Yu-Wen Hu

Does Alzheimer’s Disease Protect against Cancers? A Nationwide Population-Based Study

Background: Previous studies suggested a decreased risk of cancer among patients with Alzheimer’s disease (AD). There is still a lack of data on the specific types of cancer, the risk factors, and the impact of cholinesterase inhibitors on developing cancer in AD. Methods: We performed a nationwide population-based study of 6,960 patients with AD between 1997 and 2006 using Taiwan’s National Health Insurance database. Patterns of cancer incidence in AD patients were compared with those of the general population using standardized incidence ratios (SIRs). Results: Patients with AD had a reduced risk of developing overall cancer [SIR = 0.88, 95% confidence interval (CI) = 0.80–0.97]. Specifically, patients with AD were protected from lung cancers (SIR = 0.75, 95% CI = 0.57–0.98), especially men (SIR = 0.61, 95% CI = 0.40–0.88). In subgroup analyses, women, patients aged 60–79 years, and those diagnosed as having AD for more than 1 year were more likely to be protected from cancers. Conclusions: Our study demonstrates a decreased incidence of overall cancers in patients with AD, a finding lower than but consistent with Western countries. Patients with AD had a significantly decreased risk of lung cancer. Further investigation of genetic evidence linking AD to cancer is warranted.

Risk of cancer among patients with herpes zoster infection: a population-based study

Background: Whether the risk of cancer is increased among patients with herpes zoster is unclear. We investigated the risk of cancer among patients with herpes zoster using a nationwide health registry in Taiwan. Methods: We identified 35 871 patients with newly diagnosed herpes zoster during 2000–2008 from the National Health Insurance Research Database in Taiwan. We analyzed the standardized incidence ratios for various types of cancer. Results: Among patients with herpes zoster, 895 cases of cancer were reported. Patients with herpes zoster were not at increased risk of cancer (standardized incidence ratio 0.99, 95% confidence interval 0.93–1.06). Among the subgroups stratified by sex, age and years of follow-up, there was also no increased risk of overall cancer. Interpretation: Herpes zoster is not associated with increased risk of cancer in the general population. These findings do not support extensive investigations for occult cancer or enhanced surveillance for cancer in patients with herpes zoster.

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.

Amiodarone and the risk of cancer

In postmarketing surveillance, the US Food and Drug Administration has reported the development of lung masses, thyroid cancer, and skin cancer after amiodarone therapy.

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.

Frequency of surveillance computed tomography in non-Hodgkin lymphoma and the risk of secondary primary malignancies: A nationwide population-based study

With increasing usage of computed tomography (CT) for lymphoma patients receiving curative‐intent treatment, development of secondary primary malignancy (SPM) related to radiation from CT scans becomes an emerging issue in these long‐term survivors. We conducted a nationwide population‐based study analyzing non‐Hodgkin lymphoma (NHL) patients receiving curative‐intent treatment between January 1997 and December 2010. Patients were divided into two populations by the medium number of CT performed. The cumulative incidence of SPM in these two groups was compared using the Kaplan–Meier method. Propensity score matching was applied to eliminate potential confounders. Group stratification and multivariate analyses calculated by Cox proportional hazard models using competing risk analyses adjusted for mortality were performed to identify independent predictors for SPM. Patients receiving >8 CT scans had a significantly greater risk for developing SPM (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.61–3.13; p < 0.001) than those with ≤8 scans and this difference remained significant even after correction with propensity score matching. Among the 180 SPM identified, those receiving more CT scans had significantly higher SPM incidence in cancers of the breast (HR 11.22), stomach (HR 5.22) and liver and biliary tract (HR 2.18) in comparison to those with less exposure. The risk of SPM was estimated to increase 3% per one more CT scan performed. Our study demonstrated that after curative‐intent treatment, patients with NHL receiving more frequent surveillance CT scans would have an increased risk of SPM.

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.

Immortal time bias in retrospective analysis: is there a survival benefit in patients with glioblastoma who received prolonged treatment of adjuvant valganciclovir?

Dear Editor: We read with interest “Effects of valganciclovir as an add-on therapy in patients with cytomegalovirus-positive glioblastoma: A randomized, double-blind, hypothesis-generating study”. Stragliotto et al. reported a randomized study, VIGAS, which showed no significant difference in tumor growth or median survival in the Valganciclovir arm. However, the explorative analysis showed a significantly better median survival of 24.1 months in patients receiving >6 months of Valganciclovir versus 13.1 months in patients receiving 0–6 months of treatment. In addition, the same group conducted a retrospective study of 50 patients who received Valganciclovir, which showed the median survival was 25.0, 30.1 and 56.4 months for all patients, patients with at least 6 months of treatment and patients with continuous use, respectively. The result was significantly better than contemporary controls (13.5 months, p< 0.001). The authors suggested that long-term Valganciclovir treatment may be required for a clinical effect on outcome. Indeed, there seemed to be a “dose-response relationship”—the patients who received longer course of treatment had better outcome. Nonetheless, it is likely that “immortal time bias” could explain this result. “Immortal time” refers to a time span in the follow-up period during which the outcome could not have occurred because of exposure definition. For example, death “cannot” occurred in the first 6 months of follow-up in the group of patients who received at least 6 months of treatment (Fig. 1). More extremely, if a cohort is defined as a group of patients who received 10 years of treatment, the survival would certainly be longer than 10 years. In conventional survival analysis, the immortal time bias confers a spurious survival advantage to the treated group. The work of van Walraven et al. demonstrated that, in leading clinical journals, more than 40% of studies containing survival analyses with a time-dependent factor were susceptible to immortal time bias. Fortunately, the bias could be prevented using time-dependent analysis, such as Cox regression with treatment status as a time-dependent covariate. We are looking forward that reanalysis of the original data can be performed.

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.