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Background: Social detachment includes the subjective aspect “loneliness” and the objective aspect “social isolation,” but tools to assess both dimensions are limited. This study aims to develop a questionnaire, the Social Detachment Questionnaire for Older Population (SDQO), that considers multiple dimensions of social detachment simultaneously. Methods: The study collected 600 valid samples from individuals aged 55 and above to examine the psychometric properties of the developed SDQO. Item analysis was conducted to assess the performance of each item, and exploratory factor analysis (EFA) was employed to analyze its initial structure and eliminate less ideal items. Subsequently, confirmatory factor analysis (CFA) was used to examine the model fit of the suggested structure by EFA, using different subsamples. Internal consistency, concurrent validity, and other analyses were also performed. Results: The original 27-item SDQO was reduced to 17 items after removing 4 questions in item analysis and 6 questions in EFA. The Cronbach's alpha for the 17-item version of SDQO was 0.80. Both EFA and CFA supported its 6-factor structure, with factors identified as community activities, loneliness, personal resources, leisure activities, friendship, and family resources. SDQO also demonstrated expected performance in concurrent validity. Conclusion: The 17-item version of SDQO exhibited good reliability and validity, measuring various aspects of social detachment behavior, feelings, and resources. It holds value for future research applications.

Background: Health-related quality of life (HRQoL) is an essential outcome parameter in geriatric research; however, the available evidence is mixed regarding the factors associated with HRQoL among people with dementia. We aimed to identify factors that contribute to HRQoL among people with dementia in residential long-term care (LTC) institutions. Methods: We randomly selected 299 of 1607 registered residential LTC institutions in Taiwan. A cross-sectional survey was conducted between 2019 and 2020, including items on demographic characteristics, comorbidities, the EuroQol-5 dimensions-5 levels (EQ-5D-5L; utility and visual analog scale [VAS] scores), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), behavioral and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL (IADL). Results: In total, 1313 people with dementia from 267 institutions were enrolled (mean age, 76.4 ± 12.7 years). The mean EQ-5D-5L utility and VAS scores were 0.10 (standard deviation [SD] = 0.48) and 66.57 (SD = 20.67), respectively. In multivariate linear regression analysis, higher scores for ADL, IADL, and CDR sum of boxes were associated with higher utility scores. Higher VAS scores were associated with higher ADL and MMSE scores. Lower utility scores and VAS scores were associated with more frequent depressive symptoms. Conclusion: ADL, dementia severity, cognitive function, and depressive symptoms influenced the HRQoL of people with dementia in residential LTC institutions. Longitudinal studies should be conducted to better understand how HRQoL changes over time among people with disabilities.

Background The upper tract urothelial carcinoma (UTUC) risk associated with statin therapy in hyperlipidemic patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) remains obscure.Aim This retrospective cohort study investigated the UTUC risk for hyperlipidemic patients with CKD or ESKD associated with statin therapy.Methods From the national insurance claims data of Taiwan, we identified hyperlipidemic patients and established three pairs of statin users and non-users sub-cohorts matched by propensity scores: 401,490 pairs with normal kidney function, 37,734 pairs with CKD, and 6271 pairs with ESKD. Incidence rates and hazard ratio (HR) of UTUC were estimated, by the end of 2016, between statin and non-statin cohorts, and between hydrophilic statins users and lipophilic statins users. Time-dependent model estimated adjusted HR, and sub-distribution HR (sHR) accounting for the competing risk of deaths.Results The statin-users with ESKD were at increased UTUC risk (sHR 1.98; 95% confidence interval (CI), 1.28–3.06), significant for younger patients (40–64 years). The incidence was twofold greater in women than in men (31.8 versus 15.9 per 10,000 person-years). Receiving lipophilic statins was associated with increased UTUC risk in CKD and ESKD patients, while receiving hydrophilic statins was associated with increased UTUC risk in ESKD patients.Conclusions Patients with ESKD receiving statin were at an increased UTUC risk, significant for younger group (

Objective: Hyperlipidemic patients with end-stage renal disease (ESRD) are at a higher risk of death from cardiovascular diseases, especially from acute myocardial infarction (AMI). Studies on the efficacy of statin therapy (ST) in dialysis patients after percutaneous coronary intervention (PCI) are limited. We examine the mortality associated with ST for these patients. Methods: From dialysis-dependent hyperlipidemic patients with AMI and receiving PCI in the claims data of National Health Insurance of Taiwan in 2000–2016, we identified a cohort with ST and a cohort without ST matched by propensity score at a 1:1 ratio. Both cohorts were followed up until the end of 2017. All-cause mortalities were examined for both cohorts. Other factors associated with the deaths were also examined. Results: Among 2642 enrollees in each cohort, over 99 % had hypertension. The all-cause mortality was 23 % lower in the ST cohort than in non-ST cohort (10.8 versus 14.0 per 100 person-years) with an adjusted hazard ratio of 0.77(95 % confidence interval = 0.71–0.84). Patients with comorbidities of diabetes, cerebrovascular accident (CVA) and congestive heart failure (CHF) were also at lower risk. The case-control analysis in the ST cohort showed the estimated risk of death increased with age, and higher for females and patients with peripheral artery disease. Conclusions: The ST for hyperlipidemic patients with ESRD experiencing AMI undergoing PCI could be benefited with lower all-cause mortality, even for patients with diabetes, hypertension, CVA or CHF.

Background: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan Methods: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 μm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. Results: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 μg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. Conclusions: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Abstract Background Quantifying the informal caregiver burden is important for understanding the risk factors associated with caregiver overload and for evaluating the effectiveness of services provided in Long-term Care (LTC). Objective This study aimed to develop and validate a Caregiver Strain Index (CSI)-based score for quantifying the informal caregiver burden, while the original dataset did not fully cover evaluation items commonly included in international assessments. Subsequently, we utilized the CSI-based score to pinpoint key caregiver burden risk factors, examine the initial timing of LTC services adoption, and assess the impact of LTC services on reducing caregiver burden. Methods The study analyzed over 28,000 LTC cases in Southern Taiwan from August 2019 to December 2022. Through multiple regression analysis, we identified significant risk factors associated with caregiver burden and examined changes in this burden after utilizing various services. Survival analysis was employed to explore the relationship between adopting the first LTC services and varying levels of caregiver burden. Results We identified 126 significant risk factors for caregiver burden. The most critical factors included caregiving for other disabled family members or children under the age of three (β = 0.74, p

Studies show that statins users are at reduced risk of fracture and improved bone mineral density. However, the clinical effectiveness of statin use in patients with gout has not been investigated. This retrospective cohort study used data from Taiwan's National Health Insurance Research Database, consisting of 3443 patients with gout using statins aged 50 years and above and 6886 gout patients of non-statin users matched by sex, age and propensity score. The Cox proportional hazards regression analysis showed that statin use was associated with a reduced risk of hip fracture (adjusted hazard ratio [aHR] = 0.78, 95 % confidence interval [CI] = 0.64–0.94) after controlling for potential confounding factors. The association was significant in both genders aged 50–64 years, with aHRs of near 0.35, but not in the elderly. In addition, women aged 50–64 years who used statins also exhibited a lower risk of vertebral fracture (aHR = 0.70, 95 % CI = 0.50–0.99), but not men. In conclusion, the stating use in gout patients could reduce fracture risk for younger patients. Further research is warranted to confirm these findings.

Abstract Background Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis. Methods From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan’s National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups. Results The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43–0.53), cardiovascular events (aHR 0.92, 95%CI 0.86–0.99), cardiovascular death (aHR 0.57, 95%CI 0.45–0.72), and liver-related death (aHR 0.32, 95%CI 0.13–0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use. Conclusions This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.

Abstract Background The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. Methods Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. Results The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log–alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. Conclusion This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Abstract Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39–0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.

Abstract Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three‐round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3–6 month period and suggested a tentative cut‐off value of 21 kg/m2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ‐5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient‐reported outcomes. The AWGC consensus offers a comprehensive definition and user‐friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co‐morbidities and cancer in Asia, leading to future refinement of diagnostic criteria.

Abstract In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes.

Introduction: Social participation activities have a close association with health aging. However, the clinical significance of numbers of social participation activities and its cutoff value has not been defined. Methods: We recruited 516 people aged ≥55 years. Twelve social participation behaviors modified according to Taiwanese culture were investigated, and the adequacy of cutoff number was determined by the area under the receiver operating characteristic curve (AUC) according to the results of cluster analysis of individual activities and scores of the Brief Symptom Rating Scale-5 (BSRS-5) and the Chinese Happiness Inventory (CHI). Demographic, BSRS-5 and CHI data were then compared according to the candidate cutoff numbers. Results: The distribution of the numbers of social activities suggested that the highest partition of numbers of social activities was 3 in women and 4 in men. The AUC regarding the cluster of activity types was 0.917, with the highest Youden's J value located between 3 and 4. The AUC regarding the cluster of activity types and scores of the BSRS-5 and the CHI was 0.929, with similar cutoffs. If 3 and 4 were used as cutoffs, the between-group differences of both the CHI and the BSRS-5 were significant. More types of social activities had a different engaging frequency with the 3 and 4 cutoffs. Conclusion: Our findings found an adequate cutoff with better differential power in the psychopathology and happiness of older people that provided a basis for application in intervention and policy formation.

Summary: Background: Adult preventive health checkups with depression screening were launched in August 2011 in Taiwan; however, its impact has not yet been evaluated. This study aimed to use real-world data to assess the effectiveness of depression screening among middle-aged and older adults. Methods: A total of 4,972,228 adults aged 40 years and above who participated in a health checkup with depression screening between 2013 and 2019 and the same number of unscreened counterparts were included. The target trial emulation study was conducted to estimate the hazard ratios (HRs) for newly treated depression, psychiatric hospitalisation, and suicide. The changes in HRs during the study period were assessed using interval Cox models. Findings: The screening group had a higher rate of newly treated depression (HR 1.63 [95% CI 1.62, 1.64]) and a lower risk of psychiatric hospitalisation (HR 0.93 [95% CI 0.91, 0.95]). There was a null association between depression screening and suicide; however, a higher suicide risk was found in screened older adults aged 65 years and above. Only 10.8% received depression treatment during the study period among the screen-positive individuals. Interpretation: Health checkups with depression screening could potentially promote depression treatment and reduce the risk of psychiatric hospitalisation; however, there was no effect on suicide. The treatment rate for depression remained low after screening for depression. Further attention to enhance referral and treatment is required. Funding: The study was funded by the National Health Research Institutes, Taiwan.

Most elderly persons suffer from chronic diseases. To treat chronic diseases, good medication adherence and refilling medication as physicians’ advice are key points of pharmaceutical therapy. However, the literature revealed that only limited studies have focused on the medication adherence of the elderly in rural communities. This study evaluated the adherence to medication and the degree of refilling prescriptions as physician’s advice by the Adherence to Refills and Medications Scale (ARMS) and evaluated the factors associated with poor adherence to medication. This cross-sectional study focused on the medication use of the elderly population in rural areas in western Taiwan and analyzed related personal and social factors which influence the behaviors of pharmaceutical therapy. In conclusion, most of the elderly who lived in rural areas in western Taiwan have poor adherence (ARMS score over 12) to medication and a poor degree of refilling prescriptions as per physicians’ advice. Moreover, age ≥75 years and low urbanization were significantly associated with poor adherence. Future research is warranted to assess the effect of the interventions to improve medication adherence on chronic disease control, disability, and mortality.

The clinical characteristics and long-term outcomes of patients with ischemic stroke (IS) and atrial fibrillation detected after stroke (AFDAS) have not been clearly established. Previous studies evaluating patients with AFDAS were limited by the low prescription rates of anticoagulants and short follow-up periods. Consecutive patients hospitalized for IS between 2014 and 2017 were identified from a National Health Insurance Research Database. The included patients were categorized into three groups: (1) known diagnosis of AF (KAF) before the index stroke, (2) AFDAS, and (3) without AF (non-AF). Univariable and multivariable Cox regression analyses were performed to estimate the hazard ratio (HR) for independent variables and recurrent IS, hemorrhagic stroke, or all-cause mortality. We identified 158,909 patients with IS of whom 16,699 (10.5%) had KAF and 7,826 (4.9%) had AFDAS. The patients with AFDAS were younger, more often male, and had lower CHA2DS2-VASc scores (3.8 ± 1.9 versus 4.9 ± 1.8, p < 0.001) than the patients with KAF. Anticoagulant treatment significantly reduced the risks of all outcomes. The standardized mortality rates were 40.4, 28.6, and 18.4 (per 100 person-years) for the patients with KAF, AFDAS, and non-AF, respectively. Compared with AFDAS, KAF was associated with lower risks of recurrent IS [hazard ratio (HR): 0.91, 95% confidence interval (CI): 0.86-0.97, p < 0.01] and hemorrhagic stroke (HR: 0.88, 95% CI: 0.79-0.99, p < 0.01) and a higher risk of all-cause mortality (HR: 1.11, 95% CI: 1.07-1.16, p < 0.001). The risks of recurrent IS and hemorrhagic stroke were higher and of all-cause mortality was lower for patients with AFDAS than with KAF. There is a strong need to refine treatment modalities to reduce the high mortality in patients with KAF and AFDAS.

Abstract Background This study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases. Methods We identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality. Results Patients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03–1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1–1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03–1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3–1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71–0.87). Conclusions T2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.

Background The relationship between resting heart rate (RHR) and the risk of end‐stage renal disease (ESRD) among those without cardiovascular disease remains unclear. We aim to establish temporal consistency and elucidate the independent relationship between RHR and the risk of ESRD. Methods and Results This cohort enrolled participants from 476 347 individuals who had taken part in a screening program from 1996 to 2017. We identified 2504 participants who had ESRD, and the median follow‐up was 13 years. RHR was extracted from electrocardiography results, and the study assessed the relationship between RHR and the risk of ESRD using the Cox proportional hazards model. Of the participants, 32.6% had an RHR of 60 to 69 beats per minute (bpm), and 22.2% had an RHR of ≥80 bpm. Participants with an RHR of ≥80 bpm had a higher stage of chronic kidney disease, lower estimated glomerular filtration rate, and more proteinuria than those with an RHR of 60 to 69 bpm. Participants with an RHR of 80 to 89 and ≥90 bpm had a 24% (hazard ratio [HR], 1.24 [95% CI, 1.09–1.42]) and 64% (HR, 1.64 [95% CI, 1.42–1.90]) higher risk of ESRD, respectively. The risk of ESRD remained significantly elevated (HR, 1.32 [95% CI, 1.10–1.58] per 10‐beat increase from 60 bpm) after excluding participants who smoked; had hypertension, diabetes, or hyperlipidemia; or were overweight. Conclusions An RHR of ≥80 bpm is significantly associated with an increased risk of ESRD. These results suggest that RHR may serve as a risk factor for kidney disease in individuals without established cardiovascular disease risk factors.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.

Abstract Aims/Introduction Fatty acid desaturase (FADS) genetic polymorphisms are strongly correlated with the risk of dyslipidemia and cardiovascular disease. In this study, we examined the impact of FADS1 and FADS2 genetic variants on plasma lipid status, and assessed interactions between FADS genetic polymorphisms and plasma n‐3/n‐6 fatty acids regarding lipid status within a population of 816 Taiwanese patients with type 2 diabetes. Materials and Methods Selected tag single‐nucleotide polymorphisms (FADS1 rs174546 [T/C]; FADS2 rs174602 [A/G] and rs2072114 [A/G]) were genotyped (n = 816). Results The distribution of genotypes were compared with reports publicly available in the Genome Aggregation Database for East Asian populations (https://gnomad.broadinstitute.org). In the subgroup of patients not taking lipid‐lowering medications (n = 192), we observed that the G allele of FADS2 rs174602 was statistically significantly correlated with lower low‐density lipoprotein cholesterol (LDL‐C) concentrations (P = 0.001), whereas the G allele of rs2072114 was marginally associated with LDL‐C concentrations (P = 0.091). Using a general linear model adjusted for confounding factors, statistically significant interactions (P = 0.016) between single‐nucleotide polymorphisms in rs2072114 and a low alpha‐linolenic acid (18:3n‐3)/linoleic acid (18:2n‐6) ratio; the G allele correlated with lower LDL‐C levels among individuals with a low alpha‐linolenic acid/linoleic acid ratio. Interaction between rs174602 single‐nucleotide polymorphisms and low alpha‐linolenic acid/linoleic acid values on LDL‐C was only marginally significant (P = 0.063). Conclusions Our results show the role of n‐3/n‐6 dietary polyunsaturated fatty acids in modifying the effects of genetic susceptibility on lipoprotein concentrations in patients with type 2 diabetes. Our findings highlight the potential of interventions with dietary polyunsaturated fatty acids regarding developing individualized prevention strategies for type 2 diabetes presenting with co‐occurring dyslipidemia and cardiovascular diseases.

Abstract Background Systemic chronic inflammation occurs with age. The association of the leukocyte mitochondrial DNA copy number, a measure of mitochondrial function in aging, with the temporal profile of serum high-sensitivity C-reactive protein and mortality risk remains uncertain. The objectives of this study were to examine the association of the leukocyte mitochondrial DNA copy number with longitudinal high-sensitivity C-reactive protein levels and the association of the longitudinal high-sensitivity C-reactive protein levels with mortality risk. Methods This prospective cohort study included 3928 adults aged ≥ 55 years without systemic inflammation in the baseline examination of the Healthy Aging Longitudinal Study in Taiwan, which started in 2009. Each participant received leukocyte mitochondrial DNA copy number measurement using a fluorescence-based quantitative polymerase chain reaction at baseline, serum high-sensitivity C-reactive protein measurements at baseline and the follow-up examination five years later, and the ascertainment of all-cause death (until November 30, 2021). The relationships among the leukocyte mitochondrial DNA copy number, longitudinal serum high-sensitivity C-reactive protein levels, and time to all-cause mortality were examined using the joint longitudinal and survival modeling analysis. Results Of the 3928 participants (mean age: 69 years; 2060 [52%] were women), 837 (21%) died during follow-up. In the adjusted analysis, one standard deviation lower natural log-transformed baseline leukocyte mitochondrial DNA copy number was associated with an increase of 0.05 (95% confidence interval [CI], 0.02 to 0.08) standard deviation in serum high-sensitivity C-reactive protein in subsequent years. An increase of 1 standard deviation in instantaneous high-sensitivity C-reactive protein levels was associated with a hazard ratio (HR) for all-cause mortality of 1.22 (95% CI, 1.14 to 1.30). Similar results were obtained after further adjusting for baseline high-sensitivity C-reactive protein levels (HR [95% CI], 1.27 [1.16 to 1.38]) and after excluding those with serum high-sensitivity C-reactive protein above 10 mg/L (HR [95% CI], 1.21[1.11 to 1.31]) or 3 mg/L (HR [95% CI], 1.19 [1.06 to 1.31]) during follow-up. Conclusions A lower leukocyte mitochondrial DNA copy number was associated with persistently higher high-sensitivity C-reactive protein levels. Moreover, these higher time-varying high-sensitivity C-reactive protein levels were instantaneously associated with a higher risk of death.

Abstract Aims/Introduction The global incidence of adolescents with type 2 diabetes mellitus is increasing. This cohort study was conducted aiming to describe the characteristics, drug‐use condition, and long‐term outcomes of adolescents with type 2 diabetes mellitus. Materials and Methods Two thousand seven hundred fifty‐five newly diagnosed adolescents with type 2 diabetes mellitus (using ICD‐9‐CM: 250.x and having ≥3 clinic visits) were identified from the national health insurance dataset during 2000–2014. Treatments were classified into four groups: metformin, sulfonylurea (SU), metformin plus SU, and insulin with or without oral antidiabetic drugs. The multiple Cox regression model was used to compare the risks of mortality and hospitalization among these four groups. Results The mean follow‐up period was 5.4 years. After 1 year of antidiabetic treatment, they gradually needed intensified therapy, and at 3 years, half of them showed treatment failure. The mortality rate was 2.08 per 1,000 person‐years. Respiratory diseases (36.2%) and dysglycemia (16.4%) were the most common causes of hospitalization among these adolescents. Compared with persons taking metformin plus SU, metformin users were associated with a lower risk of all‐cause hospitalization [0.82 (0.67–0.99)]; insulin users were associated with a higher risk of dysglycemia [4.38 (2.14–8.96)], cancer [3.76 (1.39–10.1)], and respiratory hospitalization [1.66 (1.14–2.41)]; and SU users were associated with a higher risk of hospitalization for respiratory diseases [1.91 (1.13–3.23)]. Conclusions This nationwide cohort study demonstrated that adolescents with type 2 diabetes mellitus were prone to treatment failure. Furthermore, respiratory diseases and dysglycemia were the most common causes of hospitalization.

Abstract To investigate the impact of chronic hepatitis on cardiovascular events in patients with type 2 diabetes mellitus (T2DM). This nationwide retrospective cohort study included 152,709 adult patients (> 20 years) with T2DM enrolled in the National Health Insurance Diabetes Pay-for-Performance Program from 2008 to 2010 and followed up until the end of 2017. Patients were categorized into groups with hepatitis B, hepatitis C, fatty liver disease, and patients without chronic hepatitis. The incidence of cardiovascular events in patients with T2DM and hepatitis C (79.9/1000 person-years) was higher than that in patients with diabetes combined with other chronic hepatitis, or without chronic hepatitis. After adjusting for confounding factors, T2DM with fatty liver (adjusted hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.07–1.13) and hepatitis C (adjusted HR: 1.09; 95% CI: 1.03–1.12) demonstrated a significantly higher risk of cardiovascular events. The adjusted visit-to-visit coefficient of variation of HbA1c and fasting blood glucose were associated with a high risk of cardiovascular events (HRs of the highest quartile were 1.05 and 1.12, respectively). Chronic hepatitis affects cardiovascular events in adult patients with T2DM. Glucose variability could be an independent risk factor for cardiovascular events in such patients.

Abstract Frail older adults are vulnerable to stressors; thus, sleep related cognition impairment might more greatly affect frail than healthy older adults. In the present study, we investigated whether the association between sleep problems and cognition varies with physical frailty status (modified from Fried et al.). Participants 55 years and older who completed a baseline and follow-up questionnaire (median follow-up: 5.5 years), were included in the analysis. Sleep parameters were evaluated in an interview at the baseline. Cognitive decline was defined as a loss of 3 or more points on the Mini-Mental State Examination (MMSE) at follow-up. Associations between sleep problems and cognitive decline were examined using logistic regression and were stratified by baseline physical frailty status, adjusted for potential confounders. A short total sleep duration (

Abstract Persons with type 2 diabetes (T2D) have neutrophil dysfunction with a higher risk of infection than those without diabetes. We conducted this study aiming to compare the risk of pneumonia between metformin use and nonuse in persons with T2D. We identified 49,012 propensity score-matched metformin users and nonusers from Taiwan’s National Health Insurance Research Database between January 1, 2000, and December 31, 2017. We used the Cox proportional hazards model to compare the risks of pneumonia and respiratory death. The mean (SD) age of the participants was 57.46 (12.88) years, and the mean follow-up time for metformin users and nonusers was 5.47 (3.71) years and 5.15 (3.87) years, respectively. Compared with the nonuse of metformin, the adjusted hazard ratios (95% CI) for metformin use in bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death were 0.89 (0.84–0.94), 0.77 (0.73–0.82), and 0.64 (0.56–0.74), respectively. A longer cumulative duration of metformin use had further lower adjusted hazard ratios in these risks compared with nonuse. In patients with T2D, metformin use was associated with significantly lower risks of bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death; moreover, longer metformin use duration was associated with lower hazard ratios of these risks.

Abstract Background We aimed to compare cardiovascular risks among participants with T2DM with and without subsequent HTN and participants with HTN with and without subsequent T2DM. Methods From January 1, 2000, to December 31, 2018, we identified 16,236 matched pairs of T2DM participants with and without HTN (T2DM cohorts), 53,509 pairs of HTN participants with and without T2DM (HTN cohorts), and 21,158 pairs of comorbid HTN and T2DM participants with T2DM history or HTN history (comorbid cohorts) from Taiwan’s National Health Insurance Research Database. Cox proportional-hazard models were used to calculate the risk of cardiovascular disease. Results The mean follow-up time of this study was 6.75 years. Mean incident rates of coronary artery disease for T2DM cohorts, HTN cohorts, and comorbid cohorts were 16.80, 23.18, and 31.53 per 1000 person-years, respectively. The adjusted hazard ratios (HRs) (95% confidence intervals [95% CIs]) for incident coronary artery disease, stroke, and heart failure in T2DM participants with versus without HTN were 2.22 (2.07–2.37), 1.19 (1.16–1.23), and 0.92 (0.82–1.02), respectively; the adjusted HRs for HTN participants with versus without T2DM were 1.69 (1.55–1.84), 1.25 (1.21–1.30), and 0.98 (0.93–1.05), respectively; the adjusted HRs for comorbid T2DM and HTN participants with previous T2DM versus previous HTN were 2.78 (2.37–3.27), 1.20 (1.13–1.28), and 0.95 (0.88–1.03), respectively. Conclusions This nationwide cohort study demonstrated that both T2DM with subsequent HTN and HTN with subsequent diabetes were associated with higher cardiovascular disease risks.

Abstract In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10–11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

Background and aims: Physical and cognitive function decline indicates the prestage of disability and is associated with mortality among older adults. We investigated the association of metabolic disorders in midlife with physical and cognitive function decline in later life in a retrospective cohort. Material and methods: A total of 618 older adults aged ≥60 years in wave-6 (2014–2017) were enrolled in the Cardiovascular Disease Risk Factor Two-Township Study to evaluate physical (hand grip strength and 4-m walking speed) and cognitive function (Mine–Mental State Examination [MMSE] score). Repeated metabolic disorder measures in wave-2, wave-3, and wave-5 were obtained to identify three trajectory pattern groups according to each metabolic disorder through group-based trajectory modeling. Linear and logistic regressions were conducted to investigate the association of metabolic disorders in middle life with physical and cognitive function decline in later life. Results: The prevalence rates of a weak hand grip (

IntroductionWe conducted this study to compare the risk of pneumonia between thiazolidinedione (TZD) use and nonuse in persons with type 2 diabetes (T2D).MethodsWe identified 46,763 propensity-score matched TZD users and nonusers from Taiwan’s National Health Insurance Research Database between January 1, 2000, and December 31, 2017. The Cox proportional hazards models were used for comparing the risk of morbidity and mortality associated with pneumonias.ResultsCompared with the nonuse of TZDs, the adjusted hazard ratios (95% CI) for TZD use in hospitalization for all-cause pneumonia, bacterial pneumonia, invasive mechanical ventilation, and death due to pneumonia were 0.92 (0.88–0.95), 0.95 (0.91–0.99), 0.80 (0.77–0.83), and 0.73 (0.64–0.82), respectively. The subgroup analysis revealed that pioglitazone, not rosiglitazone, was associated with a significantly lower risk of hospitalization for all-cause pneumonia [0.85 (0.82–0.89)]. Longer cumulative duration and higher cumulative dose of pioglitazone were associated with further lower adjusted hazard ratios in these outcomes compared to no-use of TZDs.DiscussionThis cohort study demonstrated that TZD use was associated with significantly lower risks of hospitalization for pneumonia, invasive mechanical ventilation, and death due to pneumonia in patients with T2D. Higher cumulative duration and dose of pioglitazone were associated with a further lower risk of outcomes.

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

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

Background: The Bureau of National Health Insurance in Taiwan implemented a new reimbursement scheme incorporating bone mineral density (BMD) criteria on Jan. 1, 2011. This study aimed to investigate a real-life 11-year secular trend of adherence in new AOMs users and evaluated the change of adherence to AOMs therapy in different urbanization areas after reimbursement criteria were restrained. Methods: We used Taiwan's National Health Insurance Research Database to identify new AOMs users as our study population. The AOMs in this study included denosumab, zoledronate, ibandronate, alendronate, raloxifene, and risedronate. The first prescription date of AOMs was defined as the cohort entry date. The adherence rates within one year after initiation were assessed. Results: High adherence (≥75%) in the first year increased markedly after the new reimbursement scheme in 2011, changing from 31.8% in 2008, and 41.7% in 2011 to 54.2% in 2018. On the other hand, low adherence (

Background: Real-world cost and effectiveness analyses of the anti-osteoporosis medications (AOM) using a nationwide database in Asia were limited. The aim of this study was to evaluate the cost and effectiveness of AOMs therapy under the reimbursement of National Health Insurance in Taiwan. Methods: Using Taiwan's National Health Insurance Research Database, patients who had hospitalization due to incident hip fractures with related operation between 2008 and 2017 were identified as our study population. Patients who initiated AOMs within 1 year post incident hip fracture were matched with those did not according to the propensity score. The direct medical cost and subsequent fracture within three years were estimated. Statistically significant differences of risk for subsequent fracture between the AOM and non-AOM groups were estimated using the COX proportional hazards model. All costs were presented as New Taiwan Dollars (NTD). Results: There were 27,357 new hip fracture patients who initiated AOMs, and 76% of them were women with a mean age of 77.7 years. Among patients ages ≥70 who encountered hip fractures, those who initiated AOMs experienced fewer non-vertebral fractures (HR = 1.07 (1.02–1.13), p = 0.0114 for those ages 70–79 years old; HR = 1.11 (1.06–1.17), p

BackgroundHyperglycemia in pregnancy (HIP) increases the risk of adverse pregnancy outcomes. The increasing prevalence of overweight or obesity and the increasing proportion of pregnant women with advanced maternal age (AMA) in the recent decade may affect its prevalence. We analyzed the secular trend of HIP prevalence in 2008-2017 in Taiwan and investigated the impact of AMA in this study.MethodsThis cross-sectional study used data from Health and Welfare Data Science Center. Pregnant women who registered their data in the Birth Certificate Application in 2008-2017 were recruited. Diagnosis of HIP was defined by ICD-9-CM and ICD-10-CM codes.ResultsIn 2008-2017, 151,306-211,768 pregnant women were recruited in different years. The proportion of women with AMA increased from 15.8% to 32.1%. Meanwhile, the prevalence increased from 0.5% to 0.9% for preexisting diabetes, 0.2% to 0.4% for undiagnosed diabetes, and 11.4% to 14.5% for GDM. Maternal age was significantly associated with the prevalence of HIP. For women aged

IntroductionAdvanced liver disease with massive liver damage may affect the metabolism of hypoglycemic agents and increase the risk of hypoglycemia. We conduct this research to compare the risk of severe hypoglycemia between patients with type 2 diabetes, with and without compensated liver cirrhosis.MethodsFrom Taiwan’s National Health Insurance Research Database, we identified persons with type 2 diabetes with cirrhosis (n = 18,209) and without cirrhosis (n = 538,510) from January 1, 2000, to December 31, 2010. Cox proportional hazards models were adopted to assess risks of all-cause mortality and severe hypoglycemia.ResultsThe mean follow-up period of this study was 3.7 years. The incidence rates of death during follow-up were 26.54 and 2.75 per 1,000 patient-years [aHR 7.63 (6.70–8.70)] for patients with cirrhosis and without cirrhosis, respectively. The incidence rates of severe hypoglycemia during follow-up were 0.53 and 0.14 per 1,000 patient-years [aHR 2.74 (1.52–4.92)] for patients with and without cirrhosis, respectively. The subgroup analysis of hypoglycemia risks in patients with and without cirrhosis disclosed no significant interaction for variables such as age, sex, chronic kidney disease, sulfonylurea use, number of oral antidiabetic drugs, insulin, b-blocker, and fibrate.ConclusionThis cohort study demonstrated that patients with type 2 diabetes and compensated cirrhosis showed a higher risk of mortality and severe hypoglycemia than those without liver cirrhosis.

ABSTRACT Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes. With the continuous increase in the prevalence of diabetes since 2000, the prevalence of DKD has also been increasing in past years. The prevalence of DKD among individuals with type 2 diabetes in Taiwan increased from 13.32% in 2000 to 17.92% in 2014. The cumulative incidence of DKD among individuals with type 1 diabetes in Taiwan was higher than 30% during 1999–2012. DKD is the leading cause of end‐stage renal disease (ESRD), with a prevalence of approximately 45% in a population on chronic dialysis in Taiwan. Among individuals with type 2 diabetes, the prevalence of ESRD in the receipt of dialysis also increased from 1.32% in 2005 to 1.47% in 2014. Risk factors for DKD development are age, race, family history, hyperglycemia, hypertension, dyslipidemia, dietary patterns, and lifestyles. Prognostic factors that aggravate DKD progression include age, family history, sex, glycemic control, blood pressure (BP), microvascular complications, and atherosclerosis. This review summarizes updated information on the onset and progression of DKD, particularly in the Taiwanese population. Translating these epidemiological features is essential to optimizing the kidney care and improving the prognosis of DKD in Asian populations.

Abstract Background Our study aims to provide validity evidence for the EuroQol five dimensions questionnaire (EQ-5D) in the National Health Interview Survey of Taiwan in the 2013 wave and further interpret the EQ-5D scores for patients with chronic diseases. Another goal of the study was to use item response theory (IRT) to identify items that are informative for assessing quality of life using EQ-5D. Methods There were 17,260 participants, aged 12-64, who completed the interviews in our study. Psychometric methods, including factor analysis and the IRT model known as the Graded Response Model (GRM), were used to assess the unidimensionality of EQ-5D and its item properties. Correlation analysis was used to assess whether EQ-5D scores are associated with scores from the 36-Item Short Form Survey (SF-36). Results The EQ-5D scores have moderate internal consistency (Cronbach’s alpha: 0.60) and a scree plot suggests that the EQ-5D measure is unidimensional. The item information function analysis from the IRT model demonstrates that the first 3 items, “mobility,” “self-care,” and “usual activities” are the most informative items for patients who have chronic diseases and health-related quality of life below the 10th percentile. The EQ-5D scores have a moderate correlation (r: 0.61) with SF-36 scores. Conclusions The EQ-5D scale shows promise for use in the general population. The IRT model informs our interpretation of the EQ-5D scores. Given the time constraints in clinical settings, we suggest using the first three items in EQ-5D to measure the health-related quality of life for patients with chronic diseases.

Background: Adequate management of diabetes in patients with liver cirrhosis can be challenging. We conducted this study to investigate the liver-related long term outcomes of alpha-glucosidase inhibitors (AGIs) in patients with diabetes and cirrhosis.Methods: From National Health Insurance Research Database (NHIRD) in Taiwan, we recruited propensity-score matched alpha-glucosidase inhibitor users and non-users from a cohort of type 2 diabetes mellitus (T2DM) with compensated liver cirrhosis between 1 January 2000, and 31 December 2017, and followed them until 31 December 2018. Cox proportional hazards models with robust sandwich standard error estimates were used to assess the risk of main outcomes for alpha-glucosidase inhibitor users versus non-users.Results: The incidence rates of mortality during follow-up were 65.56 vs. 96.06 per 1,000 patient-years for alpha-glucosidase inhibitor users and non-users, respectively. The multivariable-adjusted model shows that alpha-glucosidase inhibitor users had significantly lower risks of all-cause mortality (aHR 0.63, 95% CI 0.56–0.71), hepatocellular carcinoma (aHR 0.55, 95% CI 0.46–0.67), decompensated cirrhosis (aHR 0.74 95% CI 0.63–0.87), hepatic encephalopathy (aHR 0.72, 95% CI 0.60–0.87), and hepatic failure (aHR 0.74, 95% CI 0.62–0.88) than alpha-glucosidase inhibitor non-users. Patients who received alpha-glucosidase inhibitors for a cumulative duration of more than 364 days had significantly lower risks of these outcomes than non-users.Conclusion: Alpha-glucosidase inhibitor use was associated with a lower risk of mortality, hepatocellular carcinoma, decompensated cirrhosis, and hepatic failure in patients with diabetes and compensated cirrhosis. alpha-glucosidase inhibitors may be useful for the management of diabetes in patients with compensated liver cirrhosis. Large-scale prospective studies are required to verify our results.

IntroductionWe investigated health service utilization, including hospitalizations and emergency department visits, for women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan.MethodsData from the Health and Welfare Data Science Center were used to conduct this nationwide population-based study. We identified pregnant women and the date of childbirth according to Birth Certificate Applications from 2007 to 2018. The study population was divided into four groups: known DM, newly diagnosed DM, GDM, and no DM/GDM. To assess quality of healthcare during the gestation period, trends in 30-day readmission rate, number of emergency department visits/hospitalizations per 100 childbirths, and length of hospital stay from 2008 to 2017 were examined.ResultsA total of 1830511 childbirths and 990569 hospitalizations were identified for analyses. Between 2008 and 2017, women with hyperglycemia in pregnancy (known DM, newly diagnosed DM, and GDM) had a higher rate of hospitalization, a longer length of hospital stay, and higher rates of various maternal and fetal outcomes, compared with women with no DM/GDM. Nevertheless, the differences between women with GDM and those with no DM/GDM in the aforementioned outcome measures were modest. Women with GDM had a modest decrease in the 30-day readmission rate (p for trend 0.046) with no significant difference in the number of emergency department visits during the study period.DiscussionOur findings provide evidence of the quality of healthcare for women with GDM between 2008 and 2017 in Taiwan.

Aim: To know whether metformin use has different influence on cardiovascular risks in patients with type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) as compared with metformin no-use.Methods: This study employed a retrospective cohort study design. Using propensity score matching, we recruited 55 ,224 pairs of metformin users and nonusers from Taiwan’s National Health Insurance Research Database between 1 January 2000, and 31 December 2017. Cox proportional-hazards models with robust standard error estimates were used to compare the risks of cardiovascular outcomes.Results: The mean study period of metformin users and nonusers was 11.04 (5.46) and 12.30 (4.85) years, respectively. Compared with the nonuse of metformin, the adjusted hazard ratios (95% CI) of metformin use for composited cardiovascular events, stroke, coronary artery disease, and heart failure were 0.51 (0.48–0.53), 0.62 (0.59–0.64), 0.48 (0.46–0.50), and 0.61 (0.57–0.65), respectively. The longer cumulative duration of metformin use had even lower adjusted hazard ratios compared with metformin nonuse.Conclusion: In patients with coexisting T2DM and COPD, metformin use was associated with significantly lower risks of CVD; moreover, longer duration of metformin use was associated with a lower risk of CVD. A well-designed prospective study is required to verify the results.

Optimal control of diabetes and relevant risk factors substantially reduce the risks of chronic complications and mortality. We investigated all-cause mortality rate and major causes of death between 2007 and 2018 in patients with diabetes in Taiwan. This study was conducted using data from Taiwan National Health Insurance Research Database. We selected patients with diabetes diagnosed between 2007 and 2017 (grouped according to the year of diabetes diagnosis 2007-2010 vs. 2011-2017). Information on mortality and causes of death by the end of 2018 was confirmed through linking to the National Death Registry. Standardized mortality rate (SMR) were calculated by weighting the World Health Organization (WHO) standard population (WHO 2000-2025). More than 2.7 million of patients with diabetes were analyzed and a total of 566121 deaths were identified. Overall, the SMR was 11.72 per 1000 person-years. Patients with diabetes diagnosed in 2011-2017 had a lower SMR (8.42 vs. 12.92 per 1000 person-years) than those diagnosed in 2007-2010. Similar finding were noted regarding the major causes of death (cancer, diabetes, heart disease, hypertensive disease, and cerebrovascular disease). Compared with patients who were diagnosed in 2008-2010, those who were diagnosed in 2011-2014 and 2015-2018 had a higher 3-year survival rate (0.9356 vs. 0.9438 vs. 0.946, log-rank test p

Rationale & Objective: Taiwan implemented national pay-for-performance programs for chronic kidney disease (CKD) care in 2006 and 2011; however, it is unknown whether this affected trends in maintenance dialysis. This study assessed the temporal trends in the incidence, prevalence, and mortality of individuals treated with maintenance dialysis from 2002-2016 in Taiwan. Study Design: Follow-up study using Taiwan Renal Disease System Databases. Setting & Participants: Participants who received dialysis for ≥90 days. Predictors: Age, sex, and calendar year. Outcomes: Incidence, prevalence of maintenance dialysis, or death, ascertained using the National Death Registry database. Analytical Approach: The estimated annual percentage change was assessed by a generalized linear model, and the association of the programs with changes in the incidence of maintenance dialysis was evaluated using an age-period-cohort model. Results: A total of 144,258 incident cases with a follow-up of 346 million person-years were analyzed during the observed periods. The estimated annual percentage change of the expected crude incidence rate was slightly reduced by 0.41% (95% CI, −1.06 to 0.24) and was more obvious in women and patients aged greater than 70 years; whereas, it was significantly increased in those aged greater than 75 years. After disentangling age and cohort effects, the implementation of the care programs was associated with an overall net drift of −1.09% (95% CI, −1.65 to −0.52) per year and a significant linear reduction in the period rate ratio from 1.06 (95% CI, 1.02-1.09) in the years 2002-2006 to 0.95 (95% CI, 0.92-0.98) in 2012-2016, using years 2007-2011 as reference. Limitations: The findings of the study may have limited inferences to other countries with different health care systems. Conclusions: The implementation of universal CKD care programs in Taiwan has significantly reduced the long-term trends in the incidence of maintenance dialysis; hence, devoting governmental resources to CKD care and prevention is advocated.

Abstract Background Insulin is highly recommended for diabetes management in persons with liver cirrhosis. However, few studies have evaluated its long-term effects in these persons. We conducted this study to compare the risks of mortality, liver-related complications, and cardiovascular events in persons with type 2 diabetes mellitus (T2DM) and compensated liver cirrhosis. Methods From January 1, 2000, to December 31, 2012, we selected 2047 insulin users and 4094 propensity score-matched nonusers from Taiwan’s National Health Insurance Research Database. Cox proportional hazard models were used to assess the risks of outcomes. Results The mean follow-up time was 5.84 years. The death rate during the follow-up period was 5.28 and 4.07 per 100 person-years for insulin users and nonusers, respectively. In insulin users, the hazard ratios and 95% confidence intervals (CIs) of all-cause mortality, hepatocellular carcinoma, decompensated cirrhosis, hepatic failure, major cardiovascular events, and hypoglycemia were 1.31 (1.18–1.45), 1.18 (1.05–1.34), 1.53 (1.35–1.72), 1.26 (1.42–1.86), 1.41 (1.23–1.62), and 3.33 (2.45–4.53), respectively. Conclusions This retrospective cohort study indicated that among persons with T2DM and compensated liver cirrhosis, insulin users were associated with higher risks of death, liver-related complications, cardiovascular events, and hypoglycemia compared with insulin nonusers.

Abstract Background In insulin-treated patients with type 2 diabetes mellitus (T2DM), glycemic control is usually suboptimal. Methods This study compared the risks of mortality and cardiovascular events in insulin-treated patients adding or not adding alpha-glucosidase inhibitors (AGIs). Results This cohort study included data from the Taiwan National Health Insurance Research Database. In total, 17,417 patients newly diagnosed as having T2DM and undergoing insulin therapy during 2000–2012 were enrolled. Overall incidence rates of all-cause mortality, hospitalized coronary artery disease (CAD), stroke, and heart failure were compared between 4165 AGI users and 4165 matched nonusers. The incidence rates of all-cause mortality were 17.10 and 19.61 per 1000 person-years in AGI nonusers and users, respectively. Compared with nonusers, AGI users had a higher mortality risk [adjusted hazard ratio (aHR) = 1.21, 95% confidence interval (CI) = 1.05–1.40; p = 0.01]. Regarding AGI use, aHRs (95% CI) for cardiovascular death, non-cardiovascular death, hospitalized CAD, stroke, and heart failure were 1.20 (0.83–1.74), 1.27 (1.07–1.50), 1.12 (0.95–1.31), 0.98 (0.85–1.14), and 1.03 (0.87–1.22) respectively. Conclusion AGI use was associated with higher risks of all-cause mortality and non-cardiovascular death in insulin-treated patients with T2DM. Therefore, adding AGIs in insulin-treated patients may not be appropriate.

Abstract Aims/Introduction Studies assessing the long‐term outcomes of insulin persistence are scant. We compared the risk of all‐cause mortality among patients with different degrees of insulin persistence. Materials and Methods In total, 293,210 patients with type 2 diabetes mellitus undergoing insulin therapy were enrolled during 2002–2014. Insulin persistence was defined as continual insulin treatment without a 90‐day gap of discontinuation in the 2‐year observation period. Mortality rates were compared between 111,220 patients with ≥90% insulin persistence and 111,220 matched patients with

Abstract Background Dementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers’ burden in caring demented outpatients in a multicenter cohort. Methods Patients and their caregivers, both aged ≧65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed. Results We recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7 ± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8 ± 6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (β = 0.83, p

Abstract Identifying modifiable risk factors of peritoneal dialysis (PD)-related peritonitis is of clinical importance in patient care. Mineral bone disease (MBD) has been associated with mortality and morbidity in end-stage kidney disease (ESKD) patients. However, its influence on PD related peritonitis due to altered host immunity remains elusive. This study investigated whether abnormal biomarkers of MBD are associated with the development of peritonitis in patients undergoing maintenance PD. We conducted a retrospective observational cohort study, analysing data derived from a nationwide dialysis registry database in Taiwan, from 2005 to 2012. A total of 5750 ESKD patients commencing PD therapy during this period were enrolled and followed up to 60 months or by the end of the study period. The patients were stratified based on their baseline serum parathyroid hormone (PTH) levels, calcium (Ca) levels or phosphorus (P) levels, respectively or in combinations. The primary outcome was the occurrence of first episode of peritonitis, and patient outcomes such as deaths, transfer to haemodialysis or receiving renal transplantation were censored. Peritonitis-free survival and the influence of PTH, Ca, P (individual or in combination) on the peritonitis occurrence were analysed. A total of 5750 PD patients was enrolled. Of them, 1611 patients experienced their first episode of peritonitis during the study period. Patients with low PTH, high Ca or low P levels, respectively or in combination, had the lowest peritonitis-free survival. After adjusting for age, sex and serum albumin levels, we found that the combinations of low PTH levels with either high Ca levels or low/normal P levels were significant risk factors of developing peritonitis. Abnormal mineral bone metabolism in maintenance PD patients with low serum PTH levels, in combination with either high Ca levels or low/normal P levels, could be novel risk factors of PD-related peritonitis.

BackgroundFor patients with Acute Kidney Injury (AKI), a strong and graded relationship exists between AKI severity and mortality. One of the most severe entities of AKI is Dialysis-Requiring Acute Kidney Injury (D-AKI), which is associated with high rates of mortality and end-stage renal disease (ESRD). For this high-risk population group, there is a lack of evidence regarding optimal post-AKI care. We propose that post-AKI care through the combined efforts of the nephrologist and the multidisciplinary care team may improve outcomes. Our aim here is to study for survivors of dialysis-requiring acute kidney injury, the effects of implementing early comprehensive kidney care.MethodsThis is a retrospective longitudinal cohort study of Taiwanese through analyzing the National Health Insurance Research Database (NHIRD). We included patients with acute dialysis during hospitalization from January 1, 2015 to December 31, 2018. Propensity match was done at 1:1, including estimated glomerular filtration rate (eGFR) based on CKD-EPI which was performed due to large initial disparities between these two cohorts.ResultsAfter the propensity match, each cohort had 4,988 patients. The mean eGFR based on CKD-EPI was 27.5 ml/min/1.73 m2, and the mean follow-up period was 1.4 years.The hazard ratio for chronic dialysis or ESRD was 0.55 (95% CI, 0.49–0.62; p < 0.001). The hazard ratio for all-cause mortality was 0.79 (95% CI, 0.57–0.88; p < 0.001). Both outcomes favored early comprehensive kidney care.ConclusionsFor survivors of dialysis-requiring acute kidney injury, early comprehensive kidney care significantly lowered risks of chronic dialysis and all-cause mortality.

Background: For non-dialysis patients with hyperlipidemia, statins may provide clinical benefits in reducing mortality risk; however, the optimal treatment for dialysis patients with hyperlipidemia remains debatable. We evaluated the mortality risks for hyperlipidemic patients with renal disorders associated with statin therapy (ST), using the insurance claims data of Taiwan.Methods: From hyperlipidemic patients diagnosed in 2000–2011, we identified 555,153 patients receiving statin treatment for at least 90 days continuously and 1,141,901 non-statin users, and then randomly selected, from both groups, the propensity score-matched subcohorts of statin users and nonusers in a 1:1 pair by renal function: 415,453 pairs with normal renal function , 43,632 pairs with chronic kidney disease (CKD), and 3,624 pairs with end-stage renal disease (ESRD). We compared the mortalities, by the end of 2016, from all causes, cancer, heart disease, and septicemia between statin users and non-users and between hydrophilic-statin users and lipophilic-statin users. The Cox method estimated ST users to non-user hazard ratios. The time-dependent model was also conducted as sensitivity analysis.Results: The mean ages were 58.7 ± 10.7, 64.2 ± 10.7, and 62.2 ± 10.8 years in normal renal function, CKD, and ESRD groups, respectively. Compared with non-users, statin users had reduced mortality risks from all causes for 32%–38%, from cancer for 37%–46%, from heart disease for 6%–24%, and from septicemia for 17%–21% in all three renal groups. The hydrophilic statin therapy was superior than the lipophilic statin therapy, particularly for reducing deaths from all-causes and cancer. The results under the time-dependent model were similar.Conclusion: Statin therapy is associated with reduced all-causes and non-cardiovascular mortality in ESRD patients.