Cystic fibrosis learning network telehealth innovation lab during the COVID-19 pandemic: a success QI story for interdisciplinary care and agenda setting.

INTRODUCTION: The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH. AIM: The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020. METHODS: The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan-do-study-act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform. RESULTS: Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS. CONCLUSION: Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.

Clinical Effects of Stabilized Stannous Fluoride Dentifrice in Reducing Plaque Microbial Virulence II: Metabonomic Changes.

OBJECTIVES: The clinical effects of stannous fluoride (SnF2) dentifrice in reducing symptoms of gingivitis and reducing the virulence of subgingival plaque through suppression of activation of gene expression in toll receptor based reporter cells were previously reported. This study expanded analysis of the clinical study to include evaluation of dentifrice effects on salivary metabolites using 1H Nuclear Magnetic Resonance (1H NMR) systems biology-based metabonomics. METHODS: The clinical design was reported previously (J Clin Dent2017;28:16-26). Participants included a cohort exhibiting high and low levels of gingival disease as presented at initiation of the study. Participants provided morning lavage saliva samples at baseline. Following this, participants were provided with a hygiene intervention, including a stabilized SnF2 dentifrice and a new soft bristle manual toothbrush. Following two and four weeks of assigned dentifrice use, participants again collected morning lavage saliva samples. Samples were analyzed by 1HNMR spectroscopy on a Bruker 600MHz NMR spectrometer. System-wide analyses were carried out by partial least squared (PLS) comparisons of aggregate spectra, and discrete metabolites with established spectral signatures were likewise directly compared. RESULTS: PLS analysis showed significant differences in saliva composition for saliva collected from high bleeding and low bleeding cohorts. Clear shifts in saliva composition were observed in system-wide PLS analysis following intervention of SnF2 dentifrice for both cohorts. A number of discrete spectral changes were consistently observed with SnF2 dentifrice intervention, most notably including reductions in propionic acid and butyric acid, key short chain fatty acids associated with anaerobic metabolism in dental plaques. CONCLUSIONS: These results collectively demonstrate that SnF2 dentifrice treatment was associated with broad scale modifications in saliva composition following intervention in both high and low diseased cohorts. Changes in overall salivary composition and specific reductions in saliva concentrations of propionic and butyric acid reductions occurred coincident with clinical improvements in gingivitis and gingival bleeding. These results provide support for the hypothesis that the effectiveness of SnF2 dentifrice in improving gingival health is associated with a modification of microbiome metabolism, including suppression of short chain fatty acid metabolites.

Quantitation of endotoxin and lipoteichoic acid virulence using toll receptor reporter gene.

PURPOSE: To apply quantitative Toll-like receptors (TLR) cell assays to compare lipopolysaccharides (LPSs) and lipoteichoic acids (LTAs) from different oral bacterial strains for potential pathogenicity in vitro. METHODS: The potency of LPS and LTA from different bacteria on activation of TLR reporter genes in HEK-tlr cell lines was examined. P. gingivalis LPS mix, P. gingivalis 1690 LPS, P. gingivalis 1435/50 LPS, E. coli LPS (E. coli K12), B. subtilis LTA, S. aureus LTA, E. hirae LTA and S. pyogenes LTA were examined in both TLR2 and TLR4 HEK cell line reporter assays. Solutions of LPS and LTA from selected bacteria were applied in a dose response fashion to the TLR reporter cells under standard culture conditions for mammalian cells. Reporter gene secreted-embryonic-alkaline-phosphatase (SEAP) was measured, and half maximal effective concentration (EC50) was determined for each sample. Concentration dependent TLR activation was compared to similar responses to LPS and LTA for commercial BODIPY-TR-Cadaverine and LAL biochemical (non cell based) assays. RESULTS: All LPS from P. gingivalis activated both TLR2 and TLR4 responses. E. coli LPS is a strong activator for TLR4 but not for TLR2 responses. In contrast, both B. subtilis and S. aureus LTA provoked responses only in TLR2, but not in the TLR4 assay. Interestingly, E. hirae LTA and S. pyogenes LTA did not stimulate strong TLR2 responses. Instead, both E. hirae LTA and S. pyogenes LTA mounted a reasonable response in TLR4 reporter gene assay. Both LPS and LTA showed deactivation of fluorescence in BODIPY-TR-Cadaverine while only LPS was active in LAL. As with biochemical assays, an EC50 could be determined for LPS and LTA from various bacterial strains. The EC50 is defined as a concentration of LPS or LTA that provokes a response halfway between the baseline and maximum responses. Lower EC50 means higher potency in promoting TLR responses, and in principle indicates greater toxicity to the host. CLINICAL SIGNIFICANCE: InvivoGen TLR2 and TLR4 assays distinguish specific types of microbial products, such as LPS and LTA from different bacteria. Application of EC50 determinations creates a means for quantitative and comparisons of LPS and LTA virulence in a cellular-based assay and combinations of TLR reporter cell assays along with biochemical evaluation of LPS#47;LTA in BODIPY-TR-Cadaverine and LPS in LAL assays provides a means to quantitate virulence of plaque samples with respect to both LPS and LTA. These learnings have long-term implications for patient care in that understanding the virulence of patients' plaque provides important information to assess risk of oral diseases.

Comparative Effects of 1.5% Oxalate Strips Versus 5% Potassium Nitrate Dentifrice on Dentin Hypersensitivity.

A randomized controlled trial was conducted to evaluate the safety and efficacy of a novel 1.5% oxalate sensitivity strip. Healthy adults with dentin hypersensitivity after a cool-air challenge were randomly assigned either three sensitivity strips (Crest® Sensi-Stop™ Strips, Procter and Gamble) plus regular toothpaste (experimental group) or 5% potassium nitrate dentifrice for twice-daily use (control group). First use was supervised, and response was measured immediately after first treatment and again 30 days later after direct provocation with air and tactile stimuli. A total of 79 subjects (mean age 37 years) were randomized and treated. After the first treatment, only the 1.5% oxalate strip group exhibited significant (P less than .0001) immediate sensitivity relief to both air and tactile stimulation. Repeated use improved response and, over 30 days, both treatments were effective. Between-group comparisons favored the episodic strips versus the daily-use dentifrice, with a majority of oxalate strip users having no measured air sensitivity at Day 30. Both treatments were well tolerated. A randomized clinical trial showed immediate and durable sensitivity relief for 1.5% oxalate strips and superior response when compared head-to-head versus a potassium nitrate dentifrice.

Randomized Controlled Trial Evaluating Use of Two Different Oxalate Products in Adults with Recession-Associated Dentin Hypersensitivity.

A randomized positively controlled trial was conducted to evaluate the durable effects of 1.5% oxalate strips on dentin hypersensitivity. Informed consent and baseline measurements were obtained from adults with recession and air-related dentin hypersensitivity. Eligible subjects were randomized to one of two oxalate groups, either 1.5% oxalate gel strips (Crest® Sensi-Stop™ Strips, Procter and Gamble) or a professional oxalate-acid, potassium-salt solution (Super Seal® Dental Desensitizer Liner, Phoenix Dental). Test products were professionally administered at examiner-identified sensitive test sites following each manufacturer's instructions. Subjects received a blinded overwrapped anticavity paste and manual brush, two additional reapplication visits were scheduled over a 1-week period, and subjects returned 1 month later for evaluation. Sensitivity was evaluated using air and water stimuli measured by clinicians (Schiff Index) and subjects (visual analog scale), while safety was assessed by examination. The population (N = 80) was diverse with respect to gender, ethnicity, and age (22 to 82 years). At baseline, the overall mean (SD) air sensitivity was 1.34 (0.47), with individual subject means ranging from 1 to 2.5. Repeated treatment with both the commercial and professional oxalate treatments resulted in significant (P less than .05) reductions in sensitivity for all stimuli and methods. At the 1-month posttreatment recall, there were 84% to 86% reductions in clinically measured cool-air sensitivity for each oxalate group. Groups did not differ significantly (P > .57) on examiner or self-graded air or water sensitivity. In a clinical study, use of 1.5% oxalate gel strips yielded similar benefits as professionally applied oxalate treatments for adults with recession-based dentin hypersensitivity.

Response of chronic gingivitis to hygiene therapy and experimental gingivitis. Clinical, microbiological and metabonomic changes.

PURPOSE: To compare the clinical, microbiological and metabonomic profiles of subjects with high and low levels of chronic gingival bleeding during a controlled oral hygiene regimen intervention including sequential phases of rigorous therapeutic oral hygiene followed by experimental gingivitis (EG). METHODS: Two cohorts of qualified study subjects with differences in gingival bleeding on probing levels at their baseline clinical examination were entered into the study. These two cohorts were followed through three separate study phases including a 1-week baseline phase, a 2-week phase of rigorous oral hygiene including dental prophylaxis, and a 3-week EG phase of no oral hygiene to encourage relapse of gingivitis. The 58 subjects were assessed during each phase of the study for clinical presentation of gingivitis and concurrently had plaque sampled for real-time polymerase chain reaction (RTPCR) microbiological characterization and salivary lavage samples for 'systems biology' metabonomics assessment by 1H-NMR. RESULTS: Subjects presenting with different levels of gingival bleeding on probing when they entered the study responded differently to rigorous oral hygiene and EG. Specifically, the high bleeding cohort responded sluggishly to rigorous oral hygiene and exhibited markedly greater relapse to gingivitis during EG. RTPCR analysis showed changes in bacterial populations that were associated with study phases, particularly the increases in putative periodontal pathogens during EG. However, the microbiological profiles of high- and low-susceptibility gingival bleeding patients were largely similar. Metabonomic analysis likewise revealed significant changes in metabolite composition during study phases associated with differences in plaque toxicity, especially the short chain carboxylic acids propionate and n-butyrate, which tracked clinical changes in gingivitis severity. Systems analysis of metabonomic changes suggested differences between cohorts, although analysis to date has not elucidated whether these differences are causative (population predictive) or simply diagnostic of clinical status within populations.

A clinical study to assess the effect of a stabilized stannous fluoride dentifrice on hypersensitivity relative to a marketed sodium fluoride/triclosan control.

OBJECTIVE: To evaluate the efficacy of a marketed stabilized stannous fluoride (SnF2) dentifrice in reducing dentinal hypersensitivity as compared to a marketed sodium fluoride (NaF)/triclosan dentifrice over an eight-week period. METHODS: Adults with confirmed dentinal hypersensitivity were enrolled in this randomized and controlled, parallel group, double blind, eight-week, single-center clinical trial. Random assignment to one of two dentifrice test groups via age, gender, and thermal sensitivity of enrolled test teeth was performed at baseline, with subjects assigned to twice-daily unsupervised brushing with either the marketed SnF2 dentifrice (Oral-B Pro-Expert, 0.454% SnF2 plus 0.077% NaF) or the marketed 0.32% NaF with 0.3% triclosan/copolymer dentifrice control (Colgate Total Advanced). Tactile sensitivity (Yeaple Probe) and thermal sensitivity (airblast/Schiff Air Index) evaluations of the selected test teeth were performed at baseline pre-treatment, and again at Weeks 2 and 8 of product use to compare the dentifrices' relative hypersensitivity protection effectiveness. RESULTS: Ninety-seven (97) of the 100 enrolled subjects completed the trial and were fully evaluable. At both Week 2 and Week 8, for both the thermal and tactile evaluation measurements, subjects brushing with the marketed SnF2 dentifrice experienced statistically significantly (p < 0.0001) superior average dentinal hypersensitivity improvement versus subjects assigned to the NaF/triclosan control dentifrice. Between groups, superior relative mean reduction in thermal Schiff Air Index favored SnF2 by 24% at Week 2 and 68% at Week 8, while greater relative mean tactile Yeaple Probe benefits were observed for SnF2 relative to the control by 114% after Week 2 and 184% at Week 8. The dentifrices were well-tolerated. CONCLUSION: Twice-daily brushing with a marketed SnF2 dentifrice provided superior dentinal hypersensitivity improvement versus a commercially available NaF/triclosan dentifrice, with significantly (p < 0.0001) greater relief after two weeks, and even larger relative benefits at eight weeks.

Evaluation of anti-gingivitis benefits of stannous fluoride dentifrice among triclosan dentifrice users.

PURPOSE: To evaluate the anti-gingivitis benefits of a 0.454% highly bioavailable stannous fluoride dentifrice (SnF2) relative to a 0.3% triclosan/copolymer dentifrice (triclosan/copolymer) among triclosan/copolymer dentifrice users with residual gingivitis. METHODS: This was a randomized, controlled, double-blind, parallel group, 2-month clinical study. Self-reported triclosan/copolymer dentifrice users were recruited and provided with triclosan/copolymer dentifrice to use for 1 month. After this 1-month acclimation period, subjects who had residual gingivitis at the baseline visit were randomized to either the SnF2 dentifrice or the triclosan/copolymer dentifrice (positive control). Subjects performed their treatment unsupervised using their assigned dentifrice following manufacturers' usage instructions for 2 months. The Gingival Bleeding Index (GBI) and Modified Gingival Index (MGI) were used to measure gingivitis benefits at baseline and Month 2. An analysis of covariance was performed to compare treatment groups for the post-baseline scores as well as change from baseline, with the baseline score as a covariate. All comparisons were two-sided at the 0.05 level of significance. RESULTS: A total of 150 subjects were randomized to treatment. Both treatment groups experienced significant reductions in number of bleeding sites, gingival bleeding index (GBI), and gingival inflammation (MGI) relative to baseline (P < 0.001). At Month 2, the SnF2 dentifrice group demonstrated significantly lower adjusted mean scores versus the triclosan/copolymer group for number of bleeding sites, GBI, and MGI (P < 0.001). Between-treatment group comparisons for change from baseline values showed that the improvement in number of bleeding sites from baseline for the SnF2 group was 49% greater versus that of the triclosan/copolymer group (P < 0.001), and the GBI and MGI improvements from baseline for the SnF2 group were 48% and 37%, greater, respectively, relative to the triclosan/copolymer group (P < 0.001).