A Real-world Toxicity Atlas Shows that Adverse Events of Combination Therapies Commonly Result in Additive Interactions.

PURPOSE: Combination therapies are a promising approach for improving cancer treatment, but it is challenging to predict their resulting adverse events in a real-world setting. EXPERIMENTAL DESIGN: We provide here a proof-of-concept study using 15 million patient records from the FDA Adverse Event Reporting System (FAERS). Complex adverse event frequencies of drugs or their combinations were visualized as heat maps onto a two-dimensional grid. Adverse event frequencies were shown as colors to assess the ratio between individual and combined drug effects. To capture these patterns, we trained a convolutional neural network (CNN) autoencoder using 7,300 single-drug heat maps. In addition, statistical synergy analyses were performed on the basis of BLISS independence or χ2 testing. RESULTS: The trained CNN model was able to decode patterns, showing that adverse events occur in global rather than isolated and unique patterns. Patterns were not likely to be attributed to disease symptoms given their relatively limited contribution to drug-associated adverse events. Pattern recognition was validated using trial data from ClinicalTrials.gov and drug combination data. We examined the adverse event interactions of 140 drug combinations known to be avoided in the clinic and found that near all of them showed additive rather than synergistic interactions, also when assessed statistically. CONCLUSIONS: Our study provides a framework for analyzing adverse events and suggests that adverse drug interactions commonly result in additive effects with a high level of overlap of adverse event patterns. These real-world insights may advance the implementation of new combination therapies in clinical practice.

A Pilot Study Exploring Caregivers' Experiences Related to the Use of a Smart Toothbrush by Children with Autism Spectrum Disorder.

BACKGROUND: Research on caregivers for children with intellectual disabilities, particularly those with autism spectrum disorder (ASD), has highlighted several obstacles to achieving better oral health. These include challenges with tolerating oral care, sensory processing differences, uncooperative behaviors, and communication impairments. There is limited understanding of what caregivers would consider "successful assistance" in improving oral health for these children. OBJECTIVES: This pilot study aimed to examine caregivers' and user's experiences with a Kids Smart Electric Toothbrush used by children with ASD. METHODS: It involved open-ended interviews and questionnaires with caregivers prior to utilization of the toothbrush and after 4 weeks of product use by the child. RESULTS: Seventeen children with ASD, aged 5-12, participated. A total of 58.8% of caregivers said their child brushed more often, and all reported brushing at least twice a day by week 4. Caregivers reported that children became more independent while brushing their teeth and achieved better quality brushing. Caregivers' frustration with the brushing process, satisfaction with the device, and need to assist the child with brushing were improved. Caregivers did encounter some technical difficulties with the app. CONCLUSION: This study will assist in exploring "smart" toothbrush technologies for oral hygiene in children with ASD.

Current speed sintering and high-speed sintering protocols compromise the translucency but not strength of yttria-stabilized zirconia.

OBJECTIVES: To investigate the impacts of speed and high-speed sintering on the densification, microstructure, phase composition, translucency, and flexural strength of yttria-stabilized zirconia (YSZ). METHODS: A total of 162 disc-shaped specimens (n = 18) were cold-isostatically pressed from 3YSZ (Zpex), 4YSZ (Zpex 4), and 5YSZ (Zpex Smile) powders (Tosoh Corporation) and sintered according to the following protocols: conventional (control, ∼12 h), speed (∼28 min for 3YSZ; ∼60 min for 4YSZ and 5YSZ), and high-speed (∼18 min) sintering. Dimensions of zirconia specimens after sintering and polishing (1-µm diamond grit finish) were Ø13.75 × 1 mm. Density, microstructure, phase content, translucency parameter, and biaxial flexural strength were evaluated using Archimedes', SEM, XRD, spectrophotometric, and piston-on-3-ball methods, respectively. Data were analyzed with either one-way ANOVA and Tukey's test or Kruskal-Wallis with Dunn's test (α = 0.05). RESULTS: For all YSZ compositions, conventional sintering yielded the highest density followed by speed then high-speed sintering. All sintering protocols resulted in similar strength values; however, speed and high-speed sintering protocols afforded significantly lower translucency relative to conventional sintering. XRD analysis revealed similar spectra for YSZs sintered by various protocols. The speed sintered specimens had the smallest grain size whereas the high-speed sintered 5YSZ possessed the largest grain size among all groups. SEM examination of all YSZ compositions revealed that the average pore size was an order of magnitude smaller than the average grain size. SIGNIFICANCE: Speed and high-speed sintering of YSZs yield similar strength but diminished density and translucency relative to their conventionally sintered counterparts.

Exploring dental students' attitudes toward patient-centered management of dental fear.

PURPOSE/OBJECTIVES: A patient-centered care (PCC) paradigm undergirds modern dental education. PCC is particularly relevant in the management of patient dental fear. The aims of this study were three-fold: (a) to examine the preliminary psychometric properties of an author-designed survey administered to explore dental fear knowledge and perceptions, (b) to assess how 4th-year dental students regard dental fear, (c) and to investigate the relationship between students' knowledge and perceptions of dental fear and their clinical behavior. METHODS: In 2022, 4th-year dental students (N = 453) participated in a cross-sectional study. Participants completed a 16-item survey that assessed (a) knowledge and perceptions about dental fear, (b) common biases in patient fear assessment, and (c) patient management behaviors when fear is encountered. Exploratory factor analysis, descriptive statistics, and logistic regressions were run to address the study's aims. RESULTS: Exploratory factor analysis revealed three factors, with the two strongest factors pertaining to beliefs about the importance of dental fear (α = 0.87) and self-efficacy in managing fear (α = 0.74). Participants indicated that it is important to assess for dental fear and rated their self-efficacy in ability managing it as high. Ratings on both factors slightly increased the odds of engaging in routine patient screening for dental fear. Students also displayed assessment biases commonly seen among practicing dentists. CONCLUSION(S): Results indicate educational gaps within the current behavioral-science training for dental students. Changes to improve advanced dental students' appreciation of their patients' dental fear are warranted.

Leveraging technology to increase the disseminability of evidence-based treatment of dental fear: An uncontrolled pilot study.

OBJECTIVES: U.S. and global estimates indicate that over 30% of adults fear receiving dental care, including over 20% who have visited a dentist in the last year, leading to avoidance and degraded oral and systemic health. Although evidence-based cognitive-behavioral treatments for dental fear (CBT-DF) exist, they have little impact on the millions who seek dental care annually because they are not disseminable (6 h of in-chair time, delivered only in person at a few sites). We developed a disseminable CBT-DF stepped-care treatment comprising (Step 1) a mobile-health application and, for those who remain fearful, (Step 2) a 1-h, one-on-one psychological treatment session that allows practice during exposure to the patient's most-feared stimuli. We hypothesized that the treatment would (a) be rated highly on usability and credibility and (b) result in clinically consequential (i.e., lowering fear into the 0-3 "no/low fear" zone) and statistically significant changes in global dental fear. METHOD: Racially/ethnically diverse patients (N = 48) with moderate to severe dental fear were recruited; all completed Step 1, and n = 16 completed Step 2. RESULTS: As hypothesized, users found the stepped-care treatment highly usable, credible, and helpful. Critically, this stepped-care approach produced reductions in patients' dental fear that were both clinically consequential (with half no longer fearful) and statistically significant (d = 1.11). CONCLUSIONS: This usable, credible, stepped-care approach to dental fear treatment holds promise for liberating evidence-based CBT-DF from specialty clinics, allowing broad dissemination.

Changes in Dental Outcomes After Implementation of the Philadelphia Beverage Tax.

INTRODUCTION: Beverage taxes are associated with declines in sugar-sweetened beverage sales and consumption, but few studies have evaluated the associations of these taxes with health outcomes. This study analyzed changes in dental decay after the implementation of the Philadelphia sweetened beverage tax. METHODS: Electronic dental record data were obtained on 83,260 patients living in Philadelphia and control areas from 2014 to 2019. Difference-in-differences analyses compared the number of new Decayed, Missing, and Filled Teeth with that of new Decayed, Missing, and Filled Surfaces before (January 2014-December 2016) and after (January 2019-December 2019) tax implementation in Philadelphia and control patients. Analyses were conducted in older children/adults (aged ≥15 years) and younger children (aged <15 years). Subgroup analyses stratified by Medicaid status. Analyses were conducted in 2022. RESULTS: The number of new Decayed, Missing, and Filled Teeth did not change after tax implementation in Philadelphia in panel analyses of older children/adults (difference-in-differences= -0.02, 95% CI= -0.08, 0.03) or younger children (difference-in-differences=0.07, 95% CI= -0.08, 0.23). There were similarly no post-tax changes in the number of new Decayed, Missing, and Filled Surfaces. However, in cross-sectional samples of patients on Medicaid, the number of new Decayed, Missing, and Filled Teeth was lower after tax implementation in older children/adults (difference-in-differences= -0.18, 95% CI= -0.34, -0.03; -22% decline) and younger children (difference-in-differences= -0.22, 95% CI= -0.46, 0.01; -30% decline), with similar results for number of new Decayed, Missing, and Filled Surfaces. CONCLUSIONS: The Philadelphia beverage tax was not associated with reduced tooth decay in the general population, but it was associated with reduced tooth decay in adults and children on Medicaid, suggesting potential health benefits for low-income populations.

Strategies for managing dental care for refugee patients.

AIMS: To outline key factors that contribute to oral health issues of refugees and asylum seekers and provide management strategies for dental providers to teach desensitization and fear reduction for this special population. METHODS AND RESULTS: We researched published literature in the PubMed database and incorporated lessons gained from treating refugee and asylee patients at a Vulnerable Populations Clinic (VPC) at an urban academic dental school. Refugees and asylees are at high risk for oral conditions due to a tendency to not seek routine dental treatment, psychological stressors, and various systemic factors. Oral health providers can teach patients desensitization and fear reduction by working to gain patients' trust by having effective communication and prioritizing comfort in the dental operatory. Providers should also utilize translation, psychological, and/or multicultural support services during their management of care. CONCLUSION: By having a stronger understanding of the key causes of oral health issues among refugees and asylees in the United States, dental providers can better approach managing care for this vulnerable patient population. The concepts of teaching desensitization and fear reduction utilized for this special population can be applied to managing care for the wider special needs patient community.

Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission.

Because oral transmission of SARS-CoV-2 is 3-5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 µg of FRIL (p < 0.0001) and 0.925 µg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50-100 ng FRIL or 600-800 µg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.

Penntorship: The value of mentoring during a pandemic.

COVID-19 presented learning and social challenges for dental and high-school students alike due to isolating environments with fewer interpersonal interactions. After recognizing these challenges, two pre-doctoral dental students developed Penntorship, a program at University of Pennsylvania, School of Dental Medicine, where dental students' mentor students at West Philadelphia High School (WPHS) utilizing online technology. PURPOSE: This survey study explored the benefits of a newly developed mentoring program, Penntorship, for mentors and mentees. METHODS: Seventy dental students volunteered to mentor WPHS students throughout the 2020-2021 school year. After receiving training by Mentor Independence Region, mentors coordinated weekly meetings with mentees on Zoom to assist with homework assignments, discuss interests, and assess mentee's career goals. Over six months, 185 mentor meetings were held by 56 dental students with 28 different high-school students participating in the program. Surveys were distributed and analyzed to determine outcomes of the program. RESULTS: Survey results revealed that both dental students and high-school students gained new friendships, improved communication skills, and developed a positive perspective during the pandemic. CONCLUSION: With online learning formats and social distancing during the pandemic, dental students expressed a need for more social interaction. Penntorship served to support dental students during this challenging year and filled a social need for young individuals in the community. Both mentors and mentees benefited from the program and will continue to work together in the coming academic year. *IRB approval obtained 8/30/2021.

Oral bacterial decontamination using an innovative prototype for photocatalytic disinfection.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of a prototype photocatalytic device for bacterial decontaminations of the oral cavity. METHODS: Sixty-four subjects (18-65) were selected and randomly assigned to eight groups (n = 8), according to oral disinfection protocol: (G1): distilled water (control); (G2): 1.5% hydrogen peroxide (HP); (G3): 3.0% HP; (G4): 0.12% chlorhexidine (CHX); (G5): Germinator; (G6): 1.5% HP + Germinator; (G7): 3.0%HP + Germinator; (G8): 0.12% CHX + Germinator. Stimulated saliva was collected before and after a 3-min mouthwash and/or Germinator application. The patients were kept relaxed and retained saliva 5-10 min, spitting out into the tube for 3 min. The percentage bacterial reduction was checked by counting the colony-forming units (CFUs) after culturing on blood agar plates. Data were subjected to one-way ANOVA followed by Tukey's post hoc test (α = 5%) for statistical significance. RESULTS: The highest bacterial reduction was observed in groups 3 (3.0% HP), 6 (1.5% HP + Germinator), and 7 (3.0% + Germinator), with no statistically significant difference between them (p > 0.05). Groups 6 (1.5% HP + Germinator) and 8 (0.12% CHX + Germinator) showed higher bacterial reduction than groups 2 (1.5% HP) and 4 (0.12% CHX) (p < 0.05). Finally, group 5 (Germinator) showed higher bacterial reduction than control group (DW) and group 4 (0.12% CHX) (p < 0.05). CONCLUSIONS: The photocatalytic disinfection was effective against oral bacteria and improved the antimicrobial action of 1.5% HP and 0.12%. CLINICAL SIGNIFICANCE: The photocatalytic disinfection can be an alternative protocol to provide the oral decontamination.

Residual stresses explaining clinical fractures of bilayer zirconia and lithium disilicate crowns: A VFEM study.

OBJECTIVE: To understand the stress development in porcelain-veneered zirconia (PVZ) and porcelain-veneered lithium disilicate (PVLD) crowns with different veneer/core thickness ratios and cooling rates. To provide design guidelines for better performing bilayer restorations with the aid of Viscoelastic Finite Element Method (VFEM). METHODS: The VFEM was validated by comparing the predicted residual stresses with experimental measurements. Then, the model was used to predict transient and residual stresses in the two bilayer systems. Models with two different veneer/core thickness ratios were prepared (2:1 and 1:1) and two cooling protocols were simulated (Fast: ∼300 °C/min, Slow: ∼30 °C/min) using the heat transfer module, followed by stress analysis in ABAQUS. The physical properties of zirconia, lithium disilicate, and the porcelains used for the simulations were determined as a function of temperature. RESULTS: PVLD showed lower residual stresses than PVZ. The maximum tensile stresses in PVZ were observed in the cusp area, whereas those in PVLD were located in the central fossa. The 1:1 thickness ratio decreased stresses in both layers of PVZ. Slow cooling slightly decreased residual stresses in both systems. However, the cooling rate effect was more evident in transient stresses. SIGNIFICANCE: Slow cooling is preferable for both systems. A thinner porcelain layer over zirconia lowers stresses throughout the restoration. The different stress distributions between PVZ and PVLD may affect their failure modes. Smaller mismatches in modulus, CTE, and specific heat between the constituents, and the use of low Tg porcelains can effectively reduce the deleterious transient and residual tensile stresses in bilayer restorations.

The Profound Impact of COVID-19 on the Dental Profession.

The coronavirus disease (COVID-19) pandemic has impacted the world in unprecedented ways. It is clear that this pandemic, unlike any public health challenge in recent memory, has the potential to fundamentally alter the delivery of many healthcare services, including dentistry. As evidence-based information on COVID-19 continues to emerge, this article serves as a means to disseminate current opinions, management strategies, and the impact of COVID-19 on dentistry.

Radiology of Dental Caries.

Dental caries is a dynamic, preventable, reversible, complex biofilm-mediated, multifactorial disease that involves a series of demineralization/neutrality/remineralization of dental hard tissue in primary and permanent dentition. An imbalance in the continuum with a net demineralization over time results in the initiation of caries lesions. Visual inspection and intraoral radiographs are vital in caries detection, although they are of suboptimal sensitivity for early caries lesions. Shifting toward a conservative, noninvasive approach to caries management has resulted in the development of innovative-sensitive technologies. These newer techniques may serve as adjunct for the dental practitioner in detecting earliest changes in tooth structure.

Diagnosis of Biofilm-Associated Peri-Implant Disease Using a Fluorescence-Based Approach.

Dental implants have become a routine component of daily dental practice and the demand for dental implants is expected to increase significantly in the future. Despite the high success rates of dental implants, failures do occur, resulting in discomfort, rampant destruction of the oral health, or painful and costly surgical replacement of a failed implant. Peri-implant diseases are inflammatory conditions affecting the soft/hard tissues surrounding a functional dental implant. Plenty of experimental evidence indicates that the accumulation of dental plaque at the soft tissue-implant interface and the subsequent local inflammatory response seems to be key in the pathogenesis of the peri-implant mucositis. Such peri-implant-soft tissue interface is less effective than natural teeth in resisting bacterial invasion, enhancing vulnerability to subsequent peri-implant disease. Furthermore, in certain individuals, it will progress to peri-implantitis, resulting in alveolar bone loss and implant failure. Although early diagnosis and accurate identification of risk factors are extremely important to effectively prevent peri-implant diseases, current systematic reviews revealed that a uniform classification and diagnostic methodology for peri-implantitis are lacking. Recent progress on fluorescence-based technology enabled rapid diagnosis of the disease and effective removal of plaques. Here, we briefly review biofilm-associated peri-implant diseases and propose a fluorescence-based approach for more accurate and objective diagnoses. A fluorescence-based diagnosis tool through headlights combined with special-filtered dental loupes may serve as a hands-free solution for both precise diagnosis and effective removal of plaque-biofilms.

Patient aggression toward dentists.

BACKGROUND: Workplace violence toward health care professionals is both widespread and widely overlooked. Only 4 studies of aggression toward dentists have been published-none in the United States-with the prevalence of aggression ranging from 29% through 80%. The purpose of this study was to provide an initial estimate of rates of patient aggression in dental practices in the United States. METHODS: The authors surveyed 98 dentists recruited from the faculty and alumni network of a college of dentistry. Participants completed a confidential online survey assessing whether they had experienced any of 21 specific types of aggressive behaviors from their patients. RESULTS: Past-year aggression prevalence was 22.2%, 55.0%, and 44.4% for physical, verbal, and reputational aggression, respectively. Career prevalence was 45.5%, 74.0%, and 68.7% for physical, verbal, and reputational aggression, respectively. Rates did not differ by sex, race, ethnicity, specialty, age, years practicing, or average number of patients treated per day. CONCLUSIONS: Participants reported levels of physical, verbal, and reputational aggression at rates comparable with those of other health care professionals in the United States and abroad. Additional research with larger representative samples of dentists in the United States is necessary to confirm these prevalence estimates. Future research should also investigate predictors and outcomes of patient aggression and prevention and intervention strategies. PRACTICAL IMPLICATIONS: Substantial rates of patient aggression highlight the need to address this problem in dental practices. The authors discuss implications for the dental profession, including proactive steps that could be taken to reduce patient aggression in dental offices.

Patient aggression toward dental students.

Aggression from patients is one of the risks faced by healthcare workers during a typical work week. This risk begins during training. Although rates of patient aggression have been estimated for nursing students and medical residents, studies of aggression toward dental students have not been conducted. To begin to address this knowledge gap, we surveyed 160 D.D.S. student dentists in their third- or fourth years who were attending a large urban college of dentistry during the 2018-2019 academic year. Each class had approximately 375 students, leading to a response rate of 21%. Approximately 28% of students reported experiencing at least 1 instance of physical aggression, 86% reported experiencing at least 1 instance of verbal aggression, and 36% reported experiencing at least 1 instance of reputational aggression. There were no differences in rates of experienced aggression by age or gender, but Hispanic or Latinx students were more likely to experience physical and reputational aggression than non-Hispanic White or Asian students. We discuss implications for dental education, including modifications to training clinic procedures and curriculum additions or modifications that may help prepare students to prevent and address patient aggression within the dental clinic environment.

Comorbid conditions are a risk for osteonecrosis of the jaw unrelated to antiresorptive therapy.

OBJECTIVE: Osteonecrosis of the jaw (ONJ) is commonly associated with antiresorptive therapy. There have been numerous reports of ONJ unrelated to antiresorptive therapy (ONJuat), confounding risk assessment. This study aimed to determine if ONJuat is associated with one or more particular comorbidities. STUDY DESIGN: This was a retrospective case-control study of patients with ONJuat and delayed healing (DH). Each case was matched for patient age and gender, as well as location of ONJuat or DH lesion to a control patient who had a history of dentoalveolar surgery with uneventful healing and no history of antiresorptive therapy. Comorbidity data included medical conditions and smoking. RESULTS: Of the 92 patients identified, 67 (73%) met the criteria for ONJuat and 25 (27%) for DH. The most common trigger for ONJ and DH was extraction (50%). The presence of any comorbidity (i.e., at least 1) was more prevalent in ONJuat than among controls (P = .04), and there were more comorbidities in patients with ONJuat and DH than in controls [M(SD) = 1.94 (1.2) and 2.0 (1.3) vs 1.26 (0.89); both P < .001]. CONCLUSIONS: ONJ and DH are not limited to patients with a history of antiresorptive therapy. More comorbidities may signal increased risk for ONJuat and DH.