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Background: Type 2 diabetes (T2D) and hypertension (HTN) are well-known modifiable risk factors for dementia, but their intricate attributes accounting for dementia development has not been clearly delineated. Objective: We conducted this study to investigate and compare the effects of T2D and HTN on dementia risk. Methods: We screened data of matched pairs of patients with T2D or HTN between January 1, 2000 and December 31, 2017 from Taiwan’s National Health Insurance Research Database. Fine and Gray’s subdistribution hazard models were used for calculating the risk of dementia. Results: Patients with T2D and subsequent HTN were associated with significantly higher risks of all-cause dementia (aHR 1.51, 95% CI 1.25–1.83) and vascular dementia (aHR 2.30, 95% CI 1.71–3.13) compared with those without subsequent HTN. Patients with HTN and subsequent T2D were associated with significantly higher risks of all-cause dementia (aHR 1.15, 95% CI 1.08–1.21), vascular dementia (aHR 1.25, 95% CI 1.62–1.34), and other dementia (aHR 1.31, 95% CI 1.03–1.66) compared with those without subsequent HTN. The subgroups of male and female patients, age of 50–69 and 70–90 years with subsequent comorbidity were associated with significantly higher risks of all-cause dementia and vascular dementia than those without subsequent comorbidity. Conclusion: This nationwide cohort study demonstrated that patients with T2D and subsequent HTN had association with higher risks of all-cause dementia and vascular dementia, and those with HTN and subsequent T2D were associated with higher risks of all-cause dementia, vascular dementia, and other dementia.

To investigate the association between the amount and intensity of leisure-time physical activity (LTPA) and the risk of end-stage renal disease (ESRD).The study examined a cohort of 543,667 participants aged 20 years and older who participated in a health screening program from January 1, 1996, through December 31, 2017. We identified 2520 individuals undergoing dialysis or who had a kidney transplant by linking participants' encrypted personal identification with the registry for ESRD with a median follow-up of 13 years. We classified participants into 5 categories measured by metabolic equivalent of tasks. Within each category, we analyzed the effect of moderate- and vigorous-intensity LTPA in reducing risk of ESRD. We used a Cox proportional hazards model to calculate hazard ratios (HRs).We observed a dose-response relationship between LTPA and the risk of ESRD. The fully active group had a 12% lower hazard of ESRD compared with the no reported LTPA group (HR, 0.88; 95% CI, 0.80 to 0.98) adjusting for covariates including baseline estimated glomerular filtration rate and proteinuria. Within the same category of LTPA, vigorous-intensity exercise carried a 35% lower HR for ESRD compared with moderate-intensity exercise (HR, 0.65; 95% CI, 0.52 to 0.81). The effect was observed stronger among men, younger participants, and participants with diabetes or hyperlipidemia.Sustained LTPA (≥ 150 minutes per week), particularly with vigorous intensity, significantly lowered the ESRD risk, even among individuals with comorbidities such as diabetes or hyperlipidemia. This finding suggested that patients with no reported LTPA with cardiovascular risks should engage in more LTPA to lower their risk of ESRD.

The Taiwanese government launched a universal pay-for-performance (P4P) program in 2006 to promote multidisciplinary care for patients with stage 3b-5 chronic kidney disease (CKD). This study aimed to understand the enrollments, care processes, and outcomes of the P4P program between 2010 and 2018.We conducted a population-based study using the Taiwan National Health Insurance Research Data. We divided the incident dialysis population into joining and not joining P4P groups based on whether patients had joined the pre-ESRD program before dialysis or not. Trends in the medications prescribed, anemia correction, vascular access preparation before dialysis initiation, and cumulative survival rate were compared.The program included more than 100,000 patients with late-stage CKD. Enrollment increased by almost 100% from 2010 to 2018, with increases seen in those over 75 years old (127.5%), male (96.7%), and earlier CKD stages (≥35% stage 3b in 2018). Females were more likely to stay being enrolled. The joining P4P group was prescribed more appropriate medications, such as erythropoietin-stimulating agents and statins. However, a high number of patients were still prescribed metformin (≥40%) and non-steroidal anti-inflammatory drugs (≥20%). Compared to the not joining P4P group, the patients in the P4P group had better anemia management, dialysis preparation, and post-dialysis survival.The patients in the joining P4P program group were delivered more appropriate CKD care and were associated with better survival outcomes. Polices and action plans are needed to extend the coverage of and enrollment in the P4P program.

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., This review summarizes updated information on the onset and progression of DKD, particularly in Taiwan. Translating these epidemiological features is essential to optimizing kidney care and improving the prognosis of DKD in Asian populations.

Genetic background has been considered one of the important contributors to the rate of cognitive decline among patients with Alzheimer's disease (AD). We conducted a 4-year longitudinal follow-up study, recruited 255 AD and 44 mild cognitive impairment (MCI) patients, and used a data-driven trajectory analysis to examine the influence of selected AD risk genes on the age for and the rate of cognitive decline in Han Chinese population. Genotyping of selected single-nucleotide polymorphisms in the APOE, ABCA7, SORL1, BIN1, GAB2, and CD33 genes was conducted, and a Bayesian hierarchical model was fitted to analyze the trajectories of cognitive decline among different genotypes. After adjusting for sex and education years, the APOE e4 allele was associated with an earlier mean change of -2.39 years in the age at midpoint of cognitive decline, the G allele in ABCA7 rs3764650 was associated with an earlier mean change of -1.75 years, and the T allele in SORL1 rs3737529 was associated with a later mean change of 2.6 years. Additionally, the rate of cognitive decline was associated with the APOE e4 allele and SORL1 rs3737529. In summary, APOE and SORL1 might be the most important genetic factors related to cognitive decline in Han Chinese population.

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.

Objectives: Chronic kidney disease (CKD) has emerged as a global health concern. Many studies have identified an association between hyperuricemia and CKD, and some studies have revealed that urate-lowering therapy (ULT) can attenuate CKD progression. However, only a few studies have explored the role of ULT in the prevention of new onset CKD. Methods: To compare the risk of incident CKD between users and nonusers of ULT in patients with gout, we conducted a 13-year population-based retrospective cohort study. Overall incidence of CKD was compared between 7126 ULT users and 7126 matched ULT nonusers. Results: The CKD incidence rate for both the users and nonusers of ULT was 1.7 per 100 person-years, after adjusting for sex, age, region of residence, comorbidities, and medications used. No significant difference in CKD risk (adjusted hazard ratio [aHR]: 0.97; 95% confidence interval [CI]: 0.88-1.07) was noted between the ULT users and nonusers. In the subgroup of patients with diabetes mellitus (DM) and without hypertension (HT), ULT tended to be associated with lower risk of incident CKD (aHR: 0.52; 0.95% CI: 0.28-0.97). Compared with the risk of new onset CKD in patients receiving xanthine oxidase inhibitors, those receiving uricosuric agents seemed to have a lower risk of developing CKD (aHR: 0.81, 95% CI: 0.67-0.99). Conclusion: This population-based cohort study indicated that ULT is not associated with lower risk of CKD development. However, in the subgroup of patients with DM and without HT, ULT is associated with significantly lower risk of incident CKD.

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, Patients with high insulin persistence as compared with low insulin persistence decreased the risk of mortality by 20%.

Objectives Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension. Design A retrospective cohort study. Setting A nationwide database in Taiwan. Patients From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once. Interventions Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Measurements and main results We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673). In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011). Conclusions In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.

A risk prediction model for major cardiovascular events was developed using population survey data linked to National Health Insurance (NHI) claim data and the death registry. Another set of population survey data were used to validate the model. The model was built using the Nutrition and Health Survey in Taiwan (NAHSIT) collected from 1993–1996 and linked with 10 years of events from NHI data. Major adverse cardiovascular events (MACEs) were identified based on hospital admission or death from coronary heart disease or stroke. The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), conducted in 2002 was used for external validation. The NAHSIT data consisted of 1658 men and 1652 women aged 35–70 years. The incidence rates for MACE per 1000 person-years were 13.77 for men and 7.76 for women. These incidence rates for the TwSHHH were 7.27 for men and 3.58 for women. The model had reasonable discrimination (C-indexes: 0.76 for men; 0.75 for women), thus can be used to predict MACE risks in the general population. NHI data can be used to identify disease statuses if the definition and algorithm are clearly defined. Precise preventive health services in Taiwan can be based on this model.

BackgroundFew investigations have evaluated the influences on peripheral arterial disease (PAD) risk of statin treatment in hemodialysis (HD) subjects with hyperlipidemia (HL).MethodsFrom the National Health Insurance Research Dataset, we identified 3658 HD patients with statin therapy for HL as the statin cohort, and then selected, by 1:1 propensity score matching, 3658 HD patients with HL but without statin use as the nonstatin cohort in 2000–07. The cohorts were followed through until the end of 2011. We used Cox proportional hazards regression analysis to assess the hazard ratio (HR) of PAD development.ResultsThe average follow-up period was 4.18 years; the incident PAD risk was 1.35-fold greater in statin users than in nonusers (16.87 versus 12.46/1000 person-years), with an adjusted HR (aHR) of 1.34 for PAD [95% confidence interval (CI) 1.12–1.62]. The PAD risk increases were significant for patients receiving fluvastatin (aHR 1.88; 95% CI 1.12–3.14) and atorvastatin (aHR 1.60; 95% CI 1.24–2.08). The risk increased with higher annual average statin dosage (P for trend ConclusionsHD patients with HL on statin medication were at increased PAD risk, which increased with cumulative statin dosage. Thorough considerations are needed before prescribing statins to HD patients.

The 2019 Diabetes Atlas delineated both accomplishments and challenges in diabetes care in Taiwan between 2005 and 2014. The series reported that Taiwan had significantly improved aspects of care quality for patients with diabetes. For example, the mortality rate decreased, the difference between the life expectancies of patients with diabetes and those of the general population decreased, and the rates of hospitalization because of heart diseases, cerebrovascular diseases, chronic kidney diseases, and unsatisfactory glycemic control decreased. However, despite these achievements, the 2019 Diabetes Atlas also reported some substantial challenges that have not been overcome. For example, the incidence of diabetes among women aged

Background In Taiwan, physical restraint is commonly used in institutions to protect residents from falling or injury. However, physical restraint should be used cautiously to avoid side effects, such as worse cognition, mobility, depression, and even death. Objectives To identify the rate of physical restraint and the associated risk factors in institutionalized residents in Taiwan. Methods A community-based epidemiological survey was conducted from July 2019 to February 2020 across 266 residential institutions. Among the estimated 6,549 residents being surveyed, a total of 5,752 finished the study. The questionnaires were completed by residents, his/her family or social workers. The cognition tests were conducted by specialists and a multilevel analysis approach was used to identify cognition/disability/medical history/special nursing care/BPSD risk factors for physical restraints. Results Of the 5,752 included institutionalized residents, 30.2% (1,737) had been previously restrained. Older age, lower education level, lower cognitive function, higher dependence, residents with cerebrovascular disease, pulmonary disease, dementia, and intractable epilepsy, all contributed to a higher physical restraint rate, while orthopedic disease and spinal cord injury were associated with a lower physical restraint rate. Furthermore, residents with special nursing care had a higher restraint rate. Residents with most of the behavior and psychological symptoms were also associated with an increased restraint rate. Conclusions We studied the rate of physical restraint and associated risk factors in institutionalized residents in Taiwan. The benefits and risks of physical restraint should be evaluated before application, and adjusted according to different clinical situations.

Hepatitis B virus (HBV), hepatitis C virus (HCV), and tuberculosis (TB) infections affect patient morbidity and mortality and challenge infection control procedures within dialysis facilities. Thus, updated information on the yearly infection trends in the dialysis population is pivotal to preventing and improving the management of these infectious diseases.This study used reimbursement data from the Taiwan National Health Insurance Research Database. Long-term hemodialysis (HD) patients were defined as those receiving regular HD for more than 3 months. Treated HBV, HCV, and TB cases were defined according to the diagnosis codes, together with specified prescriptions. Liver malignancy and liver-related mortality were determined by the disease diagnosis.The long-term HD population in Taiwan grew from 57,539 in 2010 to 74,203 in 2018. The mean number of treated HBV, HCV, and TB cases in the HD population was 254 (3.9 per thousand HD patients), 136 (2.0 per thousand), and 165 (2.6 per thousand), respectively. An increasing trend of treated viral hepatitis and a mildly decreasing trend in treated TB were observed. Liver outcome showed an increasing trend in liver malignancy prevalence and a stationary trend of liver-related mortality. Treated HBV and TB, liver malignancy, and liver-associated mortality were higher in men than women (all p 0.001). The burden of liver complications was higher in southern Taiwan.The increasing yearly trend of treated HBV and HCV and a stable trend of treated TB provide evidence for further infection control management and risk population identification of the HD population.

PurposeTo compare the risks of chronic kidney disease (CKD), end-stage renal disease (ESRD), sight-threatening retinopathy, and leg amputation between patients with diabetes or hypertension.MethodsFrom January 1, 2000, to December 31, 2015, we identified 28943 matched pairs of patients with diabetes with and without subsequent hypertension, 89102 pairs of patients with hypertension with and without subsequent diabetes, and 145294 pairs of patients with coexisting diabetes and hypertension with a previous history of diabetes or hypertension from Taiwan’s National Health Insurance Research Database. Cox proportional-hazard models were used for calculating the risks of CKD, sight-threatening retinopathy, and leg amputation.ResultsThe mean follow-up time of this study in different cohorts was between 3.59 and 4.28 years. In diabetes patients with vs. without subsequent hypertension, hypertension patients with vs. without subsequent diabetes, and comorbid diabetes and hypertension patients with previous diabetes vs. with previous hypertension, the adjusted HRs (95% CIs) for CKD were 2.77 (2.61-2.94), 1.73 (1.68-1.77), and 1.04 (1.02-1.07); for ESRD were 42.38 (22.62-79.4), 2.76 (2.43-3.13), and 0.72 (0.66-0.79); for sight-threatening retinopathy were 2.07 (1.85-2.3), 3.41 (3.14-3.71), and for leg amputation were 1.51 (1.43-1.58); and 4.74 (3.02-7.43), 6.27(4.72-8.31), and 1.19(1.03-1.38).ConclusionsThis study demonstrated that both diabetes and hypertension are risk factors for the development of CKD, retinopathy, and amputation. Tracing subsequent diabetes for patients with hypertension, and hypertension for patients with diabetes are important in clinical settings.

Hsing-Yi Chang,1,2 Hsin-Ling Fang,1 Te-Tien Ting,3 Jersey Liang,4 Shao-Yuan Chuang,1 Chih-Cheng Hsu,1 Chin-Yin Wu,5 Wen-Harn Pan1,2,61Institute of Population Health Sciences, National Health Research Institutes, Maoli, Taiwan; 2Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; 3School of Big Data Management, Soochow University, Taipei, Taiwan; 4Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 5Institute of Sociology, Academia Sinica, Taipei, Taiwan; 6Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanCorrespondence: Hsing-Yi ChangInstitute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, A3223, Zhunan Town, Maoli County, ROC 35053, TaiwanTel +886 37 246166Fax +886 37 586261Email hsingyi@nhri.org.twPurpose: The co-occurrence of frailty and depression in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality have rarely been investigated. We aimed to examine the co-occurrence of frailty and depressive symptoms in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality using all the information from a longitudinal study.Patients and methods: We used the Taiwan Longitudinal Study of Aging (TLSA) for this study. TLSA was initiated in 1989 and followed periodically. We included participants from 1989 to 2007, who had data on frailty and depressive symptoms. Frailty was assessed by accumulation of functional deficits in 6 dimensions including disease status, sensory dysfunction, balance, functional limitations, health risk behaviors, and life satisfaction. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). A multistate model with interval censoring was used to examine the transition between states of frailty with or without depressive symptoms, and finally to death. A mixed model was used to examine the relationships between frailty and depressive symptoms.Results: The coexistence of frailty and depressive symptoms was associated with higher mortality. Individuals with depressive symptom had a lower probability of reversal to a better state. Previous depression score predicted current frailty, but the coefficient was smaller than that of previous frailty. Previous frailty predicted current depression score, and the coefficient was stronger than that of previous depression.Conclusion: Depressive symptoms increased the mortality and decreased the probability of reversal in the frail older adults.Keywords: TLSA, cumulative functional deficits, depressive symptom, multistate model, mortality

Objective: Many women quit smoking during pregnancy resume in postpartum period and difficult to prevent. No studies had focused on their psychosocial response in Taiwan. We analyzed data from a trial of Taiwan Smoker's Helpline (TSH) to determine factors associated with smoking relapse after delivery. Materials and methods: A prospective cohort was conducted at Taipei City Hospital during Sep. 2014 and Nov. 2015 period. We collected data by self-developed questionnaire combining theory of planned behavior (TPB), Fagerstrom test for nicotine dependence (FTND) and Edinburgh Postnatal Depression Scale (EPDS) from 68 women immediately after delivery, 2 months later and followed up until 6 months. Multivariable logistic models for relapse of smoking at the end of 3rd month and 6th month were created. Results: At 6th month, 42.6% participants relapsed with odds lower among first parity (OR = 0.04, 95% CI =

Objective Iron supplementation and erythropoietin stimulating agents (ESAs) are essential for maintaining hemoglobin levels in hemodialysis patients. However, patients with autosomal-dominant polycystic kidney disease (PKD) have higher endogenous erythropoietin levels, so their recommended iron indices for hemodialysis patients may differ. This study evaluated iron profiles, including ferritin levels and transferrin saturation (TSAT) to identify factors affecting mortality in patients on dialysis, and those associated with mortality in patients with and without PKD. Design This cohort study from the Taiwan Renal Registry Data System stratified mortality risk by the presence of PKD recorded as the underlying disease. Subjects We enrolled 1346 hemodialysis patients with PKD and 82,873 hemodialysis patients without PKD. Main outcome measure The primary outcome was 3-year all-cause mortality. Predictors included time-averaged and baseline serum ferritin levels and TSAT. Multivariate Cox regression analysis adjusting for age, comorbidities, and relevant laboratory parameters was used to estimate the all-cause hazard ratios (HRs) for mortality. Results The mean ages of patients with and without PKD were 56.2±13.2 and 61.7±13.5 years and the median follow-up time was 37 (15-76) months. The adjusted mortality risks for time-averaged ferritin levels >800 ng/mL (HR=1.52; 95% confidence interval: 1.40–1.65) or TSAT levels >50% (HR=1.46; 95% confidence interval: 1.30–1.65) were significantly higher among patients without PKD than those for patients with normal iron indices. However, a U-shaped curve of mortality against ferritin/TSAT levels was not observed in patients with PKD. In the sensitivity test, there was no difference among PKD patients who underwent regular ESA therapy and those who did not. Conclusion Iron indices have different effects on mortality among patients with and without PKD. Iron supplementation, recommended serum ferritin levels, or TSAT should be monitored in hemodialysis patients, especially those without PKD. Clinicians should consider treating anemia in hemodialysis patients individually, especially in PKD.

Summary: Background: Strong evidence has shown that metabolic surgery is more effective than medical treatment in the treatment of type 2 diabetic patients. However, no study demonstrated a survival benefit and reduction of diabetes-related end-organ damage. Here, we describe the study design of a large prospective cohort study, the Taiwan Diabesity Study (TDS) which would compare the long-term survival rate and end-organ damage between overweight/obese type 2 diabetic patients receiving metabolic surgery and medical treatment. Methods: Eligibility criteria include type 2 diabetic patients with duration > 6 months, body mass index (BMI) over 25 kg/m2 and age between 20 and 67 years. Exclusion criteria are serum creatinine over 2.0 mg/dL, C-peptide below 1.0 ng/ml, recent history of cancer, and major diabetic complications. Eligible participants were recruited from six medical centers in Taiwan. The survival rate and diabetes-related end organ damage will be compared between the metabolic surgery group and medical group after follow-up for 10 years. Results: In 3 years, 1016 participants were identified from 38,751 patients. The average BMI of patients was 30.6 (±2.6) kg/m2 and the average hemoglobin A1c was 8.2% (±1.5%) with 18% of them receiving insulin treatment. Among them, 126 patients received metabolic surgery and 890 patients received conventional medical treatment. The metabolic surgery group are younger, have a higher proportion of females, higher BMI and blood lipids as compared to the medical group. Conclusion: The TDS recruited 1016 overweight/obese type 2 diabetic patients including 126 patients receiving metabolic surgery and 890 patients receiving medical treatment. Keywords: Type 2 diabetes mellitus, Obesity, Diabesity, Metabolic surgery, Bariatric surgery, Recruitment

Introduction The characteristics in dialyzer is associated with mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This study is to investigate the effects of dialyzer membranes on 3-year mortality in ESRD patients. Methods From the long-term nationwide population database database. Prevalent HD patient during 2005-2012 were enrolled. Our main analysis to calculate the effect was cox regression multivariate model. Results Overall, the mean age of all population (N=73,565) was 61.0 ± 13.6 years, observation period is 2.46 years ± 0.98 within 3 years and 64.6% used polysulfone (PS), polymethyl methacrylate (PMMA) (11.6%), polyethersulfone (11.4%), and cellulose triacetate (CTA) (10.7%), EVAL (Hazard ratio [HR] 2.72, 95% confidence interval [CI] 1.71-4.33) and CTA (HR 1.35, 95% CI 1.12-1.64) were associated with higher mortality than PS, but PMMA was not. Conclusion EVAL and CTA adversely affected mortality and PMMA had no protective role. Further investigations on membrane characters on HD patients are warranted. Taipei Medical University (TMU) (TMU-JIRB (No. N201804051).

Aim Behavioral and psychological symptoms of dementia (BPSD) are important predictors for institutional placement, caregiver distress and depression for patients with dementia. We aim to investigate BPSD in institutional residents with dementia in Taiwan. Methods We conducted a nationwide study surveying institutional residents in Taiwan. Institutional residents from 22 counties and cities in Taiwan were recruited and analyzed in our study. We recorded demographic data, severity of dementia and disability, presence of BPSD, and past medical history of institutional residents in Taiwan. We recorded the characteristics of BPSD and analyzed the possible risks of BPSD in residents with dementia. Results A total of 4722 institutional residents were recruited and analyzed in our study. The prevalence of dementia was 87.2% (4119 residents). Among residents with dementia, 1546 (37.5%) had presented BPSD in the past 3 months. The most frequent three types of BPSD were nighttime behavior (17.9%), resistance against care (13.4%) and depression (12.9%). Old age, female gender, and lower MMSE (Mini-Mental State Examination) scores were associated with BPSD. Moderate dementia (OR = 1.73, 95% CI = 1.30-2.31) and mild activities of daily living (ADL) dependence (OR = 2.13, 95% CI = 1.06-4.27) increased the risks of BPSD. Reviews of past medical history showed that orthopedic disease, eye disease, genitourinary disease, dementia, psychiatric disorder and intellectual disability were associated with increasing risks of BPSD. Conclusions We concluded that moderate dementia and mild ADL dependence increased the risks of BPSD in institutional residents with dementia. Geriatr Gerontol Int 2021; ••: ••-••.

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.

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 p p p = 0.001) and caregiver age (β = − 0.41, p = 0.001) were negatively correlated with ZBI scores. Conclusions Older caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.

In some studies, electrocardiographic early repolarization pattern (ERP) has been associated with an increased risk of death from cardiac causes. However, little is known about the prognostic significance of ERP in the middle-aged and geriatric general populations. We investigated the prevalence and long-term prognostic significance of early repolarization pattern (ERP) on electrocardiograms (ECGs) in the Healthy Aging Longitudinal Study (HALST) cohort of 4615 middle-aged and geriatric community-dwelling Han Chinese adults from Taiwan. The study subjects were followed-up for 95±22 months. A positive ERP of ≥0.1 mV was observed in 889 (19.3%) of the subjects. Kaplan-Meier survival curve analysis showed that ERP was not associated with all-cause and cardiovascular mortality (log-rank test, P=0.13 and 0.84, respectively). Cox regression analysis after adjusting for covariables revealed that age, blood pressure, smoking, diabetes, stroke, chronic kidney disease, and corrected QT interval (QTc) were associated with increased risk of all-cause mortality (P

Geriatric frailty is associated with increased mortality and links to increased inflammatory activity. Vascular adhesion protein-1 (VAP-1) is important in inflammatory process. This study investigates the relationship between plasma VAP-1 level and frailty in older adults. The cross-sectional study recruited community dwelling older adults from a hospital-based comprehensive geriatric assessment program. The demographic data, Fried Frailty Index, metabolic and inflammatory parameters were assessed. A total of 151 participants (76 women, 50.3%) were included in the analysis, and the age (mean ± standard deviation) was 77.1 ± 6.1 years. The mean plasma VAP-1 level (ng/mL) was significantly different (P = .029) among different frailty groups (346.3 ± 86.5 in the robust older adults, 371.6 ± 107.9 in the pre-frail older adults, and 416.6 ± 141.1 in the frail older adults). Multivariate ordered logistic regression analysis also demonstrated that plasma VAP-1 levels were positively associated with frailty severity (P = .039). Analysis of the frailty components with plasma VAP-1 levels showed that the elderly who had “exhaustion” (P = .016) or “weakness” (P = .025) tended to have higher plasma VAP-1 levels. The data support that VAP-1 might represent a potential plasma biomarker of frailty.

Few studies investigated the respiratory outcomes of metformin use in patients with coexistent type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD). We want to compare the long-term respiratory endpoints of metformin use and nonuse in patients with T2DM and COPD. This retrospective cohort study enrolled patients with T2DM and COPD from Taiwan’s National Health Insurance Program between January 1, 2000, and December 31, 2012. Main outcomes were hospitalized bacterial pneumonia, hospitalization for COPD, noninvasive positive pressure ventilation (NIPPV), invasive mechanical ventilation (IMV), and lung cancer. In total, 20,644 propensity score-matched metformin users and nonusers were assessed. The adjusted hazard ratios (95% confidence intervals) of metformin use relative to nonuse for bacterial pneumonia, hospitalization for COPD, NIPPV, IMV, and lung cancer were 1.17 (1.11–1.23), 1.34 (1.26–1.43), 0.99 (0.89–1.10), 1.10 (1.03–1.17), and 1.12 (0.96–1.30). Metformin use also exhibited significant dose–response relationship with respect to the risks of bacterial pneumonia, hospitalization for COPD and IMV. Consistent results were found in the sensitivity test. This nationwide cohort study demonstrated that in patients with T2DM and COPD, metformin use was associated with higher risks of pneumonia, hospitalization for COPD, and IMV. If patients with COPD use metformin, vigilance with regard to their pulmonary condition may be required.

ObjectivesAlthough studies have demonstrated the association of hyperuricemia with cardiovascular (CV) diseases, few have explored the effect of urate-lowering therapy (ULT) on the incidence of CV diseases. Therefore, we compared the risks of hospitalized coronary artery disease (CAD), stroke, heart failure (HF), and all-cause mortality between ULT users and nonusers among patients with gout.MethodsWe performed this retrospective cohort study using Taiwan's population-based National Health Insurance Research Database. In total, 5218 patients with gout were included from 2000 to 2012. We compared the incidence rates (IRs) of hospitalized CAD, stroke, HF, and all-cause mortality between ULT users and matched nonusers.ResultsThe IRs of hospitalized stroke were 0.6 and 1.0 per 100 person-years for ULT users and nonusers, respectively, after adjusting for age, sex, residence, comorbidities, and medications. ULT users showed lower adjusted hazard ratios (aHR) for hospitalized stroke (aHR: 0.52, p < 0.001) and all-cause mortality (aHR: 0.6, p = 0.02) than nonusers. Subgroup analyses revealed that uricosuric agents and xanthine oxidase inhibitors were significantly associated with lower risks of hospitalized stroke and all-cause mortality, respectively. The effect of uricosuric agents on the decrease in hospitalized stroke risk indicated a dose-response relationship.ConclusionsOur study showed lower risks of hospitalized stroke and all-cause mortality in ULT users than in nonusers among patients with gout. Therefore, patients with gout may receive ULT to mitigate the risks of hospitalized stroke and mortality.

Implementation of insulin therapy among those with diabetes is often suboptimal as a result of non-adherence or non-persistence. Studies regarding factors leading to insulin nonpersistence are limited. Therefore, we conducted this retrospective cohort study to determine the factors affecting insulin nonpersistence.A total of 274,852 persons with type 2 diabetes mellitus under insulin therapy during the period 2000-2014 were enrolled. Persons who stopped insulin therapy for90 days were defined as having insulin nonpersistence. We searched for factors associated with insulin nonpersistence during the long-term follow-up period.According to the multiple Cox regression model with a mean follow-up of 13.9 years, the factors associated with higher risk of insulin nonpersistence were age40 years, men, residing in a rural area, Charlson comorbidity index score = 4, use of two or more oral antidiabetic drugs, and hypoglycemia during follow-up. The Kaplan-Meier graph showed that patients aged40 years had significantly less insulin persistence.This nationwide cohort study indicated that persons with young-onset type 2 diabetes, less medical resources, and more comorbidities are at risk of insulin nonpersistence. Healthcare providers should regularly assess insulin persistence and help patients who are having difficulty with insulin-taking.

This study aimed to investigate the long-term outcomes of sulfonylurea (SU) use in patients with T2DM and compensated liver cirrhosis. From January 1, 2000, to December 31, 2012, we selected the data of 3781 propensity-score-matched SU users and nonusers from Taiwan’s National Health Insurance Research Database. The mean follow-up time for this study was 5.74 years. Cox proportional hazards models with robust sandwich standard error estimates were used to compare the risks of main outcomes between SU users and nonusers. The incidence of mortality during follow-up was 3.24 and 4.09 per 100 person-years for SU users and nonusers, respectively. The adjusted hazard ratios and 95% confidence intervals for all-cause mortality, major cardiovascular events, and decompensated cirrhosis in SU users relative to SU nonusers were 0.79 (0.71–0.88), 0.69 (0.61–0.80), and 0.82 (0.66–1.03), respectively. The SU-associated lower risks of death and cardiovascular events seemed to have a dose–response trend. This population-based cohort study demonstrated that SU use was associated with lower risks of death and major cardiovascular events compared with SU non-use in patients with T2DM and compensated liver cirrhosis. SUs may be useful for glycemic management for patients with liver cirrhosis.

BACKGROUND Bariatric surgery is associated with a significant improvement in depressive mood in the initial postoperative years, but the maintenance of the improvement is under debate. AIM To explore the association between bariatric surgery and major depressive disorder (MDD) in a 12-year nationwide cohort study. METHOD Using the National Health Insurance Research Database of Taiwan, we identified 2302 patients who underwent bariatric surgery in 2001-2009. These patients were matched by propensity score to 6493 obese patients who did not receive bariatric surgery. We followed the surgical and control cohorts until death, any diagnosis of MDD or 31 December 2012. We used Cox proportional hazard regression models to calculate the relative risk of MDD in those who received bariatric surgery. RESULTS Overall, there was a 1.70-fold (95% CI: 1.27-2.27) higher risk of MDD in the surgical group. Subjects receiving malabsorptive procedures showed a higher risk of MDD (3.01, 95% CI: 1.78-5.09) than those receiving restrictive procedures (1.51, 95% CI: 1.10-2.07). Stratified by follow-up period, there was a higher risk of MDD in the surgical group (2.92, 95% CI: 1.75-4.88) than in the restrictive group four years after bariatric surgery. CONCLUSIONS Bariatric surgery was significantly associated with an elevated risk of MDD. KEY MESSAGES Bariatric surgery is associated with a significant improvement in depressive mood in the initial postoperative years, but the improvement is not maintained. Less is known about the relationship between bariatric surgery and risk of major depressive disorder. This was the first nationwide cohort study which found that bariatric surgery was significantly associated with an elevated risk of MDD (aHR: 1.70; CI: 1.27-2.27), mainly with malabsorptive procedures (aHR: 3.01; CI: 1.78-5.09) and at time points more than four years after surgery (aHR: 2.92; CI: 1.75-4.88) compared with the risk in matched controls. These findings imply an association between long-term malabsorption and the postoperative incidence of MDD. Long-term malabsorption might be related to the incidence of major depressive disorder after bariatric surgery. The possible causal relationship between nutritional deficiency after bariatric surgery and major depressive disorder warrants further investigation.

Context Although α-glucosidase inhibitors (AGIs) have been shown to reduce the risk of myocardial infarction in patients with impaired glucose tolerance, the cardiovascular benefits of AGIs in those with type 2 diabetes (T2D) remains unclear. Objective We compared the clinical outcomes of adding acarbose vs sulfonylureas to metformin therapy in patients with T2D. Design, setting, and participants The study population was drawn from the database of the Diabetes Pay-for-Performance program in Taiwan. Sulfonylureas and acarbose were prescribed to 196,143 and 14,306 patients with T2D, respectively, from 2004 to 2015, who had been treated with metformin. A propensity score-matched cohort study was conducted. The patients were followed up for clinical adverse events of all-cause mortality and hospitalizations of major atherosclerotic events (i.e., myocardial infarction and ischemic stroke), heart failure, or hypoglycemia. Results A total of 14,306 propensity score-matched pairs (age, 55.8 ± 13.1 years; 47.8% men) were enrolled in the present analysis. Compared with sulfonylureas as the add-on therapy to metformin, the use of acarbose was associated with significantly lower risks of hospitalizations for major atherosclerotic events [hazard ratio (HR), 0.69; 95% CI, 0.52 to 0.91], ischemic stroke (HR, 0.68; 95% CI, 0.49 to 0.94), and hypoglycemia (HR, 0.23; 95% CI, 0.08 to 0.71), after accounting for major confounding factors. Conclusions In T2D treatment, the use of acarbose as an add-on remedy to metformin was associated with lower risks of major atherosclerotic events, ischemic stroke, and hypoglycemia compared with the use of sulfonylurea as an add-on remedy.

Background/Purpose: Diabetes mellitus (DM) and DM-related complications place a high socioeconomic burden on individuals and society. Updating nationwide information periodically is thus pivotal to preventing DM and improving its management in Taiwan. Methods: We used the National Health Insurance Research Database; disease diagnosis codes were assigned according to the International Classification of Diseases, 9th Revision, Clinical Modification. DM was defined as ≥3 outpatient visits or 1 hospitalization within a year. We excluded individuals with gestational DM, those with missing data, and those aged >100 years. Type 1 DM (T1DM) was defined based on information from the catastrophic illness registry. Results: From 2005 to 2014, total population with DM increased by 66% and age-standardized prevalence in patients aged 20–79 years increased by 41%. The DM prevalence was generally higher in men; however, the prevalence was higher in women aged ≥65 years. The prevalence of DM was approximately 50% in those aged >80 years. DM incidence increased by 19%; the increase was most obvious in patients aged 20–39 years (p

Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism.We conducted a prospective study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan. Each participant received baseline measurements of blood HbA1c and inflammatory markers levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. We used generalized linear mixed-effects regression to estimate the adjusted changes in the odds ratio for self-reported physical functioning impairment and Short Physical Performance Battery (SPPB) score according to baseline HbA1c levels (categorized into 0.5% increments from5.5% to ≥7.0%).HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term.001). Compared with participants with an HbA1c of 5.5% to6.0%, those with an HbA1c of5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04-1.50] and 1.21 [1.04-1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], -0.05 [-0.10 to 0.00] and -0.04 [-0.08 to 0.00]). These relationships were nonlinear only in participants with high soluble interleukin-6 receptor levels (48,124 pg/mL; p for interaction.05).High and low HbA1c levels at baseline are associated with faster physical functioning decline, particularly among individuals with elevated circulating soluble interleukin-6 receptor, a sign of enhanced interleukin-6 trans-signaling.

Aims To compare the hazard of cardiovascular diseases between DPP-4 inhibitor users and non-users who were on insulin therapy. Methods We conducted a population-based cohort study. 2652 patients with type 2 diabetes mellitus (T2DM) under insulin therapy were enrolled during 1997–2010. The incidence rates per 1000 person-years (PYs) of stroke, coronary heart disease (CAD) and heart failure were compared between 1326 DPP-4 inhibitor users and 1326 propensity score matched non-users. Multivariable Cox proportional hazards model was used to evaluate excess risk of the DPP-4 inhibitor non-users. Results After adjustment of age, gender, comorbidities, drugs used and diabetes duration; the incidence rate per 1000 PYs were 21.70 and 9.88 in DPP-4 inhibitor non-users and users; DPP-4 inhibitor users had lower hazard ratio (HR) of stroke (adjusted HR: 0.59, 95% CI: 0.42–0.83, p value: 0.002) compared with non-users. The incidence rates per 1000 PYs of CAD and heart failure of control versus users were 19.85 versus 13.54 and 5.56 versus 4.78; the adjusted HRs of CAD and heart failure were 0.86 and 1.11. Both were non-significant. Conclusion This nationwide study demonstrated that insulin plus DPP-4 inhibitor users had significantly lower risk of stroke as compared with non-users.

Background The effect of cardio-metabolic profile on the relationship of body mass index (BMI) with mortality is unclear. The aim of this study was to explore association between BMI and mortality at all ages, taking account of cardio-metabolic disorders. Methods We followed 377,929 individuals (≥ 20 years), who registered for health checkups in 1996–2007, until 2008 and found 9490 deaths. From multivariable Cox proportional hazards models we estimated mortality hazard ratios (HR) for those in high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and different BMIs categories (the underweight [< 18.5 kg/m2], low normal weight [18.5–21.9 kg/m2], normal weight [22–23.9 kg/m2, the referent], overweight [24–26.9 kg/m2], obese1 [27–29.9 kg/m2], and obese2 [≥ 30 kg/m2]). Population attributable risk (PAR) provided estimates of the population mortality burden attributable to high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and deviant BMIs. Results Higher blood pressure, hyperglycemia, high waist circumference, and dyslipidemia were significantly predictive of higher mortality for nearly all ages. Compared with the referent BMI, underweight (HR = 1.69, 95% confidence interval = 1.51–1.90) and low normal weight (HR = 1.19, 1.11–1.28) were significant mortality risks, while overweight (HR = 0.82, 0.76–0.89) and obese1 (HR = 0.88, 0.79–0.97) were protective against premature death. The mortality impact of obesity was largely attributable to cardio-metabolic profile and attenuated by age. The population mortality burden with high blood pressure (PAR = 7.29%), hyperglycemia (PAR = 5.15%), high waist circumference (PAR = 4.24%), and dyslipidemia (PAR = 5.66%) was similar to that in the underweight (PAR = 5.50%) or low normal weight (PAR = 6.04%) groups. Findings for non-smokers and by gender were similar. Conclusions The effect of BMI on mortality varies with age and is affected by cardio-metabolic status. Compared to any deviant BMI, abnormal cardio-metabolic status has a similar or even greater health impact at both the individual and population levels. Electronic supplementary material The online version of this article (10.1186/s12889-018-5038-0) contains supplementary material, which is available to authorized users.

Background The prevalence of diabetes is growing, and diabetes is an independent risk factor for both atrial fibrillation (AF) and stroke. However, the relative effectiveness and safety of different oral anticoagulants for diabetic patients with non-valvular AF remain unclear. We aimed to compare thromboembolic events, bleeding and mortality in diabetic AF patients treated with rivaroxaban, dabigatran and warfarin. Methods and Results Diabetic AF patients taking dabigatran (n = 322), rivaroxaban (n = 320) or warfarin (n = 1,899) were identified from the nationwide diabetes pay-for-performance program (n = 814,465) in Taiwan. Outcomes and comorbidities were evaluated by linking with Taiwan National Health Insurance Research Database. Propensity score weighting method was used to balance covariates across study groups. Patients were followed up until the first occurrence of any study outcome or the study end date. Compared with warfarin, dabigatran significantly decreased the risk of all-cause mortality (hazard ratio [HR] = 0.348, 95% confidence interval [CI] = 0.157–0.771) and gastrointestinal bleeding (HR = 0.558, 95% CI = 0.327–0.955). Relative effectiveness and safety outcomes between rivaroxaban and warfarin were comparable. Compared with rivaroxaban, dabigatran significantly decreased the risk of all-cause mortality (HR = 0.310, 95% CI = 0.121–0.798) and was associated with a borderline reduced risk for composite safety end points (HR = 0.670, 95% CI = 0.421–1.067). Conclusion In diabetic AF patients, dabigatran and rivaroxaban showed a superior or non-inferior effectiveness and safety profile compared with warfarin. Dabigatran was associated with a significantly lower risk of mortality than rivaroxaban.

Objectives To investigate whether dietary patterns are associated with frailty phenotypes in an elderly Taiwanese population. Design Cross-sectional. Setting Nutrition and Health Survey in Taiwan (NAHSIT), 2014–2016. Participants Noninstitutionalized Taiwanese nationals aged 65 years and older enrolled in the NAHSIT (N = 923). Measurements Dietary intake was assessed using a 79-item food-frequency questionnaire (FFQ). Presence of 5 frailty phenotypes was determined using modified Fried criteria and are summed into a frailty score. Using data from the NAHSIT (2014–15), reduced rank regression was used to find a dietary pattern that explained maximal degree of variation of the frailty scores. Logistic regression models were used to estimate the association between frailty and dietary pattern. The findings were validated with data from 2016. Results The derived dietary pattern was characterized with a high consumption of fruit, nuts and seeds, tea, vegetables, whole grains, shellfish, milk, and fish. The prevalence of frailty was 7.8% and of prefrailty was 50.8%, defined using the modified Fried criteria. Using data from the NAHSIT (2014–15), the dietary pattern score showed an inverse dose-response relationship with prevalence of frailty and pre-frailty. Individuals in the second dietary pattern tertile were one-third as likely to be frail as those in the first tertile (adjusted odds ratio (aOR) = 0.32, 95% confidence interval (CI) = 0.12−0.85), and those in the third tertile were 4% as likely to be frail as those in the first tertile (aOR = 0.04, 95% CI = 0.01−0.18). The dietary pattern score estimated using FFQ data from the NAHSIT 2016 was also significantly and inversely associated with frailty. Conclusion Individuals with a dietary pattern with more phytonutrient-rich plant foods, tea, omega-3-rich deep-sea fish, and other protein-rich foods such as shellfish and milk had a reduced prevalence of frailty. Further research is necessary to confirm these findings and investigate whether related dietary interventions can reduce frailty in older adults.

This study aimed to assess the benefit of adding physical function evaluations and interventions to routine elderly health examination. This is a Quasi-experimental controlled trial. 404 elderly adults (aged 70 and over) scoring 3-6 on the Canadian Study of Health and Aging Clinical Frailty Scale Chinese In-Person Interview Version (CSHA-CFS) in a 2012 annual elderly health examination were enrolled. Both the control and experimental groups received the routine annual health examination with the latter further provided with functional evaluations, exercise instruction, and nutrition education. 112 (84.8%) persons in the experiment group and 267 (98.2%) in the control group completed the study. CSHA-CFS performance of the experimental group was more likely to improve (odds ratio=9.50, 95% confidence interval (CI)=4.62-19.56) and less likely to deteriorate (OR=0.04, 95% CI=0.01-0.31) one year after intervention. Within the experimental group, Fried Frailty Index improvement percentage surpassed the deterioration percentage (29.5% vs. 0.9%, p

Background: The effect of warfarin on the risk of cardiovascular (CV) disease is unknown among chronic hemodialysis patients with atrial fibrillation (HD-AF). Methods: Population-based propensity score and prescription time-distribution matched cohort study including 6719 HD-AF patients with CHA2DS2-VASc score ≥ 2 were divided into warfarin users and nonusers and followed-up for CV events and death. Results: Warfarin treatment in HD-AF patients with AF preceding HD was associated with higher risks of developing congestive heart failure [hazard ratio (HR) = 1.82, 95% confidence interval (CI) = 1.29–2.58, p

// Hsian-Yu Wang 1, 2 , Yu-Ling Chang 3 , Chun-Chun Cheng 4 , Min-Wu Chao 4 , Su-I Lin 5, 6 , Shiow-Lin Pan 4 , Chih-Cheng Hsu 3 , Tsang-Wu Liu 7 , Han-Chin Cheng 8, 9 , Ching-Ping Tseng 2 , Shih-Jen Liu 6, 10 , Hui-Ju Tsai 11, 12, 13 , Hsing-Yi Chang 3, 14 , John T.-A. Hsu 1, 2 1 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County, Taiwan 2 Institute of Molecular Medicine and Bioengineering, National Chiao Tung University, Hsinchu City, Taiwan 3 Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan 4 The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei City, Taiwan 5 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei City, Taiwan 6 National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan 7 Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan 8 Institute of Bioinformatics and Systems Biology, National Chiao Tung University, Hsinchu City, Taiwan 9 Miaoli General Hospital, Ministry of Health and Welfare, Miaoli County, Taiwan 10 Graduate Institute of Immunology, China Medical University, Taichung City, Taiwan 11 Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan 12 Department of Public Health, China Medical University, Taichung, Taiwan, Taichung City, Taiwan 13 Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA 14 Institute of Public Health, National Yang-Ming University, Taipei City, Taiwan Correspondence to: Hsing-Yi Chang, email: hsingyi@nhri.org.tw John T.-A. Hsu, email: tsuanhsu@nhri.org.tw Keywords: NSCLC, EGFR, TKI, glucocorticoids, national health insurance research database taiwan Received: July 28, 2016 Accepted: October 29, 2016 Published: November 07, 2016 ABSTRACT The epidermal growth factor receptor (EGFR)-targeting tyrosine kinase inhibitors (TKIs) have shown remarkable benefits in non-small cell lung cancer (NSCLC) patients with drug-sensitive mutations in the EGFR gene. Responsive patients are usually continuously prescribed with TKIs until disease progression. Glucocorticoids (GCs) are potent homeostasis maintaining drugs and are frequently used in cancer patients to alleviate discomforts caused by anti-cancer therapies. Several previous studies reported that concomitant use of GCs may compromise the efficacy of chemo-therapeutics in patients with solid tumors. Little is known in the concomitant use of target therapy with GCs in treating NSCLC. In this study, we hypothesized that concomitant use of GCs in EGFR-TKI therapy may be detrimental and addressed this issue using cell cultures and xenograft studies followed by a retrospective population study based on data from the Taiwan national health insurance system. In cell cultures and xenograft studies, GCs were shown to unequally compromise the anti-cancer efficacy of TKIs in both PC9 and NCI-H1975 NSCLC cells models. In the retrospective population study, patients with similar disease status that were co-medicated with GCs had a significantly higher risk of disease progression.

BACKGROUND A previous study indicated that 31% of the elderly in Taiwan have a vitamin D deficiency. Vitamin D adequacy has been associated with physical performance in the elderly. OBJECTIVES The first aim of the current study was to identify the determinants for vitamin D deficiency. The second aim was to evaluate the association between vitamin D status and physical performance. DESIGN A total of 5664 community-dwelling participants aged ≥55 y were recruited since 2008. Plasma total 25-hydroxyvitamin D concentrations were originally determined by ELISA and calibrated to a chemiluminescence measurement. Physical performance was assessed by handgrip strength, the Short Physical Performance Battery, timed up and go, a 6-min walk test, and single-leg stands. Multiple linear regression and logistic regression were used to estimate the cross-sectional associations. RESULTS Vitamin D inadequacy (

Context The long-term safety and benefit of pioglitazone use in combination with insulin are still uncertain. Objective This study compared the risks of all-cause mortality and major cardiovascular (CV) events between pioglitazone users and nonusers receiving insulin therapy. Design, Setting and Patients We conducted a 13-year retrospective cohort study by using data from the population-based National Health Insurance Research Database in Taiwan. A total of 20 376 patients with type 2 diabetes mellitus (T2DM) receiving insulin therapy were enrolled during 2000 to 2012. Overall, the incidence rates of all-cause mortality and CV events were compared between 2579 pioglitazone users and 2579 matched nonusers. Results After adjustment for age, sex, comorbidities, Diabetes Complications Severity Index scores, and drugs used, mortality rates were 30.26 and 15.02 per 1000 person-years for pioglitazone nonusers and users, respectively. The adjusted hazard ratio (aHR) of mortality was 0.47 (95% confidence interval [CI]: 0.38–0.58, P < 0.001) for pioglitazone users compared with nonusers. The aHRs of CV and non-CV deaths were 0.78 (95% CI: 0.51–1.19) and 0.50 (95% CI: 0.38–0.66), respectively. The aHRs of hospitalized coronary artery disease, hospitalized stroke, and incident heart failure were not significantly different between pioglitazone users and nonusers. Conclusions This nationwide cohort study demonstrated that pioglitazone use reduced the risks of all-cause mortality and non-CV death for patients with T2DM undergoing insulin therapy.

Studies have suggested that phthalates may be a risk factor for microalbuminuria, whereas little is known regarding their nephrotoxic effects on adults. We enrolled 311 participants (≥18 y, N = 241;18 y, N = 70) who provided questionnaire information as well as blood and urine samples from a nationally cross-sectional study. Urinary phthalate metabolites were analyzed through liquid chromatography-tandem mass spectrometry. From the renal function index, we measured the serum level of blood urea nitrogen (BUN), and the urinary levels of microalbumin, albumin, protein and creatinine. We used multiple logistic regressions and a cumulative risk assessment of renal effect to evaluate the relationship between phthalate exposure and renal function in our participants. We aimed to assess the relationship between phthalate exposure and renal function including serum level of BUN, and urinary levels of microalbumin, albumin, protein, and creatinine in 311 participants (≥18 y, N = 241;18 y, N = 70) from a population-based study. The multiple logistic regression showed that the adjusted odds ratio of the highest tertile of estimated di-2-ethylhexyl phthalate (DEHP) daily intake in participants ≥18 y for early renal impairment (microalbumin1.9 mg/dL) was 9.40 times higher (95% confidence interval = 1.67-52.84) than the lowest tertile. The cumulative hazard index of phthalate-induced nephrotoxicity (HI

Background/Purpose: Patients with diabetes have a higher risk of developing chronic complications and cause a huge burden to the public health care system as well as on patients and their families. We studied these diabetic complications about kidney, eye and peripheral vascular diseases to understand their prevalence and distributions in a national survey. Methods: We analyzed diabetic complications using National-Health-Insurance claims filed from 2005 to 2014. We used this database to evaluate their developments of kidney, eye, and peripheral vascular diseases according to the International-Classification-of-Diseases, Ninth Revision using clinical modification diagnosis codes. Results: The prevalence of diabetic kidney disease (DKD) significantly increased from 10.49% to 17.92% from 2005 to 2014. The prevalence rate of diabetic foot significantly decreased from 1.34% to 1.05% from 2005 to 2014, and the rate of severe infection also significantly decreased from 50.69% to 45.85%. The amputation rate significantly decreased from 24.91% to 17.47% among all patients with diabetic foot. Conclusion: In this study, the trends in DKD and dialysis prevalence were similar to those of the 2012 report. The rate of increase in dialysis prevalence is lower in this study than in the 2012 report. The prevalence of diabetic foot, severe infection, and amputation in this report exhibited significantly decreasing trends. This improvement may be attributable to care from multidisciplinary teams. We should dedicate more resources to our prevention program of DKD and retinopathy to further improve outcomes in the future. Keywords: Diabetic foot, Diabetic kidney disease, Diabetic nephropathy, Diabetic retinopathy, End-stage kidney disease

Background/Purpose: Comprehensive and continuous care is crucial for patients with diabetes. The diabetes pay-for-performance (P4P) program launched by the National Health Insurance (NHI) administration in Taiwan provides a financial incentive to facilitate this goal. In this study, we explored the characteristics of patients in the P4P program between 2005 and 2014. Methods: Data of patients with diabetes enrolled in the NHI program between 2005 and 2014 were extracted from the NHI research database. Patients were classed as having diabetes if they had three or more outpatient visits within 365 calendar days with an International Classification of Diseases, 9th Revision, Clinical Modification diagnostic code of 250 or hospitalization one or more times with such a diagnosis. The trends of participating in the P4P program were analyzed. Results: Participation rate of the P4P program increased from 12.1% to 19% between 2005 and 2014. Participants were younger and more likely to be female than those not participating in the program. Lower risks of cancer-related mortality, annual mortality and heart failure were seen in patients participating in the P4P program than in those not participating. Conclusion: Older, male patients with a high disease severity may be less likely to enroll in the P4P program. Although participation rate is increasing, a broad enrollment is expected. Keywords: Diabetes, National health insurance, Pay-for-performance

Background The mammalian target of rapamycin (mTOR) inhibitor is an immunosuppressive drug used in kidney transplantation. Whether the mTOR inhibitor is associated with reduced risk of cancer development and mortality after kidney transplantation is controversial. Methods We conducted a nationwide population-based study. Patients who did not have malignancy history and received kidney transplantation between 2010 and 2013 were enrolled. Recipients who had mTOR inhibitors (n = 430) for more than 30 days comprised the study group; 1720 recipients who did not have mTOR inhibitors comprised the control group. The primary outcome is the development of cancer after kidney transplantation. These patients were followed until the first-time admission with diagnosis of cancer, death, or the end of 2014. A Cox proportional-hazard model was used to determine the risk of cancer development and all-cause mortality. Results During the 35-month median duration of observation, there were 16 and 61 patients with cancer development in the study group and the control group, respectively. The cancer incidence was 12.8 and 12.4 per 1000 person-years. There were 10 and 135 mortality cases, with the incidence rate of 7.8 and 26.9 per 1000 person-years. After multivariable adjustment, the mTOR inhibitors users were not associated with reduced risk of new cancer development as compared with control (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.46–1.60; P = .63), nor risk of all-cause mortality (HR, 0.70; 95% CI, 0.33–1.46; P = .34). Conclusions The use of mTOR inhibitors was not associated with a reduction in the risk of cancer development and all-cause mortality in kidney transplantation recipients.

The elderly population is increasing rapidly worldwide, and frailty is a common geriatric syndrome. Comprehensive dietary management strategies may have beneficial effects on frailty prevention and reversal. This 3-month single-blind, paralleled, randomized controlled trial compared the effects of micronutrients and/or protein supplements, and a personalised diet on frailty status in elderly individuals.Between 2014 and 2015, 40 prefrail or frail subjects aged=65 years were recruited at Miaoli General Hospital, Taiwan. Of these, 37 completed the study, and 36 were included in the analysis. Participants were randomly assigned to one of four treatment groups: (1) the control (2) multiple micronutrient supplements, (3) multiple micronutrients plus isolated soy protein supplement, and (4) individualised nutrition education with customised dishware and food supplements (mixed nuts and skimmed milk powder). Dietary intake, protein biomarkers, frailty score, and geriatric depression score were assessed.Individualised nutrition education with customised dishware and food supplements significantly increased the participants' intake of vegetables, dairy, and nuts, in addition to increasing the concentration of urinary urea nitrogen. It yielded a significant reduction in frailty score (p0.05) and a borderline reduction (p=0.063) in geriatric depression score. No significant beneficial changes were observed for the other two intervention groups.Our study indicated that a dietary approach with easy-to-comprehend dishware and food supplements to optimize the distribution of the consumption of six food groups improved frailty status and, potentially, psychological well-being in elderly people.

Supplemental Digital Content is available in the text, The long-term survival and life quality of hemodialysis (HD) patients depend on adequacy of dialysis via a well-functioning vascular access. Loss of primary functional patency (PFP) of an arteriovenous access (AVA) eventually happens in HD patients. The association between time to loss of PFP of AVAs and mortality in HD patients remains unclear. The retrospective nationwide population-based cohort study compared the hazards of mortality with time to loss of PFP. We enrolled 1618 adult incident HD patients who received HD via AVAs for at least 90 days between January 1, 2001 and December 31, 2013. They were divided into early (≤1 year) and late (>1 year) loss of PFP according to intervention-free intervals (time from first successful cannulation to percutaneous transluminal angioplasty [PTA]). Patients with early loss of PFP were older; had more clinic visits annually and higher Charlson comorbidity index scores; were associated with higher proportions of diabetes mellitus, coronary artery disease, heart failure, stroke, chronic obstructive pulmonary disease, cancer, and use of arteriovenous graft, diuretic, antidiabetic drugs, and aspirin (all P

Background Dipeptidyl peptidase-4 (DPP-4) inhibitors could effectively reduce HbA1C and postprandial hyperglycemia and could incur only minimal danger of hypoglycemia. Patients with uncontrolled diabetes might be treated by the complementary action of insulin plus DPP-4 inhibitors. Here, we compared the all-cause mortality risk between DPP-4 inhibitor users and nonusers with underlying insulin therapy. Methods Using the population-based National Health Insurance Research Database of Taiwan, we conducted an 11-year retrospective cohort study. A total of 3120 patients undergoing insulin therapy for type 2 diabetes mellitus (T2DM) during 2000–2010 were enrolled. The overall incidence rates for all-cause mortality of 1560 DPP-4 inhibitor users and 1560 matched DPP-4 inhibitor nonusers were compared. Results No significant difference was found in the baseline demographic and clinical variables of the two groups of patients. Median follow-up period for the matched cohort was 1.67 years. All-cause mortality was observed in 93 (6.0%) of 1560 DPP-4 inhibitor nonusers and 36 (2.3%) of 1560 DPP-4 users. The incidence rate of mortality was 11.72 for DPP-4 inhibitor users and 38.16 per 1000 person-years for DPP-4 inhibitor nonusers. After multivariate adjustment, DPP-4 inhibitor users ran a reduced mortality risk (adjusted hazard ratio 0.32, 95% CI 0.22–0.47; p