence of functional mobility and a widened periodontal ligament space had less radiographic osseous support than teeth without these findings.

Molar and nonmolar teeth compared over 6 1/2 years following two methods of periodontal therapy.

Limited information is available comparing the relative longitudinal effectiveness with respect to tooth type of scaling and root planing alone and scaling and root planing followed by flap procedures. The purpose of this study was to investigate these treatment methods as applied to molar and nonmolar teeth on a longitudinal basis in humans. Seventeen subjects with chronic periodontitis received thorough scaling and root planning as well as oral hygiene instruction. A modified Widman flap was then randomly performed for one-half of each subject's dentition. Routine recall prophylaxis and oral hygiene reinforcement were administered postsurgically every 3 to 4 months. Pocket depth and clinical attachment levels were recorded by a single calibrated examiner before therapy and at intervals up to 61/2 years following active treatment. Ten subjects remained as participants after 61/2 years. A paired t test was used to test for the mean difference in pocket depth and clinical attachment level between molar and nonmolar teeth for each treatment method. For pockets initially 4 to 6 mm, the results indicated greater pocket depth and more apical clinical attachment level on molars than nonmolars treated by either method of therapy. For pockets initially greater than or equal to 7 mm there was no difference between pocket depth on molar and nonmolar teeth following scaling and root planing alone. However, there was less overall pocket depth on nonmolars than molars following the flap procedure, indicating a greater effect of pocket reduction on nonmolar than molar teeth with the flap procedure. No difference between tooth types was found for clinical attachment level in pockets initially greater than or equal to 7 mm with either treatment method. Both treatment methods resulted in at least maintenance of pretreatment attachment levels adjacent to molar and nonmolar teeth.

A randomized four-years study of periodontal therapy.

The purpose of this study was to compare the long term effectiveness of scaling and root planing alone to scaling and root planing followed by periodontal surgery. Seventeen subjects with moderate to advanced periodontitis received through scaling and root planing as well as oral hygiene instruction. A modified Widman flap was then randomly performed for one-half of each subject's dentition. Recall prophylaxis and oral hygiene reinforcement were administered for 4 years after completion of therapy. Shallow crevices (1--3 mm)subjected to either procedure tended to increase slightly in depth and exhibit a slight loss of attachment when compared to pretreatment measurements. Moderately deep pockets (4--6 mm) treated by either procedure were reduced and demonstrated a sustained gain or maintenance of attachment level. Pockets initially greater than or equal to 7 mm exhibited the greatest reduction in depth and attachment gain. Gingivitis was reduced following either procedure for moderate and deep pockets. No difference in supragingival plaque retention was noted and both procedures reduced calculus. The results indicate that both procedures were effective in treating moderate to advanced periodontitis. However, the additional flap procedure tended to result in greater pocket reduction and attachment gain for deeper pockets.

Salt and peroxide compared with conventional oral hygiene. III. Patient compliance and acceptance.

This study was undertaken to evaluate patient compliance with, and acceptance of, a salt and peroxide oral hygiene regimen compared with conventional oral hygiene regimens without or with the use of phase-contrast microscope viewing of subgingival plaque over a period of 2 years. A total of 231 subjects with early to moderate periodontitis were randomly divided into four groups. All groups were repeatedly instructed and motivated in their respective regimens. Subjects also received scaling and root planing using clinical and microbial criteria. Compliance with, and acceptance of, the two oral hygiene regimens were determined at the end of the study using a structured self-administered questionnaire. Results indicated that 74% and 58% (P less than or equal to 0.01) of subjects in the conventional and salt/peroxide groups, respectively, used their assigned regimen 4 to 7 days a week during the entire study. More than half of the subjects (54%) using each of the oral hygiene regimens indicated that they flossed once daily. Inconvenience was cited by 23% of the conventional and 43% of the salt/peroxide groups (P less than or equal to 0.01) as the main reason for not using their regimens. Twenty-three per cent of conventional group and 14% of salt/peroxide group indicated that shared their oral hygiene supplies with others. Eighty per cent and 57% (P less than or equal to 0.01) of the conventional and salt/peroxide groups, respectively, stated that they liked their regimens. Ninety-six per cent of all subjects felt that their regimen helped their periodontal status.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of measurement variability in subjects with moderate periodontitis using a conventional and constant force periodontal probe.

This study compared the intra- and inter-examiner measurement error of the Florida Probe, Florida Disk Probe, and conventional periodontal probe in persons having moderate to severe periodontitis. Single pass measurements using the conventional probe were compared to both single and double pass (corrected) measurements using the Florida Probe and Florida Disk Probe. The mean intra-examiner standard deviations of differences in repeated site probing depth measurements ranged from 0.60 to 0.93 mm for the Florida Probe and from 0.52 to 0.89 mm for the conventional probe. Based on overall averages, the conventional probe measured deeper probing depths than the Florida Probe at the same sites. This difference was especially evident in pockets greater than or equal to 6 mm in depth. Based on sites, the mean intra-examiner standard deviations of differences in repeated relative attachment level measurements using the Florida Disk Probe ranged from 0.55 to 0.82 mm. The mean standard deviations of site measurements for attachment level obtained with the conventional probe ranged from 0.62 to 1.14 mm. Inter-examiner measurement error was greater than intra-examiner measurement error for each probing method. It was concluded that use of the Florida Probe and Florida Disk Probe may offer significant advantages in reducing measurement error for some clinical examiners. For other examiners, use of the Florida Probes do not necessarily result in less measurement error than use of conventional probing methods.

Periodontal findings in adult twins.

Gingivitis and periodontitis are among the most common diseases known to man. Although bacterial plaque is generally accepted as the primary etiologic agent, little information is available concerning the influence that host genetic factors have on these diseases. The purpose of the present study was to examine the relative contribution of environmental and host genetic factors to clinical measures of periodontal disease through the study of both reared-together twins and monozygous twins reared apart. Probing depth, clinical attachment loss, gingivitis, and plaque were assessed from the Ramfjord teeth in 110 pairs of adult twins (mean age 40.3 years), including 63 monozygous and 33 dizygous twin pairs reared together and 14 monozygous twin pairs reared apart. Bootstrap sampling was used to estimate and provide confidence limits of between-pair and within-pair variances, intraclass correlations and heritability. Based on ratios of within-pair variances or heritability estimates, a significant (P less than 0.05) genetic component was identified for gingivitis, probing depth, attachment loss and plaque. Heritability estimates indicated that between 38% to 82% of the population variance for these periodontal measures of disease may be attributed to genetic factors. While there is general agreement that bacteria are important in the pathogenesis of the periodontal diseases, future etiologic studies should consider the role of host genetic influences.

Effects of scaling and root planing on subgingival microbial proportions standardized in terms of their naturally occurring distribution.

This investigation included a cross-sectional component (284, 20-40-year-old subjects/568 sites) and a longitudinal component (19 subjects with moderate to advanced periodontitis/76 sites). Subgingival plaque samples and clinical data were obtained from all upper second bicuspids and first molars in the longitudinal subjects and from both upper first molars in the cross-sectional subjects. The purpose was to: determine/confirm changes in proportions of selected subgingival microorganisms following root planning combined with conventional oral hygiene procedures in the longitudinal subjects, evaluate those changes in terms of an estimate of the naturally occurring distribution of subgingival microorganisms based on data obtained from the cross-sectional subjects and relate shifts in the subgingival microorganisms to changes in clinical measurements. Changes following treatment at sites with pre-instrumentation probing depths greater than or equal to 4.5 mm included cocci, 18.3 to 46.9%; spirochetes, 20.9 to 3.1%; total motile organisms, 28.5 to 5.9%; Fusobacterium spp., 10.2 to 2.2%; and dark-pigmented Bacteroides spp., 14.0 to 9.7%. Translating proportions of microorganisms in samples from subjects in the longitudinal treatment study to equivalent percentile ranks within the large cross-sectional data base demonstrated that at probing depths greater than or equal to 4.5 mm cocci moved from below the 50th percentile in our estimate of the naturally occurring distribution of subgingival microorganisms to above, and spirochetes, total motile organisms and Fusobacterium spp. moved from above the 50th percentile to below. The microbiological findings were consistent with statistically significant improvements in clinical measurements. Statistically significant changes also occurred in microorganisms at sites with initial probing depths less than 4.5 mm.

Prevalence of periodontal disease in a health maintenance organization and comparisons to the national survey of oral health.

The purposes of this study were to: 1) characterize the demographics, oral health behavior, and periodontal status of a health maintenance organization sample; 2) investigate the relationship between the location of posterior proximal measurement sites and prevalence estimates for periodontal disease; and 3) compare the prevalence of persons with pockets > or = 4 mm in the present sample to the 1985 NIDR Survey of Oral Health. The sample consisted of 1,090 adults attending a large health maintenance organization. All proximal sites in one randomly selected posterior dental sextant were examined for probing depth using a constant force probe. Demographic, medical, and behavioral factors were determined by questionnaire. Results indicated that the sample consisted primarily of medically and periodontally-healthy middle-aged adults with good oral hygiene habits. Overall, the mean probing depth was 2.95 mm with 10.1% of sites/subject > or = 4 mm. A larger percent of subjects had probing depths with pockets > or = 4 mm at lingual proximal sites than buccal proximal sites. Prevalence of subjects with pockets > or = 4 mm at mesio-buccal sites in the present study was similar to NIDR Region III data (15.3% vs. 17.4% respectively). However, when data from all posterior sites were included, the overall prevalence rate in the present sample increased to 36.8%. These findings indicate that disease prevalence is dependent on the location of surfaces measured and conservatively indicate that NIDR survey data may have underestimated the prevalence of persons with periodontal pockets > or = 4 mm by at least 20%.

Association between cigarette smoking, bacterial pathogens, and periodontal status.

The purposes of this study were to determine if: 1) an association exists between cigarette smoking and signs of periodontal disease after controlling for the confounding variables of age, sex, plaque, and calculus; 2) the prevalence of 5 bacteria commonly associated with periodontal disease differs between smokers and non-smokers; and 3) the presence of any of these bacteria or smoking are associated with a mean proximal posterior probing depth > or = 3.5 mm. Plaque, calculus, gingivitis, and probing depth were measured at the proximal surfaces of all teeth in one randomly selected posterior dental sextant in 615 adults. Subgingival plaque was sampled from the same sites and assayed for the presence of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Prevotella intermedia, Eikenella corrodens, and Fusobacterium nucleatum. A subsample of non-smokers (n = 126), who were similar to smokers (n = 63) with respect to age, sex, plaque, and calculus, was randomly drawn from the original sample. These two groups were then compared on the basis of clinical and microbial parameters. The results indicated that the odds of having a mean probing depth > or = 3.5 mm were 5 times greater for smokers than the non-smoker subsample (odds ratio = 5.3; 95% CI = 2.0 to 13.8). No statistically significant difference in the prevalence of any of the bacteria was found between smokers and the non-smoker subsample. Based on logistic regression analyses of each of the 5 bacteria and smoking, mean probing depth > or = 3.5 mm was significantly associated with the presence of A. actinomycetemcomitans, P. intermedia, E. corrodens, and smoking (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Salt and peroxide compared with conventional oral hygiene. I. Clinical results.

The purposes of this 2-year longitudinal study were to: compare the clinical effectiveness of patient applied sodium bicarbonate, hydrogen peroxide, and sodium chloride (S/P) to the use of conventional oral hygiene methods and to investigate the motivational effect of using phase-contrast microscopy in teaching effective oral hygiene. Initially, 972 subjects were screened for signs of periodontitis. From these, 347 with early to moderate periodontitis were selected and each was randomly assigned to one of four home treatment regimens after scaling and root planing. The four treatment regimens included: conventional oral hygiene procedures, conventional oral hygiene procedures plus phase-contrast demonstration of subgingival microbial forms for oral hygiene motivation, S/P oral hygiene, and S/P oral hygiene plus phase-contrast demonstration of subgingival microbial forms for oral hygiene motivation. Plaque, bleeding, gingival inflammation, probing depth, and clinical attachment level were recorded at baseline, 8, 16, and 24 months. Subjects were recalled for reinforcement of oral hygiene and periodontal prophylaxis at various intervals. Data were analyzed based on disease severity, location of index sites and compliance. The results indicated that both conventional oral hygiene procedures and the S/P regimen were effective in reducing clinical signs of disease when combined with professional care. There were no differences between the two regimens in clinical effectiveness and trends favoring microscopic viewing of subgingival plaque for motivational purposes were not statistically significant.

Salt and peroxide compared with conventional oral hygiene. II. Microbial results.

This study was designed to investigate the effect of conventional oral hygiene (n = 116 subjects) versus a salt and peroxide oral hygiene regimen (n = 115 subjects) on subgingival microorganisms. Subgingival plaque for microscopic evaluation was obtained from eight index tooth sites in each of 231 adult subjects. Microbial forms were microscopically identified at baseline, 8, 16, and 24 months. For both oral hygiene groups, cocci were increased (P less than 0.05) and motile rods were decreased (P less than 0.05) at 8 months and returned to baseline by 16 months. Spirochetes were decreased (P less than 0.05) and remained low through 24 months in both oral hygiene groups. The frequency of agreement between clinical (bleeding) and microbial (greater than or equal to 15% spirochetes or motile rods or greater than or equal to 20% spirochetes + motile rods) criteria for instrumentation was 59.8%. It was also found that fewer total instrumentations for test subjects were observed when microbiological criteria were used as compared with clinical criteria. The greater number of instrumentations based on clinical criteria was highly significant (P less than or equal to 0.001). A significant change in microbial signs associated with peridontal disease may be obtained with either a conventional oral hygiene or a salt and peroxide oral hygiene home care regimen.

Periodontal bacteria in adult twins.

BACKGROUND: Both environmental and genetic factors are known to influence clinical measures of periodontal disease. The purpose of this study was to determine whether genetic factors similarly influence the presence of specific periodontal bacteria in subgingival plaque. METHODS: Reared-together and reared-apart monozygous (MZ) and dizygous (DZ) adult twins were examined clinically. Demographic and behavioral information was obtained from each subject by questionnaire. Subgingival plaque samples were obtained from the index teeth, and the presence of P. intermedia, P. gingivalis, A. actinomycetemcomitans, E. corrodens, and F. nucleatum was determined using an immunoassay. RESULTS: Microbiological and clinical data were available for 169 twin pairs. The subject-based prevalences of the bacteria in the twin groups ranged from 11% for Porphyromonas gingivalis to 40% for F. nucleatum. For all species examined, the concordance rates were not significantly different (P > 0.05) between MZ and DZ twin groups. These findings were apparent despite similar smoking histories, self-reported oral hygiene practices, and antibiotic use in the twin groups. Furthermore, MZ twins reared together were not more similar than MZ reared-apart twins with respect to any bacterial species examined. CONCLUSIONS: These findings suggest that in a population with access to routine dental care, any effects that host genes and the early family environment have on the presence of specific bacteria in subgingival plaque are not apparent in adulthood. Most twins with disease in this study had early periodontitis. Results from this study may not necessarily be extrapolated to more advanced disease states.