How different attributes are weighted in professionals' decision-making in Pediatric Dentistry-a protocol for guiding discrete choice experiment focused on shortening the evidence-based practice implementation for dental care.

BACKGROUND: Important evidence has been constantly produced and needs to be converted into practice. Professional consumption of such evidence may be a barrier to its implementation. Then, effective implementation of evidence-based interventions in clinical practice leans on the understanding of how professionals value attributes when choosing between options for dental care, permitting to guide this implementation process by maximizing strengthens and minimizing barriers related to that. METHODS: This is part of a broader project investigating the potential of incorporating scientific evidence into clinical practice and public policy recommendations and guidelines, identifying strengths and barriers in such an implementation process. The present research protocol comprises a Discrete Choice Experiment (DCE) from the Brazilian oral health professionals' perspective, aiming to assess how different factors are associated with professional decision-making in dental care, including the role of scientific evidence. Different choice sets will be developed, either focusing on understanding the role of scientific evidence in the professional decision-making process or on understanding specific attributes associated with different interventions recently tested in randomized clinical trials and available as newly produced scientific evidence to be used in clinical practice. DISCUSSION: Translating research into practice usually requires time and effort. Shortening this process may be useful for faster incorporation into clinical practice and beneficial to the population. Understanding the context and professionals' decision-making preferences is crucial to designing more effective implementation and/or educational initiatives. Ultimately, we expect to design an efficient implementation strategy that overcomes threats and potential opportunities identified during the DCEs, creating a customized structure for dental professionals. TRIAL REGISTRATION: https://osf.io/bhncv .

Use of Three-Dimensional Cell Culture Models in Drug Assays for Anti-Cancer Agents in Oral Cancer: Protocol for a Scoping Review.

Advances in the development of pharmacological treatment in oral cancer require tumor models capable of simulating the complex biology of the tumor microenvironment. The spread of three-dimensional models has changed the scenery of in vitro cell culture techniques, contributing to translational oncology. Still, the full extent of their application in preclinical drug trials is yet to be understood. Therefore, the present scoping review protocol was established to screen the literature on using three-dimensional cell culture models in drug-testing assays in the context of oral cancer. This scoping review will be conducted based on the guidelines established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines (PRISMA-ScR). We will search the PubMed/Medline, Web of Science, Scopus, and Embase databases, as well as the gray literature, including peer-reviewed research articles involving 3D models applied to drug-assessment assays in oral cancer published from 1 March 2013 until 1 March 2023. Data will be charted, and findings will be described according to the predetermined questions of interest. We will present these findings in a narrative manner.

In silico approaches for drug repurposing in oncology: Protocol for a scoping review of existing evidence.

Drug repurposing has been applied in the biomedical field to optimize the use of existing drugs, leading to a more efficient allocation of research resources. In oncology, this approach is particularly interesting, considering the high cost related to the discovery of new drugs with therapeutic potential. Computational methods have been applied to predict associations between drugs and their targets. However, drug repurposing has not always been promising and its efficiency has yet to be proven. Therefore, the present scoping review protocol was developed to screen the literature on how in silico strategies can be implemented in drug repurposing in oncology. The scoping review will be conducted according to the Arksey and O'Malley framework (2005) and the Joanna Briggs Institute recommendations. We will search the PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We will include peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between January 1, 2003, and December 31, 2021. Data will be charted and findings described according to review questions. We will report the scoping review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review guidelines (PRISMA-ScR).

Does the school environment exert influence on quality of life related to traumatic dental injury in children?

The aim of this cross-sectional study was to assess whether favorable factors related to school characteristics have a positive effect on the impact of traumatic dental injury (TDI) on oral health-related quality of life (OHRQoL). An epidemiological survey of oral health was conducted with 12-year-old schoolchildren from Quito, Ecuador. Children were examined for TDI, dental caries, and malocclusion. Individual socioeconomic data were also collected. Information on the physical environment, health practices, and occurrence of negative episodes at school was collected from the school coordinators. The Child Perceptions Questionnaire 11-14 (CPQ11-14) was used to evaluate the OHRQoL (outcome variable). Multilevel Poisson regression analysis was conducted. Severe TDI was associated with higher CPQ11-14 scores, even in the multiple model adjusted for oral health conditions, sex, individual socioeconomic variables, and school-related variables. Children from schools that had an appropriate tooth-brushing environment for their students exhibited a lower impact on OHRQoL, even after adjustment for the occurrence of TDI and other variables. A favorable school environment may exert a positive effect on OHRQoL, independent of the occurrence of TDI.

Clinical Accuracy of Two Different Criteria for the Detection of Caries Lesions around Restorations in Primary Teeth.

This is a delayed-type cross-sectional prospective accuracy study nested in a randomized clinical trial. The aim was to investigate the diagnostic accuracy of two visual criteria for caries lesions detection around restorations in primary teeth: the International Dental Federation (FDI) criteria, considering adaptation, staining, and the presence of caries, and the Caries Associated with Restorations and Sealants (CARS) system. For this, one examiner made the diagnosis and subsequent treatment decision using visual assessment in 163 children (3-10 years old) with both FDI and CARS criteria. The order of criteria used was defined by randomization. The reference standard was composed of two approaches: (1) the presence of carious tissue after restoration removal and (2) the presence of caries lesions after 6 and 12 months of follow-up. Sensitivity, specificity, and accuracy parameters were calculated at the dentin threshold. Poisson multilevel regression analyses were performed to evaluate the association of the diagnostic methods and other explanatory variables with the outcomes. Of the 651 restorations included, 480 were evaluated by the reference standard methods and were analyzed. The CARS system presented higher accuracy (0.721) than those obtained with FDI recurrence of caries (0.702), FDI marginal adaptation (0.700), and FDI marginal staining criteria (0.681). The FDI marginal staining showed the study's lowest sensitivity (0.280) and accuracy (0.681) values. The specificity values of FDI recurrence of caries and FDI marginal adaptation were lower than the CARS system. Restorations assessed after the follow-up period resulted in lower sensitivity but higher specificity than those replaced after initial evaluation. In conclusion, the CARS system is more accurate in detecting caries around restorations in primary teeth than the FDI system, in general. However, the FDI recurrence of caries and FDI marginal adaptation present similar performance to the CARS system when the dentin threshold is considered. On the other hand, marginal staining is not an accurate parameter to evaluate caries around restorations.

Does the school environment exert influence on quality of life related to traumatic dental injury in children?

Abstract The aim of this cross-sectional study was to assess whether favorable factors related to school characteristics have a positive effect on the impact of traumatic dental injury (TDI) on oral health-related quality of life (OHRQoL). An epidemiological survey of oral health was conducted with 12-year-old schoolchildren from Quito, Ecuador. Children were examined for TDI, dental caries, and malocclusion. Individual socioeconomic data were also collected. Information on the physical environment, health practices, and occurrence of negative episodes at school was collected from the school coordinators. The Child Perceptions Questionnaire 11-14 (CPQ11-14) was used to evaluate the OHRQoL (outcome variable). Multilevel Poisson regression analysis was conducted. Severe TDI was associated with higher CPQ11-14 scores, even in the multiple model adjusted for oral health conditions, sex, individual socioeconomic variables, and school-related variables. Children from schools that had an appropriate tooth-brushing environment for their students exhibited a lower impact on OHRQoL, even after adjustment for the occurrence of TDI and other variables. A favorable school environment may exert a positive effect on OHRQoL, independent of the occurrence of TDI.

The economic impact of two diagnostic strategies in the management of restorations in primary teeth: a health economic analysis plan for a trial-based economic evaluation.

BACKGROUND: Different approaches have been used by dentists to base their decision. Among them, there are the aesthetical issues that may lead to more interventionist approaches. Indeed, using a more interventionist strategy (the World Dental Federation - FDI), more replacements tend to be indicated than using a minimally invasive one (based on the Caries Around Restorations and Sealants-CARS). Since the resources related to the long-term health effects of these strategies have not been explored, the economic impact of using the less-invasive strategy is still uncertain. Thus, this health economic analysis plan aims to describe methodologic approaches for conducting a trial-based economic evaluation that aims to assess whether a minimally invasive strategy is more efficient in allocating resources than the conventional strategy for managing restorations in primary teeth and extrapolating these findings to a longer time horizon. METHODS: A trial-based economic evaluation will be conducted, including three cost-effectiveness analyses (CEA) and one cost-utility analysis (CUA). These analyses will be based on the main trial (CARDEC-03/ NCT03520309 ), in which children aged 3 to 10 were included and randomized to one of the diagnostic strategies (based on FDI or CARS). An examiner will assess children's restorations using the randomized strategy, and treatment will be recommended according to the same criteria. The time horizon for this study is 2 years, and we will adopt the societal perspective. The average costs per child for 24 months will be calculated. Three different cost-effectiveness analyses (CEA) will be performed. For CEAs, the effects will be the number of operative interventions (primary CEA analysis), the time to these new interventions, the percentage of patients who did not need new interventions in the follow-up, and changes in children's oral health-related quality of life (secondary analyses). For CUA, the effect will be tooth-related quality-adjusted life years (QALYs). Intention-to-treat analyses will be conducted. Finally, we will assess the difference when using the minimally invasive strategy for each health effect (∆effect) compared to the conventional strategy (based on FDI) as the reference strategy. The same will be calculated for related costs (∆cost). The discount rate of 5% will be applied for costs and effects. We will perform deterministic and probabilistic sensitivity analyses to handle uncertainties. The net benefit will be calculated, and acceptability curves plotted using different willingness-to-pay thresholds. Using Markov models, a longer-term economic evaluation will be carried out with trial results extrapolated over a primary tooth lifetime horizon. DISCUSSION: The main trial is ongoing, and data collection is still not finished. Therefore, economic evaluation has not commenced. We hypothesize that conventional strategy will be associated with more need for replacements of restorations in primary molars. These replacements may lead to more reinterventions, leading to higher costs after 2 years. The health effects will be a crucial aspect to take into account when deciding whether the minimally invasive strategy will be more efficient in allocating resources than the conventional strategy when considering the management of restorations in primary teeth. Finally, patients/parents preferences and consequent utility values may also influence this final conclusion about the economic aspects of implementing the minimally invasive approach for managing restorations in clinical practice. Therefore, these trial-based economic evaluations may bring actual evidence of the economic impact of such interventions. TRIAL REGISTRATION: NCT03520309 . Registered May 9, 2018. Economic evaluations (the focus of this plan) are not initiated at the moment.

O impacto econômico de duas estratégias de diagnóstico no manejo de restaurações em dentes decíduos: avaliação econômica baseada em um ensaio clínico / The economic impact of two diagnostic strategies in the management of restorations in primary teeth: a trial-based economic evaluation

O objetivo desta tese foi avaliar o impacto econômico de utilizar a estratégia Caries Around Restorations and Sealants (CARS) em substituição à estratégia da Federação Dentária Internacional (FDI) para avaliação e manejo de restaurações em dentes decíduos. Este volume apresenta dois capítulos relacionados ao objetivo da tese, sendo o primeiro um plano de avaliação econômica e o segundo uma avaliação econômica com diferentes Análises de Custo-Efetividade (CEAs). O plano de análise econômica propõe uma série de análises baseadas em um ensaio clínico randomizado. O ensaio clínico Caries Detection in Children 3 (CARDEC-03) incluiu participantes de 3 a 10 anos com pelo menos uma restauração em dente decíduo que foram aleatoriamente alocadas para um dos grupos, de acordo com a estratégia de diagnóstico (FDI ou CARS) a ser utilizada nas restaurações. Os participantes foram acompanhados por 2 anos. Para todas as avaliações, será utilizada a perspectiva da sociedade. Serão realizadas CEAs e Análise de Custo-Utilidade considerando o FDI como estratégia referência. Será realizada análise por intenção de tratar e as diferenças em custos e efeitos entre a estratégia CARS e a FDI serão avaliadas. Análises de sensibilidade determinísticas e probabilísticas serão realizadas e curvas de aceitabilidade serão construídas utilizando diferentes valores de disposição a pagar. Adicionalmente, um modelo de Markov será construído para avaliar um horizonte temporal maior. Além do plano de análises, esta tese também avaliou a custo-efetividade em utilizar a estratégia CARS em substituição à estratégia FDI para avaliação de restaurações em dentes decíduos. Para compreender melhor esta relação, foram avaliados 4 efeitos: número de novas intervenções operatórias, tempo até a necessidade de uma nova intervenção operatória, necessidade de novas intervenções operatórias e o número de novas substituições. Custos e efeitos foram comparados entre os grupos por medidas relativas, conforme a quantidade de restaurações incluídas por grupo. Simulações de Monte-Carlo avaliaram as incertezas ao redor dos parâmetros e curvas de aceitabilidades foram construídas. Dados de 163 pacientes e 650 restaurações foram utilizados para a avaliação econômica. Não houve diferença estatisticamente significante entre o custo e o número de novas intervenções operatórias das duas estratégias após 2 anos de acompanhamento. Através da análise dos dados simulados, o CARS demonstrou-se custo-efetivo nas quatro CEAs. Considerando um limiar de disposição a pagar de 100 dólares, esta estratégia apresentou Net Monetary Benefits (NMB) positivos para os efeitos número de novas intervenções operatórias, tempo até a necessidade de uma nova intervenção operatória e número de novas substituições. As simulações demonstraram que, considerando um limiar de disposição a pagar de 100 doláres, o CARS tem uma probabilidade de aproximadamente 90% de ser custo-efetivo considerando o efeito tempo até a necessidade de uma nova intervenção operatória. O pior cenário foi para o efeito necessidade de novas intervenções operatórias, no qual o CARS apresentou NMB negativo e uma probabilidade de aproximadamente 50% de ser custo-efetivo, considerando um limiar de disposição a pagar de 100 dólares. Em conclusão, o CARS é uma alternativa custo-efetiva ao FDI, sobretudo considerando o adiamento de novas intervenções operatórias em dentes decíduos.

Inhibition of CAL27 Oral Squamous Carcinoma Cell by Targeting Hedgehog Pathway With Vismodegib or Itraconazole.

Oral Squamous Cell Carcinoma (OSCC) presents an important challenge for the health systems worldwide. Thus, unraveling the biological mechanisms involved in OSCC pathogenesis is essential to the discovery of new drugs with anticancer potential. The Hedgehog (HH) pathway has shown promising results as a therapeutic target both in vitro and in vivo. This study aimed to investigate the effects of vismodegib and itraconazole on the expression of Hedgehog (HH) genes (PTCH1, SMO, and GLI1), cell cycle and cell death in OSCC cells. Alamar Blue assay was used to assess the cytotoxicity of vismodegib and itraconazole in a panel of oral cancer cell lines, including CAL27. The expression of HH signaling components after treatment with vismodegib and itraconazole, at concentrations of 25 or 50 µg/ml was evaluated by qPCR. Cell cycle and apoptosis were evaluated by flow cytometry after 72 h treatment with 50 µg/ml of vismodegib or itraconazole. HH signaling was activated in OSCC cell lines CAL27, SCC4, SCC9, and HSC3. Vismodegib and itraconazole significantly reduced CAL27 cell viability after 48 h of treatment. Gene expression of PTCH1, SMO, and GLI1 decreased in response to 24 h of treatment with vismodegib or itraconazole. Furthermore, CAL27 cells exhibited alterations in morphology, cell size, and cellular granularity. An increase in the DNA fragmentation was observed after treatment and both inhibitors induced apoptosis after 72 h. In conclusion, SMO inhibitors vismodegib and itraconazole demonstrably reduced the expression of HH genes in CAL27 OSCC cell line. In addition, treatment with vismodegib and itraconazole reduced cellular viability and altered the morphology of CAL27 cells, and also induced apoptosis.

How researchers should select the best outcomes for randomised clinical trials in paediatric dentistry?

Randomised clinical trial (RCT) is the best study design to evaluate the effect of the treatment and preventive healthcare procedures. The effects of the tested treatments on patient's health are compared in terms of outcomes, which are used to evaluate the participants' health changes. However, these outcomes should be relevant for the target population. In that way, RCTs represent the type of primary study design that provides the most reliable evidence to implement therapies into the clinical practice. In this review, an outline of some aspects related to the choice of RCTs' outcomes was presented, focusing on the conduction of relevant trials in Paediatric Dentistry. The importance and necessity of defining a primary outcome were addressed, preferentially a clinically relevant endpoint. The patients should perceive this outcome, and changes in this variable should reflect directly patient's health improvement or impairment. Moreover, considerations about the objective or subjective variables, use of surrogate outcomes, and the increasing tendency to develop core outcome sets were also presented in this review. The main idea of this manuscript is the RCTs must evaluate outcomes relevant to the children's oral health in order to contribute to the implementation of treatments in the evidence-based health practice.

Influence of different clinical criteria on the decision to replace restorations in primary teeth.

OBJECTIVES: This cross-sectional study is nested in a randomized clinical trial. It was designed to evaluate the influence of using two different clinical criteria to assess caries lesion around restorations on the decision to replace restorations in primary posterior teeth. Variables that might influence this decision were also considered. METHODS: One trained and calibrated examiner assessed 550 restorations of 160 children (3-10 years old). Children were randomized to have their restorations evaluated and subsequently treated according to World Dental Federation (FDI) or Caries Associated with Restorations and Sealants (CARS) criteria. After reaching the treatment decision, the same examiner performed another evaluation using the other criteria. Spearman's correlation coefficients and 95 % confidence intervals (95 %CI) between the scores obtained with both criteria and respective treatment decisions were calculated. Poisson multilevel regression analysis were performed between the exploratory variables related to children, restored tooth and restoration assessment; the outcome variables were decisions related to restoration replacement, any operative intervention and presence of secondary caries. RESULTS: The strongest correlation observed between the methods was for recurrence of caries. A total of 94 restorations (17.1 %) were indicated for replacement with FDI criteria and 30 (5.5 %) were indicated for replacement with CARS. Besides the diagnostic method used, number of decayed teeth and restorations with two and three restored surfaces were associated with the decision of replacement and presence of recurrent caries lesions. CONCLUSIONS: The decision to replace posterior restorations in primary teeth is influenced by the criteria used for the restorations assessment and also by the children's caries experience and multisurface restorations. The restoration material did not influence the decision of restorations replacement. CLINICAL SIGNIFICANCE: The decision to replace posterior restoration in primary teeth is strongly related to the evaluation method and not only by patients' risk factors.

The effect of two clinical criteria in the assessment of caries lesions around restorations in children (CARDEC-03): study protocol for a diagnostic randomized clinical trial.

Introduction: The detection of caries lesions around restoration can be challenging. Therefore, the use of some criteria has been proposed in order to give more objectivity to the diagnosis process. Two of them are the International Dental Federation (FDI) and the Caries Associated with Restorations and Sealants (CARS) criteria. Both methods have a different approach to caries, and it is not possible to know which one of them is the best to use in clinical practice to assess restorations in children. Thus, the present protocol aims to evaluate the effect of the use of the FDI and CARS criteria in the assessment of caries lesions around restorations in primary teeth on outcomes related to oral health in children and costs resulting from the assessments. Methods and analysis: A total of 626 restorations of children from three to 10 years were randomly assessed and are being treated following the FDI criteria (FDI group) or CARS criteria (CARS group). Participants will be followed-up after six, 12, 18, and 24 months. The primary outcome will be the need for a new intervention in the evaluated restorations. This outcome consists of several components, and each of these events will be analyzed separately as secondary outcomes. The changes in children's oral health-related quality of life and the cost of the restoration dental treatments will also be analyzed as secondary outcomes. The methods will be compared using the Cox regression model with shared frailty. A significance level of 5% will be adopted for all statistical analyses. Discussion: This will be the first randomized clinical study carried out regarding the detection of caries lesions around restorations in primary teeth. Trial registration: The study underwent registration in Clinicaltrials.gov ( NCT03520309) on 9 May 2018.

Economic evaluations in paediatric dentistry clinical trials.

Economic evaluations play an important role in identifying the cost-effectiveness of alternative healthcare programmes, informing decisions surrounding funding and the allocation of resources. This paper outlines the basic principles of economic evaluation and how it can be conducted alongside a clinical trial. Furthermore, it considers the ways in which evidence from these studies can be used, and the challenges researchers are faced with when conducting economic evaluations in the field of children's oral health.

ß-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells.

ß-Lapachone is a natural naphthoquinone originally obtained from the bark of the purple Ipe (Tabebuia avellanedae Lor, Bignoniaceae) and its therapeutic potential in human cancer cells has been evaluated in several studies. In this study, we examined the effects of ß-lapachone and its 3-iodine derivatives (3-I-α-lapachone and 3-I-ß-lapachone) on cell proliferation, cell death, and cancer-related gene expression in human oral squamous cell carcinoma cells. ß-Lapachone and its 3-iodine derivatives showed potent cytotoxicity against different types of human cancer cell lines. Indeed, treatment with these compounds induced cell cycle arrest at G2/M phase, followed by internucleosomal DNA fragmentation, and caused significant increases in phosphatidylserine externalization, caspase-8 and -9 activation, mitochondrial membrane depolarization, reactive oxygen species (ROS) production, and apoptotic cell death morphology. The apoptosis induced by the compounds was prevented by pretreatment with a pan-caspase inhibitor (Z-VAD-FMK) and an antioxidant (N-acetyl-l-cysteine). In vivo, ß-lapachone and its 3-iodine derivatives significantly reduced tumor burden and did not alter any of the biochemical, hematological, or histological parameters of the animals. Overall, ß-lapachone and its 3-iodine derivatives showed promising cytotoxic activity due to their ability to induce cell cycle arrest at G2/M phase and promote caspase- and ROS-mediated apoptosis. In addition, ß-lapachone and its 3-iodine derivatives were able to suppress tumor growth in vivo, indicating that these compounds may be new antitumor drug candidates.