Prognóstico pulpar após lesões por luxação em dentes permanentes: uma análise de riscos competitivos / A retrospective cohort study of pulp prognosis in luxated permanent teeth: a competing risk analysis

As lesões por luxação representam o grupo de lesões traumáticas dento-alveolares (LTDA) caracterizadas pelo dano simultâneo ao feixe vásculo-nervoso periapical e estruturas de sustentação dentária, em diferentes graus de complexidade, dependendo da força e direção do impacto. A patogenia das alterações pulpares decorrentes das luxações é resultado da extensão da lesão do feixe vásculo-nervoso apical e de sua capacidade de reparo, que determinam os seguintes desfechos para a polpa: manutenção da vitalidade pulpar, manutenção da vitalidade pulpar com obliteração da cavidade pulpar (OCP) ou a necrose pulpar. Entretanto, o processo de reparo pulpar pode envolver fenômenos intermediários cujos sinais e sintomas se modificam ao longo do período de acompanhamento até um diagnóstico definitivo. Sendo assim, do ponto de vista clinico, o tempo até a observação destas respostas, bem como seus fatores determinantes, representa uma informação tão importante quanto o próprio desfecho, pois tem influência direta na tomada de decisão sobre as condutas clinicas mais adequadas. A presente pesquisa consistiu num estudo clínico longitudinal retrospectivo com o objetivo de avaliar o prognóstico pulpar de dentes permanentes portadores de lesões por luxação, seu padrão cronológico e fatores determinantes, entre os pacientes atendidos na Clínica de Traumatismos Dentários da Faculdade de Odontologia da Universidade Federal de Minas Gerais no período de 2014 a 2022. Foram analisados prontuários de 224 pacientes com 427 dentes permanentes portadores de luxações, acompanhados por um período mediano de 1,4 anos (variação de 11 dias a 6,9 anos). O padrão de resposta pulpar foi classificado como manutenção da vitalidade pulpar, OCP e necrose pulpar através da avaliação clínica e radiográfica. Uma análise de sobrevivência utilizando-se o modelo de riscos competitivos foi realizada e curvas de função de incidência acumulada (FIA) foram construídas para se avaliar as taxas de cada um dos desfechos pulpares utilizando-se o estimador de Aalen-Johansen. O efeito de variáveis independentes, incluindo sexo, idade do paciente no momento do trauma, estágio de desenvolvimento radicular, grupo dentário, tipo de luxação, presença de fratura coronária concomitante e prescrição de antibioticoterapia sistêmica (ATS), foi avaliado utilizando-se um modelo multivariado de Cox causa-específico. Os dados foram analisados no programa estatístico R (versão 4.0.4, Viena, Áustria, 2021). Os resultados demonstraram manutenção da vitalidade pulpar em 38,2% da amostra (163 dentes), necrose pulpar em 28,1% (120 dentes) e OCP em 12,9% da amostra (55 dentes). O tempo mediano para o diagnóstico de necrose pulpar foi de 3 meses, enquanto o tempo para vitalidade pulpar foi de 8 meses e para OCP foi de 16 meses A probabilidade de manutenção de vitalidade pulpar diminuiu significativamente com a ocorrência de fraturas coronárias de esmalte e dentina concomitantes (HR 0,38 IC 95% [0,2 ­ 0,8] p = 0,006). A taxa de necrose pulpar foi significativamente menor em dentes com forame apical amplo (HR 0,62 IC 95% [0,4 ­ 0,96] p = 0,03) mas aumentou significativamente em dentes com luxações associadas às fraturas coronárias (HR 4,0 IC 95% [2,6 - 6,1] p = 0,001) e em dentes portadores de luxações intrusivas (HR 2,3 IC 95% [1,2 - 4,1] p = 0,007). Dentes portadores de luxações laterais ou extrusivas (HR 3,0 IC 95% [1,3 ­ 6,9] p = 0,001) ou com forame amplo (HR 2,4 IC 95% [1,2 ­ 4,7] p=0.01) apresentaram as maiores taxas de OCP.

Luxation injuries are a group of traumatic dental injuries (TDI) that involve damage to both the pulp and periodontium, with different degrees of complexity. Pulp damage results from injury to the apical neuro-vascular bundle and, depending on the repair potential, may result in the following outcomes: maintenance of pulp vitality, maintenance of pulp vitality with pulp canal obliteration (PCO) or pulp necrosis. However, the pulp healing process may involve intermediate and reversible phenomena whose signs and symptoms mimic pulp necrosis, rendering the timing of these events critical for decision-making during the follow-up period. The present study consisted in a retrospective cohort to evaluate the pulpal prognosis of luxated permanent teeth, its chronological pattern and predictive factors, among patients treated at the Dental Trauma Clinic of the Federal University of Minas Gerais, from 2014 to 2021. Records of 224 patients with 427 permanent teeth with luxations, followed up for a median period of 1.4 years (ranging from 11 days to 6.9 years) were analysed. Pulp outcomes - maintenance of pulp vitality, PCO and pulp necrosis were defined trough clinical and radiographic evaluation. A competing risk survival analysis was performed and cumulative incidence function (CIF) curves were build using the Aalen-Johansen estimator to assess the rates of each of the pulp outcomes during the follow-up period. The effect of independent variables including patient's gender and age at the time of trauma, tooth group and stage of root development, type of luxation, concomitant injuries, systemic antibiotic therapy (SAT) prescription, was evaluated using a cause-specific Cox regression model. Data were analysed in the R statistical program (version 4.0.4, Vienna, Austria, 2021). The results showed maintenance of pulp vitality in 38.2% of the sample (163 teeth), pulp necrosis in 28.1% (120 teeth) and OCP in 12.9% of the sample (55 teeth). The median time for the diagnosis of pulp necrosis was 3 months, while the time for pulp vitality was 8 months and for PCO was 16 months. The hazards of pulp vitality significantly decreased with the occurrence of concomitant coronal fractures (HR 0 .38 95% CI [0.2 ­ 0.8] p = 0.006). The hazards of pulp necrosis was significantly lower in teeth with a wide apical foramen (HR 0.62 95% CI [0.4 ­ 0.96] p = 0.03) but increased significantly in teeth with luxations associated with crown fractures (HR 4.0 CI 95% [2.6 - 6.1] p = 0.001) and in teeth with intrusive displacement (HR 2.3 CI 95% [1.2 - 4.1] p = 0.007). Teeth with lateral or extrusive luxations (HR 3.0 CI 95% [1.3 ­ 6.9] p = 0.001) or with a wide foramen (HR 2.4 CI 95% [1.2 ­ 4.7] p =0.01) showed the highest rates of PCO.

Efficiency of preeclampsia screening based on biomarkers of aneuploidy screening in first trimester / 中华围产医学杂志

Objective:To evaluate the performance of biomarkers in aneuploidy screening in the first trimester-pregnancy associated plasma protein A(PAPP-A) combined with Fetal Medicine Foundation (FMF)'s competing risk model in screening preeclampsia among our population.Methods:This study was based on a prospective cohort of singleton pregnant women who underwent aneuploidy screening in the first trimester in Nanjing Drum Tower Hospital from January 2017 to September 2020. Mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), and PAPP-A were converted into multiples of median (MoM) using the algorithm disclosed on the website of the FMF (fetalmedicine.org). The predictive outcomes of maternal factors alone or in combination with MAP, UtA-PI, and PAPP-A (alone or in combination) were calculated. Chi-square test, Fisher's exact test or rank sum test were used for comparison among groups and Bonferroni method for pairwise comparisons. Receiver operating characteristic (ROC) curve was used to evaluate the screening efficiency and to calculate the sensitivities of predicting preeclampsia, term and preterm preeclampsia at false-positive rates of 5% and 10%. The predictive performance of this model was further compared to the screening strategy that was recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China (2020). Results:Among the 5 144 singleton pregnancy women who were recruited in the cohort, 4 919 cases were included and analyzed in this study. A total of 223 cases were diagnosed as preeclampsia (4.5%), including 55 preterm (1.1%) and 168 term preeclampsia (3.4%). The median of MoM values of MAP, UtA-PI, and PAPP-A in the non-preeclampsia group were around 1.0±0.1. Statistical significance was observed in the difference of MAP, UtA-PI, and PAPP-A Mom between women with preterm preeclampsia and those without preeclampsia [1.061 (0.999-1.150) vs 0.985 (0.935-4.043), 1.115 (0.873-1.432) vs 1.039 (0.864-1.236), 0.820 (0.493-1.066) vs 1.078 (0.756-1.508)], which was also seen in the difference of MAP and PAPP-A Mom between women with term preeclampsia and those without preeclampsia [1.065 (1.002-1.133) vs 0.985 (0.935-4.043), 1.007 (0.624-1.393) vs 1.078 (0.756-1.508)] (all P<0.025). The combination screening with maternal factors+MAP+UtA-PI+PAPP-A was noted for the best efficiency. In predicting preeclampsia preterm and term preeclampsia at the false-positive rate of 10%, the sensitivity of the model was 53.0%, 76.4% and 44.6% respectively. Using the screening method recommended in Diagnosis and treatment of hypertension and pre-eclampsia in pregnancy: a clinical practice guideline in China(2020), the proportion of people at high risk of preeclampsia was 5.9% (290/4 919), and the sensitivity for predicting preterm preeclampsia was 25.5% (14/55), which was significantly lower than the combination screening with maternal factors+MAP+UtA-PI+PAPP-A [65.5% (36/55)] when using the same proportion of high-risk population. Conclusion:The preeclampsia screening model based on aneuploidy screening biomarkers in the first trimester--PAPP-A in combination with materral factors, MAP, UtA-PI, can effectively screen preterm preeclampsia in the local population without increasing the laboratory costs.

Assessing the Optimal Cutpoint for Tumor Size in Patients with Lung Cancer Based on Linear Rank Statistics in a Competing Risks Framework

PURPOSE: In clinical studies, patients may experience several types of events during follow up under the competing risks (CR) framework. Patients are often classified into low- and high-risk groups based on prognostic factors. We propose a method to determine an optimal cutpoint value for prognostic factors on censored outcomes in the presence of CR. MATERIALS AND METHODS: We applied our method to data collected in a study of lung cancer patients. From September 1, 1991 to December 31, 2005, 758 lung cancer patients received tumor removal surgery at Samsung Medical Center in Korea. The proposed statistic converges in distribution to that of the supremum of a standardized Brownian bridge. To overcome the conservativeness of the test based on an approximation of the asymptotic distribution, we also propose a permutation test based on permuted samples. RESULTS: Most cases considered in our simulation studies showed that the permutation-based test satisfied a significance level of 0.05, while the approximation-based test was very conservative: the powers of the former were larger than those of the latter. The optimal cutpoint value for tumor size (unit: cm) prior to surgery for classifying patients into two groups (low and high risks for relapse) was found to be 1.8, with decent significance reflected as p values less than 0.001. CONCLUSION: The cutpoint estimator based on the maximally selected linear rank statistic was reasonable in terms of bias and standard deviation in the CR framework. The permutation-based test well satisfied type I error probability and provided higher power than the approximation-based test.

Confidence Intervals for Cumulative Incidence Function with Competing Risks Data / 中国卫生统计

Objective The cumulative incidence function (CIF) is an important descriptive indicator for competing risk data in medical follow-up study.However,the upper and lower limits of the classic confidence interval (CI) of CIF may be exclusive the boundaries.In this paper,the CI estimators based on five different transformations and their performances are studied.Methods The CIs of CIF are constructed based on the linear (classical),log,log (-log),arcsine and logit transformation,respectively.Through the simulation study,the average deviations of the false coverage probabilities for all CIs are comprehensively investigated by the ANOVA technology.Results The simulation results show that the CIs based on linear and arcsine transformation have a large positive deviation.Log transformation is prone to fluctuations and has a minimum negative deviation,only log (-log) transformation is closest to the expected constant 0,and most robust and reliable.Conclusion Combined with the simulation results and example,CIs base on linear and log transformation are easy to have wide range and unstable performance,and can not overcome the bounds being negative or above 1;the arcsine and logit is slightly fluctuated,but their performances are relatively balanced;only performance of log(-log) is the most robust and reliable.

Recuperação das principais causas de morte do Nordeste do Brasil: impacto na expectativa de vida / Recovery of the main causes of death in the Northeast of Brazil: impact on life expectancy

Objetivo: Estimar o impacto na esperança de vida após a eliminação dos principais grupos de causas de morte no Nordeste brasileiro em 2000. Métodos: Dados sobre os óbitos registrados para os estados do Nordeste do Brasil em 2000 foram extraídos do Sistema de Informações sobre Mortalidade. Foram avaliadas as coberturas dos registros de óbitos menores de dez anos usando procedimentos indiretos. Empregou-se o método de Ledermann de redistribuição das causas de morte mal definidas, segundo o sexo. Construíram-se tábuas de vida de múltiplo decremento para os principais grupos de causas de morte, cujos impactos dos decrementos foram avaliados pela esperança de vida. Resultados: A eliminação total dos principais grupos de causas na mortalidade geral proporcionou para homens e mulheres, respectivamente, os seguintes ganhos na esperança de vida do Nordeste: doenças infecciosas e parasitárias (1,0 e 0,5 anos), neoplasmas malignos (1,4 e 1,5 anos), doenças do aparelho circulatório (4,0 e 4,0 anos), doenças do aparelho respiratório (1,1 e 0,8 anos) e causas externas (2,9 e 0,3 anos). Conclusões: Os níveis das coberturas dos óbitos foram aceitáveis, assim como as redistribuições das causas mal definidas para os estados. Considerando que as estatísticas vitais do Nordeste são pouco utilizadas, devido aos argumentos de que sua qualidade limita a produção de indicadores confiáveis da mortalidade, sua recuperação de forma direta possibilita resultados consistentes.

On the Estimation of Survival and Death Probabilities under Myocardial Infarctions in the Presence of Competing Risks Based on an Illness-Death Model.

This paper is concerned with the development of an illness-death model for the study of survivability of heart patients. The Myocardial Infarctions (MI) experienced in heart disease have been categorized as fatal and nonfatal. Fatal MI’s are easily recognizable and identified and are always reported in the case history of the patient suffering from heart disease whereas non-fatal MI’s are not easily identified and are rarely reported in the case history of the patient. Also, in the case of human population, all individuals are not equally healthy and the chance of dying varies from one person to another. Moreover illness and death are two different types of events. Illness may be transient, repetitive and reversible, whereas death is an irreversible or absorbing state. Further complexity is introduced by competition among various risks of death. The probability of an individual dying from one cause is influenced by the presence of competition from other causes. Here in our problem we have taken two health states viz. normal state and illness state due to non-fatal MI’s, and two death states viz. death state due to fatal MI and death state due to competing risk. The study population of n individuals is divided into two groups viz. n individuals who are in the normal state and n individuals 1 2 who are in the illness state due to non-fatal MI’s, at the time of start of the study. The expressions for survival and death probabilities have been obtained by using the concep of crude probability of death under competing risks. The likelihood estimates of the survival and death probabilities have also been obtained. Application of the model is discussed.

Análisis de la recurrencia de cáncer de lengua considerando la presencia de eventos competitivos / Recurrence of tongue cancer analysis considering competing risks

Objetivo: Estimar la probabilidad de recurrencia en pacientes con cáncer de lengua según la edad, el estado ganglionar patológico y el tipo de tratamiento de los pacientes considerando la muerte antes de la recurrencia como evento competitivo.Material y métodos: Serie de casos retrospectiva de 290 pacientes con cáncer de lengua, con tratamiento en el INEN, entre los años 1977 y 2000. Se excluyeron del estudio 29 pacientes tratados solo con radioterapia. De los 261 pacientes, 31 solo tuvieron tratamiento del tumor primario. Resultados: La recurrencia fue 36,8%, la recurrencia local fue la más frecuente. La incidencia acumulada de la recurrencia a los 5 años, con el método de Kaplan Meier, se estimó en 44,7%, y según el análisis de riesgos competitivos en 42,4%. En el análisis univariado considerando riesgos competitivos, las incidencias acumuladas fueron: 56,8 y 38,9% en pacientes menores o iguales que 45 y mayores que 45 años respectivamente (p = 0,1556), 29,4% y50,5% en pacientes con ganglios patológicos negativos y positivos, respectivamente (p = 0,0002), y 37,5% en pacientes con cirugía, y 47,4% con radioterapia (p = 0,03). En el análisis multivariado, con regresión de riesgos competitivos, no se encontró diferencia entre los tipos de tratamiento sobre la recurrencia (RR = 1,146, p = 0,620). Conclusiones: La pequeña diferencia entre los resultados del método Kaplan Meier y el que toma en cuenta eventos competitivos se debe a la baja tasadel evento competitivo, más aún por que se trata de muerte no relacionada con la enfermedad. La tasa de recurrencia fuesimilar al reportado en la literatura. Sólo se encontró diferencia significativa en la tasa de recurrencia en el grupo con compromiso ganglionar positivo. Aunque la comparación con los métodos estándar, Kaplan Meier y Regresión de Cox, muestra resultados similares se deben tener en cuenta los eventos competitivos.

Objective: To estimate the probability of recurrence of tongue cancer, according age, stage pathological of lymph node and treatment type, considering death before recurrence as competing event. Materials and methods: Retrospective cases series study of 290 patients with tongue cancer, who were treated at INEN between 1977 and 2000. Twenty-nine patients who were treated only with radiotherapy were excluded. Of the remaining 261 patients, 31 were treated only at the primary tumor site. Results: Recurrence was 36.8%, local recurrence was most frequent. Five year cumulative incidence of recurrence, using method of Kaplan Meier, was estimated at 44.7%; and according to the analysis of competing risks in 42.4%. In univariate analysis, using competitive risks analysis, estimated cumulative incidences were 56.8 y 38.9% in patients less than or equal to 45 years and older than 45 years of age, respectively (p=0.1556); 29.4 y 50.5% in patients with negative andpositive pathological node, respectively (p=0.0002); 37.5% in patients with surgery, and 47.4% with surgery combined with radiotherapy, (p=0.03). In multivariate analysis, using competing risks regression, no difference was found between the types of treatment over recurrence (RR=1.146; p=0.620). Conclusions: The difference in results using Kaplan Meiermethod, and competing risks analysis was small, because there was a low rate of competitive event, and even more so when the cause of death was not related to the disease at hand. Recurrence rate was similar to those reported in other studies. Only significant difference was found in teh recurrence in the group with lymph node positive. Although the comparison with standard survival analysis methods shows similar results, competitive events should be taken into account.