First-year outcomes of very low birth weight preterm singleton infants with hypoxemic respiratory failure treated with milrinone and inhaled nitric oxide (iNO) compared to iNO alone: A nationwide retrospective study.

BACKGROUND: Inhaled nitric oxide (iNO) has a beneficial effect on hypoxemic respiratory failure. The increased use of concurrent iNO and milrinone was observed. We aimed to report the trends of iNO use in the past 15 years in Taiwan and compare the first-year outcomes of combining iNO and milrinone to the iNO alone in very low birth weight preterm (VLBWP) infants under mechanical ventilation. METHODS: This nationwide cohort study enrolled preterm singleton infants with birth weight <1500g treated with iNO from 2004 to 2019. Infants were divided into two groups, with a combination of intravenous milrinone (Group 2, n = 166) and without milrinone (Group 1, n = 591). After propensity score matching (PSM), each group's sample size is 124. The primary outcomes were all-cause mortality and the respiratory condition, including ventilator use and duration. The secondary outcomes were preterm morbidities within one year after birth. RESULTS: After PSM, more infants in Group 2 needed inotropes. The mortality rate was significantly higher in Group 2 than in Group 1 from one month after birth till 1 year of age (55.1% vs. 13.5%) with the adjusted hazard ratio of 4.25 (95%CI = 2.42-7.47, p <0.001). For infants who died before 36 weeks of postmenstrual age (PMA), Group 2 had longer hospital stays compared to Group 1. For infants who survived after 36 weeks PMA, the incidence of moderate and severe bronchopulmonary dysplasia (BPD) was significantly higher in Group 2 than in Group 1. For infants who survived until one year of age, the incidence of pneumonia was significantly higher in Group 2 (28.30%) compared to Group 1 (12.62%) (p = 0.0153). CONCLUSION: Combined treatment of iNO and milrinone is increasingly applied in VLBWP infants in Taiwan. This retrospective study did not support the benefits of combining iNO and milrinone on one-year survival and BPD prevention. A future prospective study is warranted.

Risk and dose-response relationship of diabetes mellitus for endophthalmitis after cataract surgery in a nationwide cohort study in Taiwan.

BACKGROUND: To investigate the risk of endophthalmitis after cataract surgery in patients with diabetes mellitus (DM) and evaluate the dose-response relationship. METHODS: This retrospective cohort study enrolled patients who underwent bilateral cataract surgeries from 2000 to 2017 in Taiwan National Health Insurance Research Database. The endophthalmitis rates within 3 months after cataract surgery were compared between DM and non-DM cohorts using a generalised estimating equation. The diabetes complications severity index (DSCI) score was adopted to assess the dose-response effect on the endophthalmitis rate. RESULTS: A total of 883 398 patients (1 766 796 eyes) were included. Patients with DM had an increased risk of endophthalmitis after cataract surgery than patients without DM (0.261% vs. 0.242%, adjusted odds ratio = 1.09, 95% confidence interval = 1.03-1.16). The higher endophthalmitis rate in the DM group than in the non-DM group remains after excluding those with prior vitrectomy or intravitreal injection (IVI), and took IVI between the cataract surgery and endophthalmitis (p = 0.0156, 0.0048, and 0.0139). There was a significant dose-response relationship on the likelihood of endophthalmitis in DM patients when DCSI score >10. The endophthalmitis rate is highest among DM complications in patients with metabolic disorders (0.342%). CONCLUSION: DM was a risk factor for endophthalmitis after cataract surgery after adjusting for age, sex, common systemic disorders, and excluding those with prior vitrectomy or IVI and having IVI between cataract surgery and endophthalmitis. A dose-response relationship was noted in DM patients with a DCSI score >10.

Effect of febuxostat on adverse events and mortality in gout in Taiwan: An interrupted time series analysis.

OBJECTIVES: To evaluate the influence of febuxostat on adverse events and mortality in gout. METHODS: We retrospectively enrolled patients with newly diagnosed gout and prescribed urate-lowering therapy between 2006 and 2017 from the Taiwan National Health Insurance Database. These patients were divided into 2 groups: with and without comorbidities (n = 294 847 and 194 539). An interrupted time series analysis with adjustments for demographics, comorbidities, and comedication by propensity score-based stabilized weights was used to compare the trend of adverse events and mortality before vs after febuxostat was introduced in 2012. RESULTS: The proportion of febuxostat use gradually increased from 0% in 2012 to 30% in those with comorbidities and 10% in those without comorbidities in 2017. Allopurinol use decreased from 30% in 2012 to 10% in 2017. The slope of the 1-year incidence rate of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) (per 10 000 patients) significantly reduced after 2012 in those with and without comorbidities (-0.375 per quarter, P = .015 and -.253 per quarter, P = .049). The slope of the 3-year incidence rate of acute myocardial infarction (AMI) (per 1000 patients), percutaneous coronary intervention (PCI) (per 1000 patients), and all-cause mortality (per 100 patients) significantly increased after 2012 in those with comorbidities (+0.207 per quarter, P = .013; +.389 per quarter, P = .002; +.103 per quarter, P = .001). CONCLUSIONS: Febuxostat may reduce SJS and TEN in all gout patients but increase AMI, PCI, and all-cause mortality in gout patients with comorbidities.

Risk of cardiovascular disease among different fluoropyrimidine-based chemotherapy regimens as adjuvant treatment for resected colorectal cancer.

Background: Patients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives. Methods: We assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups. Results: From 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age <70 years, stage II and age ≥70 years, stage III and age <70 years, stage III and age ≥70 years) as the overall population was observed. Conclusion: Higher heart failure and ischemic stroke rates were found in the UFT group than in the other two chemotherapy groups, especially those with stage III CRC and ≥70 years of age. Careful monitoring of this subset of patients when prescribing UFT is warranted.

Comparative safety of Janus kinase inhibitors and tumor necrosis factor inhibitors in patients undergoing treatment for rheumatoid arthritis.

OBJECTIVES: Since 2010, biological disease-modifying antirheumatic drugs (bDMARDs) have been the dominant mode of treatment for rheumatoid arthritis (RA). However, the safety of DMARDs, such as tumor necrosis factor inhibitors (TNFis) and Janus kinase inhibitors (JAKis), in treating patients with RA is a concern. We compared the safety outcomes of JAKis and TNFis in RA patients in clinical settings. METHODS: Patients diagnosed with RA between 2015 and 2017 were identified from the Taiwan National Health Insurance Research Database and followed till 2018. Propensity score stabilized weighting was used to balance the baseline characteristics of the JAKis and TNFis groups. The incidences of safety outcomes, namely cardiovascular (CV) events, tuberculosis (TB), total hip replacement (THR), total knee replacement (TKR), and all-cause mortality, were compared between the 2 study groups. RESULTS: A total of 3179 patients with RA who were administered JAKis (n = 822) and TNFis (n = 2357) were included in this study. The mean follow-up duration was 2.02 years in the JAKis group and 2.10 in the TNFis group. All-cause mortality had the highest incidence rate, followed by TKR, THR, CV events, and TB. A lower incidence rate of the study outcomes was observed in the JAKis group than in the TNFis group but without statistical significance. CONCLUSION: Comparable safety issues and mortality rates were observed for JAKis and TNFis in RA patients treated in real-world settings.

Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma Treated With Targeted Therapies.

Background: The risk for major adverse cardiovascular events (MACE) with targeted therapies for patients with advanced renal cell carcinoma (RCC) in real-world practice remains unclear. Objectives: The aim of this study was to compare the risk for MACE associated with targeted cancer therapies with that associated with cytokine treatment in patients with advanced RCC. Methods: Using Taiwan's National Health Insurance Research Database, a retrospective nationwide cohort study was conducted involving patients with advanced RCC who had received targeted therapy (sunitinib, sorafenib, pazopanib, everolimus, or temsirolimus) or cytokine therapy (interleukin-2 or interferon gamma) from 2007 to 2018. Cox proportional hazards models were used to estimate the risk for MACE (a composite of myocardial infarction, ischemic stroke, heart failure, and cardiovascular death) in the cohort using the propensity score method of stabilized inverse probability of treatment weighting. Results: In this cohort of 2,785 patients with advanced RCC, 2,257 (81%) and 528 (19%) had received targeted and cytokine therapy, respectively. After stabilized inverse probability of treatment weighting, the incidence rates of MACE were 6.65 and 3.36 per 100 person-years in the targeted and cytokine therapy groups, respectively (HR: 1.80; 95% CI: 1.19-2.74). Baseline history of heart failure (HR: 3.88; 95% CI: 2.25-6.71), atrial fibrillation (HR: 3.60; 95% CI: 2.16-5.99), venous thromboembolism (HR: 2.50; 95% CI: 1.27-4.92), ischemic stroke (HR: 1.88; 95% CI: 1.14-3.11), and age ≥ 65 years (HR: 1.81; 95% CI: 1.27-2.58) were independent risk factors for targeted therapy-associated MACE. Conclusions: Among patients with advanced RCC, the risk for MACE associated with targeted cancer therapy is higher than that associated with cytokine therapy.

Safety of the endovascular aneurysm repair procedure: real-world evidence using interrupted-time series analysis.

OBJECTIVES: In Taiwan, endovascular aneurysm repair for treating abdominal aortic aneurysms (AAA) was introduced in 2004 and became reimbursable in February 2010. We evaluated the real-world practice and safety of endovascular aneurysm repair in Taiwan. METHODS: Patients who underwent repair operations for AAA (open or endovascular) from 2000 to 2016 were enrolled (n = 11485). Outcome statistics (during the index hospitalization: length of stay, rate of ischaemic bowel disease and 30-day mortality; after discharge: 30-day readmission rate, 2-year mortality, 2-year reintervention rate and 2-year paraplegia rate) were calculated for each half-year cohort. Propensity score-based stabilized weights were used to balance covariates among each half-year cohort. Interrupted time-series analysis was then performed. RESULTS: The elective and emergency ratio of AAA repair was 50:50 from 2000 to 2004 and became 60:40 from 2010 to 2016. The half-year rate of endovascular aneurysm repair was 0% in 2000 to 2004/06, 83.16% in 2010 and 98.1% in 2016. Interrupted time series analysis revealed that after endovascular aneurysm repair became reimbursable, both elective and emergency groups had a reduction in length of stay (-4.2 days, P < 0.0001; -1.5 days, P = 0.0928) and 30-day mortality (-5.22%, P = 0.0702; -7.76%, P = 0.0086) but a significant increase in the reintervention rate (5.05%, P = 0.0031; 4.36%, P = 0.0097). CONCLUSIONS: Endovascular aneurysm repair was predominantly used in treating AAAs after it was reimbursed in Taiwan. Endovascular aneurysm repair is efficacious regarding short-term outcomes but increased the 2-year reintervention rate in both groups.

Trends of adverse events and mortality after DMARDs in patients with rheumatoid arthritis: Interrupted time-series analysis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) experience adverse events because of the characteristics of the disease and the side effects of medications. We investigated the trends of adverse events and mortality associated with disease-modifying antirheumatic drugs (DMARDs). METHODS: We used the Taiwan National Health Insurance Database to enroll patients with incident RA between 2000 and 2017. The 1-year incident rate of gastrointestinal (GI) bleeding and 3-year incident rates of other adverse events and mortality for each calendar-quarter cohort were computed and adjusted using propensity score-based stabilized weights for fair comparisons. Levels and trends of the conventional DMARD era (2000-2002, Phase 1) were compared with those of the TNFi era (2003-2012, Phase 2) and OMA era (2013-2017, Phase 3) by using interrupted time series (ITS) analysis. RESULTS: All patients with RA were prescribed cDMARDs in Phase 1 (2000-2002), and 1%-3% were prescribed either TNFi in phase 2 (2003-2012) or OMAs in phase 3 (2013-2017). The cancer incidence rate was 1.90%, and its mortality rate was 4.19%. After the introduction of TNFi from 2003 to 2012, the main outcomes, except TKA, exhibited a steady or mild decrease in trends. ITS analysis revealed that the slope mildly increased in 2003-2012 compared with that in 2000-2003 by 0.13% for total knee replacement (p = .0322). In 2012-2017 (the OMA era), the events became steady. CONCLUSION: In patients with RA, the introduction of DMARDs was associated with stable adverse events and mortality rates. Moreover, the introduced new treatment for RA exhibited a good safety profile.

Effect of Blue Light-Filtering Intraocular Lenses on Insomnia After Cataract Surgery: A Nationwide Cohort Study With 10-Year Follow-up.

PURPOSE: To compare the incidence of clinically diagnosed insomnia after cataract surgery in pseudophakic eyes with blue light-filtering intraocular lenses (BF-IOLs) and non-BF-IOLs. DESIGN: Nationwide cohort study using the Taiwan National Health Insurance Research Database. METHODS: We enrolled 171,415 patients who underwent cataract surgery in both eyes between 2008 and 2013 and followed them till 2018. Propensity score matching (PSM) was used to balance the baseline characteristics between the 2 IOL groups. The Cox model and cause-specific hazard model were used to estimate the hazard ratios (HRs) and subdistribution hazard ratio (SHR). RESULTS: Overall, 19,604 (11.4%) and 151,811 (88.6%) patients had BF-IOL and non-BF-IOL implants, respectively. The BF-IOL group tended to be younger and had fewer chronic diseases. Within a mean follow-up period of 6.2 years, the incidence rates of insomnia (per 100 person-years) in the BF-IOL and non-BF-IOL groups were 2.97 and 3.21, respectively. There was no significant difference in the incidence rate of insomnia between the 2 IOL groups after treating all-cause mortality as a competing risk (SHR 0.98, 95% CI 0.95-1.01) and after PSM (HR 0.97, 95% CI 0.92-1.01), respectively. Subgroup analysis revealed no significant difference in the insomnia rate between the 2 IOL groups for various age groups, 2 sex groups, and men with and without benign prostatic hyperplasia. CONCLUSION: In Taiwan, the use of a BF-IOL for up to 10 years had no apparent disadvantage over non-BF-IOLs with respect to insomnia.

Effect of Blue Light-Filtering Intraocular Lenses on Age-Related Macular Degeneration: A Nationwide Cohort Study With 10-Year Follow-up.

PURPOSE: To determine the incidence rate of age-related macular degeneration (AMD) after cataract surgery and compare the relative incidence of AMD in pseudophakes with blue light-filtering intraocular lenses (BF-IOLs) and non-BF-IOLs. DESIGN: A nationwide cohort study conducted using the Taiwan National Health Insurance Research Database. METHODS: We enrolled 186,591 patients who underwent cataract surgery in both eyes between 2008 and 2013 and monitored them from the index date (the date of first cataract surgery) until AMD, death, loss to follow-up, or December 31, 2017, whichever occurred first. Propensity score matching (PSM) was used to balance the baseline characteristics between the BF-IOL and non-BF-IOL groups. RESULTS: BF-IOLs were implanted in 21,126 patients (11.3%) and non-BF-IOLs were implanted in 165,465 patients (88.7%). Patients in the BF-IOL group tended to be younger, with fewer men, different cataract surgery years, higher income, more nonmanual workers, more patients from urban and suburban areas, and fewer chronic diseases compared with the non-BF-IOL group. With a mean follow-up period of 6.1 years (range, 1-10 years) after cataract surgery, 12,533 and 1655 patients developed non-exudative AMD and exudative AMD, respectively. The incidence rate of non-exudative AMD and exudative AMD (per 1000 person-years) was 9.95 and 1.22 for the BF-IOL group and 11.13 and 1.44 for the non-BF-IOL group, respectively. After PSM, no statistical difference in the incidence rate of nonexudative AMD (hazards ratio, 0.95; 95% CI, 0.88-1.03) and exudative AMD (hazard ratio, 0.96; 95% CI, 0.77-1.18) was observed between the BF-IOL and non-BF-IOL groups. CONCLUSIONS: In Taiwan, the incidence rate of AMD after cataract surgery was 11.59 per 1000 person-years. The use of a BF-IOL for up to 10 years had no apparent advantage over a non-BF-IOL in the incidence of AMD.

Impact of ABCG2 Gene Polymorphism on the Predisposition to Psoriasis.

Psoriasis is a chronic inflammatory disease which is caused by the interaction between genetic and environmental factors. Evidence shows an association of psoriasis with co-morbidities including cardiovascular diseases, metabolic syndrome and hyperuricemia. Genome-wide association studies have revealed that the ABCG2 gene encoding ATP-binding cassette G2 protein was associated with inflammation and higher serum urate concentrations. In this study, we aimed to evaluate the role of ABCG2 gene polymorphisms on the susceptibility to psoriasis. The genotype distribution of two ABCG2 single nucleotide polymorphisms (SNPs), rs2231142 and rs2231137, was examined in 410 psoriasis patients and 1,089 gender-matched non-psoriasis controls. We found that heterozygotes (GT) for rs2231142 was associated with a decreased risk of psoriasis (p = 0.001; adjusted OR = 0.532; 95% CI, 0.370-0.765) after adjusting for age, as compared with homozygotes for the major allele (GG). Subjects who carried at least one polymorphic allele (homozygote or heterozygote for the minor allele) were less susceptible to psoriasis (p = 0.002; adjusted OR = 0.594; 95% CI, 0.249-0.823) and bearing higher serum urate levels (p = 0.026) than those homozygous for the major allele. Our results indicated that the ABCG2 gene polymorphism was associated with the risk of psoriasis.

Real-World Effectiveness of Adjuvant Oxaliplatin Chemotherapy in Stage III Colon Cancer: A Controlled Interrupted Time Series Analysis.

Background: The real-world effectiveness of oxaliplatin in stage III colon cancer has not been determined in a large-scale population. We aimed to assess the real-world impact of adjuvant oxaliplatin treatment on the survival of these patients. Methods: Based on Taiwan cancer registry, we evaluated 17,801 patients with resected stage III colon cancer, including 14,168 patients receiving adjuvant chemotherapy and 3,633 not receiving adjuvant chemotherapy as the control group between 2004 and 2014. We used the controlled interrupted time-series analysis to assess the three-year disease-free survival and five-year overall survival rates before (2004-2008) and after (2009-2014) the addition of oxaliplatin. Results: The introduction of oxaliplatin was associated with no significant improvement in the slopes (per half-year) of the three-year disease-free survival rate (0.2%, 95% CI: -1.7∼2.2%) and five-year overall survival rate (0.6%, 95% CI: -1.8∼3%). The patients receiving oxaliplatin-based chemotherapy also showed no significant increase in the slopes (per half-year) of the three-year disease-free survival rate (0.6%, 95% CI: -1.4∼2.6%) and five-year overall survival rate (1%, 95% CI: -1.5∼3.5%). The nonsignificant results were consistent across subgroup analyses of age (<70 vs. ≥70 years), recurrence risk (T1-3 or N1 vs. T4 or N2), and cycle of oxaliplatin use (≤6 vs. >6). However, oxaliplatin-based chemotherapy significantly increased the slope (per half-year) of the five-year OS (2%, 95% CI: 0.2∼3.8%) for patients in the high-risk group (T4 or N2). The present results were robust in several sensitivity analyses. Conclusion: Among real-world patients with stage III colon cancer, the introduction of oxaliplatin does not yield a significant improvement in survival. Future work should identify the subpopulation(s) of patients who benefit significantly from the addition of oxaliplatin.

Clinical Outcomes in Atrial Fibrillation Patients With a History of Cancer Treated With Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Cohort Study.

Background and Purpose: Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer. Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups. Results: There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50­0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24­0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23­0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56­0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05). Conclusions: Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Gonadotropin-releasing hormone antagonist associated with lower cardiovascular risk compared with gonadotropin-releasing hormone agonist in prostate cancer: A nationwide cohort and in vitro study.

BACKGROUND: We aimed to determine whether cardiovascular (CV) risk in patients with prostate cancer (PCa) differs between those who receive gonadotropin-releasing hormone (GnRH) agonist (GnRHa) therapy and those who receive GnRH antagonist therapy. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed data by comparing 666 participants receiving GnRH antagonists and 1332 propensity score-matched participants treated with GnRHa in a 1:2 fashion during the period from May 1, 2015, to September 30, 2018. Cox proportional-hazards models were used to estimate the treatment effect on CV outcomes. Furthermore, we conducted an in vitro study to investigate the effect of a GnRHa (leuprolide) or a GnRH antagonist (degarelix) on matrix metalloproteinase-9 (MMP-9) expression and invasion ability in THP-1 differentiated macrophages. RESULTS: GnRH antagonist therapy was associated with a lower risk of composite CV events of myocardial infarction, ischemic stroke, or CV death (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25-0.90) than GnRHa therapy, with a mean follow-up period of 1.21 years. Significantly lower risks of CV death (HR, 0.21; 95% CI, 0.06-0.70) and all-cause mortality (HR, 0.77; 95% CI, 0.61-0.97) were observed in the GnRH antagonist group. In the in vitro study, leuprolide, but not degarelix, significantly increased the expression of MMP-9 activity and the invasive ability of THP-1 differentiated macrophages through gelatin zymography and the matrix invasion assay, respectively. CONCLUSION: GnRH antagonists were associated with reduced risk CV events compared with the GnRHa among patients with PCa, which may be through effects on macrophages.

Comparison Between Non-vitamin K Antagonist Oral Anticoagulants and Low-Molecular-Weight Heparin in Asian Individuals With Cancer-Associated Venous Thromboembolism.

Importance: It is unclear whether the clinical benefits associated with non-vitamin K antagonist oral anticoagulants (NOACs) are similar to those associated with low-molecular-weight heparins (LMWHs) in Asian individuals with cancer and acute venous thromboembolism (VTE). Objective: To compare the risk of recurrent thromboembolic events and bleeding associated with use of a NOAC vs use of the LMWH enoxaparin in Asian individuals with cancer-associated VTE. Design, Setting, and Participants: This cohort study was conducted using data from the Chang Gung Research Database, a multi-institutional electronic medical records database in Taiwan. A cohort of 1109 patients with cancer-associated VTE were identified between January 1, 2012, and January 31, 2019. Data were analyzed from March 2019 through December 2020. Exposures: Receiving a NOAC (including rivaroxaban, apixaban, edoxaban, or dabigatran) or the LMWH enoxaparin. Main Outcomes and Measures: The primary outcomes were composite recurrent VTE or major bleeding. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. We compared risks of recurrent VTE or major bleeding between groups using Cox proportional hazards models. In addition, we conducted an analysis using a Fine and Gray subdistribution hazard model that considered death as a competing risk. Results: Among 1109 patients with cancer and newly diagnosed VTE, 578 (52.1%) were women and the mean (SD) age at index date was 66.0 (13.0) years; 529 patients (47.7%) received NOACs and 580 patients (52.3%) received the LMWH enoxaparin. Composite recurrent VTE or major bleeding occurred in 75 patients (14.1%) in the NOAC group and 101 patients (17.4%) in the enoxaparin group (weighted hazard ratio [HR], 0.77; 95% CI, 0.56-1.07; P = .11). The groups had similar risk of VTE recurrence (HR, 0.62; 95% CI, 0.39-1.01; P = .05) and major bleeding (HR, 0.80; 95% CI, 0.52-1.24; P = .32) at 12 months of follow-up. However, taking a NOAC was associated with a significantly lower risk of gastrointestinal bleeding compared with receiving enoxaparin (10 patients [1.9%] vs 41 patients [7.1%]; HR, 0.29; 95% CI, 0.15-0.59; P < .001). Findings for both primary outcomes were consistent with competing risk analyses (recurrent VTE: HR, 0.68; 95% CI, 0.45-1.01; P = .05; major bleeding: HR, 0.77; 95% CI, 0.51-1.16; P = .21). Conclusions and Relevance: This cohort study found that in real-world practice, among Asian patients with cancer-associated VTE, use of a NOAC was associated with a similar risk for recurrent VTE or major bleeding compared with use of the LMWH enoxaparin. Nonetheless, use of a NOAC was associated with a significantly lower rate of gastrointestinal bleeding. Further prospective studies are needed to confirm these findings.

Familial Aggregation of Head and Neck Cancer in Taiwan.

OBJECTIVES: Head and neck cancer (HNC) incidence has been increasing worldwide. We investigated the familial aggregation of developing HNC if a first-degree relative (FDR) is affected in a large database. METHODS: This retrospective study utilized Taiwan National Health Insurance Database to assemble a cohort of all registered beneficiaries from 1997 to 2013 and identified diagnosed HNC patients with affected FDRs. RESULTS: Of the 55,916 individuals diagnosed with HNC, 566 (1.01%) had affected FDRs. There were 525 (0.56%) males and 41 (0.05%) females. Age of onset of HNC was found to be earlier for those with an affected FDR at the fourth decade of life compared to the general population. The adjusted relative risks (RRs) of an individual with an affected FDR to develop HNC is 2.04 (95% confidence interval [CI], 1.85-2.26): 2.07 (95% CI, 1.88-2.29) if the affected relative was male, and 1.74 (95% CI, 1.31-2.30) if the affected relative was female. The greatest risk to develop HNC is if the affected individual is a twin with adjusted RR 33.04 (95% CI, 12.89-84.69). This is followed by an affected sibling at RR (95% CI) 3.46 (1.68-7.13), offspring at RR 2.28 (95% CI, 1.94-2.69), and parent at RR 1.66 (95% CI, 1.48-1.87). CONCLUSION: Familial tendency of HNC proves the probable contribution of genetic factors to develop cancer. In areca quid endemic region, there is a high likelihood that both environmental and genetic factors work in synergy to develop HNC. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:806-812, 2021.

Surgical outcomes analysis in patients with uncomplicated acute type A aortic dissection: a 13-year institutional experience.

This retrospective study aimed to clarify the short-term and mid-term outcomes of and prognostic factors for patients who underwent surgical repair for uncomplicated acute type A aortic dissection (ATAAD). Between January 2007 and June 2019, 603 consecutive patients underwent ATAAD repair at our institution. According to patients' preoperative presentations and imaging studies, uncomplicated ATAAD was found in 276 (45.8%) patients by excluding preoperative complicated factors. Patients with uncomplicated ATAAD were classified into the survivor (n = 243) and non-survivor (n = 33) groups. Clinical features, surgical information, and postoperative complications were compared. Three-year survival and freedom from reoperation rates for survivors were analyzed using the Kaplan-Meier actuarial method. The in-hospital surgical mortality rate of uncomplicated ATAAD patients was 11.9%. The non-survivor group had a higher rate of postoperative malperfusion-related complications, and a multivariate analysis revealed that repeat surgery, retrograde cerebral perfusion, and intraoperative extracorporeal membrane oxygenation support were predictors of in-hospital mortality. In the survivor group, 3-year cumulative survival and freedom from aortic reoperation rates were 89.6% (95% confidence interval [CI] 84.8-92.9%) and 83.1% (95% CI 76.8-87.7%), respectively. In conclusion, uncomplicated and complicated ATAAD rates were similar; the short-term and mid-term surgical outcomes in patients with uncomplicated ATAAD were generally acceptable.

Type of Androgen Deprivation Therapy and Risk of Dementia Among Patients With Prostate Cancer in Taiwan.

Importance: It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types. Objective: To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer. Design, Setting, and Participants: This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23 651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020. Exposures: Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy. Main Outcomes and Measures: The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison. Results: In the cohort of 23 651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11 817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes. Conclusions and Relevance: In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings.

Epidemiology of outpatient and inpatient eye injury in Taiwan: 2000, 2005, 2010, and 2015.

PURPOSE: To estimate the incidence rate of eye injuries (EI) requiring inpatient and outpatient treatment in Taiwan and compare the epidemiologic characteristics of EI (age, sex, treatment setting, seasonality, occupation, external cause, diagnosis, and surgery) in the years 2000, 2005, 2010, and 2015. METHODS: We analyzed four random samples of 1,000,000 beneficiaries each from 2000, 2005, 2010, and 2015 of the Taiwan National Health Insurance Program. The direct age-standardized rate, with 95% confidence interval (CI), was used to compare EI rates for the four calendar years. The chi-square test and chi-square test for trend were used to compare data for the four calendar years. RESULTS: Annual EI incidence rates were between 2.57% in 2000 and 3.28% in 2015. The age-standardized rates were 2.73% (95% CI, 2.70%-2.76%) in 2000, 3.37% (95% CI, 3.33%-3.41%) in 2005, 3.31% (95% CI, 3.28%-3.35%) in 2010, and 3.02% (95% CI, 2.99%-3.06%) in 2015. Manual workers had the highest EI incidence rate, followed by non-manual workers and civil servants. The proportion of EI requiring inpatient treatment declined from 1.34% in 2000 to 0.63% in 2015 (P <0.0001). Analysis of seasonality showed a consistent decrease in February in the four sampling years; however, this decrease in EI was only seen in outpatients, not in EI requiring hospitalization. The proportion of outpatients requiring surgery significantly decreased, from 2.53% in 2000 to 1.2% in 2015 (P<0.0001). However, the proportion of inpatients requiring surgery for EI as the principal diagnosis increased from 69.32% in 2000 to 83.02% in 2015 (P = 0.29), and the proportion of inpatients requiring surgery for EI as a secondary diagnosis increased from 54.86% in 2000 to 71.6% in 2015 (P = 0.0019). Among inpatients with EI, the most common cause of EI was a traffic accident (44.79%, especially motorcycles), followed by falls (9.75%) and homicide (6.05%). CONCLUSION: In Taiwan, the annual EI incidence rate slightly increased from 2000 to 2005 and then decreased through 2015. The proportion of EI patients requiring hospitalization decreased from 1.34% in 2000 to 0.63% in 2015, but the percentage of inpatients requiring surgery increased. Traffic accidents (especially those involving motorcyclists) remained the predominant external cause of EI requiring hospitalization during the study period.