Ho-Min Chen

The Impact of Diabetes Mellitus on Prognosis of Early Breast Cancer in Asia

BACKGROUND Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer-specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer. PATIENTS AND METHODS The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003-2004. DM status and other comorbidities were retrieved from Taiwans National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan-Meier method. Coxs proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality. RESULTS In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups. CONCLUSION In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.

Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer

PURPOSE The epidermal growth factor receptor inhibitors, gefitinib and erlotinib, are used as standard salvage therapy for advanced non-small-cell lung cancer (NSCLC). The aim of the present study was to compare their efficacies in this population. PATIENTS AND METHODS The Taiwan Cancer Registry and the National Health Insurance claim databases were searched for newly diagnosed patients with NSCLC from 2004 to 2007 who received gefitinib or erlotinib as third-line therapy. Overall survival (OS) and time to treatment failure (TTF) were determined from registered parameters. Treatment efficacies were compared by the log-rank test in total population and subsets with different clinical characteristics. The Coxs proportion hazard model was used to estimate the adjusted hazard ratios in multivariate analyses. RESULTS A total of 984 patients who received gefitinib (67%) or erlotinib (33%) were included. Patients receiving gefitinib or erlotinib had similar OS (median, 10.2 versus 9.9 months, p=0.524) and TTF (median, 5.5 versus 3.4 months, p=0.103). In multivariate analyses, both treatment groups had similar risk of overall mortality (adjusted hazard ratio [HR]=1.04, p=0.629) and treatment failure (adjusted HR=0.94, p=0.417). Comparing the treatments in subgroups based on age, tumour histology and gender also revealed no differences in OS and TTF. For patients who received gefitinib or erlotinib for more than 3 or 6 months, there was no difference in TTF but patients who received erlotinib had longer OS. CONCLUSIONS Gefitinib and erlotinib had similar efficacies as salvage therapy for advanced NSCLC in Taiwan.

Statin Use Is Associated With Improved Prognosis of Colorectal Cancer in Taiwan

BACKGROUND Statins are widely used for hyperlipidemia control and might also exhibit anticancer properties. This study explored whether statin use is associated with the prognosis of curatively resected colorectal cancer (CRC). MATERIALS AND METHODS Using data from the Taiwan Cancer Registry, we established a population-based cohort of patients who received curative surgery for stage I, II, or III CRC. Data related to prescription medications and comorbidities were retrieved from the database of the National Health Insurance program of Taiwan. Statin users were defined as patients who had used statins within 1 year before their cancer diagnosis. Univariate and multivariate analyses were used to compare cancer-specific survival (CSS) and overall survival (OS) between statin users and patients who had never used statins (never users). In the multivariate analysis, we used propensity scores to adjust for age, sex, diagnosis year, physician visits, hospitalization, conjunctive medications, and comorbidities. RESULTS A total of 17,115 patients were enrolled; 2145 (13%) of these patients were statin users, and 14,970 (87%) were never users. After adjusting for other potential prognostic factors, statin use was an independent predictor for longer CSS (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.68-0.88; P < .001) and OS (HR, 0.82; 95% CI, 0.74-0.92; P < .001). These associations were consistent across subgroups, including sexes, tumor stages, and age cohorts, and in CRC patients who suffered from diabetes and hypertension. CONCLUSION Statin use is associated with an improved prognosis of curatively resected CRC.

Type 2 Diabetes Mellitus Is Associated With Increased Mortality in Chinese Patients Receiving Curative Surgery for Colon Cancer

BACKGROUND We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery. METHODS From three national databases of patients in Taiwan, we selected a cohort of colon cancer patients who had been newly diagnosed with stage I or stage II colon cancer between January 1, 2004 and December 31, 2008 and had undergone curative surgery. We collected information regarding DM (type 2 DM only), the use of antidiabetic medications, other comorbidities, and survival outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS) were compared between patients with and without DM. RESULTS We selected 6,937 colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients with DM were older and less likely to receive adjuvant chemotherapy but had a similar tumor stage and grade, compared with colon cancer patients without DM. Compared with colon cancer patients without DM, patients with DM had significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7% vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and comorbidities in our multivariate analysis, DM remained an independent prognostic factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence interval: 1.18-1.49), but not for cancer-specific mortality. Among the colon cancer patients who had received antidiabetic drug therapy, patients who had used insulin had significantly shorter CSS and OS than patients who had not. CONCLUSION Among patients who receive curative surgery for early colon cancer, DM is a predictor of increased overall mortality.

Risk of hip/femur fractures during the initiation period of α‐adrenoceptor blocker therapy among elderly males: a self‐controlled case series study

AIMS This study aimed to evaluate the risk of hip/femur fractures during the initiation period of α-adrenoceptor blocker therapy using the National Health Insurance claims database, Taiwan, with a self-controlled case series design. METHODS All male beneficiaries aged over 50 years as of 2007, who were incident users of α-adrenoceptor blockers and also had a diagnosis of hip/femur fracture within the 2007-2009 study period were identified. The first day when the α-adrenoceptor blocker was prescribed was set as the index date. We partitioned the initial 21 day period following the index date as the post-exposure risk period 1, days 22-60 after the index date as the post-exposure risk period 2, the 21 day period prior to the index date as the pre-exposure risk period 1 and days 22-60 prior to the index date as the pre-exposure risk period 2. The remainder of the study period was defined as the unexposed period. The incidence rate ratio (IRR) of hip/femur fractures within each risk period compared with the unexposed period was estimated using a conditional Poisson regression model. RESULTS A total of 5875 men were included. Compared with the unexposed period, the IRR of hip/femur fractures was 1.36 (95% confidence interval 1.06, 1.74, P = 0.017) within the post-exposure risk period 1 for patients without concomitant prescriptions of anti-hypertensive agents. CONCLUSIONS Use of α-adrenoceptor blockers was associated with a small but significant increase in the risk of hip/femur fractures during the early initiation period in patients without concomitant prescriptions of anti-hypertensive agents.

Comparative Effectiveness and Safety of Dabigatran and Rivaroxaban in Atrial Fibrillation Patients.

Background We aimed to examine the comparative effectiveness and safety between dabigatran and rivaroxaban in atrial fibrillation patients. Methods and Results We conducted a population‐based, retrospective, new‐user cohort study based on the National Health Insurance claims database in Taiwan. Adult atrial fibrillation patients who initiated dabigatran (N=10 625) or rivaroxaban (N=4609) between June 1, 2012 and May 31, 2014 were identified as the overall population. A propensity score was derived using logistic regression to model the probability of receipt of rivaroxaban as a function of potential confounders. Altogether, 4600 dabigatran users were matched with 4600 rivaroxaban users to create a propensity score–matched population. The marginal proportional hazards model was applied among the propensity score–matched population as the primary analysis, and the proportional hazards model with adjustment of the quintiles of the propensity score among the overall population was used as the secondary analysis. Rivaroxaban users had a higher risk of all‐cause death than dabigatran users (hazard ratio 1.44, 95%CI 1.17‐1.78 in the primary analysis and hazard ratio 1.47, 95%CI 1.23‐1.75 in the secondary analysis). Rivaroxaban users also possessed a higher risk of gastrointestinal hemorrhage needing transfusion than dabigatran users in the primary analysis (hazard ratio 1.41, 95%CI 1.02‐1.95), but the difference diminished in the secondary analysis (hazard ratio 1.20, 95%CI 0.92‐1.56). The risks of ischemic stroke, acute myocardial infarction, arterial embolism/thrombosis, and intracranial hemorrhage were similar between the 2 groups. Conclusions Rivaroxaban therapy was associated with a statistically significant increase in all‐cause death compared with dabigatran therapy in atrial fibrillation patients.

Risk of ischemic stroke during the initiation period of α-blocker therapy among older men.

Background: Alpha-blockers are notorious for their first-dose effect of acute hypotension during the early initiation period. Because acute cerebral hypoperfusion may precipitate an episode of ischemic stroke, we aimed to provide a quantitative estimate of the risk of ischemic stroke during the early initiation period of α-blocker therapy, using a self-controlled case series design. Methods: We identified all men aged 50 years or more as of 2007 who were incident users of α-blockers and had a diagnosis of ischemic stroke during the 2007–2009 study period using claims data from Taiwan’s National Health Insurance claims database. The first day on which the α-blocker was prescribed was the index date. We partitioned different risk periods according to their relationship to the index date (pre-exposure risk periods 1 and 2 = ≤ 21 d and 22–60 d before index date, respectively; post-exposure risk periods 1 and 2 = ≤ 21 d and 22–60 d after index date, respectively); the remainder of the study period was defined as the unexposed period. We estimated the incidence rate ratio (IRR) of ischemic stroke in each risk period relative to the unexposed period using a conditional Poisson regression model. Results: A total of 7502 men were included. Compared with the risk in the unexposed period, the risk of ischemic stroke was increased in post-exposure risk period 1 among all patients in the study population (adjusted IRR 1.40, 95% confidence interval [CI], 1.22–1.61) and among patients without concomitant prescriptions for other antihypertensive agents (adjusted IRR 2.11, 95% CI 1.73–2.57). Interpretation: Alpha-blocker therapy was associated with an increased risk of ischemic stroke during the early initiation period, especially among patients who were not taking other antihypertensive agents.

Class effect of beta-blockers in survivors of ST-elevation myocardial infarction: A nationwide cohort study using an insurance claims database.

Beta-blockers can help reduce mortality following acute myocardial infarction (MI); however, whether beta-blockers exert a class effect remains controversial. This study identified all patients with first ST-elevation MI for the period of 2003 to 2010 from the National Health Insurance claims database, Taiwan. We compared patients prescribed carvedilol, bisoprolol, and propranolol. Study outcomes included all-cause death, cardiovascular death, and recurrence of MI. The propensity scores were constructed using multinomial logistic regression to model the receipt of different beta-blockers. Treating carvedilol group as a reference, we employed a simultaneous three-group comparison approach using the Cox regression model with adjustment for the propensity scores to compare the relative risks of various outcomes. Among the 16836 patients, 7591 were prescribed carvedilol, 5934 bisoprolol, and 3311 propranolol. Mean follow-up time was one year. After accounting for baseline differences, patients treated with bisoprolol (HR 0.87, 95% CI 0.72–1.05, p = 0.14) or propranolol (HR 1.07, 95% CI 0.84–1.36, p = 0.58) had a similar risk of all-cause death in comparison with carvedilol. No significant differences were observed among three beta-blocker groups with regard to the risks of cardiovascular death and recurrence of MI. Our results suggest that beta-blockers exert a possible class effect in the treatment of acute MI.

High plasma interleukin-6 levels associated with poor prognosis of patients with advanced hepatocellular carcinoma

Purpose Antiangiogenic therapy is crucial for advanced hepatocellular carcinoma (HCC) treatment. Interleukin (IL)-6 is an inflammatory response mediator that can promote angiogenesis. We explored its prognostic role in patients with advanced HCC. Methods We had two patient cohorts, both comprising patients who received sorafenib-containing therapy as the first-line treatment for advanced HCC. We explored the best cut point for pretreatment plasma IL-6 levels in the exploration cohort and then confirmed it in the validation cohort. Results In total, 55 and 73 patients constituted the exploration and validation cohorts, respectively. In the exploration cohort, a cut point of 4.28 pg/ml was the best for defining high and low IL-6 levels because it could most effectively differentiate overall survival (OS). On application of this cut point to the validation cohort, patients with high plasma IL-6 levels, compared with patients with low IL-6 levels, exhibited significantly poorer OS (median, 8.0 vs 13.9 months, P = 0.031) but similar progression-free survival or treatment response. After adjusting for patient demographics and tumor characteristics, a high plasma IL-6 level remained an independent predictor of poor OS (hazard ratio 2.594, P = 0.005). Conclusion High pretreatment plasma IL-6 levels were associated with poor prognosis of patients with advanced HCC.

Key opioid prescription concerns in cancer patients: A nationwide study.

BACKGROUND Opioids are crucial in cancer pain management. We examined the nationwide prescription patterns of opioids in Taiwan cancer patients to find the potential concerns. METHODS We reviewed the claims database of the National Health Insurance of Taiwan for patients diagnosed with cancer from 2003 to 2011. The use and cost of analgesics were analyzed. Opioids were classified into recommended strong opioids (morphine and transdermal fentanyl), recommended weak opioids (tramadol, buprenorphine, and codeine), and unrecommended opioids (propoxyphene, nalbuphine, and meperidine). RESULTS We enrolled 1,424,048 patients with cancer, and ∼50% of them took analgesics. Among analgesic users, patients who used opioids increased from 48.2% in 2003 to 52.0% in 2010. Approximately 92% of the opioid use came from recommended opioids, either strong (51%) or weak opioids (41%). The ratio of the use of short-acting strong opioids to that of long-acting opioids increased from 0.41 in 2003 to 0.63 in 2011. Transdermal fentanyl accounted for > 50% of the use of strong opioids. Among weak opioids, the use of tramadol gradually increased to 71% in 2011. On average, opioids contributed to 0.79‰ of all medical expenditures and 2.94‰ of all medication costs. CONCLUSION The use of short-acting strong opioids increased during the study period. Instead of oral opioids, transdermal fentanyl was the most commonly used opioid among Taiwan cancer patients. The use of weak opioids, particularly tramadol, was high. These concerns should be the focus of pain management education.