How can we associate an economic evaluation with a clinical trial?

Economic evaluations in Dentistry have been increasing in recent years. They are a relevant contribution if an economic issue exists. Knowing if a new intervention is an efficient way of allocating available (and scarce) resources (the concept of opportunity costs), a well-designed economic evaluation may be helpful. One option is to conduct a trial-based economic analysis, which extracts a considerable board of information from a trial. This approach produces a more controlled result since many sources of variations might be reduced. On the other hand, some aspects could not be predicted directly from the trial or even extrapolated. Thus, combining model-based analysis may be an idea. In this paper, we intended to discuss important aspects to be considered by researchers in further economic evaluations. This paper will be systematically divided into sessions related to the study design as time horizon and perspective, health effects, costs, and data analysis. In the end, we expect the reader could be able to plan a trial-based economic evaluation, which should be a careful, meticulous, quite laborious and especially transparent process

Impact of the radiographic examination on diagnosis and treatment decision of caries lesions in primary teeth – the Caries Detection in Children (CARDEC-01) trial: study protocol for a randomized controlled trial

Abstract\ud \ud Background\ud Although most clinical guidelines throughout the world indicate that clinicians take two bitewings for detecting caries lesions in primary molars of all children, evidence for this recommendation is essentially based on cross-sectional studies performed in laboratory settings or using convenience samples. The benefits and impact of performing radiographs on diagnosis and treatment decision of caries lesions in primary teeth, mainly considering relevant outcomes for patients, have not been evaluated yet. Thus, the aim of this randomized clinical trial will be to evaluate the impact of performing radiographic examination adjunct to the visual inspection for detecting and making treatment decision regarding caries lesions in primary teeth compared with visual inspection performed alone. We will consider different outcomes related to children's health and welfare.\ud \ud \ud Methods/Design\ud To reach this objective, 250 children ages 3 to 6 years who sought dental treatment in our dental school will be randomly allocated in two groups according to the diagnostic strategy used for caries detection: visual inspection performed alone or visual inspection associated to radiographic examination. Two trained and calibrated examiners will carry out the examinations and elaborate the treatment decision plan. Then, children will be treated and followed up for 2 years, with evaluations after 12 and 24 months after the inclusion of children in the study. Children will also return after 6 and 18 months to reinforce the preventive orientations. Primary outcome will be the number of dental surfaces in need of dental treatment at the follow-up. Secondary outcomes will be the components of the primary outcome separately, as well as, proportion of false-positive results, the oral health-related quality of life, cost-efficacy, cost-adjusted life years, and number of new lesions in the first permanent molars.\ud \ud \ud Discussion\ud Our working hypothesis is that radiographic examination would actually exert little influence on patient-centered outcomes, and visual inspection would be enough as diagnostic strategy for caries detection in primary teeth.\ud \ud \ud Trial registration\ud \ud \ud NCT02078453\ud \ud . Registered 4 March 2015.This trial is funded by the Fundação de Amparo à Pesquisa do Estado de\ud São Paulo – FAPESP (Grant # 2012/24243-7), CNPQ (Grants # 471817/2012-0\ud and 471817/2012-0) and CAPES, Brazilian funding agencies. The authors\ud wish to thank the participants of the Post-Graduation in Pediatric Dentistry\ud Seminar of FOUSP for the critical comments

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

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Impact of radiographic examination on diagnosis and treatment decision of caries lesions in primary teeth - The CARies DEtection in Children (CARDEC-01) trial

O objetivo deste ensaio clínico randomizado (ECR), o CARies DEtection in Children (CARDEC-01) foi comparar a detecção e tratamento de lesões de cárie em molares decíduos, realizados com a inspeção visual isolada (VIS) e inspeção visual associada ao exame radiográfico (RAD). Crianças de 3 a 6 anos que procuraram atendimento odontológico foram randomizados em dois grupos, de acordo com a estratégia de diagnóstico usada para detecção de cárie: VIS ou RAD. Os participantes foram diagnosticados e tratados de acordo com o plano de tratamento relacionado ao grupo alocado, e acompanhados por 24 meses. Nos pacientes alocados no grupo VIS, uma nova análise foi conduzida considerando os resultados com o exame radiográfico (estudo de antes-depois). Para esses participantes, foram analisados os tipos de tratamento indicados em cada estratégia: nenhum tratamento operatório, tratamento não operatório e tratamento operatório. De um total de 2.744 superfícies, houve alteração de \"nenhum tipo de tratamento\" com decisão obtida pela inspeção visual, para \"tratamento não operatório\" após o exame radiográfico em 52 superfícies, e a mudança para decisão de \"tratamento operatório\" ocorreu em 46 superfícies dentárias. Além disso, 50 superfícies tiveram sua decisão de tratamento alterada de \"tratamento não operatório\" para \"tratamento operatório\" após avaliação radiográfica. Essas alterações foram mais frequentes em crianças com maior experiência de cárie e em superfícies proximais. Para o ECR, o desfecho primário foi o número de novas intervenções operatórias no acompanhamento de 2 anos. Outros desfechos secundários foram também avaliados. Os grupos foram comparados com o teste de Mann-Whitney, utilizando análise por intenção de tratar. Assim, 252 crianças foram incluídas e randomizadas, e 216 foram acompanhadas por 2 anos (taxa de atrito de 14,3%). A mediana (intervalo interquartil) do número de superfícies que necessitaram de uma nova intervenção operatória (desfecho primário) foi de 1,0 (0,0; 5,0) no grupo VIS e de 2,0 (0,0; 5,0) no grupo RAD (p = 0,476). Para os desfechos secundários, o grupo RAD apresentou mais reparos nas restaurações e mais restaurações realizadas desde o início do estudo. Além disso, o grupo RAD apresentou maior número de resultados falso-positivos que o grupo VIS (p<0,001). Uma análise secundária foi realizada a partir dos dados do ECR, considerando o curso clínico das superfícies dentárias dos molares decíduos dos participantes no estudo. Para isso, 4.383 superfícies proximais e oclusais dos molares decíduos foram diagnosticadas com os métodos visual e radiográfico, e acompanhadas por 24 meses, para avaliação da ocorrência de uma nova intervenção operatória (nova lesão ou troca de restauração). Observou-se que o impacto terapêutico da radiografia comparado ao exame clínico realizado isoladamente foi pequeno. Além disso, nas superfícies em que houve discordância entre os métodos, houve evidências de danos consequentes das decisões terapêuticas obtidas pelo exame radiográfico por meio de resultados falsopositivos, sobrediagnóstico e viés de tempo de espera. Dessa forma, a associação simultânea do método visual e radiográfico para detecção de cárie em pré-escolares causa mais danos que benefícios. A inspeção visual realizada isoladamente é mais benéfica para crianças e, portanto, deve ser indicada para a prática clínica diária.The aim of this randomized clinical trial (RCT), the CARies Detection in Children (CARDEC-01) was to compare the detection and treatment of caries lesions in primary molars performed with clinical examination using visual inspection alone (VIS) and visual inspection associated with radiographic examination (RAD). Children aged from 3 to 6 years, who looked for dental treatment, were randomized into two groups according to the diagnostic strategy used for caries detection: VIS or RAD. Participants were diagnosed and treated according to the treatment plan related to each group, and they were followed-up for 24 months. In the participants allocated to the VIS group, new analysis was performed considering the results obtained with radiographic method (before-after study). For these children, different types of treatment indicated with each strategy were analyzed: no treatment need, nonoperative treatment, and operative treatment. From a total of 2,744 dental surfaces, changes from \"no treatment need\" decided by visual inspection to \"non-operative treatment\" after radiographic evaluation occurred in 52 surfaces, and changes to \"operative treatment\" were observed in 46 dental surfaces. In addition, 50 surfaces had their treatment decision changed from \"non-operative treatment\" to \"operative treatment\" after radiographic evaluation. These changes were more frequent in children with higher caries experience and in proximal surfaces. Considering the RCT, the primary outcome was the number of new operative interventions during 2-years follow-up. Other secondary outcomes were also evaluated. The groups were compared through Mann-Whitney test, using intention-to-treat analysis. Then, 252 children were included and randomized, and 216 were followed-up for 2 years (attrition rate of 14.3%). Median (interquartile range) of number of surfaces that needed a new operative intervention (primary outcome) was 1.0 (0.0; 5.0) in the VIS group, and 2.0 (0.0; 5.0) in the RAD group (p = 0.476). With regard to secondary outcomes, children from RAD group had more restorations with repairs, and more surfaces restored since the beginning of the study. Moreover, the RAD group presented a higher number of false-positive results than the VIS group (p <0.001). A secondary analysis was performed with the data obtained in the RCT, considering the clinical course of dental surfaces from primary molars of the children included in the main study. For this, 4,383 proximal and occlusal surfaces of primary molars were diagnosed with visual inspection and radiographic method, and followed-up during 24 months to evaluate for the occurrence of a new operative intervention (a new caries lesion or restoration replacement). It was observed that the therapeutic impact of the radiographic method compared with the clinical examination performed alone was low. Furthermore, in the surfaces with discordant results between the methods, there were evidences of harms consequent to the therapeutic decisions made by the radiographic method, due to false-positive results, overdiagnosis and lead time bias. Thus, simultaneous association between visual inspection and radiographic method for caries detection in preschoolers brings more harms than benefits. Visual inspection performed alone is more beneficial for children, and therefore, should be indicated for the daily clinical practice

Clinical performance of fluorescence-based methods for detection of occlusal caries lesions in primary teeth

Abstract We aimed to investigate the performance of fluorescence-based methods (FBMs), compared to visual inspection after histological validation, in detecting and assessing the activity status of occlusal carious lesions in primary teeth. One examiner evaluated 50 primary molars close to exfoliation in 24 children. Teeth were assessed using quantitative light-induced fluorescence (QLF) and pen-type laser fluorescence (LFpen). After exfoliation, histological validation was performed. Teeth were cut and sections were evaluated for lesion depth and activity status (after utilization of a pH indicator) under a stereomicroscope. Parameters related to the performance of the methods in detecting caries lesions at two thresholds (initial and dentin lesions) were calculated. Regarding the activity status, lesions were classified into sound+inactive or active, and the area under the ROC curve and the diagnostic odds ratio values of the methods were calculated and compared. Evaluation of red fluorescence using QLF presented higher sensitivity but lower specificity than visual inspection in detecting dentin caries lesions. However, QLF considering different parameters and LFpen had similar performance to that obtained with visual inspection. Regarding activity assessment, all FBMs and visual inspection also presented similar performance. In conclusion, FBMs did not prove advantageous for the detection and activity assessment of occlusal caries lesions in primary molars when compared to visual inspection