Comparing Clinical Outcomes of Tiotropium/Olodaterol, Umeclidinium/Vilanterol, and Indacaterol/Glycopyrronium Fixed-Dose Combination Therapy in Patients with Chronic Obstructive Pulmonary Disease in Taiwan: A Multicenter Cohort Study.

Background: Long-acting beta-agonists (LABA) and long-acting muscarinic antagonists (LAMA) combination therapy improved lung function and health-related quality-of-life and reduced exacerbation rates and dyspnea in symptomatic chronic obstructive pulmonary disease (COPD) patients. We compared the real-world effects of three fixed-dose LABA/LAMA combinations for COPD in Taiwan. Methods: This multicenter, retrospective study evaluated 1-year outcomes after LABA/LAMA combination therapy in patients with symptomatic COPD. Exacerbations and symptoms of COPD, lung functions, and therapy escalation were compared among patients using tiotropium/olodaterol, umeclidinium/vilanterol and indacaterol/glycopyrronium. Propensity score matching (PSM) was applied to balance the baseline characteristics. Results: Data of 1,617 patients were collected. After PSM, time to first moderate-to-severe COPD exacerbation was comparable among three groups, while the annualized rates of the exacerbation (episodes/patient/year) in patients receiving tiotropium/olodaterol (0.19) or umeclidinium/vilanterol (0.17) were significantly lower than those receiving indacaterol/glycopyrronium (0.38). COPD-related symptoms were stable over the treatment period, and there was no significant difference in the changes of symptom scores including CAT and mMRC among three groups at the end of the study period. Conclusion: This study presented valuable real-world outcome in terms of exacerbation and treatment response of COPD patients treated with fixed-dose LABA/LAMA regimens in Taiwan. The annualized rates of moderate-to-severe exacerbation in patients receiving tiotropium/olodaterol or umeclidinium/vilanterol were significantly lower than those receiving indacaterol/glycopyrronium, though the time to first moderate-to-severe exacerbation was similar among different fixed-dose LABA/LAMA combinations.

The association of aspirin use with overall survival of patients with inoperable non-small cell lung cancer: a retrospective study.

BACKGROUND: Studies have indicated that individuals taking aspirin have a reduced risk of cancers and have also established chemo-preventive benefit of aspirin in colorectal cancer. However, research on the association between aspirin use and the survival in patients with lung cancer has revealed inconsistent results. In this study, we investigated the effect of aspirin use on the survival of inoperable non-small cell lung cancer (NSCLC) patients. METHODS: We identified a cohort of 38,842 patients diagnosed with NSCLC between 2000 and 2012 using the Taiwan's National Health Insurance Research Database and used propensity score matching to reduce possible confounding factors. In total, 9864 patients (4932 matched pairs) were included in the matched cohort. Aspirin exposure was analyzed to identify a possible association with mortality in patients with inoperable NSCLC. Time-dependent Cox regression models were used to calculate the hazard ratios (HRs) and the 95% confidence intervals (95% CIs) that corresponded with aspirin exposure. RESULTS: A total of 4979 patients used aspirin at the time of diagnosis of NSCLC. The median overall survival (OS) of the aspirin users was 1.73 (interquartile range, 0.94-3.53) years compared with the 1.30 (interquartile range, 0.69-2.62) years of the non-aspirin users. The Cox proportional hazard model with the time-dependent covariate revealed that aspirin use was associated with a significantly longer OS (HR: 0.83, 95.0% CI: 0.80-0.86). After controlling the sociodemographic characteristics (age, sex, income, and level of urbanization) and lung cancer treatments by propensity score matching, the aspirin users still had a significantly longer OS than the non-aspirin users (HR: 0.79, 95.0% CI: 0.75-0.83). CONCLUSION: Aspirin use is associated with a longer OS in patients with inoperable NSCLC, suggesting that aspirin has a potential anticancer effect. These results warrant further randomized clinical trials to evaluate the actual role of aspirin in the treatment of NSCLC patients.

Effectiveness of Nationwide COPD Pay-for-Performance Program on COPD Exacerbations in Taiwan.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. METHODS: This retrospective cohort study used data from Taiwan's National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. RESULTS: The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: -2.98%, p<0.05, 95% confidence interval [CI]: -0.277 to -0.086; hospitalization: -1.62%, p<0.05, 95% CI: -0.232 to -0.020), whereas no significant difference was observed between the groups in terms of the changes in the prevalence of COPD-related ICU admissions. CONCLUSION: The COPD P4P program exerted a positive net effect on reducing the likelihood of COPD exacerbation, namely COPD-related ED visits and hospitalizations. Future studies should examine the long-term cost-effectiveness of the COPD P4P program.

Metformin Prolongs Survival in Type 2 Diabetes Lung Cancer Patients With EGFR-TKIs.

Background: Metformin use reportedly reduces cancer risk and improves survival in lung cancer patients. This study aimed to investigate the effect of metformin use in patients with diabetes mellitus (DM) and lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods: A nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. From January 1, 2004, to December 31, 2012, a total of 373 metformin and 1260 non-metformin lung cancer cohorts with type 2 DM and EGFR-TKI treatment were studied. Results: Metformin use was significantly associated with a reduced risk of death (hazard ratio: 0.73, 95% confidence interval [CI]: 0.62-0.85, P < .001), as well as a significantly longer median progression-free survival (9.2 months, 95% CI: 8.6-11.7, vs 6.4 months, 95% CI: 5.9-7.2 months, P < .001) and median overall survival (33.4 months, 95% CI: 29.4-40.2, vs 25.4 months, 95% CI: 23.7-27.2 months, P < 0.001). Conclusions: In conclusion, metformin may potentially enhance the therapeutic effect and increase survival in type 2 DM patients with lung cancer receiving EGFR-TKI therapy.

Nutritional supplementation in patients with chronic obstructive pulmonary disease.

Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is associated with cachexia, sarcopenia, and weight loss, and may result in poorer pulmonary function, decreased exercise capacity, and increased risk of exacerbations. Providing nutritional supplementation is an important therapeutic intervention, particularly for severely ill COPD patients with malnutrition. Higher calorie intake through nutritional supplementation significantly increases body weight and muscle strength, and improves quality of life in malnourished COPD patients. Difficulties may be experienced by these COPD patients, who are struggling to breathe and eliminate CO2 from the lungs, resulting in dyspnea, hypercapnia, hypoxia, and respiratory acidosis, which exacerbates muscle loss through oxidative stress and inflammatory responses. To overcome these problems, nutritional supplements should aim to reduce metabolic CO2 production, lower respiratory quotient, and improve lung function. Several studies have shown that high-fat supplements produce less CO2 and have lower respiratory quotient value than high-carbohydrate supplements. In addition, high-fat supplements may be the most efficient means of providing a low-volume, calorie-dense supplement to COPD patients, and may be most beneficial to patients with prolonged mechanical ventilation where hypercapnia and malnutrition are most pronounced. Further studies are required to investigate the optimal nutritional supplements for COPD patients according to their disease severity.