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There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93–1.42 or aOR 1.23; 95% CI 0.96–1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90–1.58 or aOR 1.24; 95% CI 0.90–1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions. [ABSTRACT FROM AUTHOR]

Aims: Sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) have off‐target effects on haemoconcentration and anti‐inflammation. The impact of SGLT‐2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT‐2i in comparison to dipeptidyl peptidase‐4 inhibitors (DPP‐4i) or glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). Materials and Methods: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT‐2i, DPP‐4i, or GLP‐1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT‐2i users were compared with those of DPP‐4i and GLP‐1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta‐analysis of relevant articles published before 23 May 2023, was conducted. Results: Data from 136,530 SGLT‐2i, 598,280 DPP‐4i, and 5760 GLP‐1RA users were analysed. SGLT‐2i use was associated with a lower risk of VTE than DPP‐4i (HR, 0.70; 95% CI, 0.59–0.84; p < 0·001), but not with GLP‐1RA (HR, 1.39; 95% CI, 0.32–5.94; p = 0.66). Our meta‐analysis further supported these findings (SGLT‐2i vs. DPP‐4i: HR, 0.71; 95% CI, 0.62–0.82; p < 0·001; SGLT‐2i vs. GLP‐1RA: HR, 0.91; 95% CI, 0.73–1.15; p = 0.43), suggesting the robustness of our retrospective analysis. Conclusions: In patients with DM, SGLT‐2i was associated with a lower risk of VTE compared to DPP‐4i, but not GLP‐1RA. [ABSTRACT FROM AUTHOR]

Background: Evidence about the association between types of oral anticoagulants and hazards of diabetes complications is limited in patients with atrial fibrillation (AF) and diabetes mellitus (DM).Objective: To compare the hazards of diabetes complications and mortality between patients with AF and DM receiving non-vitamin K antagonist oral anticoagulants (NOACs) and those receiving warfarin.Design: A retrospective cohort study.Setting: Nationwide data obtained from Taiwan's National Health Insurance Research Database.Patients: Patients with AF and DM receiving NOACs or warfarin between 2012 and 2017 in Taiwan were enrolled. Treatment groups were determined by patients' first initiation of oral anticoagulants.Measurements: Hazards of diabetes complications (macrovascular complications, microvascular complications, and glycemic emergency) and mortality in the NOAC and warfarin users were investigated with a target trial design. Cause-specific Cox proportional hazards models were used to estimate hazard ratios (HRs). Propensity score methods with stabilized inverse probability of treatment weighting were applied to balance potential confounders between treatment groups.Results: In total, 19 909 NOAC users and 10 300 warfarin users were included. Patients receiving NOACs had significantly lower hazards of developing macrovascular complications (HR, 0.84 [95% CI, 0.78 to 0.91]; P < 0.001), microvascular complications (HR, 0.79 [CI, 0.73 to 0.85]; P < 0.001), glycemic emergency (HR, 0.91 [CI, 0.83 to 0.99]; P = 0.043), and mortality (HR, 0.78 [CI, 0.75 to 0.82]; P < 0.001) than those receiving warfarin. Analyses with propensity score matching showed similar results. Several sensitivity analyses further supported the robustness of our findings.Limitation: The claims-based data did not allow for detailed data on patients' lifestyles and laboratory examinations to be obtained.Conclusion: Non-vitamin K antagonist oral anticoagulants were associated with lower hazards of diabetes complications and mortality than warfarin in patients with AF and DM.Primary Funding Source: Hualien Tzu Chi Hospital. [ABSTRACT FROM AUTHOR]

We aimed to determine whether hospital admissions during an extended holiday period (Chinese New Year) and weekends were associated with increased mortality risk from pulmonary embolism (PE), compared to admissions on weekdays. We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Data of newly diagnosed PEs during the months of January and February from 2001 to 2017 were obtained from patient records and classified into three admission groups: Chinese New Year (≥ 4 consecutive holiday days), weekends, and weekdays. The adjusted odds ratios (aORs) (95% confidence intervals [CIs]) for 7-day and in-hospital mortality were calculated using multivariable logistic regression models. The 7-day and in-hospital mortality risks were higher for patients admitted during the Chinese New Year holiday (10.6% and 18.7%) compared to those admitted on weekends (8.4% and 16.1%) and weekdays (6.6% and 13.8%). These higher mortality risks for holiday admissions compared to weekday admissions were confirmed by multivariable analysis (7-day mortality: aOR = 1.68, 95% CI 1.15–2.44, P = 0.007; in-hospital mortality: aOR = 1.41, 95% CI 1.05–1.90, P = 0.022), with no subgroup effects by sex or age. Hospital admission for PE over an extended holiday period, namely Chinese New Year, was associated with an increased risk of mortality. [ABSTRACT FROM AUTHOR]

Background: Acute aortic dissection is a life-threatening condition associated with high mortality rate. Findings from previous studies addressing the "weekend effect" on the mortality rate from an acute aortic dissection mortality have been inconsistent. Furthermore, the effect of admission for acute aortic dissection during the holiday season has not been previously investigated. Objective: Our aim was to evaluate the effect of admission for acute aortic dissection during holiday season or weekends on the risk of mortality. Methods: We conducted a retrospective analysis of nationwide cohort data from the Taiwan's National Health Insurance Research Database. We collected data on all adult patients hospitalized for acute aortic dissection between 2001 and 2017 in Taiwan and classified them into the following three groups based on day of admission: holiday season (at least 4 consecutive days; n = 280), weekend (n = 1 041), and weekday (n = 3 109). The following three outcomes were evaluated: in-hospital mortality, 7-day mortality, and 180-day mortality. Results: A multivariable logistic regression was used to adjust for possible cofounders on the measured outcomes. Compared to weekday admissions for acute aortic dissection, weekend admissions resulted in a 29% increase in the risk of in-hospital death (aOR = 1.29; 95% CI, 1.05–1.59; P = 0.0153), with a 25% increase in the 7-day (aOR = 1.25; 95% CI, 1.001–1.563; P = 0.0492) and 20% increase in the 180-day mortality risk (aOR = 1.20; 95% CI, 1.01–1.42; P = 0.0395). Of note, admission over the holiday season did not result in a higher mortality risk than for weekday admissions; this finding, however, might reflect insufficient statistical power on subgroup analysis. Conclusion: Patients admitted for acute aortic dissection during the weekends are at higher risk of mortality compared to those admitted on weekdays. Our finding likely reflects inadequate staffing and team experience of weekend staff and can guide healthcare policy makers to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Aim: To compare the risk of diabetes development in patients with atrial fibrillation (AF) treated with non‐vitamin K antagonist oral anticoagulants (NOACs) and warfarin. Materials and Methods: We conducted a nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. Adult patients with new onset of AF, treated with NOACs or warfarin between 2012 and 2016, were included. The NOAC cohort was further divided into dabigatran, rivaroxaban and apixaban groups. The primary outcome was incident diabetes requiring treatment with antidiabetic drugs. Fine and Gray subdistribution hazards models were used to estimate the adjusted hazard ratio (aHR). Propensity score matching was performed for each head‐to‐head comparison. Results: A total of 10 746 new‐onset AF patients were included in our study. During the mean 2.4‐year follow‐up, NOACs were associated with a lower risk of developing diabetes than warfarin (aHR = 0.80, 95% confidence interval [CI]: 0.68‐0.94, P =.007). Subgroup analyses confirmed that dabigatran, rivaroxaban and apixaban each had a reduced diabetes risk. Stratified analyses showed that the lower risk of diabetes associated with NOAC treatment was specific to patients aged 65 years or older (aHR = 0.74, 95% CI: 0.62‐0.89, P =.002) and those with good medication adherence (aHR = 0.70, 95% CI: 0.58‐0.84, P <.001). Conclusions: Taking an NOAC was associated with a lower risk of developing diabetes than taking warfarin in patients with AF. [ABSTRACT FROM AUTHOR]

Background: Previous studies in Western countries have shown that a hyperosmolar hyperglycemic state (HHS) is associated with an increased risk of venous thromboembolism (VTE); in these cases, prophylactic anticoagulant treatment is suggested. However, the association between HHS and VTE in Asian populations remains undetermined. Therefore, we aimed to evaluate whether HHS is associated with an increased risk of VTE in diabetic Taiwanese patients. Methods: This nationwide, population-based, retrospective cohort study was conducted using the Taiwan National Health Insurance Research Database. We enrolled a total of 4,723,607 admission records of patients with diabetes diagnosed with one or more of seven common diseases (pneumonia, urinary tract infection, sepsis, heart disease, stroke, malignancy, and respiratory tract disease) between 2001 and 2018 in Taiwan. The patients were divided into two groups based on the presence (n = 46,000) or absence (n = 4,677,607) of HHS. We estimated the adjusted odds ratio (aOR) for developing VTE within 90 days after the index hospitalization using multivariable logistic regression with generalized estimating equations accounting for repeated measures. Results: Overall, patients admitted with HHS had a similar risk of VTE compared with those admitted without HHS (408/46,000 vs. 39,345/4,677,607; aOR = 1.06, 95% CI: 0.97–1.17, p = 0.190). A similar non-significant association between HHS and VTE was found regardless of age and sex subgroups. Conclusions: There was no significant association between HHS and overall VTE risk in patients with diabetes in Taiwan. The results of our study may not support the use of prophylactic anticoagulant therapy in diabetic Taiwanese patients with HHS. [ABSTRACT FROM AUTHOR]

• Physical capacity declined with age in older Taiwanese rural women in communities. • Low physical capacity increased with age in Taiwanese rural women in communities. • Older women had slower GSs and lower HSs and BBS scores than younger women. • Older women had higher 5xSTS and TUG scores than younger women. • Slow GS was less common than low HS in older women. Physical capacity decline may precede physical disability. We explored age-related physical capacity decline among rural community-dwelling Taiwanese older women to provide reference values and to identify indicators of early-onset decline in physical capacity. Older women aged 65–96 were recruited from rural community centers. Physical capacity was measured by handgrip strength (HS), gait speed (GS), five-times-sit-to-stand (5xSTS), timed up and go (TUG), and the Berg balance scale (BBS). Participants were stratified into four age groups: 65–69, 70–74, 75–79, and ≥80 years. Of 137 participants, 61 % exhibited poor 5xSTS, 34–49 % showed low HS, poor TUG and BBS, and 26 % had slow GS. The mean values in GS, HS, 5xSTS, TUG, and BBS were 1.02 m/s, 17.8 kg, 14.5 s, 12.6 s, and 50 points, respectively. Abnormal mean values were first noted at age 70–74 years for 5xSTS, age 75–79 years for HS, TUG, and BBS, and age ≥80 years for GS. Also, more than half the participants exhibited the first poor 5xSTS at age 70–74 years; the first poor HS and TUG at age 75–79 years; and lastly, the first poor BBS and GS at age ≥80 years. At age 65–69 years, 14–41 % of participants reported poor performance in all measures except for GS. Low HS and poor 5xSTS and TUG performance were more common and had earlier onset than slow GS. More attention should be directed toward the 5xSTS, TUG, and HS in rural community-dwelling Taiwanese older women. [ABSTRACT FROM AUTHOR]

To study the effects of participating in a 12-week environmental volunteering program on the physical performance of older adults across different age groups We conducted a pretest–posttest pilot study with a single group. The intervention consisted of twice-weekly recycling activities and once-weekly rehabilitation exercise at community-based care centers. The recycling activities of the environmental volunteering program included sorting and handling paper products, plastics, and metals; disposing electronic products; and sorting clothes. The rehabilitation exercise program comprised a 90-min course for special needs and 30 min of health education. The evaluation tools were the handgrip strength, five-times-sit-to-stand test, sit-and-reach test, Timed Up and Go (TUG) test and usual and fast gait speeds. In total, 45 participants completed the program. After the program, the participants showed significantly great improvements compared to baseline in all outcome measures. We further divided these participants into two age subgroups [65–75 years (n = 31) and >75 years (n = 14)]. The 65–75-year subgroup only showed significant improvements in handgrip strength, TUG and usual gait speed. However, the >75-year subgroup showed significant improvements in all outcome measures. This innovative environmental volunteering program conducted in a local Taiwanese community can be a sustainable and feasible model to improve physical performance in the participants, the subgroup aged >75 years in particular. It also provides a potential avenue for researchers and policymakers to address environmental and aging-related issues. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the risk of newly diagnosed retinal vein occlusion (RVO) in patients with type 2 diabetes (T2D) using sodium-glucose cotransporter-2 inhibitors (SGLT-2i) compared to dipeptidyl peptidase-4 inhibitors (DPP-4i)., Methods: Claims data from the National Health Insurance Research Database of Taiwan were used in this nationwide retrospective cohort study. A target trial emulation framework was applied. Patients with T2D with no prior diagnosis of RVO who had newly commenced treatment with SGLT-2i or DPP-4i between May 1, 2016, and December 31, 2020, were included. Potential systematic differences in baseline characteristics between the paired groups were controlled using stabilized inverse probability of treatment weighting. The outcome of interest was incident RVO. The hazard ratio (HR) for SGLT-2i compared with that of DPP-4i was estimated using a Cox regression model., Results: Data from 123,567 and 578,665 patients receiving SGLT-2i and DPP-4i, respectively, were analyzed. The incidence of RVO was lower in patients newly receiving SGLT-2i (0.59 events per 1000 person-years) compared to those receiving DPP-4i (0.77 events per 1000 person-years) over a mean follow-up of 1.61 years. SGLT-2i users had a significantly lower risk of developing RVO compared with DPP-4i users (HR = 0.76, 95% confidence interval [CI] = 0.59-0.98). In the individual outcome analysis, SGLT-2i use was significantly associated with a lower risk of branch RVO (HR = 0.71, 95% CI = 0.52-0.96), but not central RVO (HR = 0.84, 95% CI = 0.57-1.24)., Conclusions: The risk of developing RVO was lower in patients with T2D receiving SGLT-2i compared with that in those receiving DPP-4i.

Patients with hepatocellular carcinoma (HCC) might be more vulnerable to develop stroke than other cancer patients because of HCC-associated coagulation dysfunction. However, limited studies have investigated the relationship between HCC and stroke. This nationwide population-based cohort study enrolled all patients with HCC diagnosed between 2011 and 2015 from the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database; an age- and sex-matched cohort without cancer was included. The primary outcome was the 1-year risk for first-ever stroke after the index date. The Fine and Gray competing risk regression model was used to estimate the 1-year stroke risk with adjusted hazard ratios (aHRs). After propensity score matching, each cohort has 18,506 patients with similar baseline characteristics. Compared with the cancer-free cohort, the aHRs in the HCC cohort for overall, ischemic, and hemorrhagic strokes were 1.59 [95% confidence interval (CI), 1.35-1.88], 1.38 [95% CI, 1.15-1.65], and 2.62 [95% CI, 1.79-3.84], respectively. On subgroup analysis, HCC patients without cirrhosis, those with stage 3 or 4 cancer had a higher stroke risk than cancer-free cohort. Therefore, stroke prevention should be considered in patients with HCC, especially in those without cirrhosis and with stage 3 or 4 cancer.

Background A higher risk of developing dementia is observed in patients with atrial fibrillation (AF). Results are inconsistent regarding the risk of dementia when patients with AF use different anticoagulants. We aimed to investigate the risk of dementia in patients with AF receiving non-vitamin K antagonist oral anticoagulants (NOACs) compared with those receiving warfarin. Methods and Results We conducted a nationwide population-based cohort study of incident cases using the Taiwan National Health Insurance Research Database. We initially enlisted all incident cases of AF and then selected those treated with either NOACs or warfarin for at least 90 days between 2012 and 2016. First-ever diagnosis of dementia was the primary outcome. We performed propensity score matching to minimize the difference between each cohort. We used the Fine and Gray competing risk regression model to calculate the hazard ratio (HR) for dementia. We recruited 12 068 patients with AF (6034 patients in each cohort). The mean follow-up time was 3.27 and 3.08 years in the groups using NOACs and warfarin, respectively. Compared with the HR for the group using warfarin, the HR for dementia was 0.82 (95% CI, 0.73-0.92; P =0.0004) in the group using NOACs. Subgroup analysis demonstrated that users of NOAC aged 65 to 74 years, with a high risk of stroke or bleeding were associated with a lower risk of dementia than users of warfarin with similar characteristics. Conclusions Patients with AF using NOACs were associated with a lower risk of dementia than those using warfarin. Further randomized clinical trials are greatly needed to prove these findings.

Cataract is the primary cause of visual impairment and can be corrected by cataract surgery. We investigated the impact of cataract on the risk of depression along with the benefits of cataract surgery. Patients newly diagnosed with cataract by ophthalmologists between 2001 and 2015 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. Non-cataract individuals were recruited by 1:1 matching for age, sex and index year. After propensity score matching, 233,258 patients in total were included in our study: 116,629 in each of the cataract and non-cataract cohorts. The primary outcome was the new diagnosis of depression by psychiatrists. In a mean follow-up period of 7.8 years, cataract was significantly associated with increased risk of developing depression (adjusted hazard ratio [aHR] = 1.78, 95% confidence interval [CI] 1.70-1.87, p < 0.001). We further divided the cataract cohort into surgery and non-surgery groups. Notably, cataract surgery group was associated with a decreased risk of depression compared with non-surgery patients (aHR = 0.75, 95% CI 0.71-0.79, p < 0.001). Our results emphasise the importance of regular screening for depression among cataract patients and the beneficial effect of cataract surgery in reducing the risk of depression.

Aims: To evaluate the fracture risk among patients with atrial fibrillation (AF) treated with non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin., Methods and Results: We conducted a real-world nationwide retrospective cohort study using Taiwan's National Health Insurance Research Database. All adult patients in Taiwan newly diagnosed with AF between 2012 and 2016 who received NOACs or warfarin were enrolled and followed up until 2017. Patients treated with NOACs were sub-grouped according to the NOAC used (dabigatran, rivaroxaban, and apixaban). Propensity score matching was performed for each head-to-head comparison. Cox regression analysis, with a shared frailty model, was used to calculate the adjusted hazard ratios (aHRs) for hip, vertebral, and humerus/forearm/wrist fractures. After matching, 19 414 patients were included (9707 in each NOAC and warfarin groups). The median follow-up time was 2.4 years. Compared with warfarin, NOACs were associated with a reduced fracture risk [aHR = 0.84, 95% confidence interval (CI) = 0.77-0.93; P < 0.001]. Sub-analyses revealed that each NOAC, namely dabigatran (aHR = 0.88, 95% CI = 0.78-0.99; P = 0.027), rivaroxaban (aHR = 0.81, 95% CI = 0.72-0.90; P < 0.001), and apixaban (aHR = 0.67, 95% CI = 0.52-0.87; P = 0.003), had a reduced fracture risk. Analyses including all eligible patients, without propensity score matching, generated similar results., Conclusion: Compared with warfarin, NOAC was associated with a reduced fracture risk among AF patients. Therefore, if oral anticoagulants are indicated, NOACs rather than warfarin should be considered to lower the risk of fractures. However, further studies are needed to investigate the underlying mechanisms and elucidate causality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background:  Previous studies have shown that hypothyroidism may have an impact on blood coagulation. However, how hypothyroidism and thyroxine replacement therapy (TRT) affect the risk of venous thromboembolism (VTE) remains controversial. This study aimed to examine the associations of hypothyroidism and TRT with VTE risks., Materials and Methods:  This nationwide population-based cohort study was conducted using Taiwan's National Health Insurance Research Database. We enrolled 10,818 hypothyroid patients (the exposed cohort) and 21,636 non-hypothyroid subjects (the unexposed cohort) between 2001 and 2014 after 1:2 exact matching according to age, sex, and index year. Hypothyroid patients were further divided into two groups depending on whether they received TRT or not. Adjusted hazard ratios (aHRs) for VTE were calculated using Fine and Gray competing risk models., Results:  The mean follow-up period was 7.5 years. Hypothyroidism was significantly associated with a higher risk of VTE (aHR = 1.83 [95% confidence interval [CI]: 1.44-2.33, p  < 0.001]). Among hypothyroid patients, the TRT subgroup had a non-significant trend of lower VTE risk than the non-TRT subgroup (aHR = 0.73 [95% CI: 0.52-1.01, p  = 0.058]). The analysis for individual events revealed a significant association between TRT use and a lower risk of pulmonary embolism among hypothyroid patients (aHR = 0.34 [95% CI: 0.13-0.88, p  = 0.026])., Conclusion:  The data suggest that hypothyroidism was significantly associated with an increased risk of VTE. Among hypothyroid patients, a non-significant trend of lower VTE risk in patients treated with TRT was observed. Further prospective studies or clinical trials are necessary to confirm causality., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Background Warfarin, a vitamin K antagonist, has been shown to affect bone mineral density and cause osteoporosis. However, studies investigating the relationship between non-vitamin K antagonist oral anticoagulants (NOACs) and osteoporosis are limited. We thus compared the risk of osteoporosis in patients with atrial fibrillation treated with either NOACs or warfarin. Methods and Results This nationwide, retrospective cohort study used Taiwan's National Health Insurance Research Database. All adult patients in Taiwan who were newly diagnosed with atrial fibrillation and treated with NOACs or warfarin between January 2012 and December 2015 were included and classified into their respective cohorts. Patients who received NOACs were subcategorized into the rivaroxaban, dabigatran, and apixaban subgroups. Propensity score matching was performed for each head-to-head comparison. Adjusted hazard ratios (aHRs) for the risk of osteoporosis were calculated using Cox proportional hazards regression models, with adjustment for confounders. Overall, 17 008 patients were included, with 8504 in each cohort. NOACs were associated with a lower osteoporosis risk than warfarin (aHR=0.82; 95% CI=0.68-0.97). A subgroup effect of treatment duration was identified (namely, the lower osteoporosis risk with NOAC compared with warfarin became stronger in those with longer treatment duration [ P for interaction <0.001]). Furthermore, significantly lower risks of osteoporosis were observed in the rivaroxaban (aHR=0.68; 95% CI=0.55-0.83) and apixaban (aHR=0.38; 95% CI=0.22-0.66) subgroups, but not in the dabigatran subgroup (aHR=1.04; 95% CI=0.85-1.27). Conclusions Compared with warfarin, rivaroxaban and apixaban were associated with a significantly lower risk of osteoporosis in patients with atrial fibrillation.