Cost-utility analysis of inotuzumab ozogamicin for relapsed or refractory B cell acute lymphoblastic leukemia from the perspective of Taiwan's health care system.

OBJECTIVES: We conduct a cost-utility analysis of inotuzumab ozogamicin (INO) versus chemotherapy as the standard of care (SOC) for adults with relapsed or refractory B cell acute lymphoblastic leukemia. METHODS: A Markov model incorporating transition probabilities between health states was applied to simulate disease progression. The model inputs, including overall survival, progression-free survival, and utility parameters, were obtained from the INO-VATE ALL trial and literatures. The Taiwan Cancer Registry Database and the Health and Welfare Database were utilized to identify the patient cohort and medical costs from the perspective of National Health Insurance Administration. The lifetime medical costs (in 2017 US dollars), quality-adjusted life years (QALYs) gained, and associated incremental cost-effectiveness ratio (ICER) were the main study outcomes. RESULTS: The lifetime medical costs for INO and SOC were $176,795 and $69,496, and the QALYs gained were 2.25 and 0.84, respectively. The ICER for INO versus SOC was $76,044 per QALY gained, which is slightly more than three times Taiwan's gross domestic product per capita (i.e., $73,224). Favorable economic results for INO versus SOC were found with an increased time horizon for model simulation, less discounting for the future benefit, and higher stem cell transplantation (SCT) rate after INO treatment; and among patients aged less than 55 years, with no SCT history, or in the first salvage treatment. CONCLUSIONS: INO versus SOC has higher costs but is more effective. The use of INO is favorable for patients in the early treatment course and when more future benefit associated with INO is considered.

Cost-effectiveness of statin therapy for secondary prevention among patients with coronary artery disease and baseline LDL-C 70-100 mg/dL in Taiwan.

BACKGROUND: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70-100 mg/dL in Taiwan could be cost-effective. METHODS: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. RESULTS: Moderate-intensity statin use, a treatment regimen expected to achieve LDL <70 mg/dL in the base case, resulted in a net gain of 562 QALYs but with an additional expenditure of $11.4 million per 10,000 patients over ten years. The ICER was $20,288 per QALY gained. The probabilities of being cost-effective at willingness-to-pay thresholds of one and three gross domestic product per capita ($24,329 in 2017) per QALY were 51.1% and 94.2%, respectively. Annual drug cost was the most influential factor on the ICER. CONCLUSION: Lowering the target LDL-C level from 100 to 70 mg/dL among treatment-naïve CAD patients could be cost-effective given the health benefits of preventing cardiovascular events and deaths.

Treatment patterns of lipid-lowering therapies and possible statin intolerance among statin users with clinical atherosclerotic cardiovascular disease (ASCVD) or diabetes mellitus (DM) in Taiwan.

OBJECTIVES: To assess treatment patterns of statin and/or ezetimibe and possible statin intolerance among patients initiating statin or statin plus ezetimibe and with clinical atherosclerotic cardiovascular disease (ASCVD) or diabetes mellitus (DM) in Taiwan. METHODS: A retrospective cohort study using Taiwan's 2005 to 2013 National Health Insurance Research Database (NHIRD) was conducted. Patients with history of clinical ASCVD or DM (without previous clinical ASCVD) and initiating statin or statin plus ezetimibe therapy during 2006 to 2012 were identified. The treatment initiation date was defined as index date. Treatment patterns (including discontinuation, reinitiation, subtraction, switching, and augmentation), adherence (medication possession ratio [MPR]), persistence (gap no greater than 60 d) of statin and/or ezetimibe, and possible statin intolerance during 12-month follow-up from the index date were examined. RESULTS: Among patients initiating statin or statin plus ezetimibe, 11 092 patients with history of clinical ASCVD and 31 100 patients with DM but without clinical ASCVD were analysed. The discontinuation, reinitiation, and switching rates among patients with clinical ASCVD were 54.0%, 11.3%, and 25.7% during 12-month follow-up period, respectively. Among patients with DM, the rates were 57.5%, 14.2%, and 28.5%. The MPRs of statin among clinical ASCVD and DM cohorts were 0.62 and 0.60, respectively. As for ezetimibe, the MPRs were 0.56 and 0.59. Persistence to statin treatment was 46.1% among ASCVD patients and 42.6% among DM patients. Among the ASCVD and DM cohorts, possible statin intolerance was observed among 19.9% and 21.4% of patients, respectively. CONCLUSIONS: Large number of patients with either ASCVD or DM discontinued lipid-lowering therapies with suboptimal adherence and persistence among Taiwanese population. There is a large unmet medical need to provide safe and more effective therapies, which can be used in combination with statins or alone, to reduce the risk of CV events and improve outcomes in high-risk patients.

Health-related quality of life associated with different cancer treatments in Chinese breast cancer survivors in Taiwan.

We assessed the quality of life (QoL) associated with patient's characteristics and different cancer treatments among Chinese breast cancer survivors in Taiwan. A cross-sectional survey was conducted in 2017 where 193 patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer were recruited. Three QoL questionnaires were administered: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), its breast cancer supplementary measure (QLQ-BR23) and EQ-5D-5L. Multiple linear regression was performed to assess the association between QoL and cancer treatments, with adjustment for patient's characteristics. The mean age of study participants was 55.52 years. Simple linear regression showed that cancer stage and receiving chemotherapy were significantly associated with QoL scores (p < 0.05). Significant adverse effects of chemotherapy on QoL were found among early-stage cancer women (i.e., I or II), including poor cognitive and sexual functioning, and a higher symptom burden (i.e., dyspnoea, constipation, systematic therapy side effects). Multiple linear regression also revealed that receiving chemotherapy was significantly associated with poor QoL (e.g., lower functional health and higher symptom burden measured by the QLQ-BR23), compared to none chemotherapy (p < 0.05). Receiving chemotherapy was associated with poor QoL, especially among early-stage breast cancer patients.

Nonsteroidal Anti-Inflammatory Drugs and Risk of First Hospitalization for Heart Failure in Patients with No History of Heart Failure: A Population-Based Case-Crossover Study.

INTRODUCTION: Traditional nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause salt and fluid retention and should thus be used cautiously in patients with documented heart failure. Recent studies have found that some NSAIDs, including cyclooxygenase (COX)-2 inhibitors, are associated with an increased risk of incident heart failure regardless of the related medical history of the patient. OBJECTIVE: This study aimed to investigate the potential link between NSAIDs (both COX-2 inhibitors and traditional nonselective NSAIDs) and heart failure in patients without a history of heart failure. METHODS: We conducted a case-crossover study using the National Health Insurance Research Database (NHIRD) in Taiwan. A total of 5615 subjects with a first hospitalization for heart failure between 2005 and 2013 were identified from the NHIRD. Exposure to individual NSAIDs between the case period (1-30 days before the index date) and control period (121-150 days before the index date) were retrieved. Multivariable conditional logistic regression models were used to estimate the adjusted odds ratios (aORs) of the incident heart failure associated with NSAID use after adjustments for potential confounders. Multiple sensitivity analyses, including the case-time-control analysis, were performed to test the robustness of the study results. RESULTS: Overall, NSAID use was associated with a 1.58-fold risk [aOR 1.58; 95% confidence interval (CI) 1.40-1.79] of heart failure leading to hospitalization in the main analysis, and similar results were obtained in the case-time-control analysis [aOR 1.40 (95% CI 1.18-1.67)]. The increased risks of heart failure were comparable between traditional NSAIDs [aOR 1.53 (95% CI 1.35-1.74)] and COX-2 inhibitors [aOR 1.74 (95% CI 1.25-2.44)]. Among all NSAIDs, ketorolac was associated with the highest risk of heart failure [aOR 1.98 (95% CI 1.37-2.86)]. CONCLUSION: Both traditional NSAIDs and COX-2 inhibitors were associated with an increased risk of heart failure leading to hospitalization in patients without a related history of heart failure.

Subtype-specific epidemiology of lymphoid malignancies in Taiwan compared to Japan and the United States, 2002-2012.

BACKGROUND: There are many unrevealed parts regarding lymphoma etiology. Previous studies suggested differences in lymphoma epidemiology among countries existed; however, some were one-center studies that were not enough to represent the whole population. OBJECTIVE: To provide epidemiological information on lymphoma within Taiwanese and to compare the data with that in Japan and the United States. METHODS: We used Taiwan Cancer Registry Database as our data source. Patients with lymphoma were identified through the ICD-O-3 codes and those with non-Hodgkin lymphoma (NHL) were categorized into three major types and 13 subtypes according to 2008 WHO classification. Incidence of lymphoma was adjusted according to the 2000 world standard population. RESULTS: During 2002-2012, 21 929 cases were diagnosed with four major types of lymphoma in Taiwan. Aggressive B-cell lymphoma (52.21%, N = 11 450) was the most common type of NHL. Median age at diagnosis of aggressive B-cell lymphoma was the eldest (63.0-65.0 years). Male excess in T/NK-cell lymphoma was the most obvious (sex ratio: 1.39-2.07). The incidence of NK/T-cell lymphoma, nasal type, was higher (male: 0.16-0.34 per 100 000, female: 0.06-0.16 per 100 000) in Taiwan than that in the United States and Japan. CONCLUSION: This is the first population-based study in Taiwan to investigate subtype-specific epidemiology of lymphoma. The incidence rates of lymphoma in Taiwan are mostly lower than those in the United States and higher or comparable to those in Japan except for NK/T-cell lymphoma, nasal type, whose age-adjusted incidence in Taiwan is the highest.

Rituximab maintenance improves overall survival in follicular lymphoma: A retrospective nationwide real-world analysis from Taiwan Cancer Registry Database.

Follicular lymphoma (FL) is the most frequent indolent lymphoma in Western countries, but it is less frequent in Asia. Several trials have demonstrated the progression-free benefit of rituximab maintenance for FL patients in Western countries. However, the overall survival (OS) benefits and effectiveness of rituximab maintenance in Asian FL patients remain uncertain. We utilized the Taiwan Cancer Registry Database and the National Health Insurance Research Database to investigate the roles of rituximab maintenance for newly diagnosed FL patients in Taiwan. Among 836 patients with newly diagnosed FL during 2009-2012, we enrolled patients with stage II-IV diseases receiving 4-8 cycles of rituximab-containing induction chemotherapies (R-induction). We excluded those who died or received additional chemotherapy within 180 days after R-induction. Among the 396 enrolled patients, 260 underwent rituximab maintenance (R-maintenance group), and 136 served as the observation group. The R-maintenance group received less anthracycline and fewer cycles of R-induction than the observation group, but they exhibited a significantly better OS both in the univariate and multivariate analyses [hazard ratio, 0.42; 95% confidence interval, 0.19-0.91] after adjusting for age, sex, and Ann Arbor stages. Meanwhile, we also found more patients required further therapies in the first 6 months after the cease of rituximab maintenance. In the subgroup analysis, patients older than 60 years or with stage IV diseases benefited more from rituximab maintenance. Conclusively, our nationwide study is the first one to demonstrate the OS benefit of rituximab maintenance after induction therapies in newly diagnosed FL patients from Asian populations.

Risk of stroke associated with use of nonsteroidal anti-inflammatory drugs during acute respiratory infection episode.

BACKGROUND: Previous studies suggested that acute respiratory infection (ARI) could trigger stroke and that use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased risk of stroke. In many countries, NSAIDs have been widely used among patients with ARI or common cold for pain and fever relief. However, studies evaluating whether NSAIDs use during ARI episodes may further increase the risk of stroke were very limited. METHODS AND RESULTS: During 2007 to 2011, 29 518 patients with an incident hospitalization of stroke were identified. The date of admission was defined as the index date. Using case-crossover design, we compared the following exposure status between the case period (1- to 7-d period before the index date) and matched control period (366- to 372-d period before the index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional regression models were used to estimate odds ratios adjusting potential confounders. The results suggested that NSAIDs use during ARI episodes was associated with a 2.3-fold increased risk of stroke (ischemic: adjusted odds ratio, aOR 2.27, 95% confidence interval, 95% CI, 2.00-2.58; hemorrhagic: aOR 2.28, 95% CI, 1.71-3.02). We also determined that parenteral NSAIDs were associated with much higher risk of stroke in patients with ARI. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs use, was associated with a further increased risk of stroke.

Predicting mortality and hospitalization of older adults by the multimorbidity frailty index.

BACKGROUND: Existing operational definitions of frailty are personnel-costly and time-consuming, resulting in estimates with a small sample size that cannot be generalized to the population level. The objectives were to develop a multimorbidity frailty index using Taiwan's claim database, and to understand its ability to predict adverse event. METHODS: This is a retrospective cohort study. Subjects aged 65 to 100 years who have full National Health Insurance coverage in 2005 were included. We constructed the multimorbidity frailty index using cumulative deficit approach and categorized study population according to the multimorbidity frailty index quartiles: fit, mild frailty, moderate frailty and severe frailty. The multimorbidity frailty index included deficits from outpatient and inpatient diagnosis. Associations with all-cause mortality, unplanned hospitalization and intensive care unit admission were assessed using Kaplan-Meier curves and Cox regression analyses. RESULTS: The multimorbidity frailty index incorporated 32 deficits, with mean multimorbidity frailty index score of 0.052 (standard deviation = 0.060) among 86,133 subjects included. Compared to subjects in fit category, subjects with severe frailty were associated with a 5.0-fold (adjusted hazard ratio, aHR 4.97; 95% confidence interval, 95% CI 4.49-5.50) increased risk of death at 1 year after adjusting for age and gender. Subjects with moderate frailty or mild frailty was associated with 3.1- (adjusted HR 3.08; 95% CI 2.80-3.39) or 1.9- (adjusted HR 1.86; 95% CI 1.71-2.01) folds increased risk, respectively.4.49-5.50). The risk trend of unplanned hospitalization and intensive care unit admission is similar among the study population. Besides, the association between the frailty categories and all three outcomes was slightly stronger among women. CONCLUSION: The multimorbidity frailty index was highly associated with all-cause mortality, unplanned hospitalization and ICU admission. It could serve as an efficient tool for stratifying older adults into different risk groups for planning care management programs.

Acute Respiratory Infection and Use of Nonsteroidal Anti-Inflammatory Drugs on Risk of Acute Myocardial Infarction: A Nationwide Case-Crossover Study.

Background: Previous studies have suggested that acute respiratory infection (ARI) and nonsteroidal anti-inflammatory drugs (NSAIDs) use could trigger acute myocardial infarction (AMI). In some countries, physicians prescribe NSAIDs for patients with ARI for symptom relief. However, there is no research evaluating whether NSAIDs use during ARI episodes may increase the risk of AMI. Methods: We identified 9793 patients with an incident hospitalization of AMI (index date) between 2007 and 2011. Using case-crossover design, we compared the following exposure status between the case (1-7-day before index date) and matched control period (366-372-day before index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional logistic regression models were used to estimate odds ratios adjusted for potential confounders. Results: Nonsteroidal anti-inflammatory drugs use during ARI was associated with a 3.4-fold increased risk of AMI (adjusted odds ratio [aOR] = 3.41; 95% confidence interval [CI] = 2.80-4.16), ARI without NSAIDs use was associated with a 2.7-fold increased risk (aOR = 2.65; 95% CI = 2.29-3.06), and NSAIDs use only was associated with a 1.5-fold increased risk (aOR = 1.47; 95% CI = 1.33-1.62). Moreover, parenteral NSAIDs were associated with much higher risk in ARI patients (aOR = 7.22; 95% CI = 4.07-12.81). Conclusions: Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs, was associated with a further increased risk of AMI.

[The application of the integrative management with no blind spot in the cooperative projects for prevention of blindness].

OBJECTIVE: To evaluate the management for donated funds in cooperative projects for prevention of blindness. METHODS: Retrospectively analyze the integrative management with no blind spot in the cooperative projects conducted by the Center of Preventing and Treating Blindness in Anhui Province and the International Organization for Prevention of Blindness from 1992 to 2001. RESULTS: The integrative management such as standardization of fund budget, establishment of inner-controlling system, improvement of inner-management and enhancement of project audit, returning information to donors and obtaining consent were applied in the cooperative projects for prevention of blindness. Therefore, the funds were used reasonably and projects were smoothly accomplished. CONCLUSION: The integrative management with no blind spot is effective for the management of donated funds in the cooperative projects for blindness.