• The Korean Journal of Applied Statistics
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• v.29 no.7
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• pp.1311-1327
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• 2016

We propose a multi-state model for analyzing semi-competing risks data with interval-censored or missing intermediate events. This model is an extension of the 'illness-death model', which composes three states, such as 'healthy', 'diseased', and 'dead'. The state of 'diseased' can be considered as an intermediate event. Two more states are added into the illness-death model to describe missing events caused by a loss of follow-up before the end of the study. One of them is a state of 'LTF', representing a lost-to-follow-up, and the other is an unobservable state that represents the intermediate event experienced after LTF occurred. Given covariates, we employ the Cox proportional hazards model with a normal frailty and construct a full likelihood to estimate transition intensities between states in the multi-state model. Marginalization of the full likelihood is completed using the adaptive Gaussian quadrature, and the optimal solution of the regression parameters is achieved through the iterative Newton-Raphson algorithm. Simulation studies are carried out to investigate the finite-sample performance of the proposed estimation procedure in terms of the empirical coverage probability of the true regression parameter. Our proposed method is also illustrated with the dataset adapted from Helmer et al. (2001).

• Health Policy and Management
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• v.28 no.2
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• pp.168-177
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• 2018

Background: This study investigates the potential volume and outcome association of coronary heart disease (CHD) patients who have undergone percutaneous coronary intervention (PCI) using a large and representative sample. Methods: We used a National Health Insurance Service-Cohort Sample Database from 2002 to 2013 released by the Korean National Health Insurance Service. A total of 8,908 subjects were analyzed. The primary analysis was based on Cox proportional hazards models to examine our hypothesis. Results: After adjusting for confounders, the hazard ratio of thirty-day and 1-year mortality in hospitals with a low volume of CHD patients with PCI was 2.8 and 2.2 times higher (p=0.00) compared to hospitals with a high volume of CHD patients with PCI, respectively. Thirty-day and 1-year mortality of CHD patients with PCI in low-volume hospitals admitted through the emergency room were 3.101 (p=0.00) and 2.8 times higher (p=0.01) than those in high-volume hospitals, respectively. Only 30-day mortality in low-volume hospitals of angina pectoris and myocardial infarction patients with PCI was 5.3 and 2.4 times those in high-volume hospitals with PCI, respectively. Conclusion: Mortality was significantly lower when PCI was performed in a high-volume hospital than in a low-volume hospital. Among patients admitted through the emergency room and diagnosed with angina pectoris, total PCI volume (low vs. high) was associated with significantly greater cardiac mortality risk of CHD patients. Thus, There is a need for better strategic approaches from both clinical and health policy standpoints for treatment of CHD patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6559-6564
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• 2014

Objective: To evaluate the efficacy and safety of bevacizumab in the treatment of patients with metastatic colorectal cancer (mCRC). Methods: In a single-center, observational study of 91 Chinese patients with mCRC who received bevacizumab in combination with chemotherapy was conducted. Objective response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models. Results: Treatment with bevacizumab and chemotherapy was effective and tolerable. Univariate analysis showed that PFS and OS were significantly associated with the Eastern Cooperative Oncology Group performance status (ECOG-PS) score, duration of bevacizumab exposure, and whether chemotherapy was continued after discontinuation of bevacizumab treatment. A multivariate analysis showed that the duration of bevacizumab exposure and whether chemotherapy was continued after discontinuation of bevacizumab were independent prognostic factors for PFS and OS. Conclusion: In Chinese mCRC population, the shorter the duration of exposure to bevacizumab and chemotherapy, the worse the prognosis is.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4103-4107
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• 2015

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Transarterial chemoembolisation (TACE) is the standardized therapy for intermediate stage HCC. However, the prognosis for HCC patients treated by TACE greatly varies. Thus, there is a critical need for finding biomarkers to predict the prognosis of HCC patients. The amino acid transporter-2 (ASCT2) is involved in tumorigenesis and progression of many malignancies. This study aimed to evaluate the predictive role of two single nuclear polymorphisms (SNPs, rs3826793 and rs2070246) in the ASCT2 gene in HCC patients treated by TACE. Materials and Methods: Two functional SNPs (rs3826793 and rs2070246) in the ASCT2 gene were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 448 unresectable Chinese HCC patients treated by TACE. Univariate and multivariate Cox proportional hazards models and Kaplan-Meier curves were used for the prognosis analyses. Results: There was no significant association between two SNPs (rs3826793 and rs2070246) in the ASCT2 gene and overall survival of TACE treated HCC patients. However, we demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype (P=0.023). Conclusions: We demonstrated that patients with early stage HCC carrying T genotype in rs2070246 showed better OS than those carrying CC genotype.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6369-6373
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• 2013

Background: Gastric cancer is one of the most common causes of cancer deaths all over the world and the most important reason for its high rate of death is its belated diagnosis at advanced stages of the disease. Events occur in patients which are regarded not only as themselves factors affecting patients' survival but also which can be affected by other factors. This study was designed and implemented aiming to identify these events and to investigate factors affecting their occurrence. Materials and Methods: Data from 330 patients with gastric cancer undergoing surgery at the Iran Cancer Institute from 1995-1999 were analyzed. The survival time of these patients was determined after surgery and the effects of various factors including demographic, diagnostic and clinical as well as medical, and post-surgical varuiables on the occurrence of death hazard without relapse, hazard of relapse, and death hazard with a relapse were assessed. Results: The median survival time for these patients was 16.3 months and the 5-year survival rate was 21.6%. Based on the results of multi-state model, age and distant metastases affected relapse whereas disease stage, type and extent of surgery, lymph nodes metastases, and number of renewed treatments affected death hazard without relapse. Moreover, age, type and extent of surgery, number of renewed treatments, and liver metastases were identified as factors affecting death hazard in patients with relapse. Conclusions: Most cancer studies pay heed to factors which have effect on death occurrence, but some events occur which should be taken into consideration to better describe the natural process of the disease and provide researchers with more accurate data.

• Journal of Preventive Medicine and Public Health
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• v.47 no.6
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• pp.317-326
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• 2014

Objectives: Elevated serum uric acid (UA) has been known to be associated with the prevalence of metabolic syndrome (MetS). However, no prospective studies have examined whether serum UA levels are actually associated with the development of MetS. We performed a prospective study to evaluate the longitudinal effects of baseline serum UA levels on the development of MetS. Methods: A MetS-free cohort of 14 906 healthy Korean men, who participated in a medical check-up program in 2005, was followed until 2010. MetS was defined according to the Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention. Cox proportional hazards models were performed. Results: During 52 466.1 person-years of follow-up, 2428 incident cases of MetS developed between 2006 and 2010. After adjusting for multiple covariates, the hazard ratios (95% confidence intervals) for incident MetS for the second, the third, and the fourth quartile to the first quartile of serum UA levels were 1.09 (0.92-1.29), 1.22 (1.04-1.44), and 1.48 (1.26-1.73), respectively (p for trend <0.001). These associations were also significant in the clinically relevant subgroup analyses. Conclusions: Elevated serum UA levels were independently associated with future development of MetS in Korean men during the 5-year follow-up period.

• Journal of Preventive Medicine and Public Health
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• v.51 no.2
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• pp.71-82
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• 2018

Objectives: Areca nut is widely consumed in many parts of the world, especially in South and Southeast Asia, where cardiovascular disease (CVD) is also a huge burden. Among the forms of CVD, acute coronary syndrome (ACS) is a major cause of mortality and morbidity. Research has shown areca nut chewing to be associated with diabetes, hypertension, oropharyngeal and esophageal cancers, and CVD, but little is known about mortality and re-hospitalization secondary to ACS among areca nut users and non-users. Methods: A prospective cohort was studied to quantify the effect of areca nut chewing on patients with newly diagnosed ACS by categorizing the study population into exposed and non-exposed groups according to baseline chewing status. Cox proportional hazards models were used to examine the associations of areca nut chewing with the risk of re-hospitalization and 30-day mortality secondary to ACS. Results: Of the 384 ACS patients, 49.5% (n=190) were areca users. During 1-month of follow-up, 20.3% (n=78) deaths and 25.1% (n=96) re-hospitalizations occurred. A higher risk of re-hospitalization was found (adjusted hazard ratio [aHR], 2.05; 95% confidence interval [CI], 1.29 to 3.27; p=0.002) in areca users than in non-users. Moreover, patients with severe disease were at a significantly higher risk of 30-day mortality (aHR, 2.77; 95% CI, 1.67 to 4.59; p<0.001) and re-hospitalization (aHR, 2.72; 95% CI, 1.73 to 4.26; p<0.001). Conclusions: The 30-day re-hospitalization rate among ACS patients was found to be significantly higher in areca users and individuals with severe disease. These findings suggest that screening for a history of areca nut chewing may help to identify patients at a high risk for re-hospitalization due to secondary events.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.289-294
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• 2016

Background: S100A10, of the S100 protein family, is reported to be involved in cancer cell invasion and metastasis. The aims of the present study were to immunohistochemically examine S100A10 expression in surgically resected lung adenocarcinomas, and evaluate any relationships with clinicopathological parameters and prognosis of patients. Materials and Methods: S100A10 expression was immunohistochemically studied in 202 consecutive resected lung adenocarcinomas, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of S100A10 expression on survival. Results: S100A10 expression was detected in 65 of the 202 (32.2%) lung adenocarcinomas, being significantly correlated with poorer differentiation (P =0.015), a higher pathological TNM stage (stages II and III) (P=0.004), more frequent and severe intratumoral vascular invasion (P=0.001), and a poorer prognosis (P=0.030). However, S100A10 expression was not an independent predictor of survival after controlling for clinicopathological factors. Conclusions: The present study reveals that S100A10 is expressed in a subset of lung adenocarcinomas, and this is related to some clinicopathological parameters, although further studies are required to confirm the correlation between S100A10 expression and prognosis of lung adenocarcinoma patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.2805-2809
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• 2013

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

• Journal of Preventive Medicine and Public Health
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• v.53 no.5
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• pp.342-352
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• 2020

Objectives: The aim of this retrospective cohort study was to investigate whether non-alcoholic fatty liver disease (NAFLD) was associated with incident bone mineral density (BMD) decrease. Methods: This study included 4536 subjects with normal BMD at baseline. NAFLD was defined as the presence of fatty liver on abdominal ultrasonography without significant alcohol consumption or other causes. Decreased BMD was defined as a diagnosis of osteopenia, osteoporosis, or BMD below the expected range for the patient's age based on dual-energy X-ray absorptiometry. Cox proportional hazards models were used to estimate the hazard ratio of incident BMD decrease in subjects with or without NAFLD. Subgroup analyses were conducted according to the relevant factors. Results: Across 13 354 person-years of total follow-up, decreased BMD was observed in 606 subjects, corresponding to an incidence of 45.4 cases per 1000 person-years (median follow-up duration, 2.1 years). In the model adjusted for age and sex, the hazard ratio was 0.65 (95% confidence interval, 0.51 to 0.82), and statistical significance disappeared after adjustment for body mass index (BMI) and cardiometabolic factors. In the subgroup analyses, NAFLD was associated with a lower risk of incident BMD decrease in females even after adjustment for confounders. The direction of the effect of NAFLD on the risk of BMD decrease changed depending on BMI category and body fat percentage, although the impact was statistically insignificant. Conclusions: NAFLD had a significant protective effect on BMD in females. However, the effects may vary depending on BMI category or body fat percentage.