Comparing clinical outcomes in patients with type 2 diabetes mellitus after ischaemic stroke: Sodium-glucose cotransporter 2 inhibitors users versus non-users. A propensity score matching National Cohort Study.

AIM: This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i. MATERIALS AND METHODS: Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. RESULTS: After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. CONCLUSIONS: Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

Incidence and progression of age-related macular degeneration among patients with and without obstructive sleep apnea: a national cohort study.

PURPOSE: Obstructive sleep apnea (OSA) may increase the risk of age-related macular degeneration (AMD) due to repetitive oxygen deprivation or other mechanisms, though whether OSA increases the risk of AMD progression is unknown. We analyzed associations between OSA and AMD risk in the Taiwanese population. METHODS: We identified patients diagnosed with OSA between 2000 and 2018 in the Taiwan National Health Insurance Research Database and used 1:1 propensity score matching on demographics and co-morbidities to create a non-OSA cohort. We used Cox proportional hazard modeling to investigate the risk of AMD and the risk of progression from nonexudative to exudative AMD in OSA versus non-OSA patients. RESULTS: A total of 66,869 OSA patients were matched with 66,869 non-OSA patients. The hazard ratio (HR) of AMD in the OSA cohort was 1.36 (95% confidence interval[CI]: 1.31-1.43, p<.0001). The HR for progression from nonexudative to exudative AMD for the OSA cohort was 0.94 (95%CI: 0.77-1.14, p=0.5073). CONCLUSION: OSA is associated with a higher risk of developing AMD. However, no increased risk of AMD progression is observed among people with OSA and existing non-exudative AMD.

Trajectory of change in perceived stress, coping strategies and clinical competence among undergraduate nursing students during clinical practicum: a longitudinal cohort study.

BACKGROUND: Clinical practicum is crucial for strengthening nursing students' clinical competence. However, nursing students often experience considerable stress during clinical practicum, and so they employ coping strategies to alleviate it. There is almost no empirical evidence on the change trajectory of perceived stress, coping strategies, and clinical competence among nursing students during a one-year clinical practicum. This study aimed to investigate the trajectory of change in perceived stress, coping strategies, and clinical competence among undergraduate nursing students during a one-year clinical practicum. METHODS: This study used a longitudinal cohort design. Undergraduate nursing students were recruited from a science and technology university in Taiwan to participate from February 2021 to January 2022. Perceived stress, coping strategies, and clinical competence among students in basic training practicum (T1), advanced training practicum (T2), and comprehensive clinical nursing practicum (T3) were surveyed by using the Perceived Stress Scale (PSS), Coping Behaviour Inventory (CBI), and Clinical Competence Scale (CCS). PSS, CBI, and CCS in T1, T2, and T3 were compared using a generalized estimating equation (GEE) to deal with correlated data. The level of statistical significance was set at α = 0.05. RESULTS: A total of 315 undergraduate nursing students completed the questionnaire. The study results show that the overall perceived stress of the students is the highest in T2 and the lowest in T3. The main source of stress of the students is 'taking care of patients' at T1 and 'lack of professional knowledge and skills' at T2 and T3. Students' perceived stress in 'taking care of patients' gradually decreases over time. The four coping strategies of CBI, which are 'stay optimistic', 'problem-solving', 'transference' and 'avoidance' in this order, remain the same ranking in three surveys.The main stress coping strategy used by students is 'stay optimistic', while the coping strategy 'avoidance' is used more frequently in T2 than in T1 and T3. Students' mean scores of the overall clinical competence and in the 'general nursing' and 'management' subscales in T3 are higher than those in T1 and T2. However, their mean scores in 'self-growth' and 'positivity' subscales are the highest in T1 and the lowest in T2. CONCLUSIONS: The results show that through experiential learning in clinical practicum at different stages time after time, students' overall perceived stress is the lowest and their overall clinical competence is the highest in T3. The main coping strategy used when students managed stress is 'stay optimistic'. According to the results, we suggest that clinical educators provide students with appropriate guidance strategies at different stages of stress and continue to follow up the clinical competence and retention rates of these nursing students in the workplace in the future.

Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA-B*1502 genotyping in Taiwan, 2000-2017: A nationwide longitudinal study.

OBJECTIVE: The HLA-B*1502 allele is strongly associated with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA-B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA-B*1502 genotyping before prescribing CBZ was reimbursed in June 2010. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score-based stabilized weighting (PSSW) ensured well-balanced covariates. The difference in 3-month SCAR and SJS/TEN rates between phase 2 (2011-2017) and phase 1 (2000-2009) was examined using a one-sample Z-test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA-B*1502 genotyping. RESULTS: CBZ prescriptions reduced from 7% (2000-2003) to 6% (2004-2010) and 4% (2011-2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3-month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = -.38, p = .0342) and nonusers (r = -.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates. SIGNIFICANCE: Recognizing HLA-B*1502 allele and avoiding CBZ therapy in HLA-B*1502-positive patients is critical for preventing CBZ-induced severe adverse events.

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.

The risk of incident atrial fibrillation in patients with type 2 diabetes treated with sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors: a nationwide cohort study.

BACKGROUND: Although a few meta-analyses were conducted to compare the risk of incident atrial fibrillation (AF) between sodium-glucose cotransporter-2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and other anti-hyperglycemic agents using indirect or direct comparison, the above analyses showed conflicting results with each other. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i, GLP-1RA, and dipeptidyl peptidase-4 inhibitor (DPP4i) among a large longitudinal cohort of diabetic patients. METHODS: In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, a total of 344,893, 44,370, and 393,100 consecutive patients with type 2 diabetes without preexisting AF receiving GLP-1RA, SGLT2i, and DPP4i, respectively, were enrolled from May 1, 2016, to December 31, 2019. We used 1:1 propensity score matching (PSM) to balance covariates across paired study groups. Patients were followed from the drug index date until the occurrence of AF, death, discontinuation of the index drug, or the end of the study period (December 31, 2020), whichever occurred first. RESULTS: After PSM, there were 245,442, 43,682, and 39,190 paired cohorts of SGLT2i-DPP4i, SGLT2i-GLP-1RA, and GLP-1RA-DPP4i, respectively. SGLT2i treatment was associated with lower risk of new-onset AF in participants with type 2 diabetes compared with either DPP4i [hazard ratio (HR):0.90; 95% confidential interval (CI) 0.84-0.96; P = 0.0028] or GLP-1RA [HR 0.74; 95% CI 0.63-0.88; P = 0.0007] treatment after PSM. There was no difference in the risk of incident AF between GLP-1RA and DPP4i users [HR 1.01; 95% CI 0.86-1.19; P = 0.8980]. The above findings persisted among several important subgroups. Dapagliflozin was specifically associated with a lower risk of new-onset AF compared with DPP4i (P interaction = 0.02). CONCLUSIONS: Compared with DPP4i, SGLT2i but not GLP-1RA was associated with a lower risk of incident AF in patients with type 2 diabetes.

Chinese Version of the Vision-Related Quality of Life (NEI-VFQ-25) among Patients with Various Ocular Disorders: A Pilot Study.

Background and Objectives: Subjective visual function is currently becoming an increasing appreciation in assessing the health-related quality of life. This study aimed to assess the vision-related quality of life (VRQOL) among patients with refractive errors, keratoconus, senile cataract, and age-related macular degeneration (AMD) using the Chinese version of the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25). Materials and Methods: The questionnaire of NEI-VFQ-25 was filled out in a clinical setting or by telephone/mail. Univariate and multivariate analyses were used to determine which factors are associated with the NEI-VFQ-25. Results: From June 2018 to January 2019, 28 patients with refractive error, 20 patients with keratoconus, 61 with senile cataracts, and 17 with AMD completed the questionnaire NEI-VFQ-25. There were significant differences in the NEI-VFQ-25 subscale of general vision (p = 0.0017), ocular pain (p = 0.0156), near activities (p = 0.0002), vision-specific social functioning (p = 0.007), vision-specific mental health (p = 0.0083), vision-specific dependency (p = 0.0049), color vision (p < 0.0001), peripheral vision (p = 0.0065), and total score (p < 0.0001) among four disease groups, respectively. The multiple linear regression revealed that the best-corrected visual acuity (BCVA) and disease group were important factors of the total NEI-VFQ-25. After adjusting for BCVA, patients with AMD had a worse total NEI-VFQ-25 score than patients with refractive error, keratoconus, or senile cataracts. Conclusions: Among the patients with four ocular disorders and a broad vision spectrum from normal, partial sight, low vision to legal blindness, the BCVA of their better eye was the most important factor in the VRQOL.

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.

Secular Trends in the Incidence, Prevalence, and Medications for Epilepsy from 2007 to 2015 in Taiwan: A Nationwide Population-Based Study.

BACKGROUND: Patients with epilepsy have a higher mortality rate than the general population. Up-to-date estimates of epilepsy incidence, prevalence, and medication use are critical to assist policymaking. METHODS: Using the National Taiwan Insurance Research Database, the standardized incidence and prevalence of epilepsy were estimated in each calendar year from 2007 to 2015. We used the incident cases of epilepsy to analyze the change in prescribing patterns from 2007 to 2015. Joinpoint regression was used to estimate secular trends. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence decreased from 0.72 (95% confidence interval [CI] 0.70-0.73) to 0.54 (95% CI 0.53-0.55) per 1,000 person-years, giving an annual percentage change (APC) of -2.73 (p < 0.05). Among patients younger than 20 years, the incidence did not change significantly. The age- and sex-standardized prevalence decreased from 6.94 (95% CI 6.90-6.98) to 6.86 (95% CI, 6.82-6.89) per 1,000 people, giving an APC of -0.31 (p < 0.05). However, the prevalence increased in the 35- to 49- and 50- to 64-year age-groups. The most common first-line anticonvulsant was phenytoin in 2007 and valproate in 2015. The use of levetiracetam, clobazam, and valproate increased during the study period, with APCs of 25.48% (95% CI 19.97-31.24), 6.41 (3.09-9.85), and 2.83 (1.51-4.16), respectively. The use of carbamazepine, phenytoin, and topiramate decreased; the APCs were -23.86% (95% CI -25.25 to -22.44), -6.61 (-8.40 to -4.79), and -4.29% (-7.87 to -0.57), respectively. CONCLUSIONS: The overall prevalence and incidence of epilepsy decreased slightly from 2007 to 2015. The prescribed first-line anticonvulsant also changed over time.

Effectiveness and Safety of Direct Oral Anticoagulants in an Asian Population with Atrial Fibrillation Undergoing Dialysis: A Population-Based Cohort Study and Meta-Analysis.

PURPOSE: Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear. METHODS: We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3). RESULTS: From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74-1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54-1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (-) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29-1.84];P < 0.0001) and comparable risk of major bleeding compared to those without OAC treatment. CONCLUSIONS: DOACs did not provide benefit over warfarin regarding effectiveness and safety in AF patients undergoing dialysis. The use of OAC was not associated with a lower risk of IS/SE in ESRD AF patients when compared to those without OAC use.

Postdiagnostic metformin use and survival of patients with colorectal cancer: A Nationwide cohort study.

Epidemiological evidence for the association between postdiagnostic metformin use and survival in patients with colorectal cancer (CRC) remains limited. Using the Taiwan Cancer Registry database, a cohort of 16,676 diabetic patients newly diagnosed with CRC from January 1, 2004 through December 31, 2014, followed until December 31, 2016, was identified. Postdiagnostic use of metformin (two or more prescriptions after CRC diagnosis) was defined as a time-dependent covariate with 6-month lag. Multivariate Cox regression model and stabilized inverse probability of treatment weighting (IPTW) were used to estimate adjusted effects of metformin on all-cause mortality and CRC-specific mortality during follow-up. A number of 11,438 (69%) received metformin after CRC diagnosis. Overall, 7,393 deaths, including 4,845 CRC-specific deaths, were observed during 64,322 person-years of follow-up. After adjustment for demographic and clinical covariates, metformin users had lower all-cause mortality than did nonusers (hazard ratio [HR], 0.42; 95% confidence interval [CI], 0.40-0.44) and lower CRC-specific mortality (HR, 0.41; 95% CI, 0.39-0.44). Similar but somewhat attenuated effects were observed after stabilized IPTW (HR for all-cause mortality, 0.56; 95% CI, 0.53-0.59; HR for CRC-specific mortality, 0.58; 95% CI, 0.55-0.61). Similar results were observed in stratified analyses of 2,112 patients with no prediagnostic metformin use and 14,564 patients with prediagnostic metformin use. Findings for both outcomes were consistent in multiple sensitivity analyses. Use of postdiagnostic metformin was associated with significantly lower all-cause mortality and CRC-specific mortality, regardless of prior metformin use. These findings support the use of metformin as an adjunct to standard care of diabetic patients with CRC.

Major adverse cardiovascular and limb events in patients with diabetes and concomitant peripheral artery disease treated with sodium glucose cotransporter 2 inhibitor versus dipeptidyl peptidase-4 inhibitor.

BACKGROUND: Whether sodium glucose co-transporter 2 inhibitors (SGLT2i) are associated with a lower risk of cardiovascular as well as adverse lower limb events in patients with type-2 diabetes mellitus (T2DM) and concomitant peripheral artery disease (PAD) is unclear. We aimed to evaluate the risk of cardiovascular and limb events, and death associated with the use of SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i) among a longitudinal and national cohort of patients with T2DM. METHODS: In this nationwide retrospective cohort study based on the Taiwan National Health Insurance Research Database, we identified a total of 11,431 and 93,972 consecutive T2DM patients with PAD taking SGLT2i and DPP4i, respectively, from May 1, 2016, to December 31, 2017. We used 1:1 propensity score matching (PSM) to balance covariates across study groups. Patients were followed from the drug index date until the occurrence of clinical outcomes, death, discontinuation of the index drug, or the end of the study period, whichever occurred first. RESULTS: Overall, 56% and 44% of the patients were treated with dapagliflozin and empagliflozin, respectively. The use of SGLT2i had comparable risks of ischemic stroke and acute myocardial infarction, and was associated with lower risks of congestive heart failure (CHF) [hazard ratio (HR): 0.66; 95% confidence interval (CI) 0.49-0.89; p = 0.0062], lower limb ischemia requiring revascularization (HR: 0.73; 95% CI 0.54-0.98; p = 0.0367) or amputation (HR: 0.43; 95% CI 0.30-0.62; p < 0.0001), and cardiovascular death (HR: 0.67; 95% CI 0.49-0.90; p = 0.0089) when compared with the DDP4i group after PSM. The subgroup analysis revealed consistent results for CHF and major adverse limb outcomes for SGLT2i versus DPP4i among patients aged ≥ 75 years, the presence of chronic kidney disease and established cardiovascular disease was consistent with the main analysis. CONCLUSIONS: SGLT2i were associated with lower risks of CHF and adverse lower limb events compared with DPP4i among patients with T2DM and PAD in real-world practice.

Effectiveness, safety, and major adverse limb events in atrial fibrillation patients with concomitant diabetes mellitus treated with non-vitamin K antagonist oral anticoagulants.

BACKGROUND: Evidence of adverse clinical outcomes for non-vitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation (AF) and diabetes mellitus are limited. We investigated the effectiveness, safety, and major adverse limb events for NOACs versus warfarin among diabetic AF patients. METHODS: In this nationwide retrospective cohort study collected from Taiwan National Health Insurance Research Database, we identified a total of 20,967 and 5812 consecutive AF patients with diabetes taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. We used propensity-score stabilized weighting to balance covariates across study groups. RESULTS: NOAC was associated with a lower risk of major adverse cardiovascular events (MACE) (adjusted hazard ratio (aHR):0.88; [95% confidential interval (CI) 0.78-0.99]; P = 0.0283), major adverse limb events (MALE) (aHR:0.72;[95% CI 0.57-0.92]; P = 0.0083), and major bleeding (aHR:0.67;[95% CI 0.59-0.76]; P < 0.0001) compared to warfarin. NOACs decreased MACE in patients of ≥ 75 but not in those aged < 75 years (P interaction = 0.01), and in patients with ischemic heart disease (IHD) compared to those without IHD (P interaction < 0.01). For major adverse limb events, the advantage of risk reduction for NOAC over warfarin persisted in high risk subgroups including age ≥ 75 years, chronic kidney disease, IHD, peripheral artery disease, or use of concomitant antiplatelet drugs. CONCLUSION: Among diabetic AF patients, NOACs were associated with a lower risk of thromboembolism, major bleeding, and major adverse limb events than warfarin. Thromboprophylaxis with NOACs should be considered in the diabetic AF population with a high atherosclerotic burden.

Real-world Comparisons of Direct Oral Anticoagulants for Stroke Prevention in Asian Patients with Non-valvular Atrial Fibrillation: a Systematic Review and Meta-analysis.

BACKGROUND: Whether four direct oral anticoagulants (DOACs) are superior to warfarin among Asians with non-valvular atrial fibrillation (NVAF) remains unclear in the real-world setting. METHODS: We searched PubMed and Medline + Journals@Ovid + EMBASE from September 17, 2009 to May 4, 2019 to perform a systematic review and meta-analysis of all observational real-world studies comparing four DOACs with warfarin specifically focused on Asian patients with NVAF. RESULTS: From the original 212 results retrieved, 18 studies were included in the meta-analysis. Overall, DOACs were associated with lower risks of thromboembolism (hazard ratio; [95% confidence interval], 0.70; [0.63-0.78]), acute myocardial infarction (0.67; [0.57-0.79]), all-cause mortality (0.62; [0.56-0.69]), major bleeding (0.59; [0.50-0.69]), intracranial hemorrhage (0.50; [0.40-0.62]), gastrointestinal bleeding (0.66; [0.46-0.95]), and any bleeding (0.82; [0.73-0.92]) than warfarin. There was statistic heterogeneity between DOACs for the risks of thromboembolism (P interaction = 0.03) and acute myocardial infarction (P interaction = 0.007) when compared to warfarin. However, all DOACs showed lower risks of thromboembolism and acute myocardial infarction than warfarin when pooling studies that compared individual DOAC with warfarin. With regard to the other outcomes when compared to warfarin, there was no statistical heterogeneity between DOACs. In addition, the effectiveness and safety of four DOACs versus warfarin persisted in the subgroups of either standard-dose or low-dose DOACs. CONCLUSIONS: The meta-analysis shows that the DOACs had greater effectiveness and safety compared to warfarin in real-world practice for stroke prevention, among Asian patients with NVAF.

Effectiveness and safety of non-vitamin-K antagonist oral anticoagulants versus warfarin in atrial fibrillation patients with thrombocytopenia.

Patients with thrombocytopenia were excluded from major clinical trials that investigated non-vitamin-K antagonist oral anticoagulants (NOACs) for stroke prevention in atrial fibrillation (AF). The aim of this study was to evaluate the effectiveness and safety of NOAC versus warfarin in AF patients with thrombocytopenia. From 2010 to 2017, a cohort study based on electronic medical records of a multi-center healthcare provider in Taiwan and included 8239 anticoagulated AF patients (age 77.0 ± 7.3 years, 48.0% female). Patients were divided into two subgroups: 7872 patients with a normal platelet count and 367 patients (4.4%) with thrombocytopenia, which was defined as a platelet count less than 100 × 103/µL. We performed Cox proportional hazard analyses to compare the risks of ischemic stroke or systemic embolism (IS/SE), major bleeding, and death between NOAC and warfarin therapies in patients with a normal platelet count and those with thrombocytopenia, respectively. In patients with a normal platelet count, NOAC therapy (n = 4904) was associated with a significantly lower risk of major bleeding, with no difference in the risk of IS/SE or death when compared with warfarin therapy (n = 2968). In patients with thrombocytopenia, NOAC therapy (n = 181) was associated with a lower tendency for major bleeding (aHR 0.45, 95% CI 0.16-1.14) with no significant difference in IS/SE (aHR 0.94, 95% CI 0.29-2.91) or death (aHR 0.95, 95% CI 0.46-1.95) when compared with warfarin therapy (n = 186). NOAC therapy is a reasonable choice for stroke prevention in AF patients with thrombocytopenia.

Association of maternal ethnicity and urbanicity on severe pediatric disease: a nationwide cohort study.

BACKGROUND: A healthy migrant effect on birth outcomes has been reported, however, whether this protective effect persists throughout childhood is unknown. The effect of urbanicity on child health among an immigrant population is unclear. The objective of this study was to compare the incidence rate and cumulative incidence of severe diseases among urban children of Taiwan-born mothers, rural children of Taiwan-born mothers, urban children of foreign-born mothers, and rural children of foreign-born mothers. METHODS: A nationwide cohort study was conducted for children born in Taiwan during 2004-2011 and follow-up till age 4 to 11 years old by linkage the Taiwan Birth Registry 2004-2011, Taiwan Death Registry 2004-2015, and National Health Insurance Research Database 2004-2015. Cox proportional hazards model (multivariable) was used to examine differences among the four study groups. RESULTS: There were 682,982 urban children of Taiwan-born mothers, 662,818 rural children of Taiwan-born mothers, 61,570 urban children of foreign-born mothers, 87,473 rural children of foreign-born mothers. Children of foreign-born mothers had a lower incidence of vasculitis, mainly Kawasaki disease. The incidences of congenital disorders did not differ between children of foreign-born mothers and children of Taiwan-born mothers. The incidence of psychotic disorders was higher in urban children. However, children in rural areas had a higher incidence of major trauma/burn and a higher mortality rate. CONCLUSIONS: A healthy migrant effect was only seen for Kawasaki disease. The mental health of urban children born to immigrant mothers warrants concern.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

Urate-lowering treatment and risk of total joint replacement in patients with gout.

Objectives: To examine whether gout is an independent risk factor for total joint replacement (TJR) and whether urate-lowering treatment (ULT) reduces this risk. Methods: Using the Taiwan National Health Insurance database and the UK Clinical Practice Research Datalink, 74 560 Taiwan patients and 34 505 UK patients with incident gout were identified and age and sex matched to people without gout. Cox proportional hazards models and condition logistic regression were used to examine the risk of TJR in gout patients and the association between cumulative defined daily dose (cDDD) of ULT and TJR. Results: The prevalence rates of TJR in the patients at the time of diagnosis of gout and in people without gout were 1.16% vs 0.82% in Taiwan and 2.61% vs 1.76% in the UK. After a gout diagnosis, the incidence of TJR was higher in the patients with gout compared with those without (3.23 vs 1.91 cases/1000 person-years in Taiwan and 6.87 vs 4.61 cases/1000 person-years in the UK), with adjusted HRs of 1.56 (95% CI 1.45, 1.68) in Taiwan and 1.14 (1.05, 1.22) in the UK. Compared with patients with gout with <28 cDDD ULT, the adjusted ORs for TJR were 0.89 (95% CI 0.77, 1.03) for 28-90 cDDD, 1.03 (0.85, 1.24) for 90-180 cDDD and 1.12 (0.94, 1.34) for >180 cDDD ULT in Taiwan. In the UK, the respective ORs were 1.09 (0.83, 1.42), 0.93 (0.68, 1.27) and 1.08 (0.94, 1.24). Conclusion: This population-based study provides evidence from two nation populations that gout confers significant TJR risk, which was not reduced by current ULT.

Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan.

PURPOSE: We aimed to evaluate the validity of cancer diagnosis in the National Health Insurance (NHI) database, which has routinely collected the health information of almost the entire Taiwanese population since 1995, compared with the Taiwan National Cancer Registry (NCR). METHODS: There were 26,542,445 active participants registered in the NHI database between 2001 and 2012. National Cancer Registry and NHI database records were compared for cancer diagnosis; date of cancer diagnosis; and 1, 2, and 5 year survival. In addition, the 10 leading causes of cancer deaths in Taiwan were analyzed. RESULTS: There were 908,986 cancer diagnoses in NCR and NHI database and 782,775 (86.1%) in both, with 53,192 (5.9%) in the NHI database only and 73,019 (8.0%) in the NCR only. The positive predictive value of the NHI database cancer diagnoses was 94% for all cancers; the positive predictive value of the 10 specific cancers ranged from 95% (lung cancer) to 82% (cervical cancer). The date of diagnosis in the NHI database was generally delayed by a median of 15 days (interquartile range 8-18) compared with the NCR. The 1, 2, and 5 year survival rates were 71.21%, 60.85%, and 47.44% using the NHI database and were 71.18%, 60.17%, and 46.09% using NCR data. CONCLUSIONS: Recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the NCR. Studies using NHI database data must pay careful attention to eligibility and record linkage; use of both sources is recommended.