Sequential multimodal treatments with chemotherapy and surgery for advanced soft tissue sarcoma may be associated with better survival than chemotherapy.

BACKGROUND: In patients with advanced soft tissue sarcoma (STS), surgery had been reported to be associated with superior overall survival (OS). Chemotherapy details for such patients were less reported, and whether multimodal treatment with surgery and chemotherapy provides extra survival benefit remains unclear. METHODS: We retrospectively reviewed patients with newly diagnosed advanced STS treated at National Taiwan University Hospital from January 1, 2011, to December 31, 2017. OS was calculated from the day of diagnosis of advanced STS to the day of death or last follow-up. Baseline patient characteristics and details regarding surgery and chemotherapy were recorded. RESULTS: A total of 545 patients were diagnosed with STS from 2011 to 2017, of which 226 patients had advanced STS. The median age was 54.7 years, and 54% of patients were women. Approximately 38% of patients with advanced STS underwent surgery and exhibited a trend of longer OS compared with who did not (median = 18.6 vs. 11.9 months, p = 0.083). In the chemotherapy subgroup, the benefit of surgery was more prominent (median = 21.9 vs. 16.5 months, p = 0.037). Patients who received chemotherapy prior to surgery exhibited numerically longer OS than those who underwent surgery first (median = 33.9 vs. 18.3 months, p = 0.155). After adjusting other clinical factors, chemotherapy remained an independent factor associated with favourable OS. CONCLUSION: Surgery may be more beneficial for the patients who receive chemotherapy. Our results support evaluation of sequential multimodal treatments strategy including surgery and chemotherapy in patients with advanced STS.

Osteoporosis care after hip fracture: Observation from national health insurance database and fracture liaison services.

BACKGROUND: The objective of this research was to report the trend of osteoporosis care after hip fractures from usual care (UC) and to compare the quality of care with those who received fracture liaison services (FLSs). METHODS: Data on osteoporosis care for patients with hip fracture were acquired from the National Health Insurance claims (UC group), and surveys from FLS programs (FLS group). A total of 183,300 patients receiving UC and 3010 patients receiving FLS were studied. For the two groups, common osteoporosis care indicators, such as bone mineral density (BMD) testing rate, antiosteoporosis medication commencement rate, and adherence rate were described. RESULTS: There were 2488 participants (82.7%) in the FLS group who completed Dual-energy X-ray absorptiometry (DXA) in 8 weeks, 155 (5.1%) who finished it between 8 weeks and 1 year. Even in 2018, when the DXA completion rate was at its highest, the completion rate in the UC group was only 23.5%. In terms of medication commencement, 2372 FLS patients (78.8%) received treatment within 3 months. Only 24.9% of the UC patients received antiosteoporosis medication within 3 months. Furthermore, antiosteoporosis medication adherence rate was 92.2% after 1 year and 83.9% after 2 years in the FLS group, but these were only 66.5% and 42.7%, respectively, in the UC group. CONCLUSION: Patients who received FLS had more timely BMD exams, antiosteoporosis medication treatment, and higher adherence to antiosteoporosis therapy than those who received UC. The discrepancy in rates of continuing treatment became more significant over time between both groups.

Epidemiology and clinical impact of osteoporosis in Taiwan: A 12-year trend of a nationwide population-based study.

BACKGROUND: Osteoporosis increases the fracture and mortality risk of patients and has a higher disease burden than some cancers. Therefore, global concerns regarding the prevention and treatment of osteoporosis have been raised. However, fast-aging Taiwan lacks national epidemiological data on osteoporosis in recent years. We aimed to establish and update epidemiological data on osteoporosis by analyzing national data from 2008 to 2019. METHODS: We estimated the prevalence and incidence of osteoporosis in patients aged ≥50 years based on claims data from Taiwan's National Health Insurance database from 2008 to 2019. We also analyzed the key parameters of fracture care (anti-osteoporosis medication use, bone mineral density examination rate, and length of hospital stay) to understand the secular trend of management and related clinical outcomes (imminent refracture rate and mortality). RESULTS: The number of prevalent osteoporosis increased from 2008 to 2015 and remained constant until 2019; however, the age-standardized prevalence and incidence rates declined from 2008 to 2019 (3.77%-2.91% and 2.08%-1.02%, respectively). The overall incidence rates of hip and spine fractures decreased significantly by 34% and 27%, respectively. For patients with hip and spine fractures, the immanent refracture rates were 8.5% and 12.9% and the 1-year mortality rate remained stable at approximately 15% and 6%, respectively. CONCLUSION: The age-standardized prevalence and incidence rates decreased remarkably from 2008 to 2019, while the number of prevalent osteoporosis remained steady. Patients with hip fractures encountered a high 1-year mortality rate, while the risk of imminent refracture was notable for patients with spine fractures.

Constraining in reimbursement criteria and the adherence to anti-osteoporosis medications (AOMs) in Taiwan: Urbanization makes the difference.

BACKGROUND: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. METHODS: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. RESULTS: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (<25%) decreased from 38.8% in 2008 to 14.6% in 2018. In addition, the switchers increased from 5.9% in 2008 to 9.3% in 2018, indicating a more flexible choice of AOMs. The proportion of high adherence to AOMs was highest in high-urbanization areas, and the proportion increased about two times from 30% in 2008 to 60% in 2018. CONCLUSION: The implementation of new reimbursement criteria in 2011 was associated with increased adherence to AOMs and the increase was most apparent in high-urbanization areas.

Eleven years secular trend of the initiation of anti-osteoporosis medications and subsequent fractures in Taiwan: From 2008 to 2018.

BACKGROUND: Osteoporosis is a common metabolic bone disease that benefits from many newly developed anti-osteoporosis medications (AOMs). Reimbursement policies need to allocate medical budgets properly based on evidence-based data. This study aimed to investigate the 11-year secular trend, focusing on older age and males in this adjustment wave of the National Health Insurance reimbursement. METHODS: We adopted a nationwide cohort from Taiwan's National Health Insurance Research Database (NHIRD). Patients undergoing newly initiated AOMs from 2008 to 2018 were included. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. Patients <50 years, pathological fractures, missing data, and two AOMs prescribed were excluded. The real-world trends related to subsequent fragility fracture and death within 1 and 3 years were used to evaluate the potential effects due to revision of reimbursement policies. RESULTS: Of 393,092 patients, among them, 336,229 patients met the criteria, whose mean age ranged from 73.3 to 74.4 years, and nearly 80% were female. Further analysis showed a steady increase of AOMs from 5567 (17.1%) and 8802 (27.0%) in 2008-6697 (18.3%) and 10,793 (29.5%) in 2018 for males and 80+ years respectively. The subsequent fragility fracture within one and three years post AOMs initiation was 5.81% and 11.80% in 2018. CONCLUSION: This study showed an immediate drop in AOMs prescription after the implementation of a new stricter reimbursement policy. It took 5 years to return the annual prescription number.

The real-world adherence of the first-line anti-osteoporosis medications in Taiwan: Visualize the gap between reality and expectations.

BACKGROUND: Adherence to anti-osteoporosis medications (AOMs) is crucial. National Health Insurance (NHI) in Taiwan has its own rules of reimbursement rule for AOMs. The midterm adherence remained inconclusive. Here we investigated the adherence according to the initially used AOMs, for three consecutive years. METHODS: The nationwide cohort study from 2008 to 2018, based on Taiwan's National Health Insurance Research Database, included 336,229 patients. Their adherence, indicated by medication possession ratio (MPR), to the initial AOMs was investigated yearly for three consecutive years. The overall MPRs (OMPR), including the switched AOMs, were also calculated in the first year. The Sankey diagram further visualized the patient flows toward different adherence according to the initial AOMs. RESULTS: The OMPR in the first year improved if the patients used AOMs with longer dosing intervals. 100%, 68.9%, 40.7%, and 34.0% of the patients started the treatment with zoledronate, denosumab, alendronate, and raloxifene, respectively, had OMPR ≥75% in the first year. In the 3rd year, only 20.89%, 24.13%, and 12.83% of the patients continuously treated with zoledronate, denosumab, and alendronate, respectively, had MPR ≥75%. From the Sankey diagram, we also observed that patients who had poor adherence at one year were inclined to have poor adherence or discontinue antiosteoporosis treatment in the next year. CONCLUSION: The initial AOMs and the observed adherence may provide clues for optimizing patient treatment. The real-world adherence in Taiwan was far from satisfactory in our study.

Cost and effectiveness analyses of the anti-osteoporosis medication in patients with hip fracture in Taiwan: A population-based national claims database analysis.

BACKGROUND: Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. METHODS: Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). RESULTS: There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02-1.13), p = 0.0114 for those ages 70-79 years old; HR = 1.11 (1.06-1.17), p < 0.0001 for those ages ≥80 years) and mortality (HR = 1.18 (1.14-1.22), p < 0.0001 for those ages 70-79; HR = 1.20 (1.16-1.23), p < 0.0001) within 3 years post incident fracture; meanwhile, consuming fewer medical resources in the national insurance healthcare system. (Increment cost = -16011.2 NTD, p = 0.0248 for those ages 70-79; Increment cost = -17257.9 NTD, p = 0.0032 for those ages ≥80 years) CONCLUSION: Overall, under Taiwan's national health insurance, the use of AOMs is cost-saving, especially in the population aged ≥70 years. The finding of this research was valuable for policymakers in considering healthcare policy promotion and resource allocation in the future.

Impact of pneumococcal conjugate vaccination on hospitalized childhood pneumonia in Taiwan.

BACKGROUND: A national 13-valent pneumococcal conjugate vaccine (PCV13) catch-up program among children aged 2-5 years in 2013, before routine infant immunization in 2015, successfully reduced serotype 19A-related invasive pneumococcal diseases in Taiwan. We aimed to investigate its impact on hospitalized childhood pneumonia. METHODS: We analyzed the National Health Insurance Research Database, 2001-2017, for hospitalized children aged <18 years with the diagnoses of all-cause pneumonia, lobar/pneumococcal pneumonia, and pneumococcal parapneumonic diseases. The study period was divided into 2001-2005 (pre-PCV), 2006-2012 (private sectors), and 2013-2017 (universal PCV13 vaccination). RESULTS: On pneumococcal parapneumonic diseases, the national PCV13 vaccination program was associated with an immediate decline in 2-4-year-old children and significant decreasing trends in all ages. The incidence rate ratios of 2016-2017/2011-2012 were 0.16 (95% confidence interval [CI], 0.06-0.40) and 0.18 (95% CI, 0.13-0.23) in children aged < 2 and 2-4 years, respectively. We observed an increase of lobar/pneumococcal pneumonia cases after an early decline. The intensive/invasive medical needs and the fatality of all-cause pneumonia decreased significantly in children of all ages. CONCLUSIONS: Pneumococcal parapneumonic diseases and the disease burden of lobar/pneumococcal pneumonia and lower respiratory tract infections declined after the national PCV13 vaccination program. IMPACT: The impact study of the PCV13 immunization program on childhood pneumonia in Asian countries remained limited. The unique PCV13 immunization program in Taiwan, catch-up before primary infantile series, reduced severe childhood pneumococcal pneumonia at 5 years post PCV13. The intensive and invasive medical needs and fatality of all-cause pneumonia decreased significantly in children of all ages. We observed an increase in lobar/pneumococcal pneumonia after an early decline.

Antiviral prophylaxis for hepatitis B carriers improves the prognosis of diffuse large B-cell lymphoma in Taiwan - a population-based study.

The prevention of hepatitis B virus (HBV) reactivation during rituximab treatment for diffuse large B-cell lymphoma (DLBCL) is important in the HBV-endemic area. This population-based study examines the impact of antiviral prophylaxis for DLBCL patients with HBV infections. We identified 3702 adult patients with newly diagnosed DLBCL between 2011 and 2015 receiving R-CHOP, R-CVP, CHOP or CVP from the Taiwan Cancer Registry. We further stratified them into three groups: HBsAg-negative patients (HBV-negative, N = 2921), HBV carriers who received antiviral prophylaxis (HBV + Px, N = 711), and HBV carriers who did not receive antiviral prophylaxis (HBV + No Px, N = 70). HBV + Px patients were the youngest, and 69·4% received entecavir for antiviral prophylaxis. The median overall survival (mOS) of HBV-negative and HBV + Px patients was similar (74·23 months and not reached, respectively). However, the mOS of HBV + No Px patients was only 35·61 months (P = 0·0028 compared with HBV + Px patients), indicating that antiviral prophylaxis improves OS in HBsAg-positive DLBCL patients. The multivariate analysis showed that the HBV status and antiviral prophylaxis was an independent prognostic factor. In conclusion, our population-based study illustrates the importance of antiviral prophylaxis in HBsAg-positive DLBCL patients. Under antiviral prophylaxis, the survival of DLBCL patients with HBV infections was comparable to that of HBV-negative patients.

Increased fracture risk after discontinuation of anti-osteoporosis medications among hip fracture patients: A population-based cohort study.

BACKGROUND: To compare the risks of major osteoporotic, vertebral, and non-vertebral fractures between patients who discontinued anti-osteoporosis medications. METHODS: We conducted a comparative effectiveness study with a nationwide population-based cohort study design. Patients aged ≥50 years admitted between 2012 and 2015 for incident hip fractures and receiving denosumab or bisphosphonates with sufficient compliance for at least 1 year were included. Patients were categorized into persistent or non-persistent denosumab or bisphosphonates users based on their subsequent use pattern. The main outcomes were subsequent hospitalizations for a major osteoporotic, vertebral or non-vertebral fracture. Multivariate, time-varying Cox proportional hazards model was used to evaluate the risk of major outcomes. RESULTS: Compared with persistent denosumab users, non-persistent denosumab users had a significantly higher risk of major osteoporotic fractures (hazard ratio [HR] = 1.60; 95% confidence interval [CI], 1.20-2.14), vertebral fractures (HR = 2.18; 95% CI, 1.46-3.24) and death (HR = 3.57; 95%CI, 2.63-4.84). However, the increased risk of fracture was not found in both persistent and non-persistent bisphosphonates users. Noteworthy, the increased risk of vertebral fractures in non-persistent denosumab users was more pronounced within 1 year post-discontinuation (HR = 2.90; 95% CI, 1.77-4.74) and among patients who discontinued from 2-year denosumab therapy (HR = 3.58; 95% CI, 1.74-7.40). DISCUSSION: Discontinuation of denosumab resulted in an increased risk of major osteoporotic fractures, especially vertebral fractures. The increased risk tends to reveal within 1 year post-discontinuation and be greater after a longer treatment duration. Notably, only fracture with hospitalization was identified as our research outcome, the real risk of osteoporotic fracture post discontinuation is believed to be higher, especially for vertebral fracture.

Long-term survival outcomes and prognostic factors related to ruptured intracranial aneurysms: A comparison of surgical and endovascular options in a propensity score-matched, nationwide population-based cohort study.

BACKGROUND AND PURPOSE: To determine the long-term survival outcomes of and prognostic factors for survival in patients with a ruptured intracranial aneurysm (RIA) who underwent endovascular coil embolization or surgical clipping. METHODS: We selected patients who had received a diagnosis of RIA between January 1, 2011 and December 31, 2017. Propensity score matching was performed, and Cox proportional hazards model curves were plotted to analyze all-cause mortality in patients undergoing different treatments. RESULTS: The matching process yielded a final cohort of 8102 patients (4051 and 4051 in endovascular coil embolization and surgical clipping groups, respectively) who were eligible for inclusion. In multivariate Cox regression analyses, the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for endovascular coil embolization compared with surgical clipping were 0.87 (95% CI, 0.79-0.97). The aHRs for the ages of 65 to 74, 75 to 84, and ≥85 years compared with the ages of 20 to 64 years were 1.82 (95% CI, 1.60-2.07), 3.35 (95% CI, 2.93-3.84), and 6.99 (95% CI, 5.51-8.86), respectively. Surgical clipping; old age; male sex; treatment during 2011 to 2013; presence of diabetes, congestive heart failure, hypertension, chronic kidney disease, or end-stage renal disease; history of stroke or transient ischemic attack; Charlson Comorbidity Index ≥2; attendance of nonacademic hospitals; and low income were significant independent prognostic factors for poor survival. CONCLUSIONS: Compared with surgical clipping, endovascular coil embolization led to more favorable survival outcomes in patients with RIAs.

Epidemiology, treatment patterns and survival of chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) in Taiwan, 2006-2015.

AIM/OBJECTIVE: Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) is one of the most frequent types of leukaemia/lymphoma in adults in Western countries. However, there are few studies regarding its epidemiology and treatment patterns in Asian countries. METHODS: To investigate CLL/SLL in Asian populations, we identified CLL/SLL patients diagnosed during 2006 to 2015 from the Taiwan Cancer Registry Database and estimated the incidence. Further, patients diagnosed during 2008 to 2015 were included for the analysis of treatment patterns and survivals. Treatments for CLL/SLL were retrieved from the Taiwan's National Health Insurance Research Database and survival data from the National Death Registry. RESULTS: In total, 1497 patients who were older than 20 years and had newly diagnosed CLL/SLL during 2006-2015 were identified. The age-standardized incidence rates of CLL/SLL (0.36 per 100 000 persons in 2006, and 0.54 in 2015) increased during the 10-year period. The sex ratio was ranged from 1.21 to 2.63 with male predominant during 2006 and 2015. For the analysis of treatment patterns (n = 1236), 72.8% patients received chemotherapies. The median duration between the diagnosis and start of treatments was 27 days, and monotherapy of chlorambucil, bendamustine or cyclophosphamide was the most common regimen in initial treatments. The median follow-up duration for the patients receiving therapies was 29.6 months, and 45.0% patients experienced relapse or refractory. In patients with relapse/refractory CLL/SLL, 34.1% received rituximab-containing chemotherapies. Three hundred and ninety-nine (32.3%) patients received intensive treatments, and 175 (43.9%) of them received rituximab-containing chemotherapies. The 5-year overall survival (OS) rate was 61%, and age was an important prognostic factor for CLL/SLL patients. CONCLUSIONS: This study is the first population-based study in Asia and provides comprehensive evidence of epidemiology, treatment patterns and survivals of CLL/SLL in an Asian population.

Recurrence rate and risk factors for recurrence after thoracoscopic surgery for primary spontaneous pneumothorax: A nationwide population-based study.

PURPOSE: This large-scale nationwide population-based study aimed to determine the recurrence rate and risk factors for recurrence after video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP). METHODS: This retrospective study used data from the Taiwan National Health Insurance Database to identify individuals who underwent VATS for PSP from 2007 to 2014. All patients were followed up until December 31, 2017. Study variables included demographic characteristics, intensive care unit admission, lung resection status, use of non-steroidal anti-inflammatory drugs (NSAIDs), and hospital level. The primary outcome was 1-year recurrence, and the secondary outcomes were the 1-year rate of reintervention for recurrence and overall recurrence rate. RESULTS: During the study period, 6654 patients underwent VATS for PSP (average age: 23.2 years, 89.1% male), including 910 patients (13.7%) who experienced recurrence within 1 year and 531 patients (8.0%) who required reintervention within 1 year. The overall recurrence rate was 24.8%, with an average follow-up time of 6.7 years. Age ≤18 years and the use of NSAIDs, especially ketorolac, were significant risk factors for 1-year recurrence and overall recurrence. Younger age was a risk factor for 1-year reintervention. In subgroup analysis, NSAID use was a significant risk factor for 1-year recurrence, 1-year reintervention, and overall recurrence in pediatric patients but not in adult patients. CONCLUSIONS: In Taiwan, the 1-year recurrence rate was 13.7% after VATS for PSP. Younger age and the use of NSAIDs, especially ketorolac, were significant risk factors for short- and long-term recurrence after VATS for PSP.

Systemic treatment of breast cancer with leptomeningeal metastases using bevacizumab, etoposide and cisplatin (BEEP regimen) significantly improves overall survival.

INTRODUCTION: Metastatic breast cancer (MBC) with leptomeningeal metastases (LM) has dismal survival. We aim to determine if modern systemic therapy, especially the bevacizumab, cisplatin, and etoposide (BEEP) regimen, is beneficial to MBC LM patients. METHODS: We excerpted data from a prospectively collected cytopathology database for MBC patients who were diagnosed with LM by positive cerebrospinal fluid cytology. The primary outcome was OS from cytologically confirmed LM until death. Univariate and multivariate analyses were performed to elucidate prognostic factors. RESULTS: We identified 34 patients with cytologically confirmed LM. Treatments after LM diagnosis included: intrathecal methotrexate (82.4%), systemic chemotherapy (68%; BEEP n = 19, others n = 4), and whole brain radiotherapy (n = 5, 14.7%). Three of seven HER2-positive patients (43%) also received intrathecal trastuzumab. OS was improved in 2014-2016 compared with 2011-2013 (13.57 vs 3.20 months, p = 0.004), when 12/17 (71%) versus 7/17 (41%) patients received BEEP, respectively. In the multivariate model including all treatments, BEEP (HR 0.24, p = 0.003) and intrathecal trastuzumab (HR 0.22, p = 0.035), but not intrathecal methotrexate (HR 0.86, p = 0.78), remained significant prognostic factors. CONCLUSIONS: MBC with LM is treatable-systemic BEEP are efficacious and may improve survival.

Frontline treatments in extremely elderly patients with diffuse large B-cell lymphoma: a population-based study in Taiwan, 2010-2015.

BACKGROUND: The standard frontline therapy for patients with diffuse large B cell lymphoma (DLBCL) is R-CHOP. However, patients older than 80 years are excluded from clinical trials. The importance of rituximab and anthracycline remains unknown in extremely elderly DLBCL patients. Here, we incorporated data from the Taiwan Cancer Registry Database (TCRD), National Health Insurance Research Database (NHIRD), and National Death Registry to evaluate the clinical benefits of rituximab and anthracycline in elderly patients. From the TCRD and NHIRD, we included DLBCL patients aged older than 60 years who received R-CHOP, R-CVP, CHOP, or CVP between 2010 and 2015. RESULTS: Of the 3228 eligible patients, 2559 were between 60 and 79 years (the 60-79 group), and 669 were older than 80 years (the 80+ group). The proportions of patients in the different Ann Arbor stages and the practice settings were similar in both groups. The male-to-female ratio and the Charlson comorbidity index (CCI) scores in the 80+ group were higher than those in the 60-79 group. Patients in the 60-79 group received R-CHOP more frequently than those in the 80+ group. In the 60-79 group, the median age of the patients receiving R-CVP or CVP was older than those receiving R-CHOP or CHOP. In the analysis of overall survival (OS) and time to treatment failure (TTF), R-CHOP, female sex, younger age, lower Ann Arbor stage, lower CCI score, and care at a medical center predicted a favorable prognosis in the 60-79 group. However, only R-CHOP, younger age, and lower Ann Arbor stage remained independent favorable prognostic factors in the 80+ group. CONCLUSIONS: Our population-based study demonstrated the clinical benefits of rituximab and anthracycline in extremely elderly Asian patients with DLBCL.

Direct Comparison of Low-Dose Dabigatran and Rivaroxaban for Effectiveness and Safety in Patients with Non-Valvular Atrial Fibrillation.

BACKGROUND: We aimed to examine the comparative effectiveness and safety between low-dose dabigatran and rivaroxaban in atrial fibrillation (AF) patients. METHODS: Using the National Health Insurance claims database in Taiwan, we conducted head-to-head comparisons among adult non-valvular AF patients prescribed with dabigatran 110 mg or rivaroxaban 15 mg between June 1, 2012 and May 31, 2015. A propensity score was derived using logistic regression to model the probability of receiving different non-VKA oral anticoagulants (NOACs) as a function of potential confounders, and an inverse-probability- of-treatment-weighted (IPTW) pseudo-cohort was created. A Cox proportional hazards model was used to compare clinical outcomes in the IPTW pseudo-cohort as the primary analysis. The propensity score-matched analysis was applied as the secondary analysis. RESULTS: Overall, 13505 dabigatran 110 mg users and 6551 rivaroxaban 15 mgusers were identified. In the primary analysis, the rivaroxaban 15 mg users had a higher risk of all-cause death [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.02-1.38]. In addition, the rivaroxaban 15 mg users had an increased risk of all-cause death (HR 1.25, 95% CI 1.05-1.50) in the secondary analysis. The risks of ischemic stroke, intracranial hemorrhage and gastrointestinal hemorrhage were similar between the 2 study groups in both the primary and secondary analyses. CONCLUSIONS: For non-valvular AF patients, rivaroxaban 15 mg seemed to be associated with an increased risk of all-cause death compared with dabigatran 110 mg. This was a retrospective data analysis and the results should not be over-interpreted to guide the choice of different NOACs.

National Policies Fostering Hospice Care Increased Hospice Utilization and Reduced the Invasiveness of End-of-Life Care for Cancer Patients.

BACKGROUND: In 2011, two national policies aiming to foster hospice services for terminal cancer patients took effect in Taiwan. The single-payer National Health Insurance of Taiwan started to reimburse full hospice services. The national hospital accreditation program, which graded all hospitals, incorporated hospice utilization in its evaluation. We assessed the impact of these national policies. METHODS: A cohort of 249,394 patients aged ≥18 years who died of cancer between 2008 and 2013 were identified from the National Death Registry. We retrieved utilization data of medical services and compared the health care utilization in the final month of life before and after the implementation of the new policies. RESULTS: After the policy changes, hospice utilization increased from 20.8% to 36.2%. In a multivariate analysis adjusting for patient demographics, cancer features, and hospital characteristics, hospice utilization significantly increased after 2011 (adjusted odds ratio [AOR] 2.35, p < .001), accompanied by a decrease in intensive care unit (ICU) admissions, invasive mechanical ventilation (IMV), and cardiopulmonary resuscitation (CPR; AORs 0.87, 0.75, and 0.80, respectively; all p < .001). The patients who received hospice services were significantly less likely to receive ICU admissions, IMV, and CPR (AORs 0.20, 0.12, and 0.10, respectively; all p < .001). Hospice utilization was associated with an adjusted net savings of U.S. $696.90 (25.2%, p < .001) per patient in the final month of life. CONCLUSION: The national policy changes fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients. IMPLICATIONS FOR PRACTICE: National policies fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients.

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.

Primary tumor site is a useful predictor of cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 non-mutant) metastatic colorectal cancer: a nationwide cohort study.

BACKGROUND: Previous studies have shown left-sided colorectal cancer (LCRC) and right-sided colorectal cancer (RCRC) exhibit different molecular and clinicopathological features. We explored the association between the primary tumor site and cetuximab efficacy in KRAS wild-type colorectal cancer (CRC). METHODS: This study enrolled a cohort of patients, who had received cetuximab treatment after two or more lines of chemotherapy for KRAS wild-type (exon 2 nonmutant) metastatic CRC, from the databases of Taiwan Cancer Registry (2004-2010) and National Health Insurance (2004-2011). Survival data were obtained from the National Death Registry. Time to treatment discontinuation (TTD) and overall survival (OS) after the start of cetuximab treatment were compared between patients with LCRC (splenic flexure to rectum) and RCRC (cecum to hepatic flexure). RESULTS: A total of 969 CRC patients were enrolled. Among them, 765 (78.9 %) and 136 (14.0 %) patients had LCRC and RCRC, respectively. Patients with LCRC, compared to patients with RCRC, had longer TTD (median, 4.59 vs. 2.75 months, P = .0005) and OS (median, 12.62 vs. 8.07 months, P < .0001) after the start of cetuximab treatment. Multivariate analysis revealed a right-sided primary tumor site was an independent predictor of shorter TTD (adjusted hazard ratio [HR] = 1.32, using the LCRC group as a reference, 95 % confidence interval: 1.08-1.61, P = .0072) and OS (adjusted HR = 1.45, 95 % CI: 1.18-1.78, P = .0003). CONCLUSION: Our findings demonstrate that a left-sided primary tumor site is a useful predictor of improved cetuximab efficacy in the third-line or salvage treatment of KRAS wild-type (exon 2 nonmutant) metastatic CRC.

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.