Chang-Huei Tsao

Radiation Therapy for Invasive Breast Cancer Increases the Risk of Second Primary Lung Cancer: A Nationwide Population-Based Cohort Analysis

Introduction: Although the risk factors for lung cancer are well documented, whether previous radiation therapy (RT) to treat breast cancer (BC) increases the incidence of second primary lung cancer remains unclear. We determined the overall incidence of second primary lung cancer after previous RT for all clinical stages of BC. Methods: After an analysis of the Longitudinal Health Insurance Database, 986,713 individuals were randomly enrolled from 2000 to 2010 for cohort analysis. All women with newly diagnosed invasive BC, aged 18 years or older, and without other types of malignancy before 2000 or in the follow‐up periods were enrolled and allocated to the RT or non‐RT groups. Age, comorbidities, insurance premium, urbanization level, location, date of event, and hospital care level were analyzed. The hazard ratios of parameters were calculated by Cox regression analysis. Results: A total of 7408 individuals met the inclusion criteria, including 5695 patients with BC who underwent RT and 128 (2.25%) in whom lung cancer developed. In contrast, lung cancer was diagnosed in only four of 1713 individuals in the non‐RT group (0.23%) during the follow‐up period. Cox regression analysis showed that the adjusted hazard ratio was 10.078 times higher in the RT group than in the non‐RT group for individuals with previous BC. Conclusions: The incidence of second primary lung cancer was significantly higher in the RT group than in the non‐RT group for individuals with previous BC. Patients with BC treated by RT should be extensively surveyed to assess the incidence of subsequent lung cancer.

Epidemiology and prognostic factors of inpatient mortality of Guillain-Barré syndrome: A nationwide population study over 14 years in Asian country

OBJECTIVEnThe present study aimed to evaluate the characteristics of inpatient mortality from Guillain-Barré syndrome (GBS), which is a rare and potentially life-threatening polyradiculoneuropathy, in an Asian country, as there are few big-data studies regarding this topic.nnnMETHODSnWe obtained data regarding patients with GBS from Taiwans National Health Insurance Research Database admission records. We identified patients with a discharge diagnosis of GBS during 2000-2013 using the International Classification of Diseases, 9th Revision, Clinical Modification code (357.0), and evaluated their baseline characteristics, clinical complications, and risk factors.nnnRESULTSnWe identified 5469 patients with GBS, and the crude incidence of GBS was 1.71 per 100,000 person-years. The inpatient mortality rate was 1.61% (88/5469) and 55 deaths (62.5% of all deaths) occurred before day 19 of the hospitalization (mainly during the progressive phase). The predictors of inpatient mortality included older age, a greater comorbidity burden (especially catastrophic illness), endotracheal intubation, mechanical ventilation, cardiac complications, and systemic infection. In contrast, patients who were admitted to a medical center or Neurology Department exhibited a higher survival rate.nnnCONCLUSIONSnThis 14-year nationwide study included the largest analysis of Asian patients with GBS to date, and identified various prognostic factors that predicted inpatient mortality.

Risk of Dementia in Adults With ADHD: A Nationwide, Population-Based Cohort Study in Taiwan

Objective:This study aimed to investigate the association between adults with ADHD and the risk of developing dementia. Method: Utilizing National Health Insurance Research Database of Taiwan, ADHD patients were identified and compared with age- and gender-matched controls (1:3). Results: Of the study participants, 37 (5.48%) developed dementia compared with 81 (4.0%) in the control group. Cox proportional hazards regression analysis revealed that the study participants were more likely to develop dementia. The crude hazard ratio (HR) is 3.418 (95% confidence interval [CI] = [2.289, 5.106], p < .001), and adjusted HR is 4.008 (95% CI = [2.526, 6.361], p < .001) in risk of developing dementia after adjusted for age, gender, comorbidities, geographical area of residence, urbanization level of residence, and monthly income. Conclusion: Adults with ADHD have a 3.4-fold risk of developing dementia, and other large or national data sets should be explored to support the current findings.

Increased risk of sudden sensorineural hearing loss in patients with hepatitis virus infection

The etiology of sudden sensorineural hearing loss (SSNHL) remains unclear. Possible causes of SSNHL include vascular diseases, viral infection, and autoimmune disorders. Therefore, we investigated whether hepatitis virus infection is correlated with the risk of SSNHL. Using data from the Taiwan Longitudinal Health Insurance Database, we conducted a retrospective matched-cohort study to compare patients diagnosed with hepatitis B or C virus (HBV/HCV) infections from January 1, 2000, to December 31, 2010, (N = 170,942) with frequency-matched controls (N = 512,826) at a ratio of 1:3 by sex, age, and index year. We followed each patient until the end of 2010 and evaluated the incidence of SSNHL. At the end of the follow-up period, 647 (0.38%, 647/170,942) patients developed SSNHL in the HBV/HCV group compared with 978 (0.19%, 978/512,826) in the control groups, with a statistical significance of P < 0.001 (using the log-rank test). The incidence rate ratio of SSNHL was 5.743-fold higher in the HBV/HCV group than in the control group (283.17 vs. 49.31 per 100,000 person-years, P < 0.001). The risk of SSNHL increased with HBV/HCV infection, and an adjusted hazard ratio of 5.103 (95% CI, 4.585–5.678) was determined using Cox proportional hazards regression. This study contributes to the awareness of the increased risk of SSNHL in HBV/HCV-infected populations. Our findings suggest that an underlying viral infection contributes to the development of SSNHL.

Longitudinal relationship between traumatic brain injury and the risk of incident optic neuropathy: A 10-year follow-up nationally representative Taiwan survey

Accumulating evidences had shown that traumatic brain injury was associated with visual impairment or vision loss. However, there were a limited number of empirical studies regarding the longitudinal relationship between traumatic brain injury and incident optic neuropathy. We studied a cohort from the Taiwanese National Health Insurance data comprising 553918 participants with traumatic brain injury and optic neuropathy-free in the case group and 1107836 individuals without traumatic brain injury in the control group from 1st January 2000. After the index date until the end of 2010, Cox proportional hazards analysis was used to compare the risk of incident optic neuropathy. During the follow-up period, case group was more likely to develop incident optic neuropathy (0.24%) than the control group (0.11%). Multivariate Cox regression analysis demonstrated that the case group had a 3-fold increased risk of optic neuropathy (HR = 3.017, 95% CI = 2.767–3.289, p < 0.001). After stratification by demographic information, traumatic brain injury remained a significant factor for incident optic neuropathy. Our study provided evidence of the increased risk of incident optic neuropathy after traumatic brain injury during a 10-year follow-up period. Patients with traumatic brain injury required periodic and thorough eye examinations for incident optic neuropathy to prevent potentially irreversible vision loss.

Increased long-term risk of hearing loss in patients with traumatic brain injury: A nationwide population-based study

We investigated incidences of hearing loss among patients with traumatic brain injury (TBI) to evaluate whether they had a higher risk of hearing loss than the general population.

Protective effect of N-acetylcysteine on progression to end-stage renal disease: Necessity for prospective clinical trial

BACKGROUNDnWe aimed to evaluate the potential benefits of N-acetylcysteine (NAC) on the risk of chronic kidney disease (CKD) progression to dialysis-requiring end-stage renal disease (ESRDd).nnnMETHODSnIn a population-based cohort study of 145,062 individuals, 123,608 CKD patients who were followed up for 10years were included, and CKD patients treated with NAC (ICD-9-CM) were compared with those who were not treated. Using propensity score matching, we analyzed the predictors of CKD progression to ESRDd by Cox proportional hazards regression with adjustments for sex, age, and comorbidities, and evaluated the effect of NAC using cumulative defined daily dose (cDDD).nnnRESULTSnNAC use was associated with a reduced risk for progression to ESRDd [hazard ratio (HR), 0.819; 95% confidence interval (CI), 0.781-0.965; P=0.017]. Risk reduction was proportional to cDDD in NAC users compared with that in NAC non users (HR, 0.835, 0.811, and 0.799 for cDDD 91-180, 181-360, and >360, respectively; P for trend=0.018). Risk reduction was apparent in women (P=0.001) and in younger-aged patients of 18-29years (P=0.021) and 30-39years (P=0.033), in the presence of hypertension (P=0.003), and in the absence of diabetes mellitus (P=0.042) and congestive heart failure (P=0.036).nnnCONCLUSIONnNAC use was associated with a reduced risk for progression to ESRDd. These results, obtained from retrospective data, indicate that a prospective study is warranted.

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratiou2009=u20095.66, 95% confidence intervalu2009=u20091.36–23.52). Men aged 45–70xa0years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan–Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

Increased risk of osteoporosis in patients with primary biliary cirrhosis

Background We evaluated the risk of osteoporosis in patients with primary biliary cirrhosis (PBC) using a nationwide population-based dataset. Methods In a cohort study of 986,713 individuals, we selected 2,493 PBC patients who were aged 18 years or older and had been diagnosed with PBC, based on the International Classification of Disease (ICD-9-CM) codes 571.6, during 20002010. The control cohort comprised 9,972 randomly selected, propensity matched patients (by age, gender, and index date), without PBC. Using this adjusted data, a possible association between PBC and the risk of developing osteoporosis was estimated using a Cox proportional hazard regression model. Results During the follow-up period, osteoporosis was diagnosed in 150 (6.02%) patients in the PBC cohort and in 539 (5.41%) patients in the non-PBC cohort. After adjusting for covariates, osteoporosis risk was found to be 3.333 times greater in the PBC cohort than in the non-PBC cohort when measured over 6 years after PBC diagnosis. Stratification revealed that the use of ursodeoxycholic acid (UDCA) had no significance in decreasing the risk of osteoporosis when comparing the PBC cohorts with the non-PBC cohorts (P = 0.124). Additionally, osteoporosis risk was significantly higher in PBC patients with steroid use (aHR: 6.899 vs 3.333). Moreover, when comparing the PBC cohorts to the non-PBC cohorts, the non-cirrhotic patients were prone to osteoporosis at a younger age compared to those in the cirrhotic cohorts. We also found that the associated risk of fractures is only prominent for vertebral and wrist fractures in the PBC cohort compared to that in the non-PBC cohort. Conclusion A significant association exists between PBC and subsequent risk for osteoporosis. Therefore, PBC patients, particularly those treated with steroids, should be evaluated for subsequent risk of osteoporosis.

Combination COX-2 inhibitor and metformin attenuate rate of joint replacement in osteoarthritis with diabetes: A nationwide, retrospective, matched-cohort study in Taiwan.

Background Osteoarthritis (OA) is the most common form of arthritis associated with an increased prevalence of type 2 diabetes mellitus (T2DM), however their impact on decreasing joint replacement surgery has yet to be elucidated. This study aimed to investigate if the combination of COX-2 inhibitor and metformin therapy in OA with T2DM were associated with lower the rate of joint replacement surgery than COX-2 inhibitor alone. Methods In total, 968 subjects with OA and T2DM under COX-2 inhibitor and metformin therapy (case group) between 1 January to 31 December 2000 were selected from the National Health Insurance Research Database of Taiwan, along with 1936 patients were the 1:2 gender-, age-, and index year-controls matched without metformin therapy (control group) in this study. Cox proportional hazards analysis was used to compare the rate of receiving joint replacement surgery during 10 years of follow-up. Results At the end of follow-up, 438 of all enrolled subjects (15.08%) had received the joint replacement surgery, including 124 in the case group (12.81%) and 314 in the control group (16.22%). The case group tended to be associated with lower rate of receiving the joint replacement surgery at the end of follow-up than the control group (p = 0.003). Cox proportional hazards regression (HR) analysis revealed that study subjects under combination therapy with metformin had lower rate of joint replacement surgery (adjusted HR 0.742 (95% CI = 0.601–0.915, p = 0.005)). In the subgroups, study subjects in the combination metformin therapy who were female, good adherence (>80%), lived in the highest urbanization levels of residence, treatment in the hospital center and lower monthly insurance premiums were associated with a lower risk of joint replacement surgery than those without. Conclusions Patients who have OA and T2DM receiving combination COX-2 inhibitors and metformin therapy associated with lower joint replacement surgery rates than those without and this may be attributable to combination therapy much more decrease pro-inflammatory factors associated than those without metformin therapy.