Comparison of prediction ability of two extended Cox models in nonlinear survival data analysis / 南方医科大学学报

OBJECTIVE@#To compare the predictive ability of two extended Cox models in nonlinear survival data analysis.@*METHODS@#Through Monte Carlo simulation and empirical study and with the conventional Cox Proportional Hazards model and Random Survival Forests as the reference models, we compared restricted cubic spline Cox model (Cox_RCS) and DeepSurv neural network Cox model (Cox_DNN) for their prediction ability in nonlinear survival data analysis. Concordance index was used to evaluate the differentiation of the prediction results (a larger concordance index indicates a better prediction ability of the model). Integrated Brier Score was used to evaluate the calibration degree of the prediction (a smaller index indicates a better prediction ability).@*RESULTS@#For data that met requirement of the proportion risk, the Cox_RCS model had the best prediction ability regardless of the sample size or deletion rate. For data that failed to meet the proportion risk, the prediction ability of Cox_DNN was optimal for a large sample size (≥500) with a low deletion (< 40%); the prediction ability of Cox_RCS was superior to those of other models in all other scenarios. For example data, the Cox_RCS model showed the best performance.@*CONCLUSION@#In analysis of nonlinear low maintenance data, Cox_RCS and Cox_DNN have their respective advantages and disadvantages in prediction. The conventional survival analysis methods are not inferior to machine learning or deep learning methods under certain conditions.

Development and validation of prognostic nomogram for malignant pleural mesothelioma / 中华肿瘤杂志

Objective: To development the prognostic nomogram for malignant pleural mesothelioma (MPM). Methods: Two hundred and ten patients pathologically confirmed as MPM were enrolled in this retrospective study from 2007 to 2020 in the People's Hospital of Chuxiong Yi Autonomous Prefecture, the First and Third Affiliated Hospital of Kunming Medical University, and divided into training (n=112) and test (n=98) sets according to the admission time. The observation factors included demography, symptoms, history, clinical score and stage, blood cell and biochemistry, tumor markers, pathology and treatment. The Cox proportional risk model was used to analyze the prognostic factors of 112 patients in the training set. According to the results of multivariate Cox regression analysis, the prognostic prediction nomogram was established. C-Index and calibration curve were used to evaluate the model's discrimination and consistency in raining and test sets, respectively. Patients were stratified according to the median risk score of nomogram in the training set. Log rank test was performed to compare the survival differences between the high and low risk groups in the two sets. Results: The median overall survival (OS) of 210 MPM patients was 384 days (IQR=472 days), and the 6-month, 1-year, 2-year, and 3-year survival rates were 75.7%, 52.6%, 19.7%, and 13.0%, respectively. Cox multivariate regression analysis showed that residence (HR=2.127, 95% CI: 1.154-3.920), serum albumin (HR=1.583, 95% CI: 1.017-2.464), clinical stage (stage Ⅳ: HR=3.073, 95% CI: 1.366-6.910) and the chemotherapy (HR=0.476, 95% CI: 0.292-0.777) were independent prognostic factors for MPM patients. The C-index of the nomogram established based on the results of Cox multivariate regression analysis in the training and test sets were 0.662 and 0.613, respectively. Calibration curves for both the training and test sets showed moderate consistency between the predicted and actual survival probabilities of MPM patients at 6 months, 1 year, and 2 years. The low-risk group had better outcomes than the high-risk group in both training (P=0.001) and test (P=0.003) sets. Conclusion: The survival prediction nomogram established based on routine clinical indicators of MPM patients provides a reliable tool for prognostic prediction and risk stratification.

Effect of intra-operative chemotherapy with 5-fluorouracil and leucovorin on the survival of patients with colorectal cancer after radical surgery: a retrospective cohort study / 中华医学杂志(英文版)

BACKGROUND@#The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection.@*METHODS@#1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC.@*RESULTS@#Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]).@*CONCLUSIONS@#IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery.@*TRIAL REGISTRATION@#chictr.org.cn, ChiCTR 2100043775.

Development and validation of risk prediction model for new-onset cardiovascular diseases among breast cancer patients: Based on regional medical data of Inner Mongolia / 北京大学学报(医学版)

OBJECTIVE@#To develop and validate a three-year risk prediction model for new-onset cardiovascular diseases (CVD) among female patients with breast cancer.@*METHODS@#Based on the data from Inner Mongolia Regional Healthcare Information Platform, female breast cancer patients over 18 years old who had received anti-tumor treatments were included. The candidate predictors were selected by Lasso regression after being included according to the results of the multivariate Fine & Gray model. Cox proportional hazard model, Logistic regression model, Fine & Gray model, random forest model, and XGBoost model were trained on the training set, and the model performance was evaluated on the testing set. The discrimination was evaluated by the area under the curve (AUC) of the receiver operator characteristic curve (ROC), and the calibration was evaluated by the calibration curve.@*RESULTS@#A total of 19 325 breast cancer patients were identified, with an average age of (52.76±10.44) years. The median follow-up was 1.18 [interquartile range (IQR): 2.71] years. In the study, 7 856 patients (40.65%) developed CVD within 3 years after the diagnosis of breast cancer. The final selected variables included age at diagnosis of breast cancer, gross domestic product (GDP) of residence, tumor stage, history of hypertension, ischemic heart disease, and cerebrovascular disease, type of surgery, type of chemotherapy and radiotherapy. In terms of model discrimination, when not considering survival time, the AUC of the XGBoost model was significantly higher than that of the random forest model [0.660 (95%CI: 0.644-0.675) vs. 0.608 (95%CI: 0.591-0.624), P < 0.001] and Logistic regression model [0.609 (95%CI: 0.593-0.625), P < 0.001]. The Logistic regression model and the XGBoost model showed better calibration. When considering survival time, Cox proportional hazard model and Fine & Gray model showed no significant difference for AUC [0.600 (95%CI: 0.584-0.616) vs. 0.615 (95%CI: 0.599-0.631), P=0.188], but Fine & Gray model showed better calibration.@*CONCLUSION@#It is feasible to develop a risk prediction model for new-onset CVD of breast cancer based on regional medical data in China. When not considering survival time, the XGBoost model and the Logistic regression model both showed better performance; Fine & Gray model showed better performance in consideration of survival time.

Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2 / 中国实验血液学杂志

OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Influencing factors of the adverse outcome of pulmonary tuberculosis among adolescents in Hangzhou City between 2005 and 2020: a school-based retrospective cohort study / 中华预防医学杂志

Objective: To explore the influencing factors of the adverse outcome of pulmonary tuberculosis (PTB) among adolescents in Hangzhou City between 2005 and 2020. Methods: A retrospective cohort study was used to collect the information of adolescent PTB patients with the onset of PTB occurring from January 1, 2005 to December 31 in 12 designated tuberculosis hospitals in Hangzhou, mainly including demographic, epidemiological, clinical manifestations, bacteriological characteristics and other data, through the China Management Information System for Infectious Disease Surveillance and Reporting and the follow-up survey. All patients were followed up and the end time was December 31, 2021. Multivariate Cox regression model was used to analyze the factors affecting the adverse outcome of these patients. Results: The mean age of 4 921 adolescent PTB patients was (18.9±3.6) years old, and the number of male and female patients were 3 074 and 1 847 respectively. The adverse outcome accounted for 14.7% (725) of all patients. Multivariate Cox regression model showed that eight risk factors, including management model from patients themselves or family members (HR=5.87, 95%CI: 4.55-7.64), molecular biology examination positive for PTB (HR=4.62, 95%CI: 2.98-7.19), the number of sputum smears-positive≥1 (HR=3.72, 95%CI: 2.87-4.83), non-standardized therapy regimens of PTB (HR=3.69, 95%CI: 2.95-4.64), history of retreated PTB (HR=2.22, 95%CI: 1.46-3.36), migrant adolescents (HR=1.89, 95%CI: 1.54-2.34), the number of chest X-ray scan (HR=1.83, 95%CI: 1.65-2.04), and severe PTB (HR=1.38, 95%CI: 1.02-2.05), were associated with the adverse outcome of adolescent PTB patients. Age (HR=0.94, 95%CI: 0.92-0.96), as the only protective factor, was associated with the adverse outcome of these patients. Conclusion: The management mode, molecular biological examination, chemotherapy program, history of tuberculosis, sputum smear examination, severity of tuberculosis, household residence, chest X-ray examination and age are associated with the adverse outcomes of adolescent PTB patients in Hangzhou.

Trajetórias e determinantes do alto risco cardiovascular de 30 anos entre participantes de uma coorte brasileira (Estudo CUME) / Trajectories and determinants of 30-year high cardiovascular risk among participants in a Brazilian cohort (CUME Study)

Introdução: As doenças cardiovasculares são o principal problema de saúde pública em todo o mundo. Portanto, a avaliação do risco cardiovascular, com a identificação de seus fatores de risco e de proteção e de suas trajetórias ao longo do tempo são importantes para a proposição, a consolidação e a implementação de medidas de prevenção da ocorrência de doenças cardiovasculares. Objetivo geral: Analisar a trajetória e os determinantes do alto risco cardiovascular de 30 anos em participantes da Coorte de Universidades Mineiras (Estudo CUME). Métodos: Inicialmente, foi realizada uma revisão integrativa da literatura e, em seguida, dois estudos de coorte prospectiva. A) Artigo 1 ­ revisão integrativa da literatura sobre a estimação do alto risco cardiovascular e seus fatores associados, realizada nas bases Medical Literature Analysis and Retrievel System Online, Web of Science, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature e no portal Biblioteca Virtual de Saúde; B) Artigo 2 ­ Coorte aberta prospectiva desenvolvida com 2.854 participantes do Estudo CUME, que é uma pesquisa multicêntrica conduzida com egressos de sete instituições públicas federais de ensino superior do Estado de Minas Gerais desde 2016. A incidência do alto risco cardiovascular de 30 anos foi calculada usando o escore de Framingham e seus determinantes foram estimados usando análise multivariada hierárquica pela técnica de regressão de Cox; C) Artigo 3 ­ Estudo prospectivo fechado desenvolvido com 1.286 participantes da CUME, que responderam ao questionário da linha de base em 2016, aos questionários de seguimento de dois anos (2018) e de quatro anos (2020). O risco cardiovascular foi avaliado com o escore de Framingham de 30 anos. A identificação das trajetórias do risco cardiovascular foi realizada com a técnica de modelagem de crescimento de classe latente com o uso do modelo normal censurado. A análise dos fatores independentemente associados a cada uma das trajetórias foi conduzida com a técnica de regressão logística multinominal. Resultados: Artigo 1 ­ foram selecionados 13 artigos com um ou mais fatores associados ao alto risco cardiovascular, segundo o escore de Framingham de 10 anos. Nenhum artigo investigou os fatores associados ao alto risco cardiovascular de 30 anos. Artigo 2 ­ após média de 2,62 anos de seguimento, a incidência do alto risco cardiovascular de 30 anos foi 8,1 casos/1.000 pessoas-ano no sexo feminino e 20,2 casos/1.000 pessoas-ano no sexo masculino. Sexo masculino (Hazard Ratio ­ HR: 2,34; IC 95%: 1,58 - 3,46), trabalhar (HR: 2,13; IC 95%: 1,13 - 3,99), alto consumo de alimentos processados (HR: 2,44; 95% CI: 1,21 - 4,90) e ser ativo fisicamente (HR: 0,63; IC 95%: 0,41 - 0,98) se associaram independentemente ao alto risco cardiovascular de 30 anos; Artigo 3 - Três trajetórias de risco cardiovascular de 30 anos foram identificadas: Baixo-Baixo (68,3%), Médio-Médio (26,2%) e Alto-Alto (5,5%). Ao longo do tempo, o risco cardiovascular apresentou discreto aumento para a trajetória Baixo-Baixo (2,9%), moderado aumento para a trajetória Médio-Médio (7,6%) e elevado aumento para a trajetória Alto-Alto (13%). O sexo masculino, viver em união estável, ter consumos moderado e alto de alimentos ultraprocessados se associaram positivamente às trajetórias de risco cardiovascular Médio-Médio e Alto-Alto. Ainda, ter formação profissional fora da área da saúde e estar trabalhando se associaram positivamente à trajetória de risco cardiovascular Médio-Médio, enquanto ser ativo fisicamente se associou negativamente à trajetória de risco cardiovascular Alto-Alto. Conclusão: Poucos estudos foram conduzidos para avaliar o alto risco cardiovascular de 30 anos, sendo que em nenhum deles foram estimados fatores associados ao desfecho. Nossos achados científicos indicaram que praticar atividade física reduz a incidência do alto risco cardiovascular de 30 anos. Homens, pessoas que trabalham e com consumo elevado de alimentos processados devem ser monitorados com maior cautela, pois apresentaram maior susceptibilidade de ocorrência do alto risco cardiovascular de 30 anos. Adultos jovens e com melhor situação socioeconômica possuem uma trajetória de baixo risco cardiovascular de 30 anos, entretanto, há uma tendência de piora desta trajetória ao longo do tempo devido aos maus hábitos de vida. Dessa forma, é essencial a implementação de estratégias de prevenção para evitar o adoecimento cardiovascular.

Introduction: Cardiovascular diseases are the main public health problem worldwide. Therefore, the assessment of cardiovascular risk, with the identification of its risk and protection factors and their trajectories over time, are important for proposing, consolidating and implementing measures to prevent the occurrence of cardiovascular diseases. General objective: To analyze the 30-year trajectory and determinants of high cardiovascular risk in participants of the Cohort of Universities of Minas Gerais (CUME Study). Methods: Initially, an integrative literature review was performed, followed by two prospective cohort studies. A) Article 1 ­ integrative review of the literature on the estimation of high cardiovascular risk and its associated factors, carried out in the databases Medical Literature Analysis and Retrievel System Online, Web of Science, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature and the Virtual Health Library portal; B) Article 2 ­ Prospective open cohort developed with 2,854 participants of the CUME Study, which is a multicenter research conducted with graduates from seven federal public institutions of higher education in the State of Minas Gerais since 2016. The incidence of high cardiovascular risk at 30 years was calculated using the Framingham score and its determinants were estimated using hierarchical multivariate analysis by the Cox regression technique; C) Article 3 ­ Prospective closed study developed with 1,286 participants from CUME, who answered the baseline questionnaire in 2016, the two-year follow-up questionnaire in 2018 and the four-year follow-up questionnaire in 2020. The risk Cardiovascular was assessed using the 30-year Framingham score. The identification of cardiovascular risk trajectories was performed using the latent class growth modeling technique using the normal censored model. The analysis of the factors independently associated with each of the trajectories was conducted using the multinomial logistic regression technique. Results: Article 1 ­ 13 articles were selected with one or more factors associated with high cardiovascular risk, according to the Framingham score over 10 years. No article investigated the factors associated with 30-year high cardiovascular risk. Article 2 ­ After an average of 2.62 years of follow-up, the incidence of high cardiovascular risk at 30 years was 8.1 cases/1,000 person-years in females and 20.2 cases/1,000 person-years in males. Male sex (Hazard Ratio ­ HR: 2.34; 95% CI: 1.58 - 3.46), work (HR: 2.13; 95% CI: 1.13 - 3.99), high food intake processed foods (HR: 2.44; 95% CI: 1.21 - 4.90) and being physically active (HR: 0.63; 95% CI: 0.41 - 0.98) were independently associated with high cardiovascular risk 30 years old; Article 3 - Three 30-year cardiovascular risk trajectories were identified: Low-Low (68.3%), Medium-Medium (26.2%) and High-High (5.5%). Over time, cardiovascular risk showed a slight increase for the Low-Low trajectory (2.9%), a moderate increase for the Medium-Medium trajectory (7.6%) and a high increase for the High-High trajectory (13%). Being male, living in a stable relationship, having moderate and high consumption of ultra-processed foods were positively associated with Medium-Medium and High-High cardiovascular risk trajectories. Also, having professional training outside the health area and being working were positively associated with the Medium-Medium cardiovascular risk trajectory, while being physically active was negatively associated with the High-High cardiovascular risk trajectory. Conclusion: Few studies were conducted to assess the 30-year high cardiovascular risk, and none of them estimated factors associated with the outcome. Our scientific findings indicated that practicing physical activity reduces the incidence of 30-year high cardiovascular risk. Men, people who work and with a high consumption of processed foods should be monitored with greater caution, as they were more susceptible to the occurrence of the high cardiovascular risk of 30 years. Young adults with better socioeconomic status have a 30-year trajectory of low cardiovascular risk, however, there is a tendency for this trajectory to worsen over time due to bad lifestyle habits. Thus, it is essential to implement prevention strategies to avoid cardiovascular disease.

Sobrevida de los recién nacidos con cardiopatías congénitas diagnosticadas prenatalmente / Survival of newborns with prenatally diagnosed congenital heart disease

Objetivo: Estimar la sobrevida al año de los recién nacidos con cardiopatías congénitas diagnosticadas prenatalmente y el perfil epidemiológico de sus madres. Método: Cohorte dinámica retrospectiva de 825 pacientes, ingresados entre el 1 de abril de 2003 y el 31 de marzo de 2019, con tiempo de seguimiento de 1 año, que se elaboró utilizando la base de datos del Centro de Referencia Perinatal Oriente (CERPO), Facultad de Medicina, Universidad de Chile. Resultados: Se estimó la función de supervivencia global de la muestra, obteniendo una supervivencia del 70% al año de seguimiento (error estándar (ES): 0,0164; intervalo de confianza del 95% [IC95%]: 0,66-0,73). Los recién nacidos con edad gestacional < 30 semanas tuvieron una menor sobrevida (hazard ratio [HR]: 4,17; IC95%: 1,52-11.44; p < 0,01). Los recién nacidos con un peso < 3000 g tuvieron una menor sobrevida (HR: 1,41; IC95%: 1,09-1,84; p < 0,01). La distribución de las cardiopatías congénitas según la gravedad en esta cohorte fue: riesgo vital 64%, clínicamente relevante 34% y clínicamente no relevante 2%. La menor sobrevida fue para la categoría riesgo vital (HR: 6,005; IC95%: 3,97-9,08; p < 0,01). Conclusiones: La prematuridad, el bajo peso al nacer y la gravedad de la cardiopatía se correlacionaron con una menor sobrevida.

Objective: To estimate the survival at one year of newborns with prenatally diagnosed congenital heart diseases and the epidemiological profile of their mothers. Method: Dynamic retrospective cohort of 825 patients, admitted between April 1, 2003 and March 31, 2019, with a follow-up time of 1 year, which was elaborated using the database of the Centro de Referencia Perinatal Oriente (CERPO), Faculty of Medicine, Universidad de Chile. Results: The overall survival function of the sample was estimated, resulting in a survival of 70% at one year follow-up (standard error (SE): 0.0164; 95% confidence interval [95% CI]: 0.66-0.73). Newborns with gestational age < 30 weeks had a lower survival (hazard ratio [HR]: 4.17; 95% CI: 1.52-11.44; p < 0.01). Newborns with a birth weight < 3000 g had a lower survival (HR: 1.41; 95% CI: 1.09-1.84; p < 0.01). The distribution of congenital heart disease according to severity in this cohort was: life-threatening 64%, clinically relevant 34% and clinically not relevant 2%. With a lower survival for the life-threatening category (HR: 6.005; 95% CI: 3.97-9.08; p < 0.01). Conclusions: Prematurity, low birth weight and severity of congenital heart correlated with a lower survival rate.

Efeitos do Ato de Fumar na Mortalidade de Longo Prazo após Infarto do Miocárdio por Elevação de ST / Effects of Smoking on Very-Long Term Mortality after First ST Elevation Myocardial Infarction

Resumo Fundamento O paradoxo do fumante tem sido motivo de debate para pacientes com infarto agudo do miocárdio (IM) há mais de duas décadas. Embora haja muitas evidências demonstrando que não existe tal paradoxo, publicações defendendo desfechos melhores em fumantes pós-IM ainda são lançadas. Objetivo Explorar o efeito do fumo na mortalidade de longo prazo após infarto do miocárdio por elevação de ST (STEMI). Métodos Este estudo incluiu pacientes com STEMI que foram diagnosticados entre 2004 e 2006 em três centros terciários. Os pacientes foram categorizados de acordo com a exposição ao tabaco (Grupo 1: não-fumantes; Grupo 2: <20 pacotes*anos; Grupo 3: 2-040 pacotes*anos; Grupo 4: >40 pacotes*anos). Um modelo de regressão de Cox foi utilizado para estimar os riscos relativos para mortalidade de longo prazo. O valor de p <0,05 foi considerado como estatisticamente significativo. Resultados Trezentos e treze pacientes (201 fumantes e 112 não-fumantes) foram acompanhados por um período médio de 174 meses. Os fumantes eram mais novos (54±9 vs. 62±11, p: <0,001), e a presença de fatores de risco cardiometabólicos foi mais prevalente entre os não-fumantes. Uma análise univariada do impacto do hábito de fumar na mortalidade revelou uma curva de sobrevivência melhor no Grupo 2 do que no Grupo 1. Porém, após ajustes para fatores de confusão, observou-se que os fumantes tinham um risco de morte significativamente maior. O risco relativo tornou-se maior de acordo com a maior exposição (Grupo 2 vs. Grupo 1: RR: 1,141; IC95%: 0,599 a 2.171; Grupo 3 vs. Grupo 1: RR: 2,130; IC95%: 1,236 a 3,670; Grupo 4 vs. Grupo 1: RR: 2,602; IC95%: 1,461 a 4,634). Conclusão O hábito de fumar gradualmente aumenta o risco de mortalidade por todas as causas após STEMI.

Abstract Background The smoking paradox has been a matter of debate for acute myocardial infarction patients for more than two decades. Although there is huge evidence claiming that is no real paradox, publications supporting better outcomes in post-MI smokers are still being released. Objective To explore the effect of smoking on very long-term mortality after ST Elevation myocardial infarction (STEMI). Methods This study included STEMI patients who were diagnosed between the years of 2004-2006 at three tertiary centers. Patients were categorized according to tobacco exposure (Group 1: non-smokers; Group 2: <20 package*years users, Group 3: 20-40 package*years users, Group 4: >40 package*years users). A Cox regression model was used to estimate the relative risks for very long-term mortality. P value <0.05 was considered as statistically significant. Results There were 313 patients (201 smokers, 112 non-smokers) who were followed-up for a median period of 174 months. Smokers were younger (54±9 vs. 62±11, p: <0.001), and the presence of cardiometabolic risk factors were more prevalent in non-smokers. A univariate analysis of the impact of the smoking habit on mortality revealed a better survival curve in Group 2 than in Group 1. However, after adjustment for confounders, it was observed that smokers had a significantly increased risk of death. The relative risk became higher with increased exposure (Group 2 vs. Group 1; HR: 1.141; 95% CI: 0.599 to 2.171, Group 3 vs Group 1; HR: 2.130; 95% CI: 1.236 to 3.670, Group 4 vs Group 1; HR: 2.602; 95% CI: 1.461 to 4.634). Conclusion Smoking gradually increases the risk of all-cause mortality after STEMI.

Time to Diabetic Retinopathy and Its Risk Factors among Diabetes Mellitus Patients in Jimma University Medical Center, Jimma, Southwest Ethiopia

Diabetic retinopathy is a complication of diabetes, caused by high blood sugar levels damaging the eye. Globally, diabetic retinopathy affects more than 103.12 million people. Diabetic retinopathy is among the leading causes of vision loss at the global level, including in Ethiopia. Therefore, the study aimed to assess the time to develop diabetic retinopathy and identify factors associated with diabetic retinopathy among diabetes patients. METHODS: A retrospective study was conducted from September 1, 2021, to January 30, 2022. Data was collected using semi structured questionnaire. The Cox proportional hazard model were used to determine the median time to develop diabetic retinopathy and identify predictors of diabetic retinopathy. Data was analyzed using R software. RESULTS: A total of 373 diabetes patients were included in this study. The prevalence of diabetic retinopathy was 41.3%. The median time was 41 months, ranging from 39 to 73 months. Elder age (HR=3.17, 95%CI: 1.53, 6.58), being male (HR=2.34, 95%CI: 1.35,6.15), previous family history of diabetes (HR=4.16, 95%CI: 2.19, 8.37), longer duration of diabetes (HR=2.86, 95%CI: 1.41, 5.31) received only insulin therapy (HR=3.91, 95%CI: 1.36, 7.94), and high systolic blood pressure (HR=2.32; 95%CI: 1.12, 4.39) were statistically significant factors related to development of diabetes retinopathy. CONCLUSIONS: More than half of diabetic patinets in this study were developed retinopathy diabetes within a few months of being diagnosed. As a result, we advocate that the best way to preserve our vision from diabetic retinopathy is to maintain our diabetes under control, and the high-risk population receive early screening for diabetes

Influencing factors and risk prediction model for cervical cancer recurrence / 中南大学学报(医学版)

OBJECTIVES@#Cervical cancer is the most common malignant tumor in the female reproductive system worldwide. The recurrence rate for the treated cervical cancer patients is high, which seriously threatens women's lives and health. At present, the risk prediction study of cervical cancer has not been reported. Based on the influencing factors of cervical cancer recurrence, we aim to establish a risk prediction model of cervical cancer recurrence to provide a scientific basis for the prevention and treatment of cervical cancer recurrence.@*METHODS@#A total of 4 358 cervical cancer patients admitted to the Hunan Cancer Hospital from January 1992 to December 2005 were selected as research subjects, and the recurrence of cervical cancer patients after treatment was followed up. Univariate analysis was used to analyze the possible influencing factors. Variables that were significant in univariate analysis or those that were not significant in univariate analysis but may be considered significant were included in multivariate Cox regression analysis to establish a cervical cancer recurrence risk prediction model. Line graphs was used to show the model and it was evaluated by using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis.@*RESULTS@#Univariate analysis showed that the recurrence rates of cervical cancer patients with different age, age of menarche, parity, miscarriage, clinical stage, and treatment method were significantly different (all P<0.05). Multivariate Cox regression analysis showed that RR=-0.489×(age≥55 years old)+0.481×(age at menarche >15 years old)+0.459×(number of miscarriages≥3)+0.416×(clinical stage II)+0.613×(clinical stage III/IV)+0.366×(the treatment method was surgery + chemotherapy) + 0.015×(the treatment method was chemotherapy alone). The area under the ROC curve (AUC) of the Cox risk prediction model for cervical cancer recurrence constructed was 0.736 (95% CI 0.684 to 0.789), the best prediction threshold was 0.857, the sensitivity was 0.576, and the specificity was 0.810. The accuracy of the Cox risk model constructed by this model was good. From the clinical decision curve, the net benefit value was high and the validity was good.@*CONCLUSIONS@#Patient age, age at menarche, miscarriages, clinical stages, and treatment methods are independent factors affecting cervical cancer recurrence. The Cox proportional hazards prediction model for cervical cancer recurrence constructed in this study can be better used for predicting the risk of cervical cancer recurrence.

The association of family history of herpes zoster and the risk of incident herpes zoster: the SHEZ Study

BACKGROUND@#We investigated whether family histories of herpes zoster (HZ) are associated with the risk of incident HZ in a Japanese population.@*METHODS@#A total of 12,522 Japanese residents aged ≥50 years in Shozu County participated in the baseline survey between December 2008 and November 2009 (the participation rate = 72.3%). They were interviewed at baseline by research physicians regarding the registrants' history of HZ. A self-administered questionnaire survey was conducted to evaluate the potential confounding factors. 10,530 participants without a history of HZ were followed up to ascertain the incidence of HZ during 3-years follow-up until the end of November 2012 with Japanese nationals. We estimated hazard ratios (HRs) of incident HZ according to first-degree family histories using the Cox proportional hazard regression after adjusting for age, sex, and other potential confounding factors.@*RESULTS@#Compared to no HZ history of each family member, a history of brother or sister was associated with a higher risk of incident HZ while histories of father and mother were not. The multivariable HR (95%CI) of incident HZ for a history of brother or sister was 1.67 (1.04-2.69). When comparing to no family histories of all first-degree relatives, the multivariable HRs (95%CIs) were 1.34 (0.77-2.34) for a history of brother or sister alone, but 4.81 (1.78-13.00) for a history of mother plus brother or sister. As for the number of family histories, the multivariable HRs (95%CIs) were 1.08 (0.76-1.54) for one relative (father, mother, or brother or sister) and 2.75 (1.13-6.70) for two or more relatives.@*CONCLUSION@#Family histories of mother plus brother or sister and two or more first-degree relatives were associated with a higher risk of incident HZ.

The comparison of survival between active surveillance or watchful waiting and focal therapy for low-risk prostate cancer: a real-world study from the SEER database / 亚洲男科学杂志(英文版)

To reduce treatment-related side effects in low-risk prostate cancer (PCa), both focal therapy and deferred treatments, including active surveillance (AS) and watchful waiting (WW), are worth considering over radical prostatectomy (RP). Therefore, this study aimed to compare long-term survival outcomes between focal therapy and AS/WW. Data were obtained and analyzed from the Surveillance, Epidemiology, and End Results (SEER) database. Patients with low-risk PCa who received focal therapy or AS/WW from 2010 to 2016 were included. Focal therapy included cryotherapy and laser ablation. Multivariate Cox proportional hazards models were used to compare overall mortality (OM) and cancer-specific mortality (CSM) between AS/WW and focal therapy, and propensity score matching (PSM) was performed to reduce the influence of bias and unmeasured confounders. A total of 19 292 patients with low-risk PCa were included in this study. In multivariate Cox proportional hazards model analysis, the risk of OM was higher in patients receiving focal therapy than those receiving AS/WW (hazard ratio [HR] = 1.35, 95% confidence interval [CI]: 1.02-1.79, P = 0.037), whereas no significant difference was found in CSM (HR = 0.98, 95% CI: 0.23-4.11, P = 0.977). After PSM, the OM and CSM of focal therapy and AS/WW showed no significant differences (HR = 1.26, 95% CI: 0.92-1.74, P = 0.149; and HR = 1.26, 95% CI: 0.24-6.51, P = 0.782, respectively). For patients with low-risk PCa, focal therapy was no match for AS/WW in decreasing OM, suggesting that AS/WW could bring more overall survival benefits.

Expression of Glutathione Peroxidases and Its Effect on Clinical Prognosis in Glioma Patients / 中国医学科学院学报

Objective To investigate the relationship between the expression of glutathione peroxidase(GPX)genes and the clinical prognosis in glioma patients,and to construct and evaluate the model for predicting the prognosis of glioma. Methods The clinical information and GPX expression of 663 patients,including 153 patients of glioblastoma(GBM)and 510 patients of low-grade glioma(LGG),were obtained from The Cancer Genome Atlas(TCGA)database.The relationship between GPX expression and patient survival was analyzed.The key GPX affecting the prognosis of glioma was screened out by single- and multi-factor Cox's proportional-hazards regression models and validated by least absolute shrinkage and selection operator(Lasso)regression.Finally,we constructed the model for predicting the prognosis of glioma with the screening results and then used concordance index and calibration curve respectively to evaluate the discrimination and calibration of model. Results Compared with those in the control group,the expression levels of GPX1,GPX3,GPX4,GPX7,and GPX8 were up-regulated in glioma patients(all P<0.001).Moreover,the expression levels of other GPX except GPX3 were higher in GBM patients than in LGG patients(all P<0.001).The Kaplan-Meier curves showed that the progression-free survival of GBM with high expression of GPX1(P=0.013)and GPX4(P=0.040),as well as the overall survival,disease-specific survival,and progression-free survival of LGG with high expression of GPX1,GPX7,and GPX8,was shortened(all P<0.001).GPX7 and GPX8 were screened out as the key factors affecting the prognosis of LGG.The results were further used to construct a nomogram model,which suggested GPX7 was the most important variable.The concordance index of the model was 0.843(95%CI=0.809-0.853),and the calibration curve showed that the predicted and actual results had good consistency. Conclusion GPX7 is an independent risk factor affecting the prognosis of LGG,and the nomogram model constructed with it can be used to predict the survival rate of LGG.

Incidence of gastric cancer and risk factors in Suzhou cohort / 中华流行病学杂志

Objective: To describe gastric cancer incidence in Suzhou cohort, explore the environmental risk factors of gastric cancer in Suzhou, and provide appropriate suggestions for gastric cancer prevention and control. Methods: The participants were from the Suzhou cohort of China Kadoorie Biobank. Baseline survey was conducted from 2004 to 2008, followed by long-term follow-up until December 31, 2013. After the exclusion of those who had been previously diagnosed with peptic ulcer and malignant tumor reported at baseline survey and gastric cancer within six months after enrollment, a total of 50,136 participants were included. Cox proportional risk models were used to identify risk factors of gastric cancer and their hazard ratios in Suzhou. The effect modifications of gender on the association between risk factors and gastric cancer were analyzed. Results: In the follow-up of 7.19 years (median), 374 gastric cancers cases occurred. The standardized incidence was 94.57 per 100 000 person-years. Multivariate Cox proportional risk model analysis found that age (10 years old as a age group, HR=2.20, 95%CI: 1.92-2.53, P<0.001), current smoking (HR=1.84, 95%CI: 1.10-3.07 P=0.020), consumption of preserved vegetables weekly (HR=2.28, 95%CI: 1.28-4.07, P=0.005) and daily (HR=2.05, 95%CI: 1.16-3.61, P=0.013) were risk factors for gastric cancer. Female (HR=0.44, 95%CI: 0.25-0.76, P=0.003) and refrigerator use (10 years as a limit, HR=0.85, 95%CI: 0.74-0.97, P=0.016) were protective factors for gastric cancer. Further analysis showed that there was heterogeneity between males and females in the association between refrigerator use years and the incidence of gastric cancer (P=0.009), and there was an interaction effect between gender and refrigerator use on the incidence of gastric cancer (P=0.010). Conclusions: The incidence of gastric cancer in Suzhou cohort was high. The risk factors of gastric cancer varied. There was a synergistic interaction effect between gender and refrigerator use years on the incidence of gastric cancer.

Statistical methods for relative risk estimation and applications in case-cohort study / 中华流行病学杂志

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.

Treatment and prognosis analysis of perineural invasion on sinonasal adenoid cystic carcinoma / 中华肿瘤杂志

Objective: To analyze the efficacy of sinonasal adenoid cystic carcinoma (ACC) with perineural invasion (PNI), and explore the prognostic value of PNI on sinonasal adenoid cystic carcinoma. Methods: The clinical data of 105 patients with sinonasal ACC admitted to Cancer Hospital, Chinese Academy of Medical Sciences from January 2000 to December 2016 were retrospectively reviewed. All patients were restaged according to American Joint Committee on Cancer 8th edition. Follow-up visits were conducted to obtain information of treatment failure and survival outcome. The Log rank test was used for univariate analysis of prognostic factors, and Cox regression model was used for multivariate prognostic analysis. Results: The maxillary sinus (n=59) was the most common primary site, followed by the nasal cavity (n=38). There were 93 patients with stage Ⅲ-Ⅳ. The treatment modalities included surgery alone (n=14), radiotherapy alone (n=13), preoperative radiotherapy plus surgery (n=10), and surgery plus postoperative radiotherapy (n=68). The median follow-up time was 91.8 months, the 5-year local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 72.6%, 73.0%, 52.9% and 78.0%, respectively. There were 33 patients (31.4%) with PNI-positive. The 5-year DMFS, PFS, and OS rates of PNI-positive group were 53.7%, 29.4% and 56.5%, respectively, which were significantly inferior to those of PNI-negative group (80.8%, 63.0% and 86.8%, respectively, P<0.05), while there was no significant difference in the 5-year LC rate between both groups (64.5% vs 76.5%, P=0.273). The multivariate Cox regression analysis showed PNI was one of the poor prognostic factors of DMFS (HR=3.514, 95%CI: 1.557-7.932), PFS (HR=2.562, 95%CI: 1.349-4.866) and OS (HR=2.605, 95%CI: 1.169-5.806). Among patients with PNI-positive, the 5-year LC, PFS and OS rates of patients received surgery combined with radiotherapy were 84.9%, 41.3% and 72.7%, respectively, which were significantly higher than 23.3%, 10.0% and 26.7% of patients receiving surgery or radiotherapy alone (P<0.05). Conclusion: The presence of PNI increases the risk of distant metastasis in patients with sinonasal ACC. Compared with patients with PNI-negative, the prognosis of patients with PNI-positive is relatively poor, and surgery combined with radiotherapy for PNI-positive sinonasal ACC results in good clinical outcomes.

Development and validation of nomograms for predicting stroke recurrence after firstepisode ischemic stroke / 南方医科大学学报

OBJECTIVE@#To explore the risk factors for recurrence in first-episode ischemic stroke survivors and establish a model for predicting stroke recurrence using a nomogram.@*METHODS@#We collected the data from a total of 821 first-episode ischemic stroke survivors admitted in the Department of Neurology, West China Hospital, Sichuan University from January, 2010 to December, 2018. R software was used for random sampling of the patients, and 70% of the patients were included in the training set to establish the prediction model and 30% were included in the validation set. Cox proportional risk regression model was used to analyze the factors affecting stroke recurrence, and R software rms package was used to construct the histogram and establish the visual prediction model. C-index and calibration curve were used to evaluate the performance of the model for predicting stroke occurrence.@*RESULTS@#Among the 821 survivors, the recurrence rate was 16.81% at 3 years and 19.98% at 5 years. Multivariate analysis of the training set by Cox regression model showed that an age over 65 years (HR= 2.596, P=0.024), an age of 45-64 years (HR=2.510, P=0.006), a mRS score beyond 3 (HR=2.284, P=0.004) and a history of coronary heart disease (HR=1.353, P=0.034) were all risk factors for stroke recurrence. The C-indexes of the nomogram for the 3-and 5-year relapse prediction model were 0.640 and 0.671, respectively.@*CONCLUSION@#Age, mRS score and peripheral vascular disease are the factors affecting stroke recurrence in first-episode ischemic stroke survivors, and the nomogram has a high discrimination and predictive power for predicting ischemic stroke recurrence.

A prospective cohort study of the influence of positive/negative effectivity on the mortality risk of the Chinese elderly / 北京大学学报(医学版)

OBJECTIVE@#To explore the influence of positive/negative effectivity on the mortality risk of the Chinese elderly.@*METHODS@#Using the latest four surveys data of Chinese longitudinal healthy longevity survey in 2008, 2012, and 2014, as well as 2018 and selecting 10 993 elderly people who were aged 65 and above as research objects, this paper compared the positive/negative effectivity status and differences of the elderly in different gender and age groups. And then this paper analyzed the effect of positive/negative effectivity on elderly people' s mortality risk by constructing Cox proportional hazards model.@*RESULTS@#Compared with the female elderly, the male elderly had lower negative effectivity and higher positive effectivity. With the increase of age, the negative effectivity of the elderly increased, while the positive effectivity decreased. The results showed that after adjusting for the basic demographic characteristics, health status and living habits of the respondents in the baseline survey, in the positive effectivity dimension, "clean preference" (HR=0.922, 95%CI: 0.889-0.956), "autonomy" (HR=0.933, 95%CI: 0.914-0.952) and "sense of youth" (HR=0.948, 95%CI: 0.927-0.969), had a protective effect on the mortality risk of the elderly, while in the dimension of "open-minded view", there was no significant difference in the mortality risk of the elderly with different answers. In the negative effecti-vity dimension, "tension and fear" (HR=1.039, 95%CI: 1.014-1.065), "loneliness" (HR=1.053, 95%CI: 1.029-1.079) and "uselessness" had a harmful effect on the mortality risk of the elderly. The more positive effectivity, the lower the mortality risk of the elderly (HR=0.967, 95%CI: 0.956-0.978), while the more negative effectivity, the higher the mortality risk of the elderly (HR=1.024, 95%CI: 1.013-1.035).@*CONCLUSION@#The negative effectivity of the elderly in all dimensions may increase the mortality risk of elderly people. We ought to dredge the negative emotions of the elderly in time. In the health promotion of the elderly, we should also pay attention to the encouragement of positive effectivity in all dimensions, which requires the joint efforts of families, communities and governments.