Chiu-Mei Yeh

Sitagliptin and the risk of hospitalization for heart failure: A population-based study

BACKGROUND Saxagliptin was associated with an increased risk of hospitalization for heart failure (HHF) in diabetic patients with high cardiovascular risk. This study assessed the risk of HHF during an exposure to sitagliptin in general diabetic patients. METHODS In Taiwan National Health Insurance research database, a study of the beneficiaries aged ≥ 45 years with diabetes treated with or without sitagliptin between March 2009 and July 2011 was conducted. Patients treated with sitagliptin were matched to patients never exposed to a dipeptidyl peptidase-4 (DPP-4) inhibitor by the propensity score methodology. The outcome measures were the first and the total number of HHF, and mortality for heart failure or all causes. RESULTS A total of 8288 matched pairs of patients were analyzed. During a median of 1.5 years, the first event of HHF occurred in 339 patients with sitagliptin and 275 patients never exposed to a DPP-4 inhibitor (hazard ratio: 1.21, 95% confidence interval: 1.04-1.42, P = 0.017); all-cause mortality was similar (hazard ratio: 0.87, 95% confidence interval: 0.74-1.03, P = 0.109). The risk for HHF was proportional to exposure (hazard ratio: 1.09, 95% confidence interval: 1.06-1.11, P < 0.001 for every 10% increase in adherence to sitagliptin). Overall, there were 935 events of HHF, in which the association between the number of HHF and the adherence to sitagliptin was linear. The greatest total number of HHF occurred in the patients with the highest adherence. CONCLUSIONS The use of sitagliptin was associated with a higher risk of HHF but no excessive risk for mortality was observed.

The Use of Benzodiazepine Receptor Agonists and Risk of Respiratory Failure in Patients with Chronic Obstructive Pulmonary Disease: A Nationwide Population-Based Case-Control Study

STUDY OBJECTIVES Insomnia is prevalent in patients with chronic obstructive pulmonary disease (COPD), and benzodiazepine receptor agonists (BZRAs) are the most commonly used drugs despite their adverse effects on respiratory function. The aim of this study was to investigate whether the use of BZRAs was associated with an increased risk of respiratory failure (RF) in COPD patients. DESIGN Matched case-control study. SETTING National Health Insurance Research Database (NHIRD) in Taiwan. PARTICIPANTS The case group consisted of 2,434 COPD patients with RF, and the control group consisted of 2,434 COPD patients without RF, matched for age, sex, and date of enrollment. MEASUREMENTS AND RESULTS Exposure to BZRAs during the 180-day period preceding the index date was analyzed and compared in the case and control groups. Conditional logistic regression was performed, and the use of BZRAs was associated with an increased risk of RF (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.14-2.13). In subgroup analysis, we found that the benzodiazepine (BZD) users had a higher risk of RF (aOR 1.58, 95% CI 1.14-2.20), whereas the risk in non-benzodiazepine (non-BZD) users was insignificant (aOR 0.85, 95% CI 0.51-1.44). A greater than 2-fold increase in risk was found in those who received two or more kinds of BZRAs and those using a combination of BZD and non-BZD medications. CONCLUSIONS The use of benzodiazepine receptor agonists was a significant risk factor for respiratory failure in patients with chronic obstructive pulmonary disease (COPD). Compared to benzodiazepine, the prescription of non-benzodiazepine may be safer for the management of insomnia in COPD patients.

Association of surgeon volume and hospital volume with the outcome of patients receiving definitive surgery for colorectal cancer: A nationwide population‐based study

Patients with colorectal cancer (CRC) who undergo cancer surgeries with higher‐volume providers may have better outcomes. The current debate focuses on whether it is hospital volume or surgeon volume that matters more.

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.

Risk of depressive disorder following non-alcoholic cirrhosis: a nationwide population-based study.

Background & Aims To evaluate the risk of depressive disorders among non-alcoholic patients by using the Taiwan National Health Insurance Research Database (NHIRD). Methods We conducted a retrospective study of a matched cohort of 52 725 participants (10 545 non-alcoholic cirrhotic patients and 42 180 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 11 years to determine the rates of newly onset depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in cirrhotic patients. Results During the 11-year follow-up period, 395 (3.75%) non-alcoholic cirrhotic patients and 1 183 (2.80%) control patients were diagnosed with depressive disorders. The incidence risk ratio of depressive disorders between non-alcoholic cirrhotic patients and control patients was 1.76 (95% CI, 1.57–1.98, P<.001). After adjusting for age, sex, and comorbidities, non-alcoholic cirrhotic patients were 1.75 times more likely to develop depressive disorders (95% CI, 1.56–1.96, P<.001) compared with the control patients. The hazard ratios for patients younger than 60 years old (1.31) and female (1.25) indicated that each is an independent risk factor for depressive disorders in non-alcoholic cirrhotic patients. Conclusions The likelihood of developing depressive disorders is greater among non-alcoholic cirrhotic patients than among patients without cirrhosis. Symptoms of depression should be sought in patients with cirrhosis.

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.

Incidence and risk of seizures in Alzheimer's disease: A nationwide population-based cohort study.

The reported incidence and risk factors mediating seizures in Alzheimers disease (AD) have been extremely inconsistent and relevant data is lacking in Asia. We investigated the incidence rate and risk of seizures in AD and in a large, nationwide cohort from Han Chinese. A retrospective population-based study was conducted on the data from Taiwans National Health Insurance Research Database from 2000 to 2010. To reduce selection bias, we applied propensity scores, wherein 981 patients with AD were matched to 3835 non-AD controls from a pool of 1000,000 randomly sampled cohort dataset. This approach was based on age, sex, comorbidities and previous brain conditions. Incidence rate, cumulative incidence and hazard ratios (HRs) were estimated. During the 10-year follow-up period (mean follow-up time, 4.02 years), 44 out of 937 AD patients (4.7%) developed seizures. The incidence rate in the AD cohort (11.9 per 1000 person-years) was higher than that in the matched cohort (5.7 per 1000 person-years), with an adjusted HR of 1.85 (95% confidence interval [CI], 1.20-2.83, p=0.005). The mean duration from the diagnosis of AD to the occurrence of seizure is 3.6 years. The Cox regression analysis revealed that AD itself is a significant predictor after adjustment for confounders (HR=2.01, 95% CI, 1.40-2.90, p<0.001). Moreover, age is an independent predictor, with an adjusted HR of 1.03 (95% CI, 1.00-1.05, p=0.019). In conclusion, seizure occurrence in AD is more common than in the matched cohort. Notably, advanced age carries a higher risk for development of seizures in patients with AD.

Incidence of Second Primary Malignancies Following Colorectal Cancer: A Distinct Pattern of Occurrence Between Colon and Rectal Cancers and Association of Co-Morbidity with Second Primary Malignancies in a Population-Based Cohort of 98,876 Patients in Taiwan

AbstractThe purpose of this study is to determine the features of second primary malignancies (SPMs) among patients with prior colorectal cancer (CRC) using a nationwide population-based dataset.Patients with CRC newly diagnosed between 1996 and 2011, and >1 year of follow-up were recruited from the Taiwan National Health Insurance database. Standardized incidence ratios (SIRs) of SPMs in patients with CRC were calculated.During the 16-year study period, 4259 SPMs developed among 98,876 CRC patients. The median duration of follow-up was 4.03 years. The SIR for all SPMs was 1.13 (95% confidence interval = 1.10–1.17). Compared with the general population, a higher incidence of thyroid, prostate, ovarian, and hematologic malignancies developed among patients with colon cancer, whereas the risk for bone and soft tissue cancers increased among patients with rectal cancer. The risk for breast, bladder, kidney, lung, and uterine cancers was significantly higher in patients with colon and rectal cancers than the general population. The risk for liver and biliary tract cancers declined in patients with rectal cancer. Based on multivariate analysis among patients with CRC, age ≥70 years, men, chronic obstructive pulmonary disease (COPD), cirrhosis, and dyslipidemia were independent predictors of an SPM.In conclusion, patients with CRC were at increased risk for a second cancer. The pattern of SPMs was distinct between patients with colon and rectal cancer. Age, men, COPD, cirrhosis, and dyslipidemia were independent risk factors for SPMs. Surveillance and education should be provided for survivors with respect to risk for SPMs.