European Organization for Caries Research Workshop: Methodology for Determination of Potentially Available Fluoride in Toothpastes

Toothpastes are the most universally accepted form of fluoride delivery for caries prevention. To provide anti-caries benefits, they must be able to release fluoride during the time of tooth brushing or post brushing into the oral cavity. However, there is no standard accepted procedure to measure how much fluoride in a toothpaste may be (bio) available for release. The European Organization for Caries Research proposed and supported a workshop with experts in fluoride analysis in toothpastes and representatives from industry. The objective of the workshop was to discuss issues surrounding fluoride analysis in toothpaste and reach consensus on terminology and best practices, wherever the available evidence allowed it. Participants received a background paper and heard presentations followed by structured discussion to define the problem. The group also reviewed evidence on the validity, reliability and feasibility of each technique (namely chromatography and fluoride electroanalysis) and discussed their strengths and limitations. Participants were able to reach a consensus on terminology and were also able to identify and summarize the advantages and disadvantages of each technique. However, they agreed that most currently available methods were developed for regulatory agencies several decades ago, utilizing the best available data from clinical trials then, but require to be updated. They also agreed that although significant advances to our understanding of the mechanism of action of fluoride in toothpaste have been achieved over the past 4 decades, this clearly is an extraordinarily complex subject and more work remains to be done

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Remineralization of Early Enamel Lesions with Apatite-Forming Salt

Objectives: This study sought to evaluate the remineralization of ex vivo human teeth using commercially available artificial saliva, SalivaMAX®, a supersaturated calcium phosphate rinse (SSCPR). Methods: early enamel lesions were artificially induced on ex vivo human teeth by chemical means. The teeth were exposed to the SSCPR for two minutes (experimental) or dH2O (control) four times per day for a total of 35 days. At time points of 0, 2.5, 21, and 35 days, micro-CT was utilized to determine the mineral density profile across the lesion and evaluate lesion depth. The relative percent remineralization was calculated from the initial lesion depth (Time 0) at each evaluation time. Student’s t-test was used to compare the extent of remineralization between the SSCPR and control groups for statistical significance at each time. To evaluate the changes in percent remineralization over time, a two-way ANOVA was used. Results: At Time 0 and 2.5 days, there was no difference in the percent remineralization between the SSCPR and control groups (p > 0.05). After 21 days, the teeth exposed to the SSCPR remineralized 56.7 ± 3.7%, while the control only remineralized 10.7 ± 11.0% (p p < 0.0001) for the SSCPR and control groups, respectively. Conclusions: A marked increase in remineralization occurred with the use of the SSCPR. Notably, the remineralization of the SSCPR occurred deep within the tooth and progressed toward the surface over time

Dentin Erosion: Method Validation and Efficacy of Fluoride Protection

The aging population experiences more gingival recession and root exposure which increases the opportunity for dentin erosion. This study tested the use of transverse microradiography (TMR) methods to assess dentin erosion and the interaction between fluoride and citric acid on the amount of erosion in the dentin samples. In a 4 × 3 interaction experimental design, four fluoride concentrations (0.00, 25.0, 50.0, and 100.0 mg/L) and three citric acid concentrations (0.0, 0.25, and 1.00%) were combined to form 12 experimental solutions. Forty-eight dentin samples were placed in the experimental solutions for 1 and 4 h and the amount of surface lost was determined by TMR methods. The resolution of the TMR method was 0.9 μm per pixel with a 0.1% and a 5% confidence interval of ±4.2 μm. Dentin erosion increased with the concentration of citric acid and time, the erosion decreased when concentration of fluoride was increased. Effects due to fluoride and citric acid concentrations individually, and their interaction on the amount of erosion observed was statistically significant (p &lt; 0.0001). This study found that TMR methods are appropriate and that 25.0 mg/L was the optimal fluoride concentration to protect dentin from a 1.00% citric acid challenge

Medicaid Adult Dental Benefit Impact on Dental Utilization: A University Clinic Setting

IntroductionIn 2014, the state of Colorado initiated new dental coverage benefits for adults in the Colorado Medicaid program. The goal of this study was to investigate the utilization and impact of this new dental coverage at the University of Colorado School of Dental Medicine. The utilization of dental services delivered and the numbers of patients in this program were compared before and after the implementation of the benefit.Materials and methodsThis retrospective study compared the utilization of services provided 2 years prior and 2 years after the Medicaid adult benefit was made available. Through the University of Colorado School of Dental Medicine (CU-SODM) electronic dental record, all adult Medicaid dental patients’ (ages 21+) charts were extracted for zip code, CDT dental procedure codes, with a focus on tooth extraction compared to tooth saving procedures. Graphical analysis and Pearson’s chi-squared tests were applied to assess the statistical significance of procedure utilization changes over time.ResultsAfter implementation of the Medicaid adult benefit, the number of patients seen at the school under this program increased by a factor of 4.5. The geographic range (zip code) increased with some patients coming from further distances to receive dental care. The number of patients from local zip codes increased by as much as 235%. There was a 51% increase in tooth saving procedures, which was statistically significant (P = 0.0013). Additionally, there was a 22% decrease in extractions, while not statistically significant (P = 0.0992), a downward trend was clear.DiscussionThe focus was on the utilization of Medicaid adult benefits at the dental school, which was only a small proportion of the state-wide Medicaid population. Therefore, these data are not generalizable for statewide assessments of the program. However, based on the findings at the school clinics, more adult patients utilized the benefits; and chose to receive more tooth saving procedures and less extractions after implementation of the Medicaid adult benefit. This Medicaid study conducted at the CU-SODM 2 years after the adult dental coverage can be used as a baseline for future studies

Clinical Utility of Ventricular Repolarization Dispersion for Real-Time Detection of Non-ST Elevation Myocardial Infarction in Emergency Departments.

BackgroundA specific electrocardiographic (ECG) marker of ischemia would greatly improve the speed and accuracy of detecting and treating non-ST elevation myocardial infarction (NSTEMI). We hypothesize that ischemia induces ventricular repolarization dispersion (VRD), altering the T-wave before any ST segment deviation. We sought to evaluate the clinical utility of VRD to (1) detect NSTEMI cases in the emergency department (ED) and (2) identify NSTEMI cases at high risk for in-hospital major adverse cardiac events (MACEs).Methods and resultsWe continuously recorded 12-lead Holter ECGs from chest pain patients upon their arrival to the ED. VRD was quantified using principal component analysis of the 12-lead ECG to compute a T-wave complexity ratio (ie, ratio of second to first eigenvectors of repolarization). Clinical outcomes were obtained from hospital records. The sample was composed mainly of older males (n=369; ages 63±12 years; 63% males), and 92 (25%) had NSTEMI and 26 (7%) had MACEs. Baseline T-wave complexity ratio modestly correlated with peak troponin levels (r=0.41; P&lt;0.001) and was a good classifier of NSTEMI events (area under the curve=0.70). An increased T-wave complexity ratio on the presenting ECG was strongly associated with NSTEMI (odds ratio [OR]=3.8 [2.1 to 5.8]) and in-hospital MACE (OR=8.2 [3.1 to 21.5]).ConclusionsA simple measure of global VRD on the presenting 12-lead ECG correlates with ischemic myocardial injury and can discriminate NSTEMI cases very early during evaluation. Prospective studies should validate these findings and test whether VRD can guide therapy