A Meta-analysis Comparing Toothbrush Technologies on Gingivitis and Plaque.

BACKGROUND: Research continues to show an association between oral health and systemic health, further stressing the importance of effective daily plaque removal via toothbrushing to maintain periodontal health and overall well-being. This investigation was undertaken to compare the efficacy of oscillating-rotating, sonic, and manual toothbrushes in reducing gingivitis and plaque in randomised controlled trials (RCTs) with up to 6 months' follow-up. METHODS: This meta-analysis was conducted from a single database (Procter & Gamble Oral Care Clinical Archive) including RCTs from 2007 to 2022. Three authors independently assessed study eligibility. Disagreements concerning selected studies were resolved by discussion with an expert colleague. Direct and indirect treatment comparisons along with transition rates to gingival health were calculated using participant-level data. Transition-to-health time was calculated using data from all time points. Subregion analyses evaluated number of bleeding sites and plaque reduction. RESULTS: This meta-analysis included 21 gingivitis RCTs and 25 plaque RCTs. Relative to manual and sonic brushes, oscillating-rotating brushes had a higher percentage of participants who transitioned to gingival health (72% vs 21% and 54%; P < .001). Compared with manual and sonic brushes, respectively, oscillating-rotating brushes demonstrated greater bleeding site reductions (by 52% and 29%; P < .001) and superior plaque reductions (by 19% and 5%; P < .001). Oscillating-rotating brushes provided faster transitions to health than sonic brushes and showed greater efficacy across subregions. The most advanced oscillating-rotating brush demonstrated statistically significantly greater efficacy compared with traditional oscillating-rotating, manual, and sonic brushes when analysed separately. Risk of bias was deemed low for all studies. CONCLUSIONS: Oscillating-rotating toothbrushes offer superior results for transition to health, gingivitis, and plaque reduction compared with manual and sonic brushes. The most advanced oscillating-rotating model offers enhanced efficacy vs traditional models.

Brushing Behavior Changes and Plaque Removal with an Electric Toothbrush: A clinical trial.

Purpose To evaluate changes in toothbrushing behavior and plaque removal performance with usage of a next generation oscillating-rotating electric toothbrush (NG-OR).Methods This exploratory clinical study had a two-treatment, three-period, single-group, sequential design. Generally healthy adults with a screening whole mouth mean Turesky modified Quigley-Hein Plaque Index (TQHPI) score of at least 1.75 on a 0-5 scale and who were primarily OR brush users were enrolled. Participants used each OR toothbrush in A-B-B order, where a currently marketed OR brush with a traditional mechanical drive system (T-OR) was used in period A and the NG-OR brush with a linear magnetic drive was used in period B. At Visit 1, qualifying participants brushed on-site with T-OR. After a 48h washout, participants returned for Visit 2 and brushed on-site with NG-OR. Participants then used NG-OR for 1 week, twice daily, at home and returned for Visit 3 to brush on-site with NG-OR again. For all on-site brushings, participants were instructed to brush for 2min without interactive features. Each toothbrush was tagged with a transmitter chip connected to a Motion Tracking System to record movements of the toothbrush and participant using infrared light transmission to determine Isochronicity (brushing time uniformly distributed across the dentition). Plaque was measured using TQHPI. Primary variables were Isochronicity and TQHPl whole mouth mean plaque reduction (pre-brushing minus post brushing).Results Overall, 41 participants enrolled and received treatment; 40 completed the trial. NG-OR showed significantly greater Isochronicity after a single brushing (p=0.043) and after a 1-week at-home use (p=0.001) versus T-OR. NG-OR showed 41% greater whole mouth plaque removal than T-OR (p<0.001) after a single brushing. Plaque reduction by region/surface was consistent with whole mouth results.Conclusion The NG-OR brush showed greater brushing uniformity and plaque removal versus the T-OR brush.

Brushing behaviour changes and plaque removal with an electric toothbrush: A clinical trial.

OBJECTIVE: To evaluate changes in toothbrushing behaviour and plaque removal performance with usage of a next generation oscillating-rotating electric toothbrush (NG-OR). METHODS: This exploratory clinical study had a two-treatment, three-period, single-group, sequential design. Generally healthy adults with a screening whole mouth mean Turesky modified Quigley-Hein Plaque Index (TQHPI) score of at least 1.75 on a 0-5 scale and who were primarily OR brush users were enrolled. Participants used each OR toothbrush in A-B-B order, where a currently marketed OR brush with a traditional mechanical drive system (T-OR) was used in period A, and the NG-OR brush with a linear magnetic drive was used in period B. At Visit 1, qualifying participants brushed on-site with T-OR. After a 48 h washout, participants returned for Visit 2 and brushed on-site with NG-OR. Participants then used NG-OR for 1 week, twice daily, at home and returned for Visit 3 to brush on-site with NG-OR again. For all on-site brushings, participants were instructed to brush for 2 min without interactive features. Each toothbrush was tagged with a transmitter chip connected to a Motion Tracking System to record movements of the toothbrush and participant using infrared light transmission to determine Isochronicity (brushing time uniformly distributed across the dentition). Plaque was measured using TQHPI. Primary variables were Isochronicity and TQHPl whole mouth mean plaque reduction (pre-brushing minus post-brushing). RESULTS: Overall, 41 participants enrolled and received treatment; 40 completed the trial. NG-OR showed significantly greater Isochronicity after a single brushing (p = 0.043) and after a 1-week at-home use (p = 0.001) versus T-OR. NG-OR showed 41% greater whole mouth plaque removal than T-OR (p < 0.001) after a single brushing. Plaque reduction by region/surface was consistent with whole mouth results. CONCLUSION: The NG-OR brush showed greater brushing uniformity and plaque removal versus the T-OR brush.

Novel findings on anti-plaque effects of stannous fluoride.

PURPOSE: To evaluate the antiplaque effects for 0.454% bioavailable gluconate chelated stannous fluoride (SnF2) dentifrices versus controls by clinical model, plaque index, tooth surface and tooth type in a pooled analysis. METHODS: Randomized controlled trials (RCTs) were conducted to evaluate plaque effects of SnF2 dentifrices from the same formulation family over the past 30 years. Forty-four 4-day and longer-term (≥ 2 weeks) RCTs conducted in six countries with 3,336 subjects using Turesky Modified Quigley-Hein Plaque Index, Rustogi Modification of the Navy Plaque Index, Digital Plaque Imaging Analysis, and Silness and Löe Plaque Index were included. RESULTS: In 13 and 11 longer-term studies assessing SnF2 dentifrice versus a negative or positive control, respectively, standardized differences in average plaque score of -1.15 (95% CI: -1.61, -0.69) and -0.74 (95% CI: -1.20, -0.28) were observed (P ≤ 0.011), favoring SnF2. Reductions represented a 19% and 16% benefit versus the negative and positive control, respectively. In 18 and five 4-day studies assessing SnF2 dentifrice versus a negative (NaF/SMFP) or positive (triclosan/chlorhexidine) control, respectively, differences in average 4-day plaque score of -0.27 (95% CI: -0.31, -0.23) and -0.15 (95% CI: -0.25, -0.06) were observed (P≤ 0.001) favoring SnF2. Reductions represented a 14% and 11% benefit versus the negative and positive control, respectively. Significant antiplaque benefits for SnF2 dentifrice were seen regardless of clinical model, plaque index, tooth surface or type, including brushed and unbrushed surfaces (P≤ 0.049). CLINICAL SIGNIFICANCE: Bioavailable gluconate chelated SnF2 dentifrices showed consistent plaque inhibition versus negative and positive controls across all conditions evaluated. Importantly, the effect on unbrushed surfaces illustrated the significant plaque inhibition benefit of SnF2 beyond mechanical plaque removal.

Randomized clinical trial assessing anti-gingivitis efficacy of two stannous fluoride dentifrices and zinc/arginine dentifrice.

PURPOSE: To evaluate the anti-gingivitis efficacy of two bioavailable stannous fluoride (SnF2) dentifrices versus a zinc/arginine dentifrice and a negative control dentifrice, and to compare the plaque control benefits. METHODS: This was a single-center, randomized, controlled, four-treatment, parallel-group, double-blind, 3-month clinical trial. Healthy adult subjects with gingivitis were randomly assigned to one of four different dentifrice treatment groups: SnF2 dentifrice A, SnF2 (1,100 ppm F) + sodium fluoride (350 ppm F) + sodium hexametaphosphate (Procter & Gamble); SnF2 dentifrice B, SnF2 (1,100 ppm F) + sodium fluoride (350 ppm F) + citrate (Procter & Gamble); Zn/Arg dentifrice, zinc/arginine + sodium fluoride (1,450 ppm F) (Colgate-Palmolive); negative control dentifrice, sodium monofluoro-phosphate (1,000 ppm F) + sodium fluoride (450 ppm F) (Colgate-Palmolive). Subjects brushed with their assigned treatment dentifrice and an assigned manual toothbrush (Oral-B Indicator) for 1 minute, twice daily, for the duration of the study. Gingivitis was assessed at Baseline and at Weeks 2, 4 and 12 by calculating the total number of gingival bleeding sites using the Gingival Bleeding Index, and plaque was assessed at Baseline and at Week 12 using the Turesky Modified Quigley-Hein Index. A repeated measures model was carried out across Weeks 2, 4, and 12 to determine bleeding efficacy (total number of bleeding sites). An ANCOVA with baseline plaque as the covariate was used to evaluate plaque efficacy at Week 12. RESULTS: 161 subjects were randomized (mean age= 38.8 years). 154 subjects completed the study and 153 had evaluable data at Week 12. The mean (SD) number of Baseline bleeding sites overall was 78.74 (31.16) with no significant difference between groups (P= 0.537). SnF2 dentifrice A significantly reduced the number of bleeding sites relative to the negative control dentifrice at Weeks 2, 4 and 12 by 15.4%, 13.7% and 17.2%, respectively. SnF2 dentifrice B significantly reduced the number of bleeding sites relative to the negative control dentifrice at Week 4 by 13.9% (P= 0.041). Relative to the Zn/Arg dentifrice, SnF2 dentifrice A produced significantly greater reductions in gingival bleeding sites at Weeks 2, 4 and 12 by 23.4%, 17.2% and 20.9%, respectively (P≤ 0.007). SnF2 dentifrice B produced significantly greater bleeding reductions versus the Zn/Arg dentifrice at Weeks 4 and 12 by 17.4% and 14.4%, respectively (P≤ 0.035). The Zn/Arg dentifrice did not differ significantly in the number of bleeding sites (P≥ 0.127) or plaque (P= 0.175) relative to the negative control dentifrice. Both SnF2 dentifrices significantly reduced plaque levels (P≤ 0.029) relative to both negative control dentifrice and Zn/Arg dentifrice at Week 12. All dentifrices were well tolerated. CLINICAL SIGNIFICANCE: Two different SnF2 dentifrices showed significantly reduced gingival bleeding and plaque levels relative to a Zn/arginine dentifrice.

UHPLC-MS/HRMS method for the quantitation of pyrithione metabolites in human urine.

Pyrithione glucuronide (PTG) and 2-thiopyridine glucuronide (ThPG) have been reported to be the major urinary metabolites in multiple animal species following administration of zinc pyrithione (ZnPT). However, the formation of these metabolites has never been confirmed in humans. A simple and rugged ultra-high-performance liquid chromatography high resolution mass spectrometry (UHPLC-MS/HRMS) method was developed and validated for the quantification of PTG and ThPG to investigate human metabolism of pyrithione following topical application of ZnPT as a shampoo. A UHPLC-MS/HRMS method was required due to the matrix interferences that were observed with the typical industry standard HPLC/tandem mass spectrometry (LC-MS/MS) methodology based on nominal mass triple quadrupole (QQQ) platform approach. Using UPLC-MS/HRMS, both PTG and ThPG were identified in human urine following topical application of ZnPT. The presence of these human urinary metabolites of pyrithione are consistent with findings from earlier studies in multiple animal species and suggest the metabolism of pyrithione is similar amongst those mammalian species studied.

Rapid Antigingivitis Efficacy of a Novel Stannous Fluoride Dentrifice: Results from a 12-Week Randomized Controlled Clinical Trial.

OBJECTIVE: To assess the anti-gingivitis and anti-plaque efficacy of a novel bioavailable stannous fluoride (SnF2) dentifrice to a negative control. METHODS: This was a 12-week randomized, controlled, double-blind, two-treatment, parallel group clinical study. One hundred generally healthy adults with evidence of plaque and gingivitis were enrolled into the study. Subjects were randomly assigned to one of two dentifrice treatments: (1) novel SnF2 dentifrice containing the amino acid glycine as a stabilizing chelant (Procter and Gamble) or (2) a negative control sodium monofluorophosphate dentifrice. Gingivitis was assessed using the Löe-Silness Gingivitis Index (LSGI) at baseline, Week 1, and Week 12 while plaque was evaluated according to the Turesky Modification of the Quigley-Hein Plaque Index at baseline and Week 12. RESULTS: One hundred subjects completed the trial. Subjects using the novel SnF2 dentifrice demonstrated statistically significantly fewer bleeding sites and a lower LSGI score versus those using the negative control as early as Week 1 (P less than .001). The benefit increased throughout the study, with the SnF2 dentifrice showing 33.4% fewer bleeding sites and a 16.5% lower LSGI score versus the negative control at Week 12 (P less than .001). Subjects with localized or generalized gingivitis (≥10% bleeding sites) had 6 times better odds of transitioning to generally healthy (less than 10% bleeding sites) after using the SnF2 dentifrice for 12 weeks versus the negative control. Plaque scores for the SnF2 dentifrice were also statistically significantly lower (P less than .001) than those for the negative control at Week 12. CONCLUSION: The novel SnF2 dentifrice with the amino acid glycine produced statistically significant improvements in gingival health that were seen as early as 1 week and numerically increased throughout the study.

Bioavailable gluconate chelated stannous fluoride toothpaste meta-analyses: Effects on dentine hypersensitivity and enamel erosion.

OBJECTIVES: To compare the effect of bioavailable gluconate-chelated stannous fluoride (SnF2) toothpaste with control toothpastes for treatment of dentine hypersensitivity (DH) and enamel erosion. DATA AND SOURCES: A Procter & Gamble Oral Care archive of clinical studies was reviewed from 2000 to 2020. Eligible studies were Randomised Controlled Trials (RCTs) investigating bioavailable gluconate-chelated SnF2 toothpaste efficacy compared to controls in adult participants measured following tactile (Yeaple force) and/or evaporative stimuli (Schiff score) in-vivo, duration <2 months (DH); or by erosive toothwear (profilometry) from in-situ samples, duration 10-15 days. Two authors independently assessed eligibility and resolved disagreements by discussion. A meta-analysis was undertaken and Risk of Bias (RoB) assessed using the Cochrane collaboration RoB tool for randomized parallel-group and cross-over trials. RESULTS: Fourteen RCTs (1287 participants) assessed DH relief and Six RCTs (184 participants) enamel erosion protection. For DH SnF2 toothpastes provided a 57 % (evaporative air) and 142 % (tactile) benefit versus negative controls (sodium fluoride/monofluorophosphate, 8 studies; p < 0.001). Compared to positive controls (potassium nitrate or arginine, 6 studies), a 22 % advantage (p = 0.036) was seen for evaporative air. In erosion studies, SnF2 toothpastes provided an 83 % benefit versus control toothpastes (arginine or sodium fluoride; p < 0.001) with a change (95 %CI) in average surface profilometry level (µm) of -2.02(-2.85, -1.20). CONCLUSIONS: The use of these bioavailable SnF2 toothpastes, as part of a daily oral hygiene regimen, will provide patients with enamel erosion protection, combined with alleviation of DH pain when present, improving quality of life.

The relative clinical efficacy of three 0.454% stannous fluoride dentifrices for the treatment of gingivitis over 3 months.

PURPOSE: To assess the safety and efficacy of three stannous fluoride (SnF2) dentifrices in the reduction of gingivitis versus a negative control dentifrice. METHODS: This was a randomized, controlled, double-blind, four-treatment parallel group study. 120 healthy adult volunteers with established gingivitis were enrolled and randomly assigned to one of four dentifrice treatment groups (30/group): 0.454% SnF2 + citrate dentifrice A; 0.454% SnF2 + sodium hexametaphosphate dentifrice B; 0.454% SnF2 + pyrophosphate dentifrice C; or 0.76% sodium monofluorophosphate negative control group. Subjects brushed with their assigned dentifrice and an assigned regular manual toothbrush (Oral-B Indicator) for 1 minute twice daily for 12 weeks. Number of gingival bleeding sites and Löe-Silness Gingival Index (LSGI) scores were assessed at baseline and at Weeks 2, 4 and 12. RESULTS: 120 subjects were enrolled and 112 completed the trial. Subjects had an average age (SD) of 39.31 (14.5) years; 67% of subjects were female. Overall baseline means (SD) were 81.2 (25.6) for number of bleeding sites and 1.51 (0.197) for mean LSGI score. Baseline disease levels were balanced across all treatment groups. At Week 2, SnF2 dentifrices A and B demonstrated a significant reduction in gingival bleeding sites versus the negative control; however, SnF2 dentifrice C was not significantly different from the negative control (P= 0.15). At Weeks 4 and 12, all SnF2 dentifrices demonstrated a significant gingival bleeding site reduction versus the negative control (P< 0.001). At Weeks 2, 4 and 12, the SnF2 dentifrices were rank ordered dentifrice A > dentifrice B > dentifrice C for reduction in gingival bleeding sites (P< 0.001). The same trends were seen for LSGI scores. CLINICAL SIGNIFICANCE: In this 12-week clinical study, all 0.454% SnF2 dentifrices delivered statistically significant reductions in the number of gingival bleeding sites relative to the negative control. Importantly, statistically significant efficacy differences were observed among the three 0.454% SnF2 dentifrices, demonstrating the important role that differences in formulation have on clinical efficacy.

The ability of a potassium oxalate gel strip to occlude human dentine tubules; a Novel in vitro: In situ Study.

OBJECTIVES: To determine if an oxalate strip reduced fluid flow in dentine samples and whether this reduction was maintained following a 14 day intra-oral period. METHODS: Dentine tubule fluid flow was measured by a modified Pashley cell in 40 acid-etched dentine discs 1 mm thick, diameter >10 mm, with an acquired pellicle, pre-equilibrated with Hartmann's solution and conditioned by toothbrushing, pre and post treatment (10 min) with an oxalate (3.14 %) gel strip or no treatment. One control and one test sample were exposed in-situ for 14 days to the oral environment in 20 healthy adult volunteers, and fluid flow re-measured. The appliance containing the two samples was removed for brushing with water after mealtimes when the participant brushed their teeth and for a 2 min daily soak in chlorhexidine. RESULTS: Fluid flow rate was reduced significantly immediately following treatment with the oxalate strip compared to baseline flow rate by 58 %. Following 14 days in-situ oral environment phase, a significant further reduction in fluid flow compared to baseline was identified in both control and oxalate strip treated samples, both (p < 0.0001), but the reduction was greater in the test samples, 94 % vs 87 %, p < 0.01. CONCLUSIONS: This novel investigation is the first to show fluid flow measurement using the Pashley model in dentine samples that have been housed in the mouth for 14 days. Treatment with an oxalate strip designed for dentine hypersensitivity alleviation reduced dentine fluid flow more than control providing evidence that the oxalate treatment withstood the oral environment over a prolonged time. CLINICAL SIGNIFICANCE: This study demonstrated the efficacy and durability of the oxalate precipitate over a 14 day period in achieving and maintaining dentine tubule occlusion when participants had no dietary restrictions. This demonstrates the suitability of the oxalate strip for the treatment of patients suffering from dentine hypersensitivity pain.

A randomized, controlled, two-month pilot trial of stannous fluoride dentifrice versus sodium fluoride dentifrice after oxalate treatment for dentinal hypersensitivity.

OBJECTIVES: To compare the effects of a stannous fluoride dentifrice and a sodium fluoride dentifrice on dentinal hypersensitivity when used with an oxalate-based regimen combining in-office and at-home treatment. MATERIALS AND METHODS: In this single-center, randomized, controlled, double-blind, pilot clinical trial, 30 subjects were professionally treated at baseline with a 3% oxalate/potassium salt solution on up to two target teeth, then randomized 1:1 to either 0.454% stannous fluoride or 0.243% sodium fluoride overlabeled dentifrice. Both groups were given 6 sensitivity strips (3.14% potassium oxalate gel) and a soft, manual toothbrush. Subjects were permitted to apply strips on up to two teeth, up to three times per tooth, at home as desired throughout the study. Dentinal sensitivity (cold air blast challenge) was assessed at baseline, immediately after post-professional treatment, and at day 60 using the Schiff scale and a Visual Analog Scale (VAS). RESULTS: Immediately after professional oxalate treatment, the overall mean Schiff and VAS score decreased 25.6% and 22.4% from baseline, respectively (p ≤ 0.001 for both). At day 60, further reductions in both mean scores were seen in both groups. There were no significant differences between the groups at day 60. All treatments were well tolerated. CONCLUSIONS: In subjects treated with oxalates for dentinal hypersensitivity, both stannous fluoride and sodium fluoride dentifrices are well tolerated, are feasible for routine use, and do not detract from the desensitizing effects of an in-office and at-home oxalate combination treatment regimen. CLINICAL RELEVANCE: Either stannous fluoride or sodium fluoride dentifrices can be recommended to dentinal hypersensitivity patients who undergo professional oxalate treatment.

Hypertriglyceridemia Induced Pancreatitis: Inpatient Management at a Single Pediatric Institution.

OBJECTIVES: Hypertriglyceridemia-induced pancreatitis is an important cause of acute pancreatitis (AP) in children, which lacks established guidelines. The aim of this study was to review management approaches at a single pediatric center. METHODS: This retrospective study included all inpatients younger than 21 years with AP and triglycerides (TG) of 1000 mg/dL or greater. A linear mixed effect model was used to calculate drop in TGs. The patient's diet, intravenous fluid (IVF) rate, insulin, and plasmapheresis were included in the model. RESULTS: Seventeen admissions were identified among 8 patients, average age 15 years (range, 6-19 years). Fifty percent had recurrent AP and 29% of admissions had complications including 1 death. The population was primarily female (75%), white (75%), and overweight, and 63% had diabetes. The median stay was 5.4 days. There were 14 approaches used with variations in IVF rates, insulin, plasmapheresis, and nill per os (NPO) versus feeds. Variables that reduced TG's were NPO, higher IVF rates, plasmapheresis, and insulin (P < 0.05). Importantly, NPO reduced TGs faster than those who started early nutrition. CONCLUSIONS: Hypertriglyceridemia is an important cause of pancreatitis in children. This study shares a management algorithm from a single institution. Larger studies are needed for more evidence-based guidelines.

The effects of oscillating-rotating electric toothbrushes on plaque and gingival health: A meta-analysis.

PURPOSE: To compare the effects of oscillating-rotating (O-R), sonic (side-to-side), and manual toothbrushes on plaque and gingival health after multiple uses in studies up to 3 months. METHODS: A meta-analysis was conducted on randomized clinical trials (RCTs) up to 3 months in duration to evaluate O-R electric toothbrush effectiveness regarding gingivitis reduction and plaque removal versus sonic and/or manual toothbrushes. To ensure access to subject-level data, this meta-analysis was limited to RCTs involving O-R toothbrushes from a single manufacturer conducted from 2007 to 2017 for which subject-level data were available and that satisfied criteria of duration, parallel design, examiner-graded, etc. For gingivitis studies, a one-step individual subject meta-analysis was used to assess direct and indirect treatment differences and to identify any subject-level covariates modifying treatment effects. In the two-step meta-analysis, individual participant data were first analyzed in each study independently using the last timepoint (up to 3 months), producing aggregate data for each study. Then forest plots were produced using these aggregate data with random-effects models. For plaque studies, the efficacy variables were standardized so direct comparisons could be generated using the 2-step meta-analysis. Network meta-analysis was performed to assess the indirect plaque comparisons. RESULTS: 16 parallel group RCTs with 2,145 subjects were identified assessing gingivitis via number of bleeding sites. In five and 11 gingivitis studies assessing O-R brushes versus manual and sonic brushes, respectively, a change in the average number of bleeding sites of -8.9 ( 95% CI: -15.9, -1.9) and -3.1 (95% CI: -3.8, -2.4) was observed (P ≤ 0.008). These reductions equate to a 50% and 28% bleeding benefit for O-R technology versus the respective controls. The sonic brush bleeding change versus manual was -5.9 (P = 0.062), a 34% bleeding benefit. Utilizing individual bleeding scores, subjects with localized or generalized gingivitis (≥ 10% bleeding sites) had 7.4 times better odds of transitioning to generally healthy (< 10% bleeding sites) after using an O-R brush versus manual. 20 parallel design RCTs with 2,551 subjects assessed plaque (TMQHI, RMNPI). In eight and 12 plaque RCTs assessing an O-R brush versus manual and sonic brushes, respectively, standardized changes in average plaque scores of -1.51 (95% CI: -2.17, -0.85) and -0.55 (95% CI: -0.82, -0.28) were observed (P< 0.001). These plaque reductions by O-R equate to a relative 20% and 4% greater benefit, respectively. The change for sonic versus manual was -0.93 ( 95% CI:-1.48, -0.38); (P < 0.001) which equates to a 12% plaque benefit. CLINICAL SIGNIFICANCE: This subject-level meta-analysis of studies up to 3 months provides sound evidence supporting recommendations for patients with various degrees of gingival bleeding to use oscillating-rotating electric toothbrushes over manual and sonic toothbrushes to improve plaque control and gingival health.

The effects of bioavailable gluconate chelated stannous fluoride dentifrice on gingival bleeding: Meta-analysis of eighteen randomized controlled trials.

AIM: To estimate gingivitis effects of a bioavailable gluconate chelated 0.454% stannous fluoride (SnF2 ) family of dentifrices in adult subjects versus positive (triclosan) and negative (NaF or MFP) controls when used ≤3 months. MATERIALS AND METHODS: A meta-analysis evaluated bioavailable gluconate chelated SnF2 dentifrices versus a negative or positive control for gingival bleeding. RESULTS: In 18 randomized controlled trials (RCTs) with 2,890 subjects assessing SnF2 paste versus a negative or positive control, the average number of bleeding sites was reduced by 51% and 31%, respectively. The average change (95% CI) in number of bleeding sites was -16.3 (-27.8, -4.9) versus the negative control and -3.6 (-5.4, -1.8) versus the positive control. Subjects with localized or generalized gingivitis had 3.7 times better odds (95% CI [2.8, 5.0]) of shifting to generally healthy using SnF2 versus a negative control and 2.8 times better odds (95% CI [2.1, 3.9]) of shifting to generally healthy using SnF2 versus a positive control. The individual study risk of bias was deemed to be low in all categories of bias. CONCLUSION: This meta-analysis demonstrates significant gingivitis benefits of bioavailable SnF2 dentifrices when used ≤3 months versus positive (triclosan) and negative (NaF or MFP) controls.

Clinical assessment of a manual toothbrush with CrissCross and tapered bristle technology on gingivitis and plaque reduction.

PURPOSE: The primary aim of this study was to evaluate the gingivitis-reduction efficacy of an experimental manual toothbrush with CrissCross and tapered bristle technology in comparison with a marketed control manual toothbrush with traditional design and non-tapered bristles. In addition, the study compared the two toothbrushes for plaque-reduction efficacy. METHODS: This was a randomized, controlled, parallel group, examiner-blind, single-center, 4-week clinical trial with adult subjects in good general health. All subjects had presence of gingivitis (at least 10 bleeding sites). The subjects were randomly assigned to one of two treatment groups: a manual toothbrush having CrissCross and tapered bristle technology (tapered group: Oral-B CrossAction Ultrathin manual toothbrush); or a traditional flat-trim design and regular non-tapered bristles (control group: Oral-B Indicator Soft 35 manual toothbrush). Subjects were instructed to brush twice-daily for 4 weeks with their assigned brush and a standard sodium fluoride dentifrice. At baseline, Week 2, and Week 4, gingivitis was assessed using the Mazza Modification of the Gingival Bleeding Index (Mazza GI) and pre-brushing whole-mouth plaque was measured using the Turesky Modification of the Quigley-Hein Plaque Index (TMQHPI). RESULTS: 100 subjects (50 per group) were randomized to treatment and assessed at baseline, and 97 subjects (48 in the tapered group and 49 in the control group) completed the study. At both Weeks 2 and 4, both groups showed a significant (P< 0.005) reduction versus baseline in Mazza GI and number of bleeding sites, and the tapered group showed a significantly (P< 0.001) greater reduction from baseline for both these assessments compared to the control group. By Week 4 the tapered group showed a reduction from baseline of 17.9% in Mazza GI and 38.5% in the number of bleeding sites; the corresponding figures for the control group were 7.5% and 12.6%, respectively. Both groups showed a significant (P< 0.001) reduction versus baseline in TMQHPI by Week 4, with no significant (P=0.06) between-group difference. CLINICAL SIGNIFICANCE: The twice-daily use of a manual toothbrush with CrissCross design and tapered bristles had a statistically significantly greater gingivitis reduction compared to a manual toothbrush of traditional flat-trim design and regular non-tapered bristles, which could be a clinical advantage.

A randomised controlled trial to investigate the efficacy of an oxalate strip for the management of dentine hypersensitivity pain.

OBJECTIVES: To compare a 3.14% potassium oxalate strip and 8% arginine calcium carbonate toothpaste for the reduction of dentine hypersensitivity after 2 and 4 weeks. METHODS: This was an examiner-blind, parallel study in 80 healthy adults with dentine hypersensitivity (Schiff score >2) in >1 tooth. After acclimatisation, participants were randomised to the oxalate desensitising strip with fluoride toothpaste or the arginine desensitising toothpaste control which also contained fluoride. Products were applied under supervision of study staff after measuring baseline sensitivity, thereafter the strip or control toothpaste (fingertip application) was applied after 1 and 2 weeks, and teeth brushed twice-daily with the fluoride (test group) or the fluoridated arginine control toothpaste. Sensitivity was assessed following airblast (Schiff and VAS) and tactile stimuli (Yeaple probe) at baseline, 2 and 4 weeks. RESULTS: Both groups showed significant reductions from baseline in VAS, Schiff and Yeaple sensitivity scores after 2 and 4 weeks (p < 0.0005). The oxalate group had significantly lower Schiff and higher Yeaple probe scores compared to control after both time points (p < 0.0002 and p < 0.05), but while scores favoured the oxalate group, there were no significant differences in VAS. CONCLUSIONS: This study demonstrated application of a 3.14% potassium oxalate strip combined with toothbrushing with paste was more effective in pain management of dentine hypersensitivity than brushing with arginine toothpaste. CLINICAL SIGNIFICANCE: Treatment of sensitive teeth with the oxalate strip reduced dentine hypersensitivity after 2 and 4 weeks to a significantly greater degree than a positive control sensitivity toothpaste demonstrating that oxalate strips are an effective targeted treatment for dentine hypersensitivity sufferers.

Documenting an epidemic of suffering: low health-related quality of life among transgender youth.

PURPOSE: To quantify HRQOL of TGN patients using the PedsQL 4.0 generic core scales, and to compare reported HRQOL of TGN adolescents with published data from comparison populations. METHODS: Transgender children and adolescents (N = 142; 68% natal females) ages 6-23 years (M = 15.9, SD = 3.7) attending an outpatient clinic for TGN care at an academic pediatric hospital and caregivers of children and adolescents (N = 95) completed the PedsQL 4.0 generic core scales. Scores were compared with published scores for healthy adolescents and adolescents with 10 chronic diseases. RESULTS: TGN youth reported significantly lower overall HRQOL (more than twice the clinically meaningful difference) compared to youth without chronic disease. Total self-reported TGN HRQOL (M(SD), 65.72(17.40)) was lower than all chronic disease comparison groups except for rheumatology and cerebral palsy. TGN youth reported physical functioning (M(SD), 75.33(22.87)) lower than or similar to chronically ill comparisons, but higher than rheumatology and cerebral palsy groups. Psychosocial functioning (M(SD), 59.87(17.83)) was lower than all comparison samples and similar to youth with cerebral palsy. Results were similar for parent proxy-reports of TGN youth HRQOL (LS means: 68.75; 95% CI 65.87-71.61 vs 66.16; 95% CI 62.87-69.45; p = 0.12). CONCLUSIONS: TGN youth reported low HRQOL across all domains; most were significantly lower than healthy peers or peers with chronic diseases. Clinicians should understand the magnitude of TGN youth's low HRQOL and offer them and their caregivers resources to maximize their ability to achieve their full potential for healthy and productive lives.

Bioequivalence between innovator and generic tacrolimus in liver and kidney transplant recipients: A randomized, crossover clinical trial.

BACKGROUND: Although the generic drug approval process has a long-term successful track record, concerns remain for approval of narrow therapeutic index generic immunosuppressants, such as tacrolimus, in transplant recipients. Several professional transplant societies and publications have generated skepticism of the generic approval process. Three major areas of concern are that the pharmacokinetic properties of generic products and the innovator (that is, "brand") product in healthy volunteers may not reflect those in transplant recipients, bioequivalence between generic and innovator may not ensure bioequivalence between generics, and high-risk patients may have specific bioequivalence concerns. Such concerns have been fueled by anecdotal observations and retrospective and uncontrolled published studies, while well-designed, controlled prospective studies testing the validity of the regulatory bioequivalence testing approach for narrow therapeutic index immunosuppressants in transplant recipients have been lacking. Thus, the present study prospectively assesses bioequivalence between innovator tacrolimus and 2 generics in individuals with a kidney or liver transplant. METHODS AND FINDINGS: From December 2013 through October 2014, a prospective, replicate dosing, partially blinded, randomized, 3-treatment, 6-period crossover bioequivalence study was conducted at the University of Cincinnati in individuals with a kidney (n = 35) or liver transplant (n = 36). Abbreviated New Drug Applications (ANDA) data that included manufacturing and healthy individual pharmacokinetic data for all generics were evaluated to select the 2 most disparate generics from innovator, and these were named Generic Hi and Generic Lo. During the 8-week study period, pharmacokinetic studies assessed the bioequivalence of Generic Hi and Generic Lo with the Innovator tacrolimus and with each other. Bioequivalence of the major tacrolimus metabolite was also assessed. All products fell within the US Food and Drug Administration (FDA) average bioequivalence (ABE) acceptance criteria of a 90% confidence interval contained within the confidence limits of 80.00% and 125.00%. Within-subject variability was similar for the area under the curve (AUC) (range 12.11-15.81) and the concentration maximum (Cmax) (range 17.96-24.72) for all products. The within-subject variability was utilized to calculate the scaled average bioequivalence (SCABE) 90% confidence interval. The calculated SCABE 90% confidence interval was 84.65%-118.13% and 80.00%-125.00% for AUC and Cmax, respectively. The more stringent SCABE acceptance criteria were met for all product comparisons for AUC and Cmax in both individuals with a kidney transplant and those with a liver transplant. European Medicines Agency (EMA) acceptance criteria for narrow therapeutic index drugs were also met, with the only exception being in the case of Brand versus Generic Lo, in which the upper limits of the 90% confidence intervals were 111.30% (kidney) and 112.12% (liver). These were only slightly above the upper EMA acceptance criteria limit for an AUC of 111.11%. SCABE criteria were also met for the major tacrolimus metabolite 13-O-desmethyl tacrolimus for AUC, but it failed the EMA criterion. No acute rejections, no differences in renal function in all individuals, and no differences in liver function were observed in individuals with a liver transplant using the Tukey honest significant difference (HSD) test for multiple comparisons. Fifty-two percent and 65% of all individuals with a kidney or liver transplant, respectively, reported an adverse event. The Exact McNemar test for paired categorical data with adjustments for multiple comparisons was used to compare adverse event rates among the products. No statistically significant differences among any pairs of products were found for any adverse event code or for adverse events overall. Limitations of this study include that the observations were made under strictly controlled conditions that did not allow for the impact of nonadherence or feeding on the possible pharmacokinetic differences. Generic Hi and Lo were selected based upon bioequivalence data in healthy volunteers because no pharmacokinetic data in recipients were available for all products. The safety data should be interpreted in light of the small number of participants and the short observation periods. Lastly, only the 1 mg tacrolimus strength was utilized in this study. CONCLUSIONS: Using an innovative, controlled bioequivalence study design, we observed equivalence between tacrolimus innovator and 2 generic products as well as between 2 generic products in individuals after kidney or liver transplantation following current FDA bioequivalence metrics. These results support the position that bioequivalence for the narrow therapeutic index drug tacrolimus translates from healthy volunteers to individuals receiving a kidney or liver transplant and provides evidence that generic products that are bioequivalent with the innovator product are also bioequivalent to each other. TRIAL REGISTRATION: ClinicalTrials.gov NCT01889758.

Spiritual Struggle in Parents of Children with Cystic Fibrosis Increases Odds of Depression.

OBJECTIVE: Spiritual struggle (SS) is associated with poorer health outcomes including depression. The study's main objectives were to characterize change in depression over time, examine longitudinal associations between SS and depression, and determine the extent to which experiencing SS at baseline was predictive of developing depression at follow-up. METHODS: A two-site study collected questionnaire responses of parents (N = 112; 72% female) of children with cystic fibrosis followed longitudinally. Generalized linear mixed effects modeling examined the association between depression and SS over time and assessed potential mediators, moderators, and confounders. RESULTS: Prevalence of depression increased from baseline to follow-up (OR: 3.6, P < 0.0001), regardless of degree of SS. Parents with Moderate/Severe SS were more likely to have depressive symptoms, compared to parents without SS (OR: 15.2, P = 0.0003) and parents who had Mild SS (OR: 10.2, P = 0.0001). Being female and feeling less "at peace" also significantly predicted increased depression (OR: 2.5, P = 0.0397, and OR: 1.15, P = 0.0419, resp.). Experiencing SS at baseline was not predictive of having depression subsequently at follow-up. CONCLUSIONS: Parents experiencing SS were significantly more likely to report depressive symptoms. Interventions to reduce SS have shown efficacy and may be considered.

Longitudinal Cardiovascular Outcomes of Sleep Disordered Breathing in Children: A Meta-Analysis and Systematic Review.

Objectives: The presence of sleep disordered breathing (SDB) is known to impact long-term cardiovascular morbidity in adults; however, the long-term effects in children are poorly understood. We aimed to systematically review and synthesize studies published to date on the long-term effects of SDB in children. Study Design: Meta-analysis and systematic review using PubMed, CINAHL, Embase, and Scopus (all indexed years). Methods: We searched for English-language articles containing original human data from prospective studies, with ≥7 participants, in children ≤18 years of age. Data regarding study design, demographics, clinical characteristics, outcomes, level of evidence, and risk of bias were obtained. Articles were independently reviewed by three investigators. Retrospective and cross-sectional studies were excluded. Results: Of 1701 identified abstracts, 25 articles (combined n = 1418) were ultimately included. All studies reported longitudinal outcomes following treatment of SDB, 21 studies exclusively reporting outcomes after adenotonsillectomy. Therefore, studies were combined to objectively assess the effect of SDB treatment on cardiovascular outcomes. Although all cardiovascular parameters were within the normal range at baseline, at follow-up there was a significant decrease in mean pulmonary artery pressure, right ventricular end diastolic diameter, heart rate, mitral Em/Am ratio, and C-reactive protein. There was no significant change in interventricular septum thickness, left ventricular parameters (shortening fraction, systolic and end diastolic diameters, ejection fraction, posterior wall thickness, isovolumetric relaxation time), left atrial diameter, and aortic and pulmonary valve peak velocities. Conclusions: Studies assessing the long-term cardiovascular effects of SDB in children are limited. The available literature indicates effects on autonomic function, right, and left heart function following treatment for SDB. However, well-designed, large-scale, prospective cohort studies (using standardized outcomes) are needed to better understand the relationship of cardiovascular morbidity in the context of pediatric SDB.