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Abstract Carotid intima-media thickness (cIMT), a marker of subclinical atherosclerosis, has been found to be associated with incident stroke. High-sensitivity C-reactive protein (CRP) and fibrinogen have been demonstrated to be associated with atherosclerosis. Previous studies on heritability estimates of IMT, CRP, and fibrinogen among Chinese populations are limited. This study aims to estimate the heritability of these risk factors in residents who participated in the Taichung Community Health Study (TCHS) and their family members. A total of 2671 study subjects from 805 families were enrolled in the study, selected from a random sample of TCHS participants and their family members. CRP, and fibrinogen were obtained from each participant, and a questionnaire interview was conducted. cIMT was measured by high-resolution B-mode ultrasound and expressed as the mean of the maximum. Heritability estimates and the familial correlation of cIMT, CRP, and fibrinogen among family pairs were determined with SAGE software. With multivariate adjustments, significant heritability was found for cIMT (h2 = 0.26, P

Abstract Background Sleeping problems and cognitive impairment are common in elders. Baseline sleep duration and cognitive status are predictors of mortality. But few studies have explored whether longitudinal changes in sleep duration and cognitive function are related to mortality in older adults. The present study investigated the time-varying relationships of sleep duration and cognitive function with subsequent mortality among community-dwelling elders by using 12 years of repeated-measure data. Methods Taichung Community Health Study for Elders (TCHS-E) is a retrospective, population-based cohort that started in 2009 (wave 1) with a total of 912 elders aged 65 years or above. Follow up was conducted in 2010 (wave 2), 2018 (wave 3), and 2020 (wave 4). Sleep duration and Mini-Mental State Examination (MMSE) forms were executed at baseline and three visits during follow-up. Time-varying Cox proportional hazards regression estimated adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (CIs). Results During about 12 years (9,396 person-years) follow-up, 329 deaths from all causes were documented, including 102 deaths due to expanded cardiovascular disease (CVD). In the multivariable-adjusted, time-varying Cox proportional hazard model, the adjusted HR values of all-cause mortality were 1.47 (1.02–2.12) for sleep duration > 9 h/day (vs. 7 h/day) and 1.81 (1.26–2.59) for MMSE

Abstract Background This study aimed to explore trends, in 3 periods, in the intake of energy and macronutrients among Taiwanese older adults. Methods Study subjects were those aged ≥65 years in the Nutrition and Health Survey in Taiwan 1999–2000 as well as the surveys in 2005–2008 and 2013–2016. Twenty-four-hour dietary recall data were obtained. This study used the 3 nutrition survey datasets for 1999–2000, 2005–2008, and 2013–2016, including data on the questionnaire, physical examination, and dietary intakes. Each nutrition survey involved the face-to-face household interview, and individual’s dietary intake of carbohydrate, fat, and protein (% of energy) was estimated. Subsequently, intake statuses of the three macronutrients were classified into below, meeting, and above intake categories. Results In the 2013–2016 survey, approximately 40% of the older adults had a low intake of energy. The prevalence of older adults with a meeting intake of carbohydrate, fat, and protein have increased from the 1999–2000 to 2013–2016 periods. The prevalence of people having a low intake of carbohydrate declined from the 1999–2000 period to the 2013–2016 period. The prevalence of high fat intake in 2013–2016 was approximately 5% higher than that in 1999–2000. In the 2013–2016 period, the prevalence of low intake of carbohydrate, fat, and protein were 25.9, 24.5, and 4.9%, respectively; moreover, the prevalence of high intake of the aforementioned macronutrients were 38.7, 36.2, and 17.6%, respectively. Conclusions Our study provides important evidence on the dietary patterns, as well as their changes over time among Taiwanese older adults. Such information would be useful for health policy makers about the burden of unbalanced diet and for nutrition educators on planning nutrition promotion interventions about well-balanced dietary for the older persons.

Introduction A body shape index (ABSI) is independently associated with mortality in general population, but studies on the predictability of ABSI in the risk of mortality in patients with type 2 diabetes (T2D) are limited. We aimed to examine the independent and joint association of ABSI, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and body roundness index (BRI) with mortality in patients with T2D.Research design and methods The study included 11 872 patients (46.5% women) aged 30 years and older and who took part in diabetes care management program of a medical center in Taiwan. Body indices were evaluated by anthropometric measurements at baseline between 2001 and 2016, and their death status was followed up through 2021. Multivariate Cox regression models were used to assess the effect of body indices on mortality.Results During a mean follow-up of 10.2 years, 560 cardiovascular disease (CVD) deaths and 3043 deaths were recorded. For ABSI, WC, WHR, WHtR and BRI, all-cause mortality rates were statistically significantly greater in Q4 versus Q2. For BMI and WHtR, all-cause mortality rates were also statistically significantly greater in Q1 versus Q2. The combination of BMI and ABSI exhibited a superiority in identifying risks of all-cause mortality and CVD mortality (HRs: 1.45 and 1.37, both p

Abstract Background Obesity and cognitive impairment prevalence increases as age increases. Recent growing evidence finds links between obesity and cognitive impairment in older adults. However, the association between the two is controversial. This study aims to identify obesity marker trajectory patterns, and to assess whether these patterns are associated with cognitive impairment and cognitive decline during a 10-year follow-up period among community-dwelling older adults. Methods A total of 626 older adults aged 65 and older were involved in the study, with at least two repeated measurements at baseline, one-year or 10-year follow-up. Cognitive function was measured through the Mini Mental State Examination. Obesity markers included body mass index, waist circumference, waist-to-hip (WHR), fat mass (FM), and abdominal fat (AF) measured by dual-energy X-ray absorptiometry. Multivariate logistic regression analyses were performed to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of cognitive impairment and cognitive decline for obesity marker trajectory patterns. Results After a 10-year follow-up, 168 older adults with incident cognitive impairment and 156 with rapid cognitive decline were defined as the top 25th percentile of cognitive decline. Four distinct trajectory groups of obesity markers were identified. In multivariate logistic regression analyses, a low likelihood of cognitive impairment was observed in the consistently high-level group from FM trajectory (ORs = 0.41, 95% CI = 0.20–0.85); the high-level U-shaped group from WHR trajectory (0.43, 0.22–0.84); and the median-level flat inverse U-shaped, consistently high-level, and low-level flat U-shaped groups from AF trajectory (0.44, 0.26–0.77; 0.33, 0.18–0.61; 0.39, 0.18–0.82). In addition, a low likelihood of rapid decline was found in the low-level, slightly increasing trend group from WHR trajectory (0.43, 0.22–0.85). Conclusion FM and AF trajectories with consistent high levels and WHR trajectory with high level with U-shaped group are associated with low risks of incident cognitive impairment in older adults. Similarly, WHR trajectory with a low but slowly increasing trend is associated with a decreased risk of cognitive decline.

Abstract Background Decreased skeletal muscle mass and low physical performance are independently associated with increased mortality in elderly individuals. However, little is known about the effects of skeletal muscle mass combined with physical performance on the prediction of mortality risk among community-dwelling older adults. This study aimed to determine the combined effects of skeletal muscle mass and physical performance on total mortality. Methods A community-based prospective cohort study was conducted among 641 participants aged 65 and older in 2009. The height-adjusted skeletal muscle index (hSMI) and the weight-adjusted SMI (wSMI) were determined by dual-energy X-ray absorptiometry examination. Physical performance tests measured at baseline included gait speed (GS), timed up-and-go (TUG) test, timed chair stand (TCS), weight-adjusted leg press (WaLP), and handgrip strength (HS). Cox proportional hazards regression models were applied to determine the adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (95% CIs) for baseline skeletal muscle mass, physical performance, and traditional risk factors. Results During the follow-up of 12 years, 198 (30.89%) participants died. Low hSMI, low GS, high TUG, high TCS, low WaLP, and low HS were associated with high risks of mortality after the adjustment for confounders. The results of receiver operating characteristic (ROC) curve analyses revealed the values of ROC for models with additional consideration for TUG or all indicators significantly improved the discriminatory ability of mortality compared with the model with traditional factors (all P

Abstract Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are used as non-invasive indicators for detecting atherosclerosis and arterial stiffness, two well-known predictors of mortality in patients with type 2 diabetes mellitus (T2DM). ABI and baPWV have independent associations with mortality; however, their joint and interactive effects on mortality have not been assessed in patients with T2DM. This work aims to evaluate the independent, joint, and interactive associations of ABI and baPWV with all-cause and expanded cardiovascular disease (CVD) mortality in patients with T2DM. This observational study included 2160 patients with T2DM enlisted in the Diabetes Care Management Program database of China Medical University Hospital from 2001 to 2016 and then followed their death status until August 2021. Cox proportional hazard models were used to evaluate the independent, joint, and interactive effects of ABI and baPWV on the risk of all-cause and expanded CVD mortality. A total of 474 patient deaths occurred after a mean follow-up of 8.4 years, and 268 of which were attributed to cardiovascular events. Abnormal ABI (≤ 0.9) and highest baPWV quartile were independently associated with increased risks of all-cause [ABI: hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.30–2.11; baPWV: 1.63, 1.16–2.27] and expanded CVD mortality (ABI: 2.21, 1.62–3.02; baPWV: 1.75, 1.09–2.83). The combination of abnormal ABI (≤ 0.9) and highest baPWV quartile was associated with a significantly higher risk of all-cause (4.51, 2.50–8.11) and expanded CVD mortality (9.74, 4.21–22.51) compared with that of the combination of normal ABI and lowest baPWV quartile. Significant interactions were observed between ABI and baPWV in relation to all-cause and expand CVD mortality (both p for interaction

Introduction Observational studies support the relationship between C-reactive protein (CRP) level and diabetic nephropathy (DN) in patients with diabetes. The research question regarding whether the relationship between serum high-sensitivity C-reactive protein (hsCRP) level and DN is causal lacks experimental evidence. Therefore, this study aimed to evaluate the causality between hsCRP and DN based on Mendelian randomization (MR) analysis.Research design and methods A total of 2332 participants with type 2 diabetes from the Taiwan Biobank database was analyzed. Genetic risk scores (GRSs), which comprise four validated CRP loci as two instrumental variables, were calculated as unweighted and weighted scores to evaluate the causal relationship of hsCRP with DN risk. The two-stage regression model was used to estimate OR and 95% CI.Results The analyses of the observational study showed that the hsCRP level was significantly associated with DN after multivariate adjustment (adjusted OR 1.15; 95% CI 1.01 to 1.32). Unweighted/weighted GRSs for log-transformed hsCRP satisfied MR assumptions 1 and 3, respectively; that is, a significant association with hsCRP was observed but that with DN was absent (adjusted OR 1.00, 95% CI 0.92 to 1.09; 1.00, 0.72 to 1.39, respectively). The MR analyses demonstrated that a 1-unit increase in the log-transformed genetically predicted hsCRP by unweighted and weighted GRSs was associated with DN, demonstrating ORs of 1.80 (95% CI 1.51 to 2.14) and 1.67 (95% CI 1.40 to 1.98), respectively.Conclusions The current study provided experimental evidence that hsCRP level was causally related to DN. These findings suggest that the elevated hsCRP may be a causal risk factor for DN in patients with type 2 diabetes.

Abstract Background Sleep duration is associated with mortality. However, prior studies exploring whether sleep duration predicts subsequent long-term mortality in patients with diabetes are limited. This study aims to examine whether metabolic factors affect the associations between baseline sleep duration and subsequent risks of all-cause, expanded, and non-expanded cardiovascular disease (CVD) mortalities among patients with type 2 diabetes (T2D). Methods A total of 12,526 T2D patients aged 30 years and older, with a follow-up period ≥ 3 years, were identified from the Diabetes Case Management Program of a medical center in Taiwan. Sleep duration was measured using computerized questionnaires by case managers, and the time frame for this question was 1 month prior to the interview date. Sleep duration in relation to subsequent mortality from all causes, expanded CVD, and non-expanded CVD was examined using Cox proportional hazard models. Results Within 10 years of follow-up, 2918 deaths (1328 CVD deaths and 1590 non-CVD deaths) were recorded. A J-shaped association was observed for all-cause, expanded CVD, and non-expanded CVD mortalities, and the lowest risks were observed for patients with 5–7 h of sleep. The significant joint effects included sleep duration of more or less than 7 h with age ≥ 65 years [adjusted HRs: 4.00 (3.49–4.60)], diabetes duration ≥ 5 years [1.60 (1.40–1.84)], age at diabetes diagnosis ≤ 45 years [1.69 (1.38–2.07)], insulin use [1.76 (1.54–2.03)], systolic blood pressure/diastolic blood pressure > 130/85 mmHg [1.24 (1.07–1.43)], triglyceride ≥ 150 mg/dL [1.38 (1.22–1.56)], HbA1c ≥ 7% [1.31 (1.13–1.52)], and body mass index

Abstract Many studies had established the chronic kidney disease (CKD) prediction models, but most of them were conducted on the general population and not on patients with type 2 diabetes, especially in Asian populations. This study aimed to develop a risk prediction model for CKD in patients with type 2 diabetes from the Diabetes Care Management Program (DCMP) in Taiwan. This research was a retrospective cohort study. We used the DCMP database to set up a cohort of 4,601 patients with type 2 diabetes without CKD aged 40–92 years enrolled in the DCMP program of a Taichung medical center in 2002–2016. All patients were followed up until incidences of CKD, death, and loss to follow-up or 2016. The dataset for participants of national DCMP in 2002–2004 was used as external validation. The incident CKD cases were defined as having one of the following three conditions: ACR data greater than or equal to 300 (mg/g); both eGFR data less than 60 (ml/min/1.73 m2) and ACR data greater than or equal to 30 (mg/g); and eGFR data less than 45 (ml/min/1.73 m2). The study subjects were randomly allocated to derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression model was used to identify the risk factors of CKD in the derivation set. Time-varying area under receiver operating characteristics curve (AUC) was used to evaluate the performance of the risk model. After an average of 3.8 years of follow-up period, 3,067 study subjects were included in the derivation set, and 786 (25.63%) were newly diagnosed CKD cases. A total of 1,534 participants were designated to the validation set, and 378 (24.64%) were newly diagnosed CKD cases. The final CKD risk factors consisted of age, duration of diabetes, insulin use, estimated glomerular filtration rate, albumin-to-creatinine ratio, high-density lipoprotein cholesterol, triglyceride, diabetes retinopathy, variation in HbA1c, variation in FPG, and hypertension drug use. The AUC values of 1-, 3-, and 5-year CKD risks were 0.74, 0.76, and 0.77 in the validation set, respectively, and were 0.76, 0.77, and 0.76 in the sample for external validation, respectively. The value of Harrell’s c-statistics was 0.76 (0.74, 0.78). The proposed model is the first CKD risk prediction model for type 2 diabetes patients in Taiwan. The 1-, 3-, and 5-year CKD risk prediction models showed good prediction accuracy. The model can be used as a guide for clinicians to develop medical plans for future CKD preventive intervention in Chinese patients with type 2 diabetes.

The reorientational dynamics of A-site cations in two-dimensional organic-inorganic hybrid perovskites play an important role in determining their physical properties. Here the authors use solid state NMR and isotope labelling to reveal multiple modes of reorientational motions of methylammonium cations and the role of structural rigidity of the organic spacers on their dynamics.

Abstract Background Dyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes. Methods We identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality. Results Over a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22–1.37), 1.05 (1.01–1.09), and 1.10 (1.03–1.16), respectively; those of cardiovascular mortality were 1.27 (1.16–1.39), 1.08 (1.02–1.15), and 1.16 (1.07–1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline. Conclusions Blood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.

Abstract Hypertension (HTN), which frequently co‐exists with diabetes mellitus, is the leading major cause of cardiovascular disease and death globally. This study aimed to develop and validate a risk scoring system considering the effects of glycemic and blood pressure (BP) variabilities to predict HTN incidence in patients with type 2 diabetes. This research is a retrospective cohort study that included 3416 patients with type 2 diabetes without HTN and who were enrolled in a managed care program in 2001–2015. The patients were followed up until April 2016, new‐onset HTN event, or death. HTN was defined as diastolic BP (DBP) ≥ 90 mm Hg, systolic BP (SBP) ≥ 140 mm Hg, or the initiation of antihypertensive medication. Cox proportional hazard regression model was used to develop the risk scoring system for HTN. Of the patients, 1738 experienced new‐onset HTN during an average follow‐up period of 3.40 years. Age, sex, physical activity, body mass index, type of DM treatment, family history of HTN, baseline SBP and DBP, variabilities of fasting plasma glucose, SBP, and DBP and macroalbuminuria were significant variables for the prediction of new‐onset HTN. Using these predictors, the prediction models for 1‐, 3‐, and 5‐year periods demonstrated good discrimination, with AUC values of 0.70–0.76. Our HTN scoring system for patients with type 2 DM, which involves innovative predictors of glycemic and BP variabilities, has good classification accuracy and identifies risk factors available in clinical settings for prevention of the progression to new‐onset HTN.

Abstract This study aimed to explore the associations between renal-related and arterial stiffness biomarkers with all-cause and expanded cardiovascular disease (CVD) mortality in a general Taiwanese population. This prospective community-based cohort study included 4883 subjects aged ≥ 20 years who were followed up until December 31, 2016. Renal-related biomarkers consisted of blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (UACR). Arterial stiffness biomarker consisted of brachial-ankle pulse wave velocity (baPWV). The death status of the subjects was ascertained by matching information from death records with the identification number and date of birth of the subjects. Cox proportional hazard models with restricted cubic splines estimated the hazard ratios and 95% confidence intervals for all-cause mortality and expanded CVD mortality. During a mean 8.3 years of follow up, 456 deaths were recorded, 146 of which were due to expanded CVD mortality. The multivariable-adjusted hazard ratios of all-cause mortality was 1.53 (95% CI 1.21–1.94) for BUN (≥ 20 mg/dL vs.

Abstract Background This study determined (1) whether a change in frailty status after a 1 year follow up is associated with healthcare utilization and evaluated (2) whether a change in frailty status after a 1 year follow up and health care utilization are associated with all-cause mortality in a sample of Taiwan population. Methods This work is a population-based prospective cohort study involving residents aged ≥65 years in 2009. A total of 548 elderly patients who received follow-ups in the subsequent year were included in the current data analysis. Fried frailty phenotype was measured at baseline and 1 year. Information on the outpatient visits of each specialty doctor, emergency care utilization, and hospital admission during the 2 month period before the second interview was collected through standardized questionnaires administered by an interviewer. Deaths were verified by indexing to the national database of deaths. Results At the subsequent 1 year follow-up, 73 (13.3%), 356 (64.9%), and 119 (21.7%) elderly participants exhibited deterioration, no change in status, and improvement in frailty states, respectively. Multivariate logistic analysis showed the high risk of any type of outpatient use (odds ratios [OR] 1.94, 95% confidence interval [CI] 1.02–3.71) among older adults with worse frailty status compared with those who were robust at baseline and had unchanged frailty status after 1 year. After multivariate adjustment, participants with high outpatient clinic utilization had significantly higher mortality than those with low outpatient clinic visits among unchanged pre-frail or frail (hazard ratios [HR] 2.79, 95% CI: 1.46–5.33) and frail to pre-frail/robust group (HR 9.32, 95% CI: 3.82–22.73) if the unchanged robustness and low outpatient clinic visits group was used as the reference group. Conclusions The conditions associated with frailty status, either after 1 year or at baseline, significantly affected the outpatient visits and may have increased medical expenditures. Combined change in frailty status and number of outpatient visits is related to increased mortality.

Background: Whether diabetes mellitus (DM) patients with chronic kidney disease (CKD) can glean individual renal benefit from dihydropyridine calcium channel blockers (DCCBs) remains to be determined. We conducted a nationwide, population-based, propensity score matching cohort study to examine the effect of DCCBs on CKD progression in DM patients with CKD.Methods: One million individuals were randomly sampled from Taiwan’s National Health Insurance Research Database. The study cohort consisted of DM patients with CKD who used DCCBs. The comparison cohort was propensity-matched for demographic characteristics and comorbidities. The endpoint was advanced CKD or end-stage renal disease (ESRD). The Cox proportional hazards model was used to calculate the risks.Results: In total, 9,761 DCCB users were compared with DCCB nonusers at a ratio of 1:1. DCCB users had lower risk of advanced CKD and ESRD than nonusers—with adjusted hazard ratio [aHR; 95% confidence interval (CI)] of 0.64 (0.53–0.78) and 0.59 (95% CI, 0.50–0.71) for advanced CKD and ESRD, respectively. DCCB users aged ≥65 years had the lowest incidence rates of advanced CKD and ESRD—with aHR (95% CI) of 0.47 (0.34–0.65) and 0.48 (0.35–0.65) for advanced CKD and ESRD, respectively. Finally, cumulative DCCB use for >1,100 days was associated with the lowest advanced CKD and ESRD risks [(aHR, 0.29 (95% CI, 0.19–0.44)].Conclusion: DM patients with CKD who used DCCBs had lower risk of progression to advanced CKD and ESRD than nonusers did.

Abstract Background Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults. Methods A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used. Results A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 μm for every one unit of increase in cystatin C level and by 0.07 and 0.14 μm for every one unit of increase in ACR, respectively (all p

Abstract Background Cognitive impairment is accompanied with high rates of comorbid conditions, leading ultimately to death. Few studies examine the relation between cognitive transition and mortality, especially in Asian population. This study evaluated baseline cognition and cognitive transition in relation to all-cause mortality among community-dwelling older adults. Methods We conducted a community-based prospective cohort study among 921 participants of Taichung Community Health Study for Elders in 2009. Cognitive function was evaluated by the Mini-Mental State Examination. Cognitive impairment was considered if the total score is less than 27, 24, and 21 for a participant’s educational level of more than 6 years, equal or less than 6 years, and illiteracy, respectively. One-year transition in cognitive function was obtained among 517 individuals who were assessed in both 2009 and 2010. Mortality was followed up until 2016. Cox proportional hazards models were applied to estimate the adjusted hazard ratios of mortality for baseline cognitive impairment and one-year transition in cognitive status. Results After a follow-up of 6.62 years, 160 deaths were recorded. The multivariate adjusted hazard ratio (95% confidence interval) for baseline cognitive impairment was 2.08 (1.43, 3.01). Significantly increased mortality risk was observed for cognitively impaired–normal and impaired–impaired subgroups over 1 year as compared with those who remained normal [2.87 (1.25, 6.56) and 3.79 (1.64, 8.73), respectively]. The area under the receiver operating characteristic curves demonstrated that baseline cognition and one-year cognitive transition had no differential predictive ability for mortality. Besides, there was an interaction of cognitive impairment and frailty, with an additive mortality risk [5.41 (3.14, 9.35)] for the elders who presented with both. Conclusion Baseline cognitive impairment rather than one-year progression is associated with mortality in a six-year follow-up on older adults.

Abstract Background This study investigated whether visit-to-visit fasting plasma glucose (FPG) variability, as measured by the coefficient of variation (CV), increased peripheral artery disease (PAD) risk. Methods Individuals with type 2 diabetes from the National Diabetes Care Management Program during the period 2002–2004, ≥ 30 years of age, and free of PAD (n = 30,932) were included and monitored until 2011. Cox proportional hazards regression models were implemented to analyze related determinants of PAD. Results A total of 894 incident cases of PAD were identified during an average 8.2 years of follow-up, resulting in a crude incidence rate of 3.53 per 1000 person-years. Both FPG-CV and HbA1c were significantly associated with PAD after multivariate adjustment, with corresponding hazard ratios of 1.24 [95% confidence interval (CI) 1.04–1.47] for FPG-CV in the third tertile and 1.50 (95% CI 1.10–2.04) for HbA1c ≥ 10%. The findings of the sensitivity analysis remained consistent after excluding potential confounders, demonstrating the consistency of the results. Conclusions The associations between HbA1c, variability in FPG-CV, and PAD suggest a linked pathophysiological mechanism, suggesting the crucial role of glycemic variability in clinical management and therapeutic goals in preventing PAD in type 2 diabetes.

BackgroundAlthough carotid sonographic features have been used as predictors of recurrent stroke, few large-scale studies have explored the use of machine learning analysis of carotid sonographic features for the prediction of recurrent stroke.MethodsWe retrospectively collected electronic medical records of enrolled patients from the data warehouse of China Medical University Hospital, a tertiary medical center in central Taiwan, from January 2012 to November 2018. We included patients who underwent a documented carotid ultrasound within 30 days of experiencing an acute first stroke during the study period. We classified these participants into two groups: those with non-recurrent stroke (those who has not been diagnosed with acute stroke again during the study period) and those with recurrent stoke (those who has been diagnosed with acute stroke during the study period). A total of 1,235 carotid sonographic parameters were analyzed. Data on the patients' demographic characteristics and comorbidities were also collected. Python 3.7 was used as the programming language, and the scikit-learn toolkit was used to complete the derivation and verification of the machine learning methods.ResultsIn total, 2,411 patients were enrolled in this study, of whom 1,896 and 515 had non-recurrent and recurrent stroke, respectively. After extraction, 43 features of carotid sonography (36 carotid sonographic parameters and seven transcranial color Doppler sonographic parameter) were analyzed. For predicting recurrent stroke, CatBoost achieved the highest area under the curve (0.844, CIs 95% 0.824–0.868), followed by the Light Gradient Boosting Machine (0.832, CIs 95% 0.813–0.851), random forest (0.819, CIs 95% 0.802–0.846), support-vector machine (0.759, CIs 95% 0.739–0.781), logistic regression (0.781, CIs 95% 0.764–0.800), and decision tree (0.735, CIs 95% 0.717–0.755) models.ConclusionWhen using the CatBoost model, the top three features for predicting recurrent stroke were determined to be the use of anticoagulation medications, the use of NSAID medications, and the resistive index of the left subclavian artery. The CatBoost model demonstrated efficiency and achieved optimal performance in the predictive classification of non-recurrent and recurrent stroke.

Background: Air pollution is speculated to affect the reproductive health of women. However, a longitudinal association between exposure to air pollution and dysmenorrhea has not been identified, which this study aimed to examine this point.Methods: Two nationwide databases, namely the Taiwan Air Quality Monitoring database and the Taiwan National Health Research Institutes database were linked. Women with a history of dysmenorrhea (International Classification of Disease, Ninth Revision, Clinical Modification code 625.3) before 2000 were excluded. All participants were followed from January 1, 2000 until the diagnosis of dysmenorrhea, withdrawal from National Health Insurance, or December 31, 2013. Furthermore, air pollutants were categorized into quartiles with three cut-off points (25th, 50th, and 75th percentiles). The Cox regression model was used to calculate the hazard ratios of dysmenorrhea.Results: This study enrolled 296,078 women. The mean concentrations of yearly air pollutants were 28.2 (±12.6) ppb for nitric oxides (NOx), 8.91 (±7.93) ppb for nitric oxide (NO), 19.3 (±5.49) ppb for nitrogen dioxide (NO2), 0.54 (±0.18) ppm for carbon monoxide (CO), and 31.8 (±6.80) μg/m3 for PM2.5. In total, 12,514 individuals developed dysmenorrhea during the 12-year follow-up. Relative to women exposed to Q1 concentrations of NOx, women exposed to Q4 concentrations exhibited a significantly higher dysmenorrhea risk [adjusted hazard ratio (aHR)= 27.9, 95% confidence interval (CI) = 21.6–31.3]; similarly higher risk was found for exposure to NO (aHR = 16.7, 95% CI = 15.4–18.4) and NO2 (aHR = 33.1, 95% CI = 30.9–37.4). For CO, the relative dysmenorrhea risk in women with Q4 level exposure was 28.7 (95% CI = 25.4–33.6). For PM2.5, women at the Q4 exposure level were 27.6 times (95% CI = 23.1–29.1) more likely to develop dysmenorrhea than those at the Q1 exposure level.Conclusion: Our results showed that women would have higher dysmenorrhea incidences while exposure to high concentrations of NO, NO2, NOx, CO, and PM2.5.

Abstract Background Previous studies have reported the associations of frailty phenotype or its components with mortality. However, studies that explored the effects of transition in frailty status on mortality were far less in Asian or Chinese. The aim of this study was to evaluate baseline frailty status and one-year change of frailty status in relation to all-cause mortality in Taiwanese community-dwelling older adults who participated in the Taichung Community Health Study for Elders. Methods We conducted a community-based prospective cohort study. A total of 921 community-dwelling elderly men and women aged 65–99 years in Taichung City were enrolled in 2009–2010 and were followed up through 2016. We adopted the definition of frailty proposed by Fried et al., including five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity. Cox proportional hazards models were used to determine adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (CIs) for frailty at baseline and one-year change in frailty status. Results There were 160 deaths during the follow-up period. The mortality rates in groups of robust and frail were 20.26 and 84.66 per 1000 person-years respectively. After multivariate adjustment, the HR (CIs) for baseline frailty was 2.67 (1.73–4.12). Poor endurance and energy [1.88 (1.03–3.42)], slowness [2.60 (1.76–3.83)] and weakness [1.65 (1.16–2.33)] were found to be predictors of mortality. Increased risks in mortality for subgroups of robust-to-frail [2.76 (1.22–6.27)], frail-to-robust [3.87 (1.63, 9.19)], and frail-to-frail [4.08 (1.92–8.66)] over one-year period were observed compared with those remaining robust. Conclusion Baseline frailty status and one-year change in frailty status are associated with 6-year all-cause mortality among Taiwanese elderly adults. Frailty may be useful for identifying older adults at high risks for mortality prevention.

Human pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer type with a very high mortality rate. Inflammatory cytokine such as tumor necrosis factor- alpha (TNF-α) plays a pivotal role in the progression of PDAC. Recently, suppression of cell invasion by preventive agents has received considerable attention in the prevention of metastatic tumors. Several clinical studies suggested that natural forms or analogues of fat-soluble vitamins such as vitamin A and vitamin D can work as anti-cancer agents to inhibit the development of cancer. In this study, our results demonstrated that co-treatment of 13-cis retinoic acid (13-cis RA) and 1,25-dihydroxyvitamin D3 (1,25-VD3) significantly inhibited TNF-α mediated cell invasion in PDAC in vitro. Cotreatment of 13-cis RA and 1,25-VD3 also inhibited TNF-α mediated expression of matrix metalloproteinase-9 (MMP-9) protein through blocking c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-κB) signaling pathways. Our results demonstrated that treatment of TNF-α lead to a decreased expression of tissue inhibitor of metalloproteinase- 3 (TIMP-3) protein and an induction of MMP-9 protein and cell invasion through an upregulation of microRNA-221 (miR-221) in human PDAC cells. Moreover, treatment of SP600125 (a specific inhibitor of JNK pathway) or cotreatment of 13-cis RA and 1,25-VD3 significantly induced a decreased expression of miR-221 and an increased expression of TIMP-3 protein. These results suggest that 13-cis RA and 1,25-VD3 significantly suppress TNF-α mediated cell invasion and therefore potentially act as preventive agents against PDAC.

Our study used data collected in Chung-Hsing Village in Taiwan in May 1998 to evaluate the distribution of triglycerides and the association between hypertriglyceridemia and its correlates in elderly people. All individuals aged 65 and over were recruited as study subjects. A total of 1093 persons, out of 1774 registered residents, were contacted in face-to-face interviews. The response rate was 61.6%. However, only 586 respondents had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. To study the significant correlates of hypertriglyceridemia, t-tests, ANOVAs, chi-square analysis and multivariate logistic regression were used. Among the study population, 66.0% were men and 34.0% were women. The mean age was 73.1 ± 5.3 years. The mean triglyceride values were 1.65 ± 0.93 mmol/L in men and 2.02 ± 1.44 mmol/L in women (p < 0.01). The proportions of hypertriglyceridemia were 18.7% in men and 27.6% in women (p < 0.05). After controlling the other covariates, analysis by multivariate logistic regression showed that the factors significantly related to hypertriglyceridemia were high systolic pressure, abnormal glutamic pyruvic transaminase, hypercholesterolemia and hyperglycemia. Thus, these results support the hypothesis that it is important to examine the other cardiovascular risk factors if one cardiovascular risk factor is observed. The data also suggest one should determine the triglyceride level when abnormal glutamic pyruvic transaminase is identified in an elderly subject.

BackgroundThere is emerging interest in multimorbidity in type 2 diabetes (T2D), which can be either concordant (T2D related) or discordant (unrelated), as a way of understanding the burden of disease in T2D. Current diabetes guidelines acknowledge the complex nature of multimorbidity, the management of which should be based on the patient's individual clinical needs and comorbidities. However, although associations between multimorbidity, glycated haemoglobin (HbA1c), and mortality in people with T2D have been studied to some extent, significant gaps remain, particularly regarding different patterns of multimorbidity, including concordant and discordant conditions. This study explores associations between multimorbidity (total condition counts/concordant/discordant/different combinations of conditions), baseline HbA1c, and all-cause mortality in T2D.Methods and findingsWe studied two longitudinal cohorts of people with T2D using the UK Biobank (n = 20,569) and the Taiwan National Diabetes Care Management Program (NDCMP) (n = 59,657). The number of conditions in addition to T2D was used to quantify total multimorbidity, concordant, and discordant counts, and the effects of different combinations of conditions were also studied. Outcomes of interest were baseline HbA1c and all-cause mortality. For the UK Biobank and Taiwan NDCMP, mean (SD) ages were 60.2 (6.8) years and 60.8 (11.3) years; 7,579 (36.8%) and 31,339 (52.5%) were female; body mass index (BMI) medians (IQR) were 30.8 (27.7, 34.8) kg/m2 and 25.6 (23.5, 28.7) kg/m2; and 2,197 (10.8%) and 9,423 (15.8) were current smokers, respectively. Increasing total and discordant multimorbidity counts were associated with lower HbA1c and increased mortality in both datasets. In Taiwan NDCMP, for those with four or more additional conditions compared with T2D only, the mean difference (95% CI) in HbA1c was -0.82% (-0.88, -0.76) p < 0.001. In UK Biobank, hazard ratios (HRs) (95% CI) for all-cause mortality in people with T2D and one, two, three, and four or more additional conditions compared with those without comorbidity were 1.20 (0.91-1.56) p < 0.001, 1.75 (1.35-2.27) p < 0.001, 2.17 (1.67-2.81) p < 0.001, and 3.14 (2.43-4.03) p < 0.001, respectively. Both concordant/discordant conditions were significantly associated with mortality; however, HRs were largest for concordant conditions. Those with four or more concordant conditions had >5 times the mortality (5.83 [4.28-7.93] p ConclusionsMultimorbidity patterns associated with the highest mortality differed between UK Biobank (a population predominantly comprising people of European descent) and the Taiwan NDCMP, a predominantly ethnic Chinese population. Future research should explore the mechanisms underpinning the observed relationship between increasing multimorbidity count and reduced HbA1c alongside increased mortality in people with T2D and further examine the implications of different patterns of multimorbidity across different ethnic groups. Better understanding of these issues, especially effects of condition type, will enable more effective personalisation of care.

Evidence suggests the existence of association between a large panel of modifiable biomarkers representing inflammation, coagulation, paraoxonase, and endothelial activation pathways and carotid atherosclerosis. Thus, this study investigated whether CRP, FGA, FGB, FGG, PON1, and EDNRA gene variants affected plasma hs-CRP, fibrinogen levels, and thickness of carotid intima media thickness (IMT). Nineteen single-nucleotide polymorphisms of CRP, FGA, FGB, FGG, PON1, and EDNRA genes were examined in 480 participants from 160 families. Carotid IMT was measured by ultrasound. Generalized linear models with generalized estimating equation were utilized to consider the dependence of subjects within families. In the recessive model, homozygotes for the minor alleles of rs1800789, rs1800790 and rs4220 SNPs in FGB gene indicated a reduced risk of IMT (Exp. β = 0.89, 0.89, 0.88), which remained significant after adjustment for confounding factors. Significant interaction effects between CRP SNP rs1130864 and rs3093059 and gender for IMT were observed with a significant association in men only. Men carrying minor-minor genotype of CRP SNP rs1130864 and rs3093059 had 0.70- and 0.78-fold lower IMT than men carrying minor-major/major-major genotype. We also observed that the interaction of CRP SNP rs1130864 and rs3093059 with obesity on IMT, hs-CRP and fibrinogen levels. These results support the hypothesis that inflammatory genes are involved in atherosclerosis, most likely via complex gene-gender and gene-obesity interactions.

The treatment of human colorectal cancer (CRC) cells through suppressing the abnormal survival signaling pathways has recently become a significant area of focus. In this study, our results demonstrated that decyl caffeic acid (DC), one of the novel caffeic acid derivatives, remarkedly suppressed the growth of CRC cells both in vitro and in vivo. The inhibitory effects of DC on CRC cells were investigated in an in vitro cell model and in vivo using a xenograft mouse model. CRC cells were treated with DC at various dosages (0, 10, 20 and 40 μM), and cell survival, the apoptotic index and the autophagy level were measured using an MTT assay and flow cytometry analysis, respectively. The signaling cascades in CRC were examined by Western blot assay. The anti-cancer effects of DC on tumor growth were examined by using CRC HCT-116 cells implanted in an animal model. Our results indicated that DC differentially suppressed the growth of CRC HT-29 and HCT-116 cells through an enhancement of cell-cycle arrest at the S phase. DC inhibited the expression of cell-cycle regulators, which include cyclin E and cyclin A proteins. The molecular mechanisms of action were correlated to the blockade of the STAT3 and Akt signaling cascades. Strikingly, a high dosage of DC prompted a self-protection action through inducing cell-dependent autophagy in HCT-116 cells. Suppression of autophagy induced cell death in the treatment of DC in HCT-116 cells. DC seemed to inhibit cell proliferation of CRC differentially, and the therapeutic advantage appeared to be autophagy dependent. Moreover, consumption of DC blocked the tumor growth of colorectal adenocarcinoma in an experimental animal model. In conclusion, our results suggested that DC could act as a therapeutic agent through the significant suppression of tumor growth of human CRC cells.

Prediction model mainly focused on specific diseases, such as diabetes, hypertension, cardiovascular disease, or patients with cancer, or populations of Europe and America, thereby limiting its generalization. This study aimed to develop and validate a 10-year mortality risk score by using data from a population-representative sample of adults. Data were collected from 2,221 Taichung Community Health study participants aged ≥40 years. The baseline period of the study was 2004, and all participants were followed up until death or in 2016. Cox's proportional hazards regression analyses were used to develop the prediction model. A total of 262 deaths were ascertained during the 10-year follow-up. The all-cause mortality prediction model calculated the significant risk factors, namely, age, sex, marital status, physical activity, tobacco use, estimated glomerular filtration rate, and albumin-to-creatinine ratio, among the baseline risk factors. The expanded cardiovascular disease (CVD) mortality prediction model consisted of six variables: age, sex, body mass index, heart disease plus heart disease medication use, stroke plus medication use, and ankle-brachial index. The areas under receiver operating curves of the 3-, 5- and 10-year predictive models varied between 0.97, 0.96, and 0.88 for all-cause mortality, and between 0.97, 0.98, and 0.84 for expanded CVD mortality. These mortality prediction models are valid and can be used as tools to identify the increased risk for mortality.

This study assessed the interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and the interactions of gene and physical activity on handgrip strength, arm muscle mass-adjusted handgrip (armGrip), gait speed (GS), timed up and go (TUG), and leg press strength (LPS). Nine single nucleotide polymorphisms (SNPs) containing three IGF-1 SNPs (rs6214, rs5742692, and rs35767), two AKT2 SNPs (rs892119 and rs35817154), two FOXO1 SNPs (rs17446593 and rs10507486), and two FOXO3 SNPs (rs9480865 and rs2153960) were genotyped in 472 unrelated elders with a mean age of 73.8 years. We observed significant interactions of IGF-1 SNP rs6214 and rs35767 with regular physical activity on TUG and GS; and AKT2 SNP rs892119 and FOXO3 SNP rs9480865 with regular physical activity on armGrip. Genotype GG of IGF-1 rs6214 and rs35767 in individuals without regular physical activity had poor performance in TUG and GS, as well as GG of AKT2 rs892119 decreased armGrip in individuals without regular physical activity. After FDR adjustment, no significant gene-gene interactions were found. A sedentary lifestyle may increase the risk of impairing physical performance and regular physical activity is a remedy for sarcopenia, even a little regular physical activity can overcome carrying some risk alleles in this pathway.

Background & aimsWhether living liver donors have a higher risk of biliary tract disease compared with non-donors remains unknown.MethodsData were collected from the Taiwan Longitudinal Health Insurance Database for the 2003-2011 period. The study cohort comprised 1,446 patients aged ≥ 18 years who had served as living liver donors. The primary outcome was the incidence of biliary tract disease. Cox proportional hazards modeling was used to determine the hazard ratios.ResultsThe incidence density rate of biliary tract disease was 13.9-fold higher in the liver donor (LD) cohort than in the non-LD cohort (10.2 vs. 0.71 per 1,000 person-years), with an adjusted hazard ratio (HR) of 14.2 (95% confidence interval [CI] = 7.73-26.1). Stratified by comorbidity, the relative risk of biliary tract disease was higher in the LD cohort than in the non-LD cohort for both patients with or without comorbidity. The incidence density rate of biliary tract disease was significantly higher in the first 3 years (13.5 per 1,000 person-years in the LD cohort). The highest adjusted HR of biliary tract disease for LD patients compared with the non-LD cohort was 22.4 (95% CI = 10.8-46.1) in the follow-up ≤ 3 years.ConclusionLiving liver donors had a higher risk of biliary tract disease compared with non-donors.

Background/Aims: Brachial–ankle pulse wave velocity (baPWV) reflects the stiffness of muscular arteries. Albuminuria is recognized as a marker of vascular dysfunction. We assessed the association between arterial stiffness and albuminuria in a population-based longitudinal study. Methods: 1116 adults aged ≥ 40 years in the Taichung Community Health Study (TCHS) in 2004 attended a follow-up visit in 2011. Albuminuria was defined as an urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Arterial stiffness was defined as BaPWV ≥ 1540 cm/sec in males and BaPWV ≥ 1480 cm/sec in females, respectively. ∆baPWV was calculated as baPWV at follow-up minus baPWV at baseline, while ∆UACR was calculated as UACR at follow-up minus UACR at baseline. Multiple linear and logistic regression analyses were used to explore the relationship between albuminuria and arterial stiffness. Results: Among 652 subjects without arterial stiffness at baseline, 209 (32%) subjects developed incident arterial stiffness after an average of 6.6 years. In male subjects, baseline albuminuria was associated with development of arterial stiffness (odds ratio: 4.47, 95% confidence interval [CI]: 1.04–19.31) and ∆baPWV was modestly positively associated with ∆UACR. Conclusion: Our results indicated that male adults with albuminuria had an increased risk for developing arterial stiffness.

With an increasing geriatric population, the need for effective management of chronic conditions and medication use in the elderly is growing. Medication use in the elderly presents significant challenges due to changes in pharmacodynamic and pharmacokinetic profiles. We aimed to examine the impact of a collaborative physician-pharmacist medication therapy management (MTM) program for polypharmacy elderly patients. Methods: Elderly patients with multiple chronic conditions on polypharmacy were enrolled in this prospective, randomized, and controlled study over 16 months of implementation. The intervention group consisted of patients randomized to a collaborative pharmacist-physician MTM program. They were monitored continuously by a clinical pharmacist, while patients in the control group received only usual care with follow-up assessment. Primary outcome was economic differences, measured in total medical expenditure. Secondary outcomes of clinical and humanistic effects were compared between the two groups. Results: The total number of enrolled patients was 87 and 91 in the MTM and usual groups, respectively. The difference-in-difference estimate on medical expenditure during the 16-month implementation period was $3,758,373 New Taiwan Dollars ($127,015 US Dollars) less than the usually care group. Impact was also seen in humanistic outcomes while lipid profiles and mortality trended toward improvement. Conclusion: The pharmacist-physician collaborative MTM program for polypharmacy elderly had significant cost savings and improvement in humanistic measures, demonstrating the importance of clinical pharmacists and MTM programs for elderly patients in Taiwan. The results suggest the possibility of clinical benefits, but the study was not substantially powered to find a statistical difference.

Abstract Studies on the aberrant control of extracellular matrices (ECMs) have mainly focused on the role of malignant cells but less on that of stromal fibroblasts during cancer development. Herein, by using paired normal and prostate cancer-associated stromal fibroblasts (CAFs) derived from a coculture cell model and clinical patient samples, we demonstrated that although CAFs promoted prostate cancer growth, matrix metalloproteinase-3 (MMP-3) was lower in CAFs but elevated in prostate cancer cells relative to their normal counterparts. Furthermore, hydrogen peroxide was characterized as the central modulator for altered MMP-3 expression in prostate cancer cells and CAFs, but through different regulatory mechanisms. Treatment of CAFs but not prostate cancer cells with hydrogen peroxide directly inhibited mmp-3 promoter activity with concomitant nuclear translocation of nuclear factor-κB (NF-κB), indicating that NF-κB is the downstream pathway for the transcriptional repression of MMP-3 in CAFs. Hydrogen peroxide reduced thrombospondin 2 (an MMP-3 suppressor) expression in prostate cancer cells by upregulating microRNA-128. To the best of our knowledge, this is the first study to demonstrate the crucial role of reactive oxygen species in the switching expression of MMP-3 in stromal fibroblasts and prostate cancer cells during tumor progression, clarifying how the tumor microenvironment modulates ECM homeostasis control.

Abstract We assessed gene–gene and gene-physical activity interactions of polymorphisms in C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and lymphotoxin α (LTA) genes on lower extremity performance in community-dwelling elders in Taiwan. Five SNPs (rs1205, rs1130864, rs1800947, rs2794520, and rs3093059) of CRP gene, three SNPs (rs909253, rs1041981, and rs2239704) of LTA gene, and three SNPs (rs3093662, rs1800629, and rs1799964) of TNF-α gene of 472 unrelated elders were genotyped. Lower extremity performance included timed up-and-go test (TUG), walking speed, weight-adjusted leg press (waLP), and timed chair stand (TCS). We detected significant interactions between physical activity with CRP rs2794520, rs1205, and rs3093059; LTA rs909253 and rs1041981; and TNF-α rs1799964 for TCS in women after covariate adjustment (all P

Purpose: The association between neurodegenerative diseases and transfusion remains to be investigated.Methods: The study population comprised 63,813 patients who underwent a blood transfusion and 63,813 propensity score-matched controls between 2000 and 2010. Data were obtained from the Taiwan National Health Insurance Research Database, which is maintained by the National Health Research Institutes. A Cox regression analysis was conducted to elucidate the relationship between blood transfusions and the risk of dementia.Results: A multivariate Cox regression analysis of factors, such as age, sex, cardiovascular ischemia disease, and depression, revealed that patients who underwent a blood transfusion showed a 1.73-fold higher risk of dementia [95% confidence interval (CI) = 1.62-1.84] and a 1.37-fold higher risk of Alzheimer’s disease (AD) [95% CI = 1.13-1.66] than those who did not. Patients who received a transfusion of washed red blood cells showed a 2.37-fold higher risk of dementia (95% CI = 1.63-3.44) than those who did not.Conclusion: Blood transfusion, especially transfusion of any type of red blood cells is associated with an increased risk of dementia.

Gene effects on osteoporosis have been studied separately and may have been masked by gene-gene and gene-environment interactions. We evaluated gene-gene and gene-physical activity interactions of the variants of tumor necrosis factor-α (TNF-α) and vitamin D receptor (VDR) genes on osteoporosis. A total of 472 elders were included. Seven variants (TNF-α: rs1799964, rs1800629, rs3093662; VDR: rs7975232, rs1544410, rs2239185, rs3782905) were genotyped. Bone mineral densities of the lumbar spine, femoral neck, and total hip were measured by dual-energy X-ray absorptiometry. Predictive models' ability to discriminate osteoporosis status was evaluated by areas under the receiver operating characteristics (AUROC) curve. After multivariable adjustment, significant interactions of TNF-α rs1800629 and VDR rs3782905 were observed on overall and lumbar spine osteoporosis. In elderly women, we found that those carrying the CG/CC genotype of VDR rs3782905 were significantly associated with increased odds of overall osteoporosis compared with those carrying the GG genotype of VDR rs3782905 among those carrying TNF-α rs1800629 GG genotype. The adjusted odds ratios (ORs) for VDR rs3782905 CG/CC genotype in elderly women carrying TNF-α rs1800629 AG/AA and GG genotypes were 0.1 (0.01, 0.98) and 3.54 (1.51, 8.30), respectively. We observed significant differences in AUROCs between the model with traditional covariates plus variants and their interaction term and the model with traditional covariates only (AUROCs: 0.77 and 0.81; p = 0.028). Although the sample size of this study may have been relatively small, our results suggest that the interaction of the CG/CC genotype of VDR rs3782905 with TNF-α rs1800629 GG genotype was associated with increased odds of overall and lumbar spine osteoporosis in elderly women.

Background: The evidence indicates that the optimal observation period following renal biopsy ranges between 6 and 8 h. This systematic review and meta-analysis explored whether differences exist in the complication rates of renal biopsies performed in outpatient and inpatient settings. Methods: We searched the MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from 1985 to February 2020. Two reviewers independently selected studies evaluating the bleeding risk from renal biopsies performed in outpatient and inpatient settings and reviewed their full texts. The primary and secondary outcomes were risks of bleeding and major events (including mortality) following the procedure, respectively. Subgroup analysis was conducted according to the original study design (i.e., prospective or retrospective). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effect meta-analysis. Heterogeneity was assessed using the I2 test. Results: Data from all 10 eligible studies, which included a total of 1801 patients and 203 bleeding events, were included for analysis. Renal biopsies in outpatient settings were not associated with a higher bleeding risk than those in inpatient settings (OR = 0.81; 95% CI, 0.59–1.11; I2 = 0%). The risk of major events was also comparable across both groups (OR = 0.45; 95% CI, 0.16–1.29; I2 = 4%). Conclusions: Similar rates of bleeding and major events following renal biopsy in outpatient and inpatient settings were observed.

The best macronutrient percentages of dietary intake supporting longevity remains unclear. The strength of association between dietary intake and mortality in patients with type 2 diabetes (T2DM) should be quantified as a basis for dietary recommendations. Our study cohort consisted of 15,289 type 2 diabetic patients aged 30 years and older in Taiwan during 2001–2014 and was followed up through 2016. Percentages of macronutrient intakes were calculated as dietary energy intake contributed by carbohydrate, protein, and fat, divided by the total energy intake using a 24 h food diary recall approach. Cox proportional hazard models were applied to examine the temporal relation of macronutrient intakes with all-cause and cause-specific mortality. The average follow-up time was 7.4 years, during which 2784 adults with T2DM died. After multivariable adjustment, people with fourth and fifth quintiles of total energy, second and third quintiles of carbohydrate, and fourth quintiles of protein intakes were likely to have lower risks of all-cause and expanded cardiovascular disease (CVD) mortality. People with fifth quintiles of total energy intake were likely to have decreased non-expanded CVD mortality. We found a significant interaction between gender and fat intake on all-cause and expanded CVD mortality. Fat intake was associated with all-cause, expanded and non-expanded CVD mortality among males with T2DM. Total energy, carbohydrate, and protein intakes were associated with lower risks of all-cause and expanded CVD mortality, with minimal risks observed at ≥1673 Kcal total energy, 43–52% carbohydrate intake, and 15–16% protein intake among people with T2DM.

Background: Direct evidence of lung cancer risk in Asian users of angiotensin-converting enzyme inhibitors (ACEIs) is lacking. Methods: The ACEI cohort comprised 22,384 patients aged ≥ 18 years with a first prescription of ACEI. The comparison angiotensin receptor blocker (ARB) cohort consisted of age-, sex- and comorbidity-matched patients at a ratio of 1:1. The primary outcome was the incidence of lung cancer, which was evaluated using a proportional hazard model. Results: The overall incidence rates of lung cancer in the ACEI and ARB cohorts were 16.6 and 12.2 per 10,000 person-years, respectively. The ACEI cohort had a significantly higher risk of lung cancer than the ARB cohort (adjusted hazard ratio [aHR]. = 1.36; 95% confidence interval [CI]. = 1.11−1.67). Duration−response and dose−response analyses revealed that compared with patients who did not receive ACEIs, patients who received ACEIs for more than 45 days per year (aHR = 1.87; 95% CI = 1.48−2.36) and patients who received more than 540 defined daily doses of ACEIs per year (aHR =1.80; 95% CI = 1.43−-2.27) had a significantly higher risk of lung cancer. The cumulative incidence of lung cancer was also significantly higher in the ACEI cohort than in the ARB cohort (log-rank test, p = 0.002). Conclusions: ACEI use is associated with an increased risk of lung cancer compared with ARB use. Patients using ARBs have a significantly lower risk of lung cancer than non-ARB users.

Background: Sitagliptin, a dipeptidyl peptidase-4 inhibitor possibly affects bone turnover. We conducted this cohort study to determine whether sitagliptin is associated with an increased risk of fracture.Methods: The sitagliptin cohort included 1,578 patients aged 20 years and above. The nonsitagliptin cohort comprised propensity-score matched patients at a ratio of 1:1. The primary outcome was the incidence of fractures, which was evaluated using Kaplan–Meier survival analysis and proportional hazards modeling.Results: The mean age of patients in the sitagliptin and nonsitagliptin cohorts was 63.1 and 63.3 years, respectively. The incidence of fractures in the sitagliptin cohort was 46 per 1,000 person-years and that in the nonsitagliptin cohort was 40.8 per 1,000 person-years. Compared with patients in the nonsitagliptin cohort, those in the sitagliptin cohort who received sitagliptin for ≥250 days had a higher risk of fracture (aHR = 1.32, 95% CI = 1.06–1.64).Conclusion: Using sitaglipin ≥250 days was associated with an increased risk of fracture.

Rheumatoid arthritis (RA) is characterized by the infiltration of a number of pro-inflammatory cytokines into synovial fluid and patients with RA often develop joint destruction and deficits in muscle mass. The growth factor myostatin is a key regulator linking muscle mass and bone structure. We sought to determine whether myostatin regulates rheumatoid synovial fibroblast activity and inflammation in RA. We found that levels of myostatin and interleukin (IL)-1β (a key pro-inflammatory cytokine in RA) in synovial fluid from RA patients were overexpressed and positively correlated. In in vitro investigations, we found that myostatin dose-dependently regulated IL-1β expression through the ERK, JNK, and AP-1 signal-transduction pathways. Computational analysis confirmed that miR-21-5p directly targets the expression of the 3′ untranslated region (3′ UTR) of IL-1β. Treatment of cells with myostatin inhibited miR-21-5p expression and miR-21-5p mimic prevented myostatin-induced enhancement of IL-1β expression, showing an inverse correlation between miR-21-5p and IL-1β expression during myostatin treatment. We also found significantly increased paw swelling in an animal model of collagen-induced arthritis (CIA), compared with controls; immunohistochemistry staining revealed substantially higher levels of myostatin and IL-1β expression in CIA tissue. Our evidence indicates that myostatin regulates IL-1β production. Thus, targeting myostatin may represent a potential therapeutic target for RA.

Introduction: Mentorship has been noted as critical to medical students adapting to clinical training in the medical workplace. A lack of infrastructure in a mentoring program might deter relationship building between mentors and mentees. This study assessed the effect of a redesigned clinical mentoring program from the perspective of clerks. The objective was to assess the benefits of the redesigned program and identify potential improvements. Methods: A redesigned clinical mentoring program was launched in a medical center according to previous theoretical and practical studies on clinical training workplaces, including the elements of mentor qualifications, positive and active enhancers for mentor–mentee relationship building, the timing of mentoring performance evaluation, and financial and professional incentives. A four-wave web survey was conducted, comprising one evaluation of the former mentoring program and three evaluations of the redesigned clinical mentoring program. Sixty-four fifth-year medical students in clerkships who responded to the first wave and to at least two of the three following waves were included in the study. A structured and validated questionnaire encompassing 15 items on mentor performance and the personal characteristics of the clerks was used. Mixed linear models were developed for repeated measurements and to adjust for personal characteristics. Results: The results revealed that the redesigned mentoring program improved the mentors’ performance over time for most evaluated items regarding professional development and personal support provided to the mentees. Conclusions: Our findings serve as an improved framework for the role of the institution and demonstrate how institutional policies, programs, and structures can shape a clinical mentoring program. We recommend the adoption of mentorship schemes for other cohorts of medical students and for different learning and training stages involved in becoming a physician.

Chronic exocrine pancreatic insufficiency can lead to osteoporosis. However, the incidence and risk of osteoporosis after acute inflammation of pancreas remained known. Thus, we conducted a population-based cohort study to clarify the association between acute pancreatitis (AP) and osteoporosis.Patients newly diagnosed with AP with index date between 2000 and 2011 were identified from the National Health Insurance Research Database. Osteoporosis were defined according to the International Classification of Diseases, Ninth Revision, Clinical Modification codes. We applied age-, sex-, and comorbidities-adjusted variable Cox proportional hazard models for assessing the association between AP and osteoporosis. Moreover, these models were used to adjust for the influences of patient characteristics and comorbidities.In this study, 4,016 patients were included in the AP cohort (males, 67.9%; mean age, 51.8 years) and 4,016 matched controls in the non-AP cohort. After a mean follow-up period of 4.97 and 5.21 years in the AP and non-AP cohorts, respectively, the incidence of osteoporosis was 8.22 per 1000 person-years in the AP cohort. The AP cohort had a higher risk [adjusted hazard ratio (aHR) = 1.27, 95% confidence interval (CI) = 1.02-1.58] of osteoporosis than did the non-AP cohort. The risk of osteoporosis was highest in the female patients of the AP cohort (aHR = 2.26, 95% CI = 1.85-2.76) and patients aged 50-64 years (aHR = 4.14, 95% CI = 3.13-5.47).AP patients are at a risk of osteoporosis, especially female gender and age 50-64 years. Those with > 3 episodes of AP had highest significant risk of developing osteoporosis.

Hepatitis C virus (HCV) infection is associated with increased systemic oxidative stress, which leads to cardiovascular events, diabetes, and chronic kidney disease. Similarly, cataract is also associated with increased oxidative stress. The association between HCV infection and increased risk of cataract remains unclear.A total of 11,652 HCV-infected patients and 46,608 age- and sex-matched non-HCV infected patients were identified during 2003-2011. All patient data were tracked until a diagnosis of cataract, death, or the end of 2011. Cumulative incidences and hazard ratios (HRs) were calculated.The mean follow-up durations were 5.29 and 5.86 years for the HCV and non-HCV cohorts, respectively. The overall incidence density rate for cataract was 1.36 times higher in the HCV cohort than in the non-HCV cohort (1.86 and 1.37 per 100 person-y, respectively). After adjusting for age, sex, comorbidities of diabetes, hypertension, hyperlipidemia, asthma, chronic obstructive pulmonary disease, coronary artery disease, and anxiety, patients with HCV infection had an increased risk of cataract compared with those without HCV infection [adjusted HR = 1.23, 95% confidence interval (CI) = 1.14-1.32]. HCV-infected patients receiving interferon-ribavirin therapy had a 1.83 times higher (95% CI = 1.40-2.38) risk of cataract than non-HCV infected patients did.HCV infection, even without the complication of cirrhosis, is associated with an increased risk of cataract, and this risk is higher in HCV-infected patients undergoing interferon-ribavirin therapy.

Delay in diagnosis may affect the survival of breast cancer patients. The purpose of this study was to investigate delayed diagnosis for breast cancer patients in Taiwan. Methods: This study was conducted via one-to-one interviews with structured questionnaires in hospital outpatient visit. Included were 600 breast cancer patients seeking medical care in two medical centers in central Taiwan. Results: Average delay in breast cancer diagnosis was 27.8 days. Service level of the patients' first visit and number of hospitals patients visited before obtaining a correct diagnosis were significantly associated with delay in diagnosis. Logistic regression analysis found that patients who had visited two, and three or more hospitals before getting a correct diagnosis had longer delays in diagnosis than patients who had visited one hospital (odds ratio = 2.23 and 9.26, 95% confidence interval 1.37–3.63 and 95% CI:3.87–22.15, respectively). Conclusion: Results of this study are anticipated to serve as a reference for the government and medical institutions to develop policies to reduce the number of hospitals visited before diagnosis for breast cancer patients, and ultimately to achieve the goal of early detection and treatment.

Background: Prognosis of the aged population requiring maintenance dialysis has been reportedly poor. We aimed to develop prediction models for one-year cost and one-year mortality in aged individuals requiring dialysis to assist decision-making for deciding whether aged people should receive dialysis or not. Methods: We used data from the National Health Insurance Research Database (NHIRD). We identified patients first enrolled in the NHIRD from 2000−2011 for end-stage renal disease (ESRD) who underwent regular dialysis. A total of 48,153 Patients with ESRD aged ≥65 years with complete age and sex information were included in the ESRD cohort. The total medical cost per patient (measured in US dollars) within one year after ESRD diagnosis was our study’s main outcome variable. We were also concerned with mortality as another outcome. In this study, we compared the performance of the random forest prediction model and of the artificial neural network prediction model for predicting patient cost and mortality. Results: In the cost regression model, the random forest model outperforms the artificial neural network according to the mean squared error and mean absolute error. In the mortality classification model, the receiver operating characteristic (ROC) curves of both models were significantly better than the null hypothesis area of 0.5, and random forest model outperformed the artificial neural network. Random forest model outperforms the artificial neural network models achieved similar performance in the test set across all data. Conclusions: Applying artificial intelligence modeling could help to provide reliable information about one-year outcomes following dialysis in the aged and super-aged populations; those with cancer, alcohol-related disease, stroke, chronic obstructive pulmonary disease (COPD), previous hip fracture, osteoporosis, dementia, and previous respiratory failure had higher medical costs and a high mortality rate.

Objective: To assess risk factors for postoperative pelvic cellulitis in women undergoing laparoscopic-assisted vaginal hysterectomy (LAVH). Materials and Methods: A total of 195 patients who underwent LAVH for benign gynecological diseases during the period 2007–2008 were enrolled. Among them, 11 patients developed pelvic cellulitis (group 1, cases) and 184 did not (group 2, controls). Results: The proportion of patients in American Society of Anesthesiologists physical status scale (ASA) class II was significantly higher in group 1 (p=0.017). The grade of pelvic adhesion was significantly more severe in group 1 (p=0.044). The mean length of hospital stay in group 1 was significantly longer than in group 2. Logistic regression analysis revealed that patients in ASA class II were six times more likely to develop postoperative pelvic cellulitis than patients in ASA class I. In addition, the analysis showed that there was a twofold increase in risk for pelvic cellulitis with each single-grade increase in the degree of pelvic adhesion. Women with postoperative pelvic cellulitis also had a significantly increased length of hospital stay. Conclusion: Understanding the risk factors for postoperative pelvic infection, such as systemic disease, pelvic adhesion, and prolonged hospital stay, comprehensive care of patients, and correction of modifiable risk factors will help reduce the rate of postoperative pelvic cellulitis in women undergoing LAVH.

Background: Sympathetic activity, including cervical ganglia, is involved in the development of cardiac arrhythmias. Objective: The present study investigated the association between cervical spondylosis and arrhythmia, which has never been reported before. Methods: Patients newly diagnosed with cervical spondylosis (CS) with an index date between 2000 and 2011 were identified from the National Health Insurance Research Database. We performed a 1:1 case-control matched analysis. Cases were matched to controls according to their estimated propensity scores, based on demographics and existing risk factors. Cox proportional hazard models were applied to assess the association between CS and arrhythmia. Results: The CS cohort comprised 22,236 patients (males, 42.6%; mean age, 54.4 years) and non-CS cohort comprised 22,236 matched controls. There were 1441 events of arrhythmia in CS cohort and 537 events of arrhythmia in non-CS cohort, which 252 and 127 events of atrial fibrillation in CS and non-CS cohort, 33 and 12 events of ventricular tachycardia in CS cohort and non-CS cohort, 78 and 35 events of supraventricular tachycardia in CS cohort and non-CS cohort. The CS cohort had an arrhythmia incidence of 11.1 per 1000 person-years and a higher risk [adjusted hazard ratio (aHR) = 3.10, 95% confidence interval (CI) = 2.80–3.42] of arrhythmia, 2.54-fold aHR of ventricular tachycardia (95% CI = 1.70–3.79), and 2.22-fold aHR of atrial fibrillation (95% CI = 1.79–2.76) compared with non-CS cohort. Conclusions: Cervical spondylosis is associated with a higher risk of arrhythmia.

As the number of terminal cancer patients increases, several care models have been adopted to provide better care quality and reduce medical expenditure. This study compared inpatient medical expenditure and family satisfaction in a hospice ward (HW) and general ward (GW) for terminal cancer patients in Taiwan. Methods: We enrolled terminal cancer patients who were admitted and died during the same admission period in a tertiary care hospital in Taiwan from January 2003 to December 2005. These patients were allocated into three groups: inpatient care in HW alone; inpatient care in GW alone; and inpatient care in mixed group (initially in GW, then transferred to HW). Inpatient medical expenditure and family satisfaction were compared between the three groups. Results: A total of 1942 patients were recruited and allocated into HW (n = 292), GW (n = 1511) and mixed (n = 139) groups. The average medical expenditure per person or per inpatient day was lower in the HW than the GW or mixed group. Subjects who had ever been admitted to the intensive care unit or received cardiopulmonary resuscitation in the GW or mixed groups required more expenditure on medical care than that in the HW group. Daily medical expenditure in the HW group also was much lower than that in the GW and mixed groups, based on length of stay and cancer type. The family satisfaction score was significantly higher in the mixed and/or HW group than the GW group. Conclusion: For terminal cancer patients, hospice care can improve family satisfaction while reducing medical expenditure in Taiwan.

The association between subclinical hypothyroidism (SCH) and cancer mortality is seldom discussed.A total of 115,746 participants without thyroid disease history, aged 20 and above, were recruited from four nationwide health screening centers in Taiwan from 1998 to 1999. SCH was defined as a serum thyroid-stimulating hormone (TSH) level of 5.0-19.96 mIU/L with normal total thyroxine concentrations. Euthyroidism was defined as a serum TSH level of 0.47-4.9 mIU/L. Cox proportional hazards regression analyses were used to estimate the relative risks (RRs) of death from cancer for adults with SCH during a 10-year follow-up period.Among 115,746 adults, 1,841 had SCH (1.6%) and 113,905 (98.4%) had euthyroidism. There were 1,532 cancer deaths during the 1,034,082 person-years follow-up period. Adjusted for age, gender, body mass index, diabetes, hypertension, dyslipidemia, smoking, alcohol drinking, betel nut chewing, physical activity, income, and education level, the RRs (95% confidence interval) of cancer deaths among subjects with SCH versus euthyroid subjects were 1.51 (1.06 to 2.15). Cancer site analysis revealed a significant increased risk of bone, skin and breast cancer among SCH subjects (RR 2.79, (1.01, 7.70)). The risks of total cancer deaths were more prominent in the aged (RR 1.71, (1.02 to 2.87)), in females (RR 1.69 (1.08 to 2.65)), and in heavy smokers (RR 2.24, (1.19 to 4.21)).Subjects with SCH had a significantly increased risk for cancer mortality among adult Taiwanese. This is the first report to demonstrate the association between SCH and cancer mortality.