San-Chi Chen

Rheumatoid Arthritis and the Risk of Bipolar Disorder: A Nationwide Population-Based Study

Background Studies have suggested that chronic inflammation plays an essential role in the pathophysiology of both rheumatoid arthritis (RA) and bipolar disorder. The most common clinical features associated with RA are anxiety and depression. The risk of bipolar disorder among patients with RA has not been characterized adequately. Objective To determine the association between RA and the subsequent development of bipolar disorder and examine the risk factors for bipolar disorder among patients with RA. Methods We identified patients who were diagnosed with RA in the Taiwan National Health Insurance Research Database. A comparison cohort was created by matching patients without RA with those with RA according to age, sex, and comorbidities. The occurrence of bipolar disorder was evaluated in both cohorts. Results The RA cohort consisted of 2,570 patients, and the comparison cohort consisted of 2,570 matched control patients without RA. The incidence of bipolar disorder (incidence rate ratio  = 2.13, 95% confidence interval [CI]  = 1.12–4.24, P =  .013) was higher among patients with RA than among control patients. Multivariate, matched regression models revealed that asthma (hazard ratio [HR]  = 2.76, 95% CI 1.27–5.96, P =  .010), liver cirrhosis (HR  = 3.81, 95% CI  = 1.04–14.02, P =  .044), and alcohol use disorders (HR  = 5.29, 95% CI  = 1.71–16.37, P =  .004) were independent risk factors for the development of bipolar disorder among patients with RA. Conclusion RA might increase the incidence of bipolar disorder development. Based on our data, we suggest that, following RA diagnosis, greater attention be focused on women with asthma, liver cirrhosis, and alcohol use disorder. Prospective clinical studies of the relationship between RA and bipolar disorder are warranted.

Use of Radioactive Iodine for Thyroid Cancer and Risk of Second Primary Malignancy: A Nationwide Population-Based Study.

BACKGROUND Radioactive iodine (RAI) is widely used for the treatment of thyroid cancers. However, information on associations between RAI dose and second primary malignancy (SPM) is lacking. METHODS Patients without antecedent cancer age 20 years or older and newly diagnosed with thyroid cancer were recruited from the Taiwan National Health Insurance database between 1997 and 2010. Standardized incidence ratios (SIRs) for the cancers were calculated to compare the incidence of thyroid cancer with the general population. The association between RAI dosage and cancer development was estimated using time-dependent Cox regression analysis. All statistical tests were two-sided. RESULTS A total of 692 cases of SPM were identified among 20 235 patients with thyroid cancer. Regarding the latter, 79.7% of the patients were women, the median age was 46 years, and the follow-up period included 134 178 person-years. The SIR for any SPM was 1.41 (95% confidence interval [CI] = 1.31 to 1.52). A statistically significantly higher SIR was observed in leukemia (2.74), non-Hodgkins lymphoma (2.38), prostate (2.30), lung and mediastinum (1.93), pancreas (1.83), kidney (1.81), breast (1.48), and colon-rectum (1.31) cancers. Cumulative RAI dose (per 30 mCi increase) conferred a strong risk for SPM (adjusted hazard ratio [aHR] = 1.01, 95% CI = 1.01 to 1.02, P < .001) and leukemia (aHR = 1.03, 95% CI = 1.02 to 1.04, P < .001) occurrences. A cumulative RAI dose greater than 150 mCi possessed a statistically significant risk for all cancer combined (aHR = 1.30) and leukemia (aHR = 6.03). CONCLUSIONS An increased risk of SPM was observed for thyroid cancer patients, especially with cumulative RAI doses over 150 mCi.

Risk of Cancer in Patients with Iron Deficiency Anemia: A Nationwide Population- Based Study

Objective This study evaluated the risk of cancer among patients with iron deficiency anemia (IDA) by using a nationwide population-based data set. Method Patients newly diagnosed with IDA and without antecedent cancer between 2000 and 2010 were recruited from the Taiwan National Health Insurance Research Database. The standardized incidence ratios (SIRs) of cancer types among patients with IDA were calculated. Results Patients with IDA exhibited an increased overall cancer risk (SIR: 2.15). Subgroup analysis showed that patients of both sexes and in all age groups had an increased SIR. After we excluded patients diagnosed with cancer within the first and first 5 years of IDA diagnosis, the SIRs remained significantly elevated at 1.43 and 1.30, respectively. In addition, the risks of pancreatic (SIR: 2.31), kidney (SIR: 2.23), liver (SIR: 1.94), and bladder cancers (SIR: 1.74) remained significantly increased after exclusion of patients diagnosed with cancer within 5 years after IDA diagnosis. Conclusion The overall cancer risk was significantly elevated among patients with IDA. After we excluded patients diagnosed with IDA and cancer within 1 and 5 years, the SIRs remained significantly elevated compared with those of the general population. The increased risk of cancer was not confined to gastrointestinal cancer when the SIRs of pancreatic, kidney, liver, and bladder cancers significantly increased after exclusion of patients diagnosed with IDA and cancer within the first 5 years. This finding may be caused by immune activities altered by IDA. Further study is necessary to determine the association between IDA and cancer risk.

Secondary Primary Malignancy Risk among Patients with Esophageal Cancer in Taiwan: A Nationwide Population-Based Study

Background To evaluate the risk and sites of metachronous secondary primary malignancies (SPMs) among patients with esophageal cancer. Methods Newly diagnosed esophageal cancer patients between 1997 and 2011 were recruited. To avoid surveillance bias, SPMs that developed within one year were excluded. Standardized incidence ratios (SIRs) of metachronous SPMs in these patients were calculated by comparing to the cancer incidence in the general population. Risk factors for SPM development, included age, sex, comorbidities and cancer-related treatments, were estimated by Cox proportional hazards models. Results During the 15-year study period, 870 SPMs developed among 18,026 esophageal cancer patients, with a follow-up of 27,056 person-years. The SIR for all cancers was 3.53. The SIR of follow-up period ≥ 10 years was 3.56; 5–10 years, 3.14; and 1–5 years, 3.06. The cancer SIRs of head and neck (15.83), stomach (3.30), lung and mediastinum (2.10), kidney (2.24) and leukemia (2.72), were significantly increased. Multivariate analysis showed that age ≥ 60 years (hazard ratio [HR] 0.74), being male (HR 1.46) and liver cirrhosis (HR 1.46) were independent factors. According to the treatments, major surgery (HR 1.24) increased the risk, but chemotherapy was nearly significant. Conclusions Patients with esophageal cancer were at increased risk of developing metachronous SPMs. The SIR remained high in follow-up > 10 years, so that close monitoring may be needed for early detection of SPM among these esophageal cancer patients.

The association between prostate cancer and mood disorders: a nationwide population-based study in Taiwan

BACKGROUND This study identified possible risk factors for newly diagnosed mood disorders, including depressive and bipolar disorders, in prostate cancer patients. METHODS From 2000 to 2006, two cohorts were evaluated on the occurrence of mood disorder diagnosis and treatment. For the first cohort, data of patients diagnosed with prostate cancer was obtained from the Taiwan National Health Insurance (NHI) Research Database. As the second cohort, a cancer-free comparison group was matched for age, comorbidities, geographic region, and socioeconomic status. RESULTS Final analyses involved 12,872 men with prostate cancer and 12,872 matched patients. Increased incidence of both depressive (IRR 1.52, 95% CI 1.30-1.79, P <0.001) and bipolar disorder (IRR 1.84, 95% CI 1.25-2.74, P = 0.001) was observed among patients diagnosed with prostate cancer. Multivariate matched regression models show that cerebrovascular disease (CVD) and radiotherapy treatment could be independent risk factors for developing subsequent depressive and bipolar disorders. CONCLUSION We observed that the risk of developing newly diagnosed depressive and bipolar disorders is higher among Taiwanese prostate cancer patients. Clinicians should be aware of the possibility of increased depressive and bipolar disorders among prostate cancer patients in Taiwan. A prospective study is necessary to confirm these findings.

Risk of Second Non-Breast Primary Cancer in Male and Female Breast Cancer Patients: A Population-Based Cohort Study

Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person-years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46–1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70–2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80–4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37–2.98), thyroid (SIR: 2.30, 95% CI: 2.02–2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56–2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60–47.69), skin (SIR: 8.24, 95% CI: 3.02–17.94) and head and neck (SIR: 4.41, 95% CI: 2.35–7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients.

Risk of Cancer in Patients with Cholecystitis: A Nationwide Population-based Study

OBJECTIVE The objective of this study was to evaluate the risk of cancer in patients diagnosed with cholecystitis and possible interactions between cholecystitis and cholecystectomy. METHODS A retrospective population-based cohort study was conducted among patients diagnosed with cholecystitis that were registered in the National Health Insurance Research Database in Taiwan between January 1, 2000 and December 31, 2010. Standardized incidence ratios (SIRs) were calculated to compare the incidence of cancer in these patients to that of the general population. Adjusted hazard ratios (HRs) were also calculated to investigate whether cholecystitis increased the risk for specific cancers. RESULTS During a median observation period of 5.4 years, 1541 cancers occurred in 20,431 patients with cholecystitis, yielding a SIR of 1.97 (95% confidence interval [CI], 1.88-2.07). A significantly greater risk of biliary tract cancer (adjusted HR 1.72; 95% CI, 1.08-2.75) was observed after adjusting for potential risk factors. In contrast, cholecystectomy was found to attenuate the cancer risk, with the reduction of adjusted HR from 2.34 (95% CI, 1.62-3.37) to 1.28 (95% CI, 0.76-2.14). CONCLUSION Cholecystitis is an independent risk factor to extrahepatic biliary tract cancers, whereas cholecystectomy can attenuate the cancer risk of cholecystitis.

Is 1-year follow-up adequate for adult tuberculosis contacts?

To eliminate tuberculosis (TB) on a global scale, the identification and neutralisation of latently infected high-risk individuals is of paramount importance [1]. Active TB contacts are well documented with an increased risk for both latent TB infection (LTBI) and the development of active TB disease [2]. Contact investigation is an important and effective active case-finding strategy, but also requires abundant public health resources [3]. Risk of active TB after the first year should not be ignored: extended follow-up in adult TB contacts is needed http://ow.ly/I9t28

Risk of Ischemic Stroke in Patients With Gastric Cancer: A Nationwide Population-Based Cohort Study.

Abstract Improvements in therapeutic modalities have prolonged the survival of gastric cancer patients. Comorbidities such as thromboembolic events that emerge as a result of disease complexities and/or treatments received have not been considered. The objectives of this study are to examine the relationship between gastric cancer and ischemic stroke, and to determine predictive risk factors. A nationwide population-based cohort study was conducted using data from the Taiwan National Health Insurance database. A total of 45,060 gastric cancer patients and non-cancer counterparts without antecedent stroke were recruited. Hazard ratios (HRs) and the cumulative incidence of ischemic stroke were calculated, and risk factors for ischemic stroke were assessed. Gastric cancer patients were associated with higher risk of ischemic stroke (HR 1.11, 95% confidence interval [CI] 1.03–1.19, P = 0.007), especially in participants younger than 65 years (HR 1.61, 95% CI 1.39–1.86, P < 0.001) and in female participants (HR 1.30, 95% CI 1.14–1.49; P < 0.001) when compared with the matched cohort. Independent risk factors of ischemic stroke in gastric cancer patients included age, hypertension, atrial fibrillation, dyslipidemia, and having received major surgery for gastric cancer. Our findings suggest the importance of stroke surveillance and prevention strategies in high-risk patients. Having received major surgery for gastric cancer is a significant risk factor in these patients.

Secondary Solid Organ Neoplasm in Patients with Acute Lymphoblastic Leukemia: A Nationwide Population-Based Study in Taiwan.

Background Acute lymphoblastic leukemia (ALL) is more common in children than in adults. Secondary neoplasms (SNs) in childhood ALL have been widely reported. However, only one study has demonstrated SNs in adult ALL. Because of the poorer survival of adult ALL, the incidence might be underestimated. Objective To evaluate the incidence and risk factors of secondary solid organ neoplasms among adult and child ALL patients. Methods Newly diagnosed ALL patients between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent or combined malignancies were excluded. Standardized incidence ratios (SIRs) were analyzed to compare the risk of our cohort to general population in the same age, sex and calendar year. Risk factors for SN development were analyzed by Cox proportional hazards models. Effects of treatments were treated as time-dependent variables. Results The 15-year cumulative incidence of SN was 1.9% and 8.4% in 1,381 child and 2,154 adult ALL patients, respectively. The SIR was significantly increased in child ALL (SIR 6.06), but not in adult ALL (SIR 1.16). The SIRs of follow-up periods were 5.14, 2.24, .87 and .71 at ≥ 10 years, 5–10 years, 1–5 years and 0–1, respectively. Overall, 15 SNs developed, and CNS tumors (SIR 11.56) were the most common type. Multivariate analysis showed that age ≥ 20 years (hazard ratio [HR] 5.04), end-stage renal disease (HR 18.98) and cranial irradiation (HR 8.12) were independent risk factors for cancer development. Conclusions When compared with the general population, child ALL shows a increased risk of developing SNs. CNS tumors are the most common type, and cranial irradiation is an independent risk factor. With longer follow-up, the risk of SNs increases. Hence, physicians need to pay more attention on the risk of developing SNs in long-term ALL survivors with risk factors.