Relationship between 1-, 3-, and 6-Month Gingival Bleeding Outcomes.

INTRODUCTION: Results from systematic reviews and meta-analyses show generally consistent antigingivitis effects between 3- and 6-mo observation time points with twice-daily use of stannous fluoride (SnF2) dentifrice. However, the relationship between 1-, 3-, and 6-mo gingivitis responses has not been investigated. METHODS: This pooled analysis was conducted to understand the relationship of 1-, 3-, and 6-mo gingival bleeding outcomes. Number of bleeding sites, derived from Löe-Silness Gingival Index (LSGI) or Gingival Bleeding Index, was identified as the primary end point of the analysis for the biological and clinical relevance. Randomized, double-blinded, controlled clinical studies meeting the following predefined selection criteria were identified: 1) published and unpublished gingivitis clinical trials conducted from 1995 to 2022 comparing efficacy of 0.454% SnF2 dentifrices to negative controls (sodium fluoride or sodium monofluorophosphate dentifrice) and 2) studies with a 3-mo assessment and at least a 1- or 6-mo assessment. RESULTS: The search resulted in ten 6-mo and fourteen 3-mo studies meeting selection criteria. A mixed-effects model was performed on the pooled data to assess gingival bleeding outcomes across time. The bleeding efficacy significantly increased between months 1 and 3 (P < 0.0001) and plateaued between months 3 and 6 (P = 0.007), supporting the fact that bleeding reduction relative to control established by 1 mo will increase and be maintained through 3 and 6 mo (R2 = 0.857). In addition, gingival bleeding and gingivitis efficacy, as measured by LSGI, were found to be highly correlated (R2 = 0.874). CONCLUSION: A clear relationship has been demonstrated between 1-, 3-, and 6-mo gingival bleeding outcomes in gingivitis clinical studies comparing SnF2 dentifrice to negative control dentifrice. These findings have important implications to the dental practice and scientific research as antigingivitis efficacy evaluations can be observed as early as 1 mo and are consistent with those seen at 3 or 6 mo. KNOWLEDGE TRANSFER STATEMENT: Outcomes from this investigation indicate that the clinical evaluation of antigingivitis efficacy at 1 mo is predictive of that at 3 and 6 mo, supporting studies of 1-mo duration as a viable method of knowledge acquisition. This more efficient, expedited research design has positive implications for patient care, clinical practice guidelines, protocols, and policies.

The effects of different levels of brush end rounding on gingival abrasion: a double-blind randomized clinical trial.

OBJECTIVE: The objective of this study was to evaluate the effect of different levels of filament end rounding on gingival abrasions (GAs). METHODS: The study was a crossover, split-mouth, contra-lateral, double-blinded, randomized design using professional brushing. Three manual toothbrushes, with 0%, 40-50% and >90% end-rounded filaments, were investigated. Participants refrained from all oral hygiene procedures for 48 h prior to each of the three visits. Prior to brushing, oral soft tissue (OST) and GAs were assessed. Based on the randomization, during every visit contra-lateral quadrants were brushed with one of the three test brushes. After brushing, GAs were re-assessed. The means of the GAs prebrushing and post-brushing and differences per brush were calculated. Subanalyses were performed based on the size of the abrasion and its location. RESULTS: A total of 46 generally healthy participants without periodontitis completed the study and provided a full data set. All brushes had statistically significant increases of abrasions following their use (P < 0.001). Non-end-rounded brushes provided significantly more GAs than did the 40-50% and the >90% brushes (P ≥ 0.001). A subanalysis showed that significantly more small-sized (P ≥ 0.002) abrasions located at the gingival margin (P < 0.001) occurred when a non-end-rounded brush was used. No significant differences were found between the 40-50% and >90% end-rounded brushes in any of the analyses. OST deviations were not observed. CONCLUSIONS: Based on the results of this experiment involving professional brushing, it can be concluded that 40-50% or greater end-rounded filaments can provide a significant reduction in gingival abrasions compared to non-end-rounded filaments.

A randomized clinical trial comparing plaque removal efficacy of an oscillating-rotating power toothbrush to a manual toothbrush by multiple examiners.

OBJECTIVE: To determine whether multiple examiners can demonstrate consistent plaque removal advantages for an oscillating-rotating power toothbrush versus a manual toothbrush. METHODS: This was a replicate-use, single brushing, examiner-blind, randomized, two-treatment, four-period crossover clinical trial involving four examiners. Subjects were randomized to one of four treatment sequences involving two toothbrushes: an oscillating-rotating power toothbrush or a manual toothbrush. At each of the four visits, subjects arrived having abstained from oral hygiene for 24 h prior, and brushed with their assigned toothbrush and a marketed fluoride dentifrice under supervision unaided by a mirror. Plaque was assessed by each examiner using the Turesky-Modified Quigley-Hein Plaque Index at each study period before and after brushing. Data was analysed separately for each examiner using the analysis of covariance for crossover design. RESULTS: Ninety-five subjects between the ages of 18 and 70 met the entrance criteria and were enrolled in the study. Eighty-seven subjects completed all four periods of the study. Both brushes delivered a significant plaque reduction when compared to baseline. Significant treatment differences were observed for all four examiners - ranging from 0.10 to 0.16 - in favor of the oscillating-rotating brush (P < 0.001). There were no adverse events reported or observed for either brush. CONCLUSIONS: All four examiners demonstrated the power toothbrush removed significantly more plaque after a single brushing than the standard manual toothbrush. Both brushes were well tolerated.

A randomized 12-week clinical comparison of an oscillating-rotating toothbrush to a new sonic brush in the reduction of gingivitis and plaque.

OBJECTIVE: To evaluate the efficacy of a marketed oscillating-rotating (O-R) power toothbrush (Oral-B Triumph with SmartGuide and FlossAction brush head, D34/EB25) to a new sonic toothbrush (Sonicare FlexCare Platinum) in the reduction of gingivitis and plaque over a 12-week test period. METHODS: This was a single center, randomized, open label, examiner-blind, two-treatment, parallel group study. Subjects who met the entrance criteria were enrolled in the study and randomly assigned to either the O-R or sonic treatment group. Subjects brushed with their assigned toothbrush and a marketed fluoride dentifrice for two minutes twice daily at home for 12 weeks. Gingivitis and plaque were evaluated at Baseline, Week 6, and Week 12. Gingivitis was assessed using the Modified Gingival Index (MGI) and Gingival Bleeding Index (GBI), and plaque was assessed using the Rustogi Modified Navy Plaque Index (RMNPI). Data were analyzed using an Analysis of Covariance (ANCOVA) with Baseline as the covariate. RESULTS: In total, 130 subjects (65 per group) were randomized to treatment and 127 subjects completed the study. Both brushes produced statistically significant (p < 0.001) reductions in gingivitis and plaque measures relative to Baseline. At Week 12, the O-R brush demonstrated significantly greater reductions than the sonic brush in whole mouth gingivitis measures (p = 0.007). Additionally, the O-R brush presented significantly fewer bleeding sites (p < 0.007) and significantly greater reductions in whole mouth plaque measures (p < or = 0.035) at Weeks 6 and 12 versus the sonic brush. The benefit for the O-R brush versus the sonic brush at Week 12 was 11.7% for gingivitis, 19.8% for number of bleeding sites, and 12.2% for whole mouth plaque. There were no adverse events reported or observed for either brush. CONCLUSION: The oscillating-rotating toothbrush demonstrated statistically significantly greater reductions in whole mouth plaque at Weeks 6 and 12, as well as significantly greater gingivitis reductions over the long-term (12 weeks), compared to the new sonic toothbrush.

Gingival abrasion and recession in manual and oscillating-rotating power brush users.

OBJECTIVE: To assess gingival recession (GR) in manual and power toothbrush users and evaluate the relationship between GR and gingival abrasion scores (GA). METHODS: This was an observational (cross-sectional), single-centre, examiner-blind study involving a single-brushing exercise, with 181 young adult participants: 90 manual brush users and 91 oscillating-rotating power brush users. Participants were assessed for GR and GA as primary response variables. Secondary response variables were the level of gingival inflammation, plaque score reduction and brushing duration. Pearson correlation was used to describe the relationship between number of recession sites and number of abrasions. Prebrushing (baseline) and post-brushing GA and plaque scores were assessed and differences analysed using paired tests. Two-sample t-test was used to analyse group differences; ancova was used for analyses of post-brushing changes with baseline as covariate. RESULTS: Overall, 97.8% of the study population had at least one site of ≥1 mm of gingival recession. For the manual group, this percentage was 98.9%, and for the power group, this percentage was 96.7% (P = 0.621). Post-brushing, the power group showed a significantly smaller GA increase than the manual group (P = 0.004); however, there was no significant correlation between number of recession sites and number of abrasions for either group (P ≥ 0.327). CONCLUSIONS: Little gingival recession was observed in either toothbrush user group; the observed GR levels were comparable. Lower post-brushing gingival abrasion levels were seen in the power group. There was no correlation between gingival abrasion as a result of brushing and the observed gingival recession following use of either toothbrush.

The plaque removal efficacy of a novel power brush head.

OBJECTIVE: To assess the plaque removal efficacy of an oscillating/rotating power toothbrush with novel brush head (Oral-B Precision Clean) in comparison to an American Dental Association (ADA) reference manual toothbrush. METHODS: This was a replicate-use, single-brushing, two-treatment, examiner-blind, randomized, four-period (visit) study with a crossover design. At each visit, subjects disclosed their plaque with disclosing solution for one minute, and an examiner performed a baseline (pre-brushing) plaque examination (Rustogi, et al. Modification of the Navy Plaque Index). Subjects were then instructed to brush for two minutes (according to manufacturer's instructions) with their assigned power toothbrush or as they normally do with the ADA manual brush under supervision, after which they again disclosed their plaque and were given a post-brushing plaque examination. RESULTS: Both the power brush and manual brush showed statistically significant plaque reductions from baseline for the whole mouth, along the gingival margin, and on approximal surfaces. The power brush showed statistically significant advantages (p < 0.001) over the manual brush in plaque reduction for whole mouth (28.8%), gingival margin (44.3%), and approximal surfaces (20.7%). CONCLUSION: The oscillating/rotating power toothbrush with a novel brush head showed statistically significantly superior plaque reduction (whole mouth, gingival margin, and approximal surfaces) compared to a manual toothbrush.

A clinical evaluation of the plaque removal efficacy of five manual toothbrushes.

OBJECTIVE: To assess and compare the plaque removal efficacy of five different Oral-B manual toothbrushes: CrossAction Pro-Health (CAPH), CrossAction (CA), Exceed (EX), Advantage 123 (ADV 123), and Indicator (IND). METHODS: This was a single-use, five-treatment, examiner-blind, randomized, five-period (visit) crossover study, with 10 different treatment sequences (groups) that determined the order in which the five toothbrushes were assigned at study visits. Three toothbrushes had an advanced CrissCross bristle design (CAPH, CA, EX), while two had more standard designs with straight bristles (ADV 123 and IND). At the first visit, subjects disclosed their plaque with disclosing solution, and an examiner performed a baseline plaque examination using the Rustogi, et al. Modification of the Navy Plaque Index (RMNPI). Subjects brushed for one minute with their assigned toothbrush under supervision, after which they again disclosed their plaque and were given a second plaque examination. The same procedure was followed for each of the visits in turn. RESULTS: All five manual toothbrushes showed a statistically significant (p < 0.0001) reduction in plaque from baseline for the whole mouth (84% to 93%), gingival margin (74% to 88%), and approximal surfaces (95% to 99%). For pair-wise treatment comparisons for all three plaque measures, CAPH, CA, and EX demonstrated statistically significantly better plaque removal than ADV 123 and IND (all p < 0.018). No other treatment comparisons were statistically significant. CONCLUSION: All five manual toothbrushes showed highly effective plaque reduction for whole mouth, gingival margin, and approximal surfaces. Comparisons between brushes showed consistent advantages for CAPH, CA, and EX compared to ADV 123 and IND for all three plaque measures, indicating that advances in toothbrush design can further enhance plaque removal.

Clinical evaluation of brushing time and plaque removal potential of two manual toothbrushes.

AIM: To compare plaque removal efficacy of Oral-B CrossAction (CA) used for 1 min with an American Dental Association (ADA) manual toothbrush used for 2 or 5 min in an examiner-blind, three-treatment, six-period crossover study. MATERIALS AND METHODS: After refraining from all oral hygiene procedures for 23-25 h, subjects were randomly assigned to one of nine possible six-period (visit) treatment sequences. Plaque was assessed at baseline (Rustogi Modified Navy Plaque Index). Post-brushing scores were recorded after brushing with a marketed dentifrice and the assigned toothbrush for the specified duration. The same procedure was followed at each of six subsequent visits. Clinical measurements were carried out by the same examiner. RESULTS: Forty subjects completed the study. All three treatments effectively removed plaque from the whole mouth, along the gingival margin and from approximal surfaces. Whole mouth and gingival margin plaque removal scores with CA for 1 min did not differ significantly from scores with the ADA toothbrush used for 2 min. The ADA brush used for 5 min showed significantly greater whole mouth (P < 0.001) and gingival margin (P < 0.001) plaque reduction than the two other treatments. Approximal plaque removal scores did not differ between the three treatments. CONCLUSIONS: Efficient plaque removal can be achieved after 1 min of brushing with CA. The amount of plaque removed did not differ significantly from that achieved with the ADA brush after 2 min of brushing. Greater whole mouth and gingival margin plaque removal scores were seen with the ADA brush after 5 min.

Efficacy of a single evening dose of syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple common cold symptoms.

OBJECTIVE: The aim of this study was to evaluate the efficacy of a single night-time dose of a syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate in subjects with multiple cold symptoms. MATERIALS: A syrup containing 15 mg dextromethorphan hydrobromide, 7.5 mg doxylamine succinate, 600 mg paracetamol and 8 mg ephedrine sulfate (Wick MediNait produced by WICK Pharma, Germany, a subsidiary of Procter & Gamble GmbH; test syrup) or placebo (placebo syrup) for oral administration. METHODS: This was a randomized, double-blind, placebo-controlled, multi-center, parallel design study. At enrollment, eligible subjects had to have at least moderate nasal congestion and a runny nose, at least mild cough and at least mild pain with one or more of the following: sore throat, sore chest, headache or body pain/aches. Subjects were randomized into either Group T (test syrup) or Group P (placebo syrup). On the evening of enrollment, subjects rated baseline symptoms, ingested the assigned study product and completed symptom-relief assessments at 3 hours post-dosing. Within one hour of awakening the following morning, subjects completed night-time symptom relief and sleep satisfaction assessments. All symptoms were recorded using an Interactive Voice Response system. Treatment comparisons were made after adjusting for the severity of baseline symptom using analysis of covariance. RESULTS: Of 485 subjects who took the study product, 432 (224 in Group T; 208 in Group P) were evaluable for analysis. For the primary endpoint (composite of nasal congestion/runny nose/cough/pain relief scores 3 hours post-dosing), subjects in Group T had clinically and statistically significantly greater relief than Group P (p = 0.0002). Each individual symptom score also showed statistically significant improvement at this time point (p < or = 0.017). The next morning, Group T continued to show clinically and statistically significant benefits over Group P on the composite score and each of the individual symptoms (p < or = 0.003). Evidence of benefit with the test syrup was also seen in the higher score for overall night-time relief (p < 0.0001) and greater satisfaction on sleep (p = 0.002) compared to placebo syrup. Improvement in individual symptoms after 3 hours was obtained in 16-42% more subjects in Group T than in Group P, whereas the percentage of subjects in Group T having Good or Very Good relief the morning after dosing increased by 25-68% compared to subjects in Group P. 14 subjects (5 in Group T; 9 in Group P) reported AEs but none of these occurred with an incidence greater than 1%. There were no serious AEs. CONCLUSIONS: The results confirm the multisymptom benefit of a single dose of the test syrup containing paracetamol, dextromethorphan hydrobromide, doxylamine succinate and ephedrine sulfate and support its role as an effective and convenient therapy for symptoms of nasal congestion, runny nose, cough and pain/body aches associated with the common cold and for increasing sleep quality disturbed by the common cold.

Comparison of gastric pH with omeprazole magnesium 20.6 mg (Prilosec OTC) o.m. famotidine 10 mg (Pepcid AC) b.d. and famotidine 20 mg b.d. over 14 days of treatment.

BACKGROUND: The onset of acid inhibition for proton pump inhibitors is slower than with H2RAs and generally considered to be at a steady-state after 5 days. Thus, little direct comparison data exists between H2RAs and proton pump inhibitors for gastric acid suppression on day 1 of therapy. Furthermore, the durability of their acid suppression has not been systematically compared. AIM: To compare the effects of 20.6 mg omeprazole magnesium o.m. (Ome-Mg 20), famotidine 10 mg b.d. (Fam 10) and famotidine 20 mg b.d. (Fam 20) on intragastric pH on day 1 and throughout 14 days of dosing. METHODS: The study was a randomized, double-blind, three-dosing regimens, three-period crossover. Healthy adults with frequent heartburn (> or =2 days/week) underwent 24-h gastric pH monitoring on days 0 (baseline), 1, 3, 7 and 14. RESULTS: Thirty-one subjects were included in the per-protocol analyses. On day 1, the mean percentage time pH > 4 (pH4%) was higher for Ome-Mg 20, 44.6%, than for Fam 10, 36.7% (P = 0.032), and not different from Fam 20, 46.9% (P = 0.541). The pH4% was higher for Ome-Mg 20 than either famotidine regimen on all subsequent monitoring days (P < 0.001). The 24-h area under the mean intragastric pH curve showed a similar pattern. Furthermore, after day 1, Ome-Mg 20 demonstrated an increasing and sustained effect in contrast to a decreasing effect for famotidine, consistent with H2RA tolerance. CONCLUSION: Gastric acid suppression on Ome-Mg 20 mg o.m. over 14 days was comparable with Fam 10 mg b.d. or Fam 20 mg b.d. on day 1, and superior thereafter.

Comparison of Prilosec OTC (omeprazole magnesium 20.6 mg) to placebo for 14 days in the treatment of frequent heartburn.

PURPOSE: Consumer surveys have identified an over-the-counter (OTC) medication that provides complete and long-lasting relief of frequent heartburn as an unmet consumer need. The purpose of the two identical studies reported in this paper was to evaluate the safety and effectiveness of 10.3 and 20.6 mg omeprazole magnesium, referred to as Ome-Mg 10 and Ome-Mg 20, respectively (equivalent to 10 and 20 mg omeprazole) for the treatment of frequent heartburn administered as a novel 14-day OTC regimen. SUBJECTS AND METHODS: Subjects with frequent heartburn (heartburn two or more days per week) took Ome-Mg 10, Ome-Mg 20, or placebo for 14 consecutive mornings. Statistical analyses compared percentage of subjects with no heartburn 24 h after the first dose, after the last dose (day 14), and percentage of days that subjects were heartburn-free. Nocturnal heartburn and heartburn rated no more than mild were also assessed. RESULTS: Twenty-four hours following the first dose, nearly 50% of subjects receiving Ome-Mg 20 reported no heartburn, and more than 80% receiving Ome-Mg 20 had no more than mild heartburn. Both doses were significantly more effective than placebo on days 1 and 14 for percentage of subjects heartburn-free for 24 h (P < or = 0.003), and across all 14 days for percentage of heartburn-free days (P < 0.001). Ome-Mg 20 was significantly more effective than placebo in preventing nocturnal heartburn across all 14 days (P < 0.001). Ome-Mg was well tolerated. CONCLUSION: These trials demonstrated the safety and effectiveness of a novel 14-day regimen of Ome-Mg 20 in completely preventing heartburn for 24 h establishing it as an excellent self-care treatment for frequent heartburn and supporting the approval of Prilosec OTC.

Fitting multivariate polynomial growth curves in two-period crossover designs.

We discuss the statistical analysis of data from two clinical trials using crossover designs. In both studies, response was observed repeatedly over time in each treatment period. The first study involves repeated measurements of a single response variable whereas the second involves bivariate response. Methods are described for fitting polynomial growth curves to achieve data reduction in a two-stage approach to the analysis of crossover designs. Thus, a multivariate parametric analysis frequently can be conducted even when the sample sizes are somewhat small as is the case in many crossover designs. Hypotheses that are usually of interest in crossover designs can be tested in the second stage of the analysis. Methods for testing the multivariate general linear hypothesis as a basis for statistical inference in such problems are discussed.

Effect of air-supported, continuous, postural oscillation on the risk of early ICU pneumonia in nontraumatic critical illness.

STUDY OBJECTIVES: We hypothesized that continuous, automatic turning utilizing a patient-friendly, low air loss surface would reduce the incidence of early ICU pneumonia in selected groups of critically ill medical patients. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: Medical ICU of a large community teaching hospital. PATIENTS: One hundred twenty-four critically ill new admissions to the medical ICU at Charity Hospital in New Orleans. INTERVENTIONS: Patients were prospectively randomized within one of five diagnosis-related groups (DRG)--sepsis (SEPSIS), obstructive airways disease (OAD), metabolic coma, drug overdose, and stroke--to either routine turning on a standard ICU bed or to continuous turning on an oscillating air-flotation bed for a total of five days. MEASUREMENTS AND RESULTS: Patients were monitored daily during the treatment period for the development of pneumonia. The incidence of pneumonia during the first five ICU days was 22 percent in patients randomized to the standard ICU bed vs 9 percent for the oscillating bed (p = 0.05). This treatment effect was greatest in the SEPSIS DRG (23 percent vs 3 percent, p = 0.04). Continuous automatic oscillation did not significantly change the number of days of required mechanical ventilation, ICU stay, hospital stay, or hospital mortality overall or within any of the DRGs. CONCLUSIONS: We conclude that air-supported automated turning during the first five ICU days reduces the incidence of early ICU pneumonia in selected DRGs; however, this form of automated turning does not reduce other measured clinical outcome parameters.

Multivariate nonparametric analysis for the two-period crossover design with application in clinical trials.

Nonparametric methods are presented for the analysis of the two-treatment, two-period crossover design with multivariate response. After forming within-subject sums and differences, the usual tests, including those for carry-over effects and direct treatment effects, can be constructed using a multivariate analysis of variance. When the assumptions relevant to traditional analysis are in question, multivariate nonparametric tests based on ranks provide a realistic alternative. However, multivariate response gives rise to a wider class of hypotheses than is seen in crossover designs with univariate response. We discuss these hypotheses and formulate nonparametric tests for associated analyses.

Analysis of the 2 x 2 crossover design with subsampling.

Subsampling can be used in experimental design to investigate extraneous sources of variability. One useful strategy is to make independent replicate measurements of the response variate. This can be achieved in clinical studies, for example, by dividing a blood or urine specimen from each of a sample of subjects into aliquots and processing these through a chemistry laboratory in such a way that the replicate determinations are independent. This procedure can be used to increase design efficiency. This paper addresses considerations in the design and analysis of the 2 x 2 crossover plan with this type of subsampling.

Analysis of crossover designs with multivariate response.

Crossover designs involve observing the same response variate under different experimental conditions for each subject. Univariate methods are commonly used for analysis of data arising in these designs, but multivariate procedures offer a more general approach. The general multivariate linear model provides a natural framework for the simplest data structure as well as more complex settings with two or more response variates and measurements repeated over time. Multivariate models for crossover designs provide a unified approach that clarifies specification of hypotheses, assumptions required, and testing procedures in a wide class of applications that include longitudinal data as a special case. We focus on the 2 x 2 crossover design, but also describe models for analysing more complex crossover designs.

Regression toward the mean in 2 x 2 crossover designs with baseline measurements.

Clinical trials often involve the study of patients whose values for some quantitative characteristic are in the extreme of the distribution for the normal population. Subsequent observation of the characteristic of interest will ordinarily tend to regress toward the mean of the distribution even in the absence of a treatment effect. We consider the impact of regression toward the mean in the analysis of data arising in 2 x 2 crossover trials with two baseline measurements. The usual summary statistics can be especially misleading in the presence of regression toward the mean.