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Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

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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 .

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ABSTRACT Objective: To assess children's self-reported distress during dental procedures and investigate risk factors. Material and Methods: A total of 163 children (3-10 years old) were included from a clinical trial on diagnostic strategies for evaluating restorations in primary teeth. Treatment plans were elaborated based on the clinical examination performed at the baseline of the study. Dentists performed 742 dental procedures, and an external evaluator collected children's self-reported distress through the Wong Backer Facial Scale (WBFS) and dentists' opinions about children's behavior during the treatment. Kruskal-Wallis Test was performed to compare the distress and the dentists' perception of the different dental procedures, and multilevel ordered logistic regression analysis was conducted to the evaluate association between explanatory variables and the outcomes. Results: More complex procedures caused more distress in children (p=0.017), with a 5.5 times higher risk than simple operative treatments. Similarly, dentists reported children's worse behavior (p<0.001). Older children (older than 7 years) reported less distress than younger children (OR 0.52; CI 0.30-0.87; p=0.014). Patients reported greater distress in the first consultations, reducing the chance of higher scores by 16% in the next interventions. Conclusion: Children experience higher levels of distress during their first treatment appointments. More complex operative procedures and the child's age below 7 years were risk factors associated with greater distress during dental treatment.

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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.

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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.

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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).

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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.

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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.

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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.

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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.

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