Wen-Yi Shau

Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials

Background The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD. Methods Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison. Results 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model. Conclusion Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.

Risk of new acute myocardial infarction hospitalization associated with use of oral and parenteral non-steroidal anti-inflammation drugs (NSAIDs): a case-crossover study of Taiwan's National Health Insurance claims database and review of current evidence

BackgroundPrevious studies have documented the increased cardiovascular risk associated with the use of some nonsteroidal anti-inflammatory drugs (NSAIDs). Despite this, many old NSAIDs are still prescribed worldwide. Most of the studies to date have been focused on specific oral drugs or limited by the number of cases examined. We studied the risk of new acute myocardial infarction (AMI) hospitalization with current use of a variety of oral and parenteral NSAIDs in a nationwide population, and compared our results with existing evidence.MethodsWe conducted a case-crossover study using the Taiwans National Health Insurance claim database, identifying patients with new AMI hospitalized in 2006. The 1-30 days and 91-120 days prior to the admission were defined as case and matched control period for each patient, respectively. Uses of NSAIDs during the respective periods were compared using conditional logistic regression and adjusted for use of co-medications.Results8354 new AMI hospitalization patients fulfilled the study criteria. 14 oral and 3 parenteral NSAIDs were selected based on drug utilization profile among 13.7 million NSAID users. The adjusted odds ratio, aOR (95% confidence interval), for risk of AMI and use of oral and parenteral non-selective NSAIDs were 1.42 (1.29, 1.56) and 3.35 (2.50, 4.47), respectively, and significantly greater for parenteral than oral drugs (p for interaction < 0.01). Ketorolac was associated with the highest AMI risk among both of oral and parenteral NSAIDs studied, the aORs were 2.02 (1.00, 4.09) and 4.27 (2.90, 6.29) respectively. Use of oral flurbiprofen, ibuprofen, sulindac, diclofenac, and parenteral ketoprofen were also significantly associated with increased AMI risk. The results of the present study were consistent with the majority of evidence from previous studies.ConclusionsThe collective evidence revealed the tendency of increased AMI risk with current use of some NSAIDs. A higher AMI risk associated with use of parenteral NSAIDs was observed in the present study. Ketorolac had the highest associated risk in both oral and parenteral NSAIDs studied. Though further investigation to confirm the association is warranted, prescribing physicians and the general public should be cautious about the potential risk of AMI when using NSAIDs.

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.

Utilization of antidepressants in Taiwan: a nationwide population-based survey from 2000 to 2009

This study examined trends in antidepressant utilization in Taiwan between 2000 and 2009.

Radiofrequency ablation is superior to ethanol injection in early-stage hepatocellular carcinoma irrespective of tumor size.

Background Randomized trials suggest that radiofrequency ablation (RFA) may be more effective than percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC). However, the survival advantage of RFA needs confirmation in daily practice. Methods We conducted a population-based cohort study using the Taiwan Cancer Registry, National Health Insurance claim database and National Death Registry data from 2004 through 2009. Patients receiving PEI or RFA as first-line treatment for newly-diagnosed stage I-II HCC were enrolled. Results A total of 658 patients receiving RFA and 378 patients receiving PEI treatment were included for final analysis. The overall survival (OS) rates of patients in the RFA and PEI groups at 5-year were 55% and 42%, respectively (p < 0.01). Compared to patients that received PEI, those that received RFA had lower risks of overall mortality and first-line treatment failure (FTF), with adjusted hazard ratios (HRs) [95% confidence interval (CI)] of 0.60 (0.50-0.73) for OS and 0.54 (0.46-0.64) for FTF. The favorable outcomes for the RFA group were consistently significant for patients with tumors > 2 cm as well as for those with tumors < 2 cm. Consistent results were also observed in other subgroup analyses defined by gender, age, tumor stage, and co-morbidity status. Conclusion RFA provides better survival benefits than PEI for patients with unresectable stage I-II HCC, irrespective of tumors > 2 cm or ≤ 2 cm, in contemporary clinical practice.

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.

Persistence of antidepressant treatment for depressive disorder in Taiwan

OBJECT We sought to explore factors associated with persistence of antidepressant treatment in Taiwan and to compare persistence rates across various antidepressants. METHOD This was a retrospective cohort study using medical claims in Taiwan. We collected data of all new antidepressant users with depressive disorder, aged 18 years or older, during the study period from January 1, 1998, to July 4, 2009. Overall antidepressant treatment persistence was defined as undergoing treatment for 180 days without exceeding a 30-day gap. We also assess the cause of treatment change of initial monotherapy, including discontinuation, switching or combination. The competing risks method was used to estimate cause-specific cumulative incidence and to determine associated factors. RESULTS Only 17.4% of patients continued overall antidepressant treatment and 7.6% continued initial antidepressant monotherapy for 180 days or more. Most patients change initial monotherapy through discontinuation, followed by switching and combination. Male gender, older age, comorbidity with anxiety or sleep disorders, and more concomitant use of drugs were associated with lower discontinuation rate. In terms of antidepressant comparisons, we found that patients treated with selective serotonin reuptake inhibitors are less likely to change initial monotherapy. CONCLUSION The overall persistence of antidepressant treatment in Taiwan was lower than in other countries.

Antidepressant use and the risk of upper gastrointestinal bleeding in psychiatric patients: a nationwide cohort study in Taiwan.

Abstract The magnitude of risk between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding (UGIB) is still unknown in patients with psychiatric diseases. The aim of this study was to quantify the risk of UGIB induced by use of antidepressants with different affinities for serotonin transporters in psychiatric patients using Taiwan’s nationwide health insurance claims database. We conducted a propensity score- matched retrospective cohort study and identified 304,606 psychiatric patients who initiated antidepressant treatment during the 2005–2006 period. Antidepressants were classified as high- (HA group), intermediate- (IA group), or low-affinity (LA group) serotonin reuptake inhibitors. Patients in the LA group were matched 1:1 to those in the HA and IA groups according to their propensity scores. Subjects who were successfully matched were followed up from the date of antidepressant initiation to first hospitalization for UGIB, drug discontinuation, transition to or addition of antidepressants in another group, or the study’s end (whichever occurred first). A total of 153,486 psychiatric patients were successfully matched, and 498 first UGIB events were identified. Compared with the LA group, patients in the HA group had a higher risk for UGIB (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.11–1.71). The HR (95% CI) of the IA group was 1.11 (95% CI, 0.88–1.41). The trend for elevated UGIB risk with increasing affinity of serotonin transporters was statistically significant (P < 0.01). Elderly patients and those with prior UGIB history were more susceptible to the harmful effects. Our findings suggest that the use of high-affinity serotonin reuptake inhibitors may increase the risk for UGIB in psychiatric patients.

A model measuring therapeutic inertia and the associated factors among diabetes patients: A nationwide population‐based study in Taiwan

This article presents an analysis conducted on the patterns related to therapeutic inertia with the aim of uncovering how variables at the patient level and the healthcare provider level influence the intensification of therapy when it is clinically indicated. A cohort study was conducted on 899,135 HbA1c results from 168,876 adult diabetes patients with poorly controlled HbA1c levels. HbA1c results were used to identify variations in the prescription of hypoglycemic drugs. Logistic regression and hierarchical linear models (HLMs) were used to determine how differences among healthcare providers and patient characteristics influence therapeutic inertia. We estimated that 38.5% of the patients in this study were subject to therapeutic inertia. The odds ratio of cardiologists choosing to intensify therapy was 0.708 times that of endocrinologists. Furthermore, patients in medical centers were shown to be 1.077 times more likely to be prescribed intensified treatment than patients in primary clinics. The HLMs presented results similar to those of the logistic model. Overall, we determined that 88.92% of the variation in the application of intensified treatment was at the within‐physician level. Reducing therapeutic inertia will likely require educational initiatives aimed at ensuring adherence to clinical practice guidelines in the care of diabetes patients.

Development and Validation of a Pharmacy-Based Comorbidity Measure in a Population-Based Automated Health Care Database

To develop the Pharmacy‐Based Disease Indicator (PBDI), and to evaluate its performance versus the diagnosis‐based Deyo version of the Charlson Index in predicting subsequent‐year hospitalization in adults.