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Objective: To evaluate the association between paternal metformin use and risk of congenital malformations in offspring., Design: Population based, cross national cohort study., Setting: Norway and Taiwan., Participants: 619 389 offspring with paternal data during the period of sperm development (three months before pregnancy) in the Norwegian cohort during 2010-21 and 2 563 812 in the Taiwanese cohort during 2004-18., Main Outcome Measures: The primary outcome was any congenital malformation, and the secondary outcome was organ specific malformations, classified according to the European surveillance of congenital anomalies guidelines. Relative risks were estimated with an unadjusted analysis and with analyses restricted to the cohort of men with type 2 diabetes mellitus and those using overlap propensity score weighting to control for severity of diabetes and other potential confounders. Sibling matched comparisons were conducted to account for genetic and lifestyle factors. Relative risk estimates for Norwegian and Taiwanese data were pooled using a random effects meta-analytical approach., Results: Paternal data on metformin use during the period of sperm development was available for 2075 (0.3%) offspring in Norway and 15 276 (0.6%) offspring in Taiwan. Among these offspring, 104 (5.0%) in Norway and 512 (3.4%) in Taiwan had congenital malformations. Increased risks of any congenital malformation associated with paternal metformin use were observed in the unadjusted analysis and attenuated with increasing control of confounding. The relative risks of any malformations with paternal metformin use were 1.29 (95% confidence interval 1.07 to 1.55) in Norway and 1.08 (0.99 to 1.17) in Taiwan in the unadjusted analysis and 1.20 (0.94 to 1.53) and 0.93 (0.80 to 1.07), respectively, in the analysis restricted to fathers with type 2 diabetes mellitus. In the overlap propensity score weighting analysis restricted to fathers with type 2 diabetes mellitus, the relative risks were 0.98 (0.72 to 1.33) in Norway and 0.87 (0.74 to 1.02) in Taiwan, resulting in a pooled estimate of 0.89 (0.77 to 1.03). No associations were observed between paternal metformin use and any organ specific malformations. These findings were consistent in sibling matched comparisons and sensitivity analyses., Conclusions: The findings suggest that paternal use of metformin during the period of sperm development is not associated with congenital malformations in offspring, including organ specific malformations. Metformin can therefore continue to be considered a suitable initial oral agent for managing glucose levels in men with type 2 diabetes mellitus who plan on having children., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this work was supported by the Norwegian Research Council and by the National Science and Technology Council of Taiwan; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. The authors had full access to all the data in this study and take responsibility for the integrity of the data and the accuracy of the data analysis., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To develop an intrinsic capacity (IC) score and to investigate the association between IC transition with overall and cause-specific mortality, incident disability and healthcare utilization., Design: Retrospective cohort study SETTING AND PARTICIPANTS: Data from 1852 respondents aged ≥ 65 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed., Measurements: Transitions of IC score were categorized into three groups: (1) Improved IC (IC 2003-1999 >0), (2) Stable IC (IC 2003-1999 = 0), (3) Worsened IC (IC 2003-1999 <0). Cox regression and subdistribution hazard models were used to investigate IC transitions and 4-year overall and cause-specific mortality, respectively. Logistic regression were employed to develop weighted IC score (wIC, 0-16) and assess its association with incident disability and healthcare utilization. Similar analysis were repeated using non-weighted IC (nIC, 0-8) to ensure robustness., Results: Comparing to decreased wIC group, stable or increased wIC participants had significantly lower 4-year all-cause mortality, and death from infection, cardiometabolic/cerebrovascular diseases, organ failure and other causes. (Hazard ratio (HR) ranged from 0.36 to 0.56, 95% CI ranged from 0.15 to 1.00, p ≤ 0.049 in the stable wIC group; HR ranged from 0.41 to 0.51, 95% CI ranged from 0.22 to 0.94, p ≤ 0.034 in the increased wIC group). Moreover, individuals with stable or increased wIC demonstrated lower risk of incident disability and hospitalization. (Odds ratio (OR) = ranged from 0.34 to 0.70, 95% CI ranged from 0.19 to 1.00, p ≤ 0.048). Participants with stable wIC also exhibited reduced risk of emergency department visits (OR = 0.58, 95% CI = 0.41 to 0.82, p = 0.002). These results were generally consistent in the nIC model., Conclusion: Participants with stable or increased IC experienced significantly lower all-cause and most cause-specific mortality, incident disability, and healthcare utilization, which was independent of baseline IC and comorbidities. The findings remained consistent across weighted and non-weighted IC model., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: GLP-1 receptor agonists and SGLT2 inhibitors are increasingly being used in people with type 2 diabetes on the basis of findings from randomised clinical trials; however, little is known of whether clinical outcomes are affected by frailty in real-world settings. We aimed to compare the clinical effectiveness and safety of GLP-1 receptor agonists and SGLT2 inhibitors in managing type 2 diabetes, with a specific focus on stratifying people by their frailty status., Methods: In this retrospective, nationwide, longitudinal study, we identified people (aged ≥20 years) with type 2 diabetes who newly initiated either a GLP-1 receptor agonist or an SGLT2 inhibitor during the period Jan 1, 2017 to Dec 31, 2019 from the Taiwan National Health Insurance database. Individuals were excluded if they had been diagnosed with cancer, received dialysis for kidney failure, or had prescriptions for a GLP-1 receptor agonist or an SGLT2 inhibitor, within 1 year before the index date. Mortality data were collected from the Taiwan National Death Registry. Eligible individuals were categorised into three frailty subgroups-fit, mild frailty, and moderate or severe frailty-on the basis of the multimorbidity frailty index. Propensity score matching (1:1) was used to balance covariates between recipients of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup. Clinical outcomes of interest included three-point major adverse cardiovascular events (non-fatal acute myocardial infarction, non-fatal stroke, and fatal cardiovascular disease), all-cause mortality, hospitalisation for heart failure, dialysis or renal transplant, severe diabetic foot complications, retinopathy, hospitalisation for severe hyperglycaemia, and hospitalisation for severe hypoglycaemia. The association between the use of a GLP-1 receptor agonist versus an SGLT2 inhibitor and the risk of the outcomes of interest among each frailty subgroup was examined using a subdistribution hazard model., Findings: We identified 320 210 people with type 2 diabetes, of whom 280 163 met the eligibility criteria, who initiated either a GLP-1 receptor agonist (n=22 968; mean age 57·7 years [SD 13·9], 11 338 [49·4%] were female, and 11 630 [50·6%] were male) or SGLT2 inhibitor (n=257 195; mean age 58·8 years [12·3], 107 988 [42·0%] were female, and 149 207 [58·0%] were male) during 2017-19. After matching, 11 882, 7210, and 3414 pairs of GLP-1 receptor agonist and SGLT2 inhibitor users were assigned in the fit, mild frailty, and moderate or severe frailty subgroups. All clinical outcomes were comparable between users of GLP-1 receptor agonists and SGLT2 inhibitors among each frailty subgroup, except for a higher risk of hospitalisation for severe hyperglycaemia with GLP-1 receptor agonists than with SGLT2 inhibitors in the mild frailty subgroup (subdistribution hazard ratio 1·25 [95% CI 1·13-1·38]; p<0·0001) and a higher risk of dialysis or renal transplant with GLP-1 receptor agonists than with SGLT2 inhibitors in the fit (2·43 [1·82-3·23]; p<0·0001), mild frailty (3·93 [3·03 -5·09]; p<0·0001), and moderate or severe frailty (2·60 [2·03-3·31]; p<0·0001) subgroups., Interpretation: Formulating clear and updated guidelines on the use of GLP-1 receptor agonists and SGLT2 inhibitors according to frailty status could improve management of type 2 diabetes., Funding: Ministry of Education, Taiwan., Competing Interests: Declaration of interests F-YH, EC-HT, and C-YW have received a research grant, awarded to the National Taiwan University, from Novo Nordisk. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: The aim of this study was to examine the longitudinal relationships between the trajectories of distinct subtypes of various domains of social supports and risk of subjective motoric cognitive risk (MCR) syndrome., Design: Longitudinal cohort study., Setting and Participants: 2,279 participants in the Taiwan Longitudinal Study on Aging (TLSA) between 1999 and 2011., Method: A group-based multi-trajectory modeling (GBMTM) was implemented to identify distinct trajectory subtypes within various social support domains, encompassing social networks, emotional support, instrumental support, as well as working and economic status. Logistic regression models were then utilized to evaluate the associations between these trajectory subtypes and the risk of subjective MCR., Results: Among 2,279 participants, GBMTM identified four distinct trajectory subtypes: "low social support" (n = 371), "medium social support " (n = 862), "high social support" (n = 292), and "high social support with employment" (n = 754). The incidence rates of subjective MCR for these groups were 9.4%, 9.0%, 4.1%, and 0.8%, respectively. After adjusting for age, sex, education level, and comorbidities, both "low social support" (adjusted odds ratio (aOR) 4.07, 95% CI [1.60-10.34]) and "medium social support" (aOR 3.10, 95% CI [1.26-7.66]) were significantly associated with an increased risk of subjective MCR compared to the "high social support with employment" group., Conclusions and Implications: The current study demonstrates that social support significantly reduces the risk of subjective MCR, with lower support levels correlating to higher risk, necessitating further intervention studies to confirm the link between social support and risk of subjective MCR., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Despite the frequent co-administration of antidepressants and benzodiazepines, the association between such concomitant use during pregnancy and the risk of congenital malformations remains inadequately explored. This study aims to examine the association between concomitant use of antidepressants and benzodiazepines during the first trimester and organ-specific congenital malformations., Methods: We conducted a population-based cohort study using Taiwan's National Birth Certificate Application database, the Maternal and Child Health database, and Taiwan's National Health Insurance database. Pregnant people aged 15-50 years with singleton births between Jan 1, 2004, and Dec 31, 2018, were included. Use of antidepressants and benzodiazepines was defined as at least one prescription during the first trimester, and concomitant use was defined as the overlapping prescription of both drugs with an overlapping prescription period. The primary outcomes were overall congenital malformations and eight organ-specific malformations, consisting of the nervous system, heart, respiratory system, oral cleft, digestive system, urinary system, genital system, and limb malformations. Logistic regression models with propensity score fine stratification weighting approach were used to control for measured confounders. Analyses controlling for confounding by indication and sibling comparison analyses were done to address unmeasured confounders. No individuals with lived experience participated in the research or writing process., Findings: The cohort included 2 634 021 singleton pregnancies, and 8599 (0·3%) individuals were concomitant users of antidepressants and benzodiazepines during the first trimester (mean age at delivery was 31·8 years [SD 5·2] for pregnancies with exposure to antidepressants and benzodiazepines vs 30·7 years [SD 4·9] for pregnancies without exposure). All study participants were female, and information about ethnicity was not available. Absolute risk of overall malformations was 3·81 per 100 pregnancies with exposure, compared with 2·87 per 100 pregnancies without exposure. The propensity score-weighted odds ratios (weighted ORs) did not suggest an increased risk for overall malformations (weighted OR 1·10, 95% CI 0·94-1·28), heart defects (1·01, 0·83-1·23), or any of the other organ-specific malformations, except for digestive system malformations, for which the weighted OR remained statistically significant after adjustment (1·63, 1·06-2·51). The absence of an increased risk for overall congenital malformations associated with concomitant use of antidepressants and benzodiazepines was supported by the analyses controlling for confounding by indication and sibling-matched comparisons., Interpretation: The findings of this study suggest that the concomitant use of antidepressants and benzodiazepines during the first trimester is not associated with a substantial increase in risk for most malformation subtypes. However, considering other potential adverse effects of using both medications concomitantly, a thorough assessment of the risks and benefits is crucial for clinical decision making., Funding: National Science and Technology Council., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: This study aimed to use the Social Vulnerability Index (SVI) to encapsulate the complex and multidimensional nature of social determinants and their influence on alcohol intake and mortality in middle-aged and older individuals., Design: Cohort study., Setting and Participants: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with 3945 study participants aged 50 years and older., Methods: The TLSA questionnaire defined SVI (51 items including living conditions, social support, socially oriented activities of daily living, social engagement and leisure, empowerment of life, satisfaction about life, and socioeconomic status) and alcohol intake (behavior as well as type and frequency of alcohol intake). Multivariate Cox proportional hazard models were used to estimate the association between alcohol intake and mortality, stratified by sex and SVI groups., Results: Men with high social vulnerability and high alcohol intake exhibit an elevated mortality risk [adjusted hazard ratio (aHR), 1.51; 95% CI, 1.01-2.24], whereas notably, women in similar social circumstances but with moderate alcohol intake face a quintupled mortality risk (>35 g/wk; aHR, 5.67; 95% CI, 2.37-13.61). The impact of alcohol and social vulnerability on mortality was more pronounced in men younger than 65. Among them, those with high social vulnerability and moderate (35-140 g/wk; aHR, 2.83; 95% CI, 1.50-5.36) to high (>140 g/wk; aHR, 2.24; 95% CI, 1.15-4.35) alcohol intake was associated with an increased risk of mortality., Conclusions and Implications: Various factors throughout the life course of both men and women significantly impact the risk of all-cause mortality due to alcohol intake, underscoring the importance of social vulnerability as a determinant of both alcohol intake behavior and mortality risk., Competing Interests: Disclosures All authors declare no conflict of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The use of benzodiazepines and Z-hypnotics during pregnancy has raised significant concerns in recent years. However, there are limited data that capture the prescription patterns and predisposing factors in use of these drugs, particularly among women who have been long-term users of benzodiazepines and Z-hypnotics before pregnancy., Methods: This population-based cohort study comprised 2 930 988 pregnancies between 2004 and 2018 in Taiwan. Women who were dispensed benzodiazepines or Z-hypnotics during pregnancy were identified and further stratified into groups based on their status before pregnancy: long-term users (with a supply of more than 180 days within a year), short-term users (with a supply of less than 180 days within a year), and nonusers. Trends in the use of benzodiazepines or Z-hypnotics and concomitant use with antidepressants or opioids were assessed. Logistic regression models were utilized to identify factors associated with use of these drugs during pregnancy, and interrupted time series analyses (ITSA) were employed to evaluate utilization patterns of these drugs across different pregnancy-related periods., Results: The overall prevalence of benzodiazepine and Z-hypnotic use was 3.5% during pregnancy. Among prepregnancy long-term users, an upward trend was observed. The concomitant use of antidepressants or opioids among exposed women increased threefold (from 8.6% to 23.1%) and sixfold (from 0.3% to 1.7%) from 2004 to 2018, respectively. Women with unhealthy lifestyle behaviors, such as alcohol abuse (OR 2.48; 95% CI, 2.02-3.03), drug abuse (OR 10.34; 95% CI, 8.46-12.64), and tobacco use (OR 2.19; 95% CI, 1.96-2.45), as well as those with psychiatric disorders like anxiety (OR 6.99; 95% CI, 6.77-7.22), insomnia (OR 15.99; 95% CI, 15.55-16.45), depression (OR 9.43; 95% CI, 9.07-9.80), and schizophrenia (OR 21.08; 95% CI, 18.76-23.69), and higher healthcare utilization, were more likely to use benzodiazepines or Z-hypnotics during pregnancy. ITSA revealed a sudden decrease in use of benzodiazepines and Z-hypnotics after recognition of pregnancy (level change -0.55 percentage point; 95% CI, -0.59 to -0.51). In contrast, exposures to benzodiazepines and Z-hypnotics increased significantly after delivery (level change 0.12 percentage point; 95% CI, 0.09 to 0.16)., Conclusions: In this cohort study, an increased trend of benzodiazepine and Z-hypnotic use during pregnancy among prepregnancy long-term users, as well as concomitant use with antidepressants or opioids were found. The findings have highlighted the existence of various risk factors associated with the use of these drugs during pregnancy. Utilization patterns varied across different stages of pregnancy, highlighting the need for prescription guidelines and educational services for women using these drugs during pregnancy., (© 2024 John Wiley & Sons Ltd.)

Aims: This study aims to ascertain dementia incidence from 2004 to 2017 in Taiwan, and to examine the disease course in comorbidity, treatments, healthcare usage, and mortality among older people with incident dementia preceding the diagnosis of dementia and afterwards., Methods: Taiwan National Health Insurance data on people aged ≥ 65 years with incident dementia from January 2004 to December 2017 were excerpted to estimate annual incidence rates and annualized percentage changes(APCs). For people diagnosed before 2013, annual mortality rates and causes of death during 5-years' follow-up were determined. Changes in 22 diseases/conditions, hospital visits and admissions, and psychotropic medication prescriptions commonly associated with dementia, were examined from 3 years preceding the index diagnosis until 5 years afterwards., Results: From 2004 to 2017, the annual incidence of dementia in Taiwan increased from 30,606 to 50,651, and by > 90 % in women; age-standardized annual incidence increased significantly, with an APC of 0.4 %(p = 0.02). For 372,203 incident cases from 2004 to 2013, annual mortality was∼12 % during 5-years' follow-up. The prevalence of most comorbidities increased by 65-150 % after being diagnosed with dementia. People with incident dementia had increased healthcare usage 1 year before diagnosis, which peaked 1 year afterwards. Psychotropic medication prescriptions increased gradually over 3 years before diagnosis, peaked 3 months afterwards, gradually declined during the next 2 years, then remained stable., Conclusion: The incidence of dementia in Taiwan has increased gradually over time, with an annual mortality risk of∼12 %. Older people with dementia had more healthcare needs and comorbid conditions after dementia diagnosis, highlighting the exigency of person-centered dementia care., Competing Interests: Declaration of competing interest All authors have declared: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024. Published by Elsevier B.V.)

Background: Sarcopenia and intrinsic capacity (IC) declines pose significant challenges to healthy aging, particularly in the rapidly growing octogenarian population. This study aimed to elucidate the relationship between sarcopenia and declines in IC across multiple cohorts of community-dwelling older adults., Methods: Data from four Taiwanese cohorts were analyzed. Sarcopenia was diagnosed based on the Asian Working Group for Sarcopenia (AWGS) 2019 criteria (algorithm 1: categorized as either having possible sarcopenia or not (robust); algorithm 2: categorized as robust, possible sarcopenia or sarcopenia). IC was operationalized using the World Health Organization's Integrated Care for Older People (ICOPE) framework (step 1 and step 2), encompassing six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being. Multivariable logistic regression models were adopted to assess the association between sarcopenia and IC decline., Results: Among 599 octogenarians (median age 82.2 years, 54.8% male), the prevalence of possible sarcopenia (algorithm 1) was 64.6%. When adopting algorithm 2, the prevalence of possible sarcopenia and sarcopenia was 46,2% and 32.1%, respectively. After adjusting for covariates, participants with possible sarcopenia or sarcopenia (algorithm 2) were more likely to exhibit declines in vitality (ICOPE Step 1: possible sarcopenia aOR 3.65, sarcopenia aOR 4.74; ICOPE Step 2: possible sarcopenia aOR 5.11, sarcopenia aOR 14.77) and cognition (ICOPE Step 1: possible sarcopenia aOR 2.40, sarcopenia aOR 2.12; ICOPE Step 2: possible sarcopenia aOR 2.02, sarcopenia aOR 2.51) compared to robust individuals., Conclusions: This study underscores the robust association between sarcopenia and declines in vitality and cognition among octogenarians, highlighting the importance of sarcopenia screening and management in promoting healthy longevity in this vulnerable population., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Objective: This study aimed to evaluate the efficacy of integrated multidomain interventions and primary health care on intrinsic capacity (IC) and related biomarkers., Design: An ancillary analysis from the Taiwan Integrated Geriatric Care (TIGER) study: a randomized controlled trial., Setting and Participants: A total of 398 community-dwelling older adults aged ≥65 years with ≥3 chronic conditions., Methods: Participants were randomized into the 12-month pragmatic multidomain intervention or usual care groups. The primary outcome was the change in IC and its subdomains (locomotion, cognition, vitality, psychological, and sensory) at baseline and 3-, 6-, 9-, and 12-month follow-ups. Generalized linear mixed models were used to evaluate the multidomain intervention effects on these changes., Results: The intervention arm had greater improvement in IC than the usual care arm (overall difference 1.5; 95% CI 0.5-2.5; P = .005), mainly from subdomains of locomotion (overall difference 1.4; 95% CI 0.5-2.4; P = .004) and cognition (2.9; 95% CI 2.1-3.7; P < .001). Changes in neutrophil-to-lymphocyte ratio (NLR -2.4; 95% CI -3.9 to -0.8, P = .003), serum levels of albumin (35.1; 95% CI 23.1-47.2; P < .001), dehydroepiandrosterone sulfate (DHEA-S 2.8; 95% CI 1.9-3.8; P < .001), free androgen index (FAI 1.5; 95% CI 1.1-1.9; P < .001), and vitamin D (4.0; 95% CI 2.0-6.1; P < .001) were associated with changes in IC over time., Conclusions and Implications: The incorporation of multidomain interventions into primary health care significantly enhanced IC over the 12-month program. Changes in NLR, FAI, and serum levels of albumin, DHEA-S, vitamin D were associated with changes in IC over time., Trial Registration: ClinicalTrials.gov Identifier: NCT03528005., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Importance: Intrinsic capacity (IC), defined by the World Health Organization's Integrated Care for Older People (ICOPE) framework, is crucial for promoting healthy aging. Understanding the associations between IC impairments and age-related biomarkers can provide insights into the underlying pathophysiological mechanisms and potential interventions., Objective: To investigate the associations between IC impairments (ICOPE step 1 and step 2, respectively) and aging-related biomarkers, including inflammatory and cardiometabolic markers, in community-dwelling middle-aged and older adults., Design, Setting, and Participants: Cross-sectional analysis of data from 755 participants (aged 50-64 years, n=212; 65-74 years, n=357; ≥75 years, n=186) enrolled in the Gan-Dau Healthy Longevity Plan, a community-based survey in Taipei City, Taiwan, from 2022., Exposures: IC impairments assessed by ICOPE Step 1 (screening) and Step 2 (in-depth assessment) across six domains: locomotion, vitality, vision, hearing, cognition, and psychological well-being., Main Outcomes and Measures: Levels of inflammatory biomarkers (albumin, white blood cell count, neutrophils, lymphocytes, monocytes, neutrophil-to-lymphocyte ratio [NLR], lymphocyte-to-monocyte ratio [LMR], platelet-to-lymphocyte ratio [PLR]) and cardiometabolic biomarkers (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, fasting glucose, triglycerides, triglyceride-glucose [TyG] index)., Results: Of the 755 participants, the mean age was 68.5 years, and 68.2% were women. The proportion of participants with any IC impairment increased with age: 63.2% for those aged 50-64, 65.8% for those aged 65-74, and 74.7% for those aged ≥75 years based on ICOPE Step 1. For ICOPE Step 2, the proportions were 59.9%, 56.9%, and 64.0%, respectively. Impairments in locomotion and cognition were significantly higher in the oldest age group (≥75 years). Adjusted for covariates, IC impairment (ICOPE Step 2) was associated with higher levels of neutrophil count (β = 3.17, p = 0.015) and NLR (β = 0.34, p = 0.021) in those aged 50-64 years, and higher levels of monocyte count in those aged 65-74 years (β = 0.65, p = 0.001) and ≥75 years (β = 0.68, p = 0.037)., Conclusions and Relevance: In conclusion, IC impairments were associated with alterations in specific inflammatory biomarkers, suggesting potential interactions between IC, age, and inflammatory processes. Longitudinal studies are warranted to establish causal relationships and elucidate the underlying mechanisms linking IC impairments, immune dysregulation, and the aging process., Competing Interests: The authors declare no conflicts of interest.

Background: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan., Methods: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection., Results: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes., Conclusion: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects., (© 2024 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Polypharmacy and potentially inappropriate medications (PIM) are widely recognized as vital quality indicators of pharmacotherapy in older adults. As Taiwan and Japan grapple with the ongoing challenges of population aging, obtaining an accurate understanding of the prevalence of these indicators is crucial for developing effective strategies to optimize pharmacotherapy in older populations. The present study aims to comprehensively evaluate the prevalence of polypharmacy and PIMs in Taiwan and two Japanese cohorts, shedding light on the similarities and differences in prescribing practices across these populations., Methods: This study employed a cross-sectional design to investigate individuals aged ≥65 years in Taiwan, as well as two Japanese cohorts: Japan Cohort 1 (dispensing data from chain pharmacies; year 2014 and 2019) and Japan Cohort 2 (claims data; year 2017 and 2019). The prescription records of these participants were collected from the national claims database in Taiwan for the years 2014, 2017, and 2019. To identify polypharmacy and hyper-polypharmacy, the study defined the use of 5-9 and 10+ drugs, respectively. Furthermore, the study identified PIMs based on the STOPP-J criteria. Notably, the study further explored the most frequently used PIMs (by categories) in Taiwan., Results: In the year 2019, the prevalence of polypharmacy exhibited similar rates in Taiwan (35.4%) and Japan Cohort 2 (33.1%), while surpassing that of Japan Cohort 1 (25.6%). Nonetheless, the incidence of PIMs in Taiwan was the highest (66.5%), exceeding those of the two Japanese cohorts (Cohort 1: 43.7% and Cohort 2: 40.2%) in the same year. Notably, the top three categories of commonly used PIMs in Taiwan comprised non-steroidal anti-inflammatory drugs (NSAIDs), antithrombotic drugs, and benzodiazepines., Conclusions: This study highlights the varying prevalence of polypharmacy and PIMs between Taiwan and Japan, but emphasizes the need for collaborative efforts towards optimizing pharmacotherapy in older adults., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

The existence of intrinsic capacity (IC) subtypes and their distinct impacts on age-related outcomes remain unexplored. This study sought to investigate IC impairment trajectories across domains and their associations with the risk of age-related outcomes, including falls, functional limitations, reduced quality of life (QoL) and mortality at 4- and 8-year follow-ups. The study sample comprised 1,782 older adults residing in the community from the Taiwan Longitudinal Study on Ageing (TLSA). Utilizing group-based multitrajectory modeling, distinct subtypes of IC decline trajectories across various domains were identified. Cox proportional hazard models and multivariable logistic regression analyses were employed to assess the associations between the identified subtypes and age-related outcomes. We identified four subtypes of IC decline: robust with mild decline (n=902), hearing loss with cognitive decline (n=197), physio-cognitive decline (PCD) with depression (n=373), and severe IC decline (n=310). Over the 4-year study period, compared to the robust with mild decline group, hearing loss with cognitive decline group exhibited a significantly higher risk of diminished QoL (OR=2.53 [1.66-3.86], p<0.01), whereas those in the PCD with depression group experienced an elevated risk of falls (OR=1.62 [1.18-2.23], p<0.01), as well as functional limitation (OR=2.61 [1.81-3.75], p<.01). Individuals in the severe IC decline group faced a substantially increased risk of all outcomes of interest. Distinct subtypes of IC decline across different domains have varying impacts on age-related outcomes, highlighting the need for a personalized approach to promote healthy ageing at the population level, while further investigation into specific pathophysiological mechanisms is warranted as well.

Background: Infectious diseases are the leading cause of deaths in adults aged 65 years or older. Studies of adverse infection outcomes have been limited to specific infections and acute episodes and have not investigated longitudinal trends of cumulative infections. We aimed to identify distinct trajectories of longitudinal infection episodes in older adults and to assess their corresponding risk of all-cause mortality., Methods: In this retrospective cohort study, we included people aged 65 years or older who were admitted to hospital between Jan 1 and Dec 31, 2011, with one of the following infections: urinary tract, pneumonia, sepsis, cellulitis, cholecystitis, peritonitis, endocarditis, and meningitis. Participants were identified from Taiwan's National Health Insurance Research Database. We analysed infection episodes on a quarterly basis during a 5-year period (2011-15) and used group-based trajectory modelling to identify distinct trajectories. We examined the associations between infection trajectories and all-cause mortality using Kaplan-Meier curves and the Cox proportional hazard model., Findings: Among 79 666 eligible older adults, we identified four distinct infection trajectories over the 5-year follow-up: infrequent (58 619 [73·6%]), increasing (9746 [12·2%]), decreasing (9069 [11·4%]), and frequent (2232 [2·8%]). Compared with people with infrequent infections, the adjusted hazard ratios for all-cause mortality were 2·96 (95% CI 2·82-3·11) in participants with frequent infections, 2·15 (2·09-2·22) in those with increasing infections, and 1·85 (1·80-1·91) in those with decreasing infections., Interpretation: Older adults with multiple infection episodes, irrespective of type, pathogens, and distinct infection pattern, had greater risk of all-cause mortality compared with those with infrequent infections. Further research to define the overall infection burden in older adults is needed for risk stratification and to inform prevention strategies., Funding: The Interdisciplinary Research Center for Healthy Longevity of National Yang Ming Chiao Tung University from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education, the National Science and Technology Council, and the Ministry of Science and Technology in Taiwan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Benzodiazepines and Z-hypnotics are commonly prescribed for anxiety and insomnia during pregnancy, but the evidence regarding potential adverse neonatal outcomes is insufficient because of poor control for confounding factors in previous studies. We therefore aimed to evaluate the association between the use of benzodiazepines or Z-hypnotics during early pregnancy and adverse neonatal outcomes (stillbirth, preterm birth, and small for gestational age)., Methods: We did a nationwide, population-based cohort study in Taiwan using three data sources: Taiwan's National Birth Certificate Application database, the National Health Insurance database, and the Maternal and Child Health Database. The study cohort included all singleton pregnancies of females aged 15-50 years who gave birth between Jan 1, 2004, and Dec 31, 2018. Pregnancies without valid information were excluded. Benzodiazepine and Z-hypnotic use was defined as at least one benzodiazepine or Z-hypnotic prescription during early pregnancy (the first 20 weeks of pregnancy). The primary outcomes were stillbirth (fetal death at or after 20 weeks' gestation), preterm birth (<37 weeks' gestation), and small for gestational age (birthweight below the 10th percentile for gestational age by sex). Logistic regression models with propensity score fine stratification weighting were used to control for potential confounders and examine the association between benzodiazepines or Z-hypnotics use during early pregnancy and the risk of adverse neonatal outcomes. Odds ratios (ORs) and 95% CIs were reported. We used confounding by indication control analyses, a sibling control study, and a paternal negative control design to account for unmeasured confounders. The risk associated with exposure during late pregnancy was also assessed., Findings: Between Oct 7, 2021, and June 10, 2022, we analysed the study data. The cohort included 2 882 292 singleton pregnancies; of which, 75 655 (2·6%) of the mothers were dispensed one or more benzodiazepines or Z-hypnotics during early pregnancy. Women exposed during pregnancy were older (mean age at delivery was 31·0 years [SD 5·3] for exposed women vs 30·6 years [4·9] for unexposed women), had a higher prevalence of psychiatric disorders, and were more likely to have unhealthy lifestyle behaviours than unexposed women. Information about ethnicity was not available. Early pregnancy exposure was associated with adverse neonatal outcomes compared with non-exposure. The propensity score-weighted OR was 1·19 (95% CI 1·10-1·28) for stillbirth, 1·19 (1·16-1·23) for preterm birth, and 1·16 (1·13-1·19) for small for gestational age. After controlling for confounding by indication, there was no significant association between drug exposure and stillbirth risk; however, this attenuation was not observed for preterm birth and small for gestational age. In models with sibling controls that accounted for familial confounding and genetic factors, early exposure to benzodiazepines or Z-hypnotics was not associated with an increased risk of stillbirth and preterm birth, but it remained significantly associated with small for gestational age. The paternal negative control analyses with point estimates close to the null indicated no strong evidence of unmeasured confounding shared by the mother and the father. Substantially increased risks of stillbirth and preterm birth were observed for late pregnancy exposure., Interpretation: Benzodiazepine or Z-hypnotic use in early pregnancy is not associated with a substantial increase in the risk of stillbirth and preterm birth after accounting for unmeasured confounding factors. Clinicians should be aware of the increased risk of small for gestational age and caution should be taken when prescribing these medications during late pregnancy., Funding: National Science and Technology Council, Taiwan., Translation: For the Taiwanese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The rapid identification of Influenza A virus and its variants, which cause severe respiratory diseases, is imperative to providing timely treatment and improving patient outcomes. Conventionally, two separate assays (total test duration of up to 6 h) are required to initially differentiate Influenza A and B viruses and subsequently distinguish the pdm H1N1 and H3N2 serotypes of Influenza A virus. In this study, we developed a multiplex real-time RT-PCR method for simultaneously detecting Influenza A and B viruses and subtyping Influenza A virus, with a substantially reduced test duration. Clinical specimens from hospitalized patients and outpatients with influenza-like symptoms in Eastern Taiwan were collected between 2011 and 2015, transported to Hualien Tzu Chi Hospital, and analyzed. Conventional RT-PCR was used to subtype the isolated Influenza A viruses. Thereafter, for rapid identification, the multiplex real-time RT-PCR method was developed and applied to identify the conserved regions that aligned with the available primers and probes. Accordingly, a multiplex RT-PCR assay with three groups of primers and probes (MAF and MAR primers and MA probe; InfAF and InfAR primers and InfA probe; and MBF and MBR primers and MB probe) was established to distinguish these viruses in the same reaction. Thus, with this multiplex RT-PCR assay, Influenza B, Influenza A pdm H1N1, and Influenza A H3N2 viruses were accurately detected and differentiated within only 2.5 h. This multiplex RT-PCR assay showed similar analytical sensitivity to the conventional singleplex assay. Further, the phylogenetic analyses of our samples revealed that the characteristics of these viruses were different from those reported previously using samples collected during 2012-2013. In conclusion, we developed a multiplex real-time RT-PCR method for highly efficient and accurate detection and differentiation of Influenza A and B viruses and subtyping Influenza A virus with a substantially reduced test duration for diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality., Design: Retrospective cohort study., Setting and Participants: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed., Methods: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively., Results: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index)., Conclusions and Implications: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Despite the recognized impact of intrinsic capacity (IC) impairment on healthy aging, international comparisons in different sociocultural contexts are scarce. This study aimed to compare IC impairment among community-dwelling older adults in Japan and Taiwan to explore the context of healthy aging in different countries., Design: Comparative observational study., Setting: National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) in Japan and Longitudinal Aging Study of Taipei (LAST) in Taiwan., Participants: 794 individuals (age range, 60.0-86.5 years) from NILS-LSA and 1,358 (60.0-96.7 years) from LAST., Measurements: IC impairment was evaluated across the domains of locomotion, cognition, vitality, sensory capacity, and psychological well-being. Participants were categorized as having impaired IC or healthy. We investigated associations between IC impairment, falls, and all-cause mortality., Results: IC impairment was present in 54.9% and 37.3% of participants in the NILS-LSA and LAST cohorts, respectively. Male NILS-LSA participants with impaired IC (odds ratio [OR]:1.50, 95% confidence interval [CI]:1.03-2.20), with hearing loss (OR:1.98, 95% CI:1.00-3.90) were more likely to fall. In LAST, impaired locomotion (OR:2.14, 95% CI:1.46-3.14) increased the risk of falls. Men with impaired IC (hazard ratio [HR]; 2.14, 95% CI:1.10-4.15) and visual impairment (HR:2.21, 95% CI:1.15-4.25) and women with impaired psychological well-being (HR:4.94, 95% CI:1.28-18.97) in the NILS-LSA cohort had greater risk for all-cause mortality; however, this was not shown for LAST participants., Conclusion: The prevalence and distribution of IC impairment and associated biomarkers differed significantly between participants in Japan and Taiwan. However, the associations with adverse outcomes remained similar, emphasizing the need for tailored interventions for healthy aging., Competing Interests: None.

Background: Chinese populations have been reported higher incidence of all strokes and intracerebral hemorrhage. However, few large-scale studies have evaluated changes of stroke epidemiology in the 21st century., Methods: We explored the rates of incidence of all first-ever strokes, subtypes, and 1-month case fatality by using data from the Taiwan National Health Insurance Research Database since 2004. Also, we investigated sex differences in stroke. Time-trend analysis was performed for incidence and case fatality rates of all strokes and subtypes in both sexes., Results: The age-adjusted incidence of all strokes per 100,000 person-years decreased by 16%, from 251 (95% confidence interval [CI] 249-253) in 2004 to 210 (95% CI 209-212) in 2011 (p<0.001); it was always higher in Chinese men than in women. Among pathological subtypes, the incidence of intracerebral hemorrhage markedly decreased by 26% over the years (p<0.001), while that of ischemic stroke slightly decreased by 8%. However, when stratified by sex, the incidence of ischemic stroke decreased significantly in only women, not in men (men: p = 0.399, women: p = 0.004). Regarding the incidence of subarachnoid hemorrhage, it remained unchanged. Furthermore, the rate of 1-month case fatality decreased significantly for all strokes in both sexes (p<0.001)., Conclusions: In Taiwan, the incidence rate of first-ever stroke decreased in both Chinese men and women in the early 21st century. Men had a higher incidence rate than women. Furthermore, a marked decrease was noted in the incidence of intracerebral hemorrhage, while a slight decrease was noted in that of ischemic stroke; however, the decreased incidence of ischemic stroke was significant in only women., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Tsai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To investigate the relationship between dietary diversity and healthy aging (in terms of mobility performance, physical functions, cognitive functions, and depressive symptoms) among community-dwelling middle-aged and older adults by using a nationally representative population-based cohort study., Methods: Data from 3213 study participants in the Taiwan Longitudinal Study on Aging (TLSA) were retrieved for analysis, and all participants were divided into five groups according to the quintile of dietary variety scores (DVSs). In the 4-year follow-up study, multivariate logistic regression models were applied to investigate the associations between DVS subgroups and declines in mobility performance, physical function (activities of daily living (ADLs) and instrumental activities of daily living (IADLs)), cognitive function and depressive symptoms., Results: In this study, the DVS quintile identified people who were significantly vulnerable in diet quality. Among those in the lowest DVS quintile, the proportions consuming seafood, eggs, and beans/legumes per week were 0.3 %, 7.8 % and 12.6 %, respectively, while among those in the highest DVS quintile, the proportions were 40.2 %, 83.1 %, and 82.7 %, respectively. "Inverse" dose-response associations were observed between the DVS and the risks of decline in mobility performance, physical function (ADLs and IADLs), cognitive function, and depressive symptoms. These risks decreased with the higher DVS quintile group as compared to the lowest DVS quintile group. Even after adjustments for demographics, health behaviors (e.g., physical activity) and comorbidities, participants in the highest DVS quintile group were still associated with the lowest risk of decline in ADLs (adjusted odds ratio (aOR) 0.59 [95 % confidence interval (CI) 0.37-0.94], p < 0.05) and IADLs (aOR 0.53 [0.39-0.73], p < 0.01). However, no such association was observed in the risk of worsened mobility performance, cognitive function and depressive symptoms., Conclusions: In conclusion, higher dietary diversity has protective effects in declines in multidimensional outcomes associated with healthy aging, particularly physical functions (ADL and IADL), among community-dwelling middle-aged and older adults. Intervention studies are needed to confirm the causal relationships between dietary diversity and healthy aging., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present study aimed to determine whether a recently proposed cerebral small vessel disease (CSVD) classification scheme could differentiate the 5-year all-cause mortality in middle-to-old aged asymptomatic CSVD. Stroke-free and non-demented participants recruited from the community-based I-Lan Longitudinal Aging Study underwent baseline brain magnetic resonance imaging (MRI) between 2011 and 2014 and were followed-up between 2018 and 2019. The study population was classified into control (non-CSVD) and CSVD type 1-4 groups based on MRI markers. We determined the association with mortality using Cox regression models, adjusting for the age, sex, and vascular risk factors. A total of 735 participants were included. During a mean follow-up of 5.7 years, 62 (8.4%) died. There were 335 CSVD type 1 (57.9 ± 5.9 years), 249 type 2 (65.6 ± 8.1 years), 52 type 3 (67.8 ± 9.2 years), and 38 type 4 (64.3 ± 9.0 years). Among the four CSVD types, CSVD type 4 individuals had significantly higher all-cause mortality (adjusted hazard ratio = 5.0, 95% confidence interval 1.6-15.3) compared to controls. This novel MRI-based CSVD classification scheme was able to identify individuals at risk of mortality at an asymptomatic, early stage of disease and might be applied for future community-based health research and policy., (© 2021. The Author(s).)

Activin A, a cytokine belonging to the transforming growth factor-β family, has been shown to play pivotal roles in tissue remodeling after renal injury and is present in elevated levels in diabetic patients. However, the association between activin A and albuminuria remains unclear. We aimed to evaluate their association by using cross-sectional data from community-dwelling middle-aged and older adults in Taiwan. We assessed 466 participants (67% male; mean age 71 ± 13 years) from the I-Lan Longitudinal Aging study for whom data pertaining to serum activin A level and urine albumin-to-creatinine ratio (UACR) were available. Of these, 323 (69%) had normal albuminuria, 123 (26%) had microalbuminuria, and 20 (4%) had overt albuminuria. Patients with overt albuminuria and microalbuminuria had significantly higher activin A concentrations than those in the normal albuminuria group (p < 0.001). Circulating activin A was significantly correlated with multiple risk factors, including higher systolic blood pressure and higher UACR. Univariate and multivariate results indicated that activin A level was an independent variable for albuminuria. The cutoff value of 602 pg/mL of activin A demonstrated a sensitivity of 70.6% and specificity of 75.7% (AUC 0.774) in diagnosing overt albuminuria. In conclusion, middle-aged and older adults with elevated activin A levels were associated with a higher incidence of albuminuria., (© 2021. The Author(s).)

The cumulative effect of multiple pharmaceutics with anticholinergic properties (i.e., anticholinergic burden), can serve as an indicator of suboptimal prescribing in the elderly. Yet, no research is available concerning the effect of different compositions of score on adverse outcomes under the same anticholinergic burden. This population-based cohort study investigated whether different combinations of medications with anticholinergic properties have different impacts on adverse outcomes in the elderly using the Anticholinergic Risk Scale (ARS) and Anticholinergic Cognitive Burden Scale (ACB) scores. We included 116,043 people aged 65 years and older from Taiwan's Longitudinal Health Insurance Database and measured their monthly anticholinergic burden over a 10-year follow-up period (from January 1, 2002, to December 31, 2011). We analyzed the association between different anticholinergic score compositions and adverse outcomes (emergency department visits, all-cause hospitalizations, fracture-specific hospitalizations, and incident dementia) via generalized estimating equations. Cumulative effects of multiple medications with low anticholinergic activity were associated with a greater risk for emergency department visits and all-cause hospitalizations (emergency department visits for 65-74 year olds (y/o): ACB 1 + 1 + 1, adjusted odds ratio (aOR) 2.05 (1.99-2.12); ACB 1 + 2, aOR 2.04 (1.91-2.17); and ACB 3, aOR 1.62 (1.57-1.66)). In contrast, using medications with greater potency had a greater impact on central adverse outcomes (incident dementia for 65-74 y/o: ACB 1 + 1 + 1, aOR 3.30 (2.84-3.84); ACB 1 + 2, aOR 5.84 (4.59-7.41); and ACB 3, aOR 9.15 (8.38-9.99)). The quantity of anticholinergics (even with low score) an older person used matters in risk of emergency department visit and all-cause hospitalization but the potency of anticholinergics (i.e., those with high score) matters in risk of fracture-specific hospitalization and incident dementia., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

Aim: To investigate the prognostic significance of hospitalization-associated muscle weakness for short-term and long-term functional declines among oldest old hospitalized patients., Methods: We conducted a retrospective cohort study in the Geriatric Evaluation and Management Unit (GEMU) of a tertiary medical center in Taiwan. Data from patients admitted to the GEMU were collected, including demographic characteristics, underlying diseases, functional assessments, and nutritional status. Handgrip strength was measured at admission and before discharge, and hospitalization-associated muscle weakness was defined accordingly. Functional status was ascertained by a telephone survey, and functional decline was defined based on a comparison with each patient's functional status before discharge., Results: Overall, data from 555 patients were retrieved, and 431 patients (mean age: 86.0 ± 6.2 years, 78.5% males) were included in the study, with a mean Barthel Index score of 74.7 ± 20.8, Mini-Mental State Examination (MMSE) score of 19.1 ± 6.8, Geriatric Depression Scale (GDS-5) score of 2.2 ± 1.6, Mini-Nutritional Assessment-Short Form (MNA-SF) score of 8.9 ± 3.0, Cumulative Illness Rating Scale-Geriatric (CIRS-G) score of 2.2 ± 0.9, and the regular use of 6.7 ± 3.5 medications. Patients with a 1-month postdischarge functional decline had significantly lower body weight and body mass index, more severe frailty and more hospitalization-associated muscle weakness. Patients with a 6-month postdischarge functional decline had lower body weight, BMI, MMSE scores, MNA-SF scores, handgrip strength, Barthel Index scores, and Braden Scale scores. BMI (OR: 0.815, 95% CI: 0.691-0.962, P = 0.015) and hospitalization-associated muscle weakness (OR: 1.227, 95% CI: 1.147-1.332, P < 0.001) were significantly associated with a 1-month postdischarge functional decline. Hospitalization-associated muscle weakness (OR: 1.067, 95% CI: 1.035-1.101, P < 0.001), the risk of pressure sores (Braden Scale, OR: 0.767, 95% CI: 0.646-0.910, P = 0.002), and BMI (OR: 0.914, 95% CI: 0.838-0.998, P = 0.045) were independently associated with a 6-month postdischarge functional decline., Conclusions: Hospitalization-associated muscle weakness significantly predicts functional decline among oldest old patients hospitalized for acute conditions. Further interventional studies are needed to examine the causal relationship between hospitalization-associated muscle weakness and clinical outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Backgrounds: To investigate the efficacy of a community group-based intervention among community-dwelling older adults with physio-cognitive decline syndrome (PCDS)., Methods: A prospective cluster randomized controlled trial included 733 community-dwelling older adults with adjusted Montreal Cognitive Assessment (MoCA adj) scores >18 from 40 community-based sites across Taiwan. PCDS was defined as the concomitant presence of physical declines, i.e., slowness and/or weakness plus dysfunction in any cognitive domain. The multidomain intervention integrated physical exercise, cognitive training, nutritional advices and health education lessons. Conventional health education in control group entailed periodic telephone calls to offer participants health education and advice. The primary outcome was the mean differences of MoCA adj total scores and all domains of MoCA adj between baseline and 6- and 12-month follow-up in each group of PCDS, cognitive dysfunction, mobility-type frailty and normal functioning, and the secondary outcomes included the changes of frailty score, handgrip strength, gait speed and physical activity. Intervention effects were analysed using a generalized linear mixed model., Results: Overall, 18.9% of the study sample had PCDS. Multidomain intervention for 12 months significantly improved cognitive performance in people with PCDS, and those with cognitive dysfunction only. An early benefit on visuo-spatial executive function was seen in older adults with mobility-type frailty. Intervention also improved frailty scores among participants with mobility-type frailty, handgrip strength for participants with PCDS, and gait speed in the normal group., Conclusions: PCDS is a potentially reversible condition that may prevent subsequent disability and dementia, which deserves further investigation to confirm the long-term effects., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Healthcare expenditure on pharmaceuticals, especially innovative oncology drugs, is escalating. Current knowledge on this topic is largely limited to studies conducted upon reimbursement of new drugs. We investigated how endogenous factors (e.g., changed reimbursement criteria, such as an expanded indication) and exogenous factors (e.g., competing drugs) affect the level and trends of innovative oncology drug utilization in the Taiwan National Health Insurance (NHI) system, both upon reimbursement and afterward. This retrospective longitudinal study analyzed monthly data (January 2009 to December 2014) from the NHI Research Database on the consumption (prescribing volume) of 15 innovative oncology drugs reimbursed by the NHI between 2007 and 2013. Effects of endogenous and exogenous factors on drug utilization were evaluated using interrupted time series analyses. In segmented regression analyses, changed drug prescribing volume after the indication expanded (endogenous factor) was statistically significant; however, drug volume did not change significantly after prescription restrictions changed. First-competitors and non-first-competitors (exogenous factors) were significantly associated with drug prescription levels or utilization rates. Taking sorafenib as an example, the post-reimbursement drug prescribing volume did not change significantly after its therapy line changed (endogenous factor), whereas the reimbursement of first-competitors (exogenous factor) was significantly associated with a lower level or usage rate of sorafenib. Utilization of innovative oncology drugs in Taiwan changed dramatically after NHI reimbursement, driven largely by expanded indications and new competitors. Drug utilization evaluations should investigate both endogenous and exogenous factors., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Background: Clinical guidelines for specific conditions fragment care provision for elders. The International Consortium for Health Outcomes Measurement (ICHOM) has developed a global standard set of outcome measures for comprehensive assessment of older persons. The goal of this study was to report value-based health metrics in Taiwan using this ICHOM toolset., Methods: The cross-sectional study of baseline data excerpted from a prospective longitudinal cohort, which recruited people ≥65 years old with ≥3 chronic medical conditions between July and December 2018. All participants received measurements of physical performance, anthropometric characteristics, health-related behaviors, Charlson Comorbidity Index, and Montreal Cognitive Assessment. The ICHOM toolset comprises three tiers: 1 includes frailty and having chosen a preferred place of death; 2 includes polypharmacy, falls, and participation in decision-making; and 3 includes loneliness, activities of daily living, pain, depression, and walking speed. These items were converted into a 0-10 point value-based healthcare score, with high value-based health status defined as ≥8/10 points., Results: Frequencies of individual ICHOM indicators were: frail 11.7%, chose preferred place of death 14.4%, polypharmacy 31.5%, fell 17.1%, participated in decision-making 81.6%, loneliness 26.8%, limited activities of daily living 22.4%, pain 10.4%, depressed mood 13.0%, and slowness 38.5%. People with high disease burden (OR 0.40, 95% CI 0.21-0.76, p = 0.005) or cognitive impairment (OR 0.49, 95%CI 0.27-0.87, p = 0.014) were less likely to have high value-based healthcare status., Conclusions: The ICHOM Standard Set Older Person health outcome measures provide an opportunity to shift from a disease-centric medical paradigm to whole person-focused goals. This study identified advanced age, chronic disease burden and cognitive impairment as important barriers to achieving high value-based healthcare status.

Frailty is common among older people and results in adverse health outcomes. We investigated whether exposure to PM 2.5 is associated with frailty. This cross-sectional study involved 20,606 community-dwelling participants aged ≥ 65 years, residing in New Taipei City, Taiwan. Analytic data included phenotypic frailty, disease burden by Charlson Comorbidity Index (CCI), urban or rural residence, and household income. PM 2.5 exposure was calculated from air quality monitoring records, with low exposure defined as the lowest quartile of the study population. 1,080 frail participants (5.2%) were older, predominantly female, had more comorbidities, lived rurally, and had low PM 2.5 exposure (all p < 0.001). In multinomial logistic regression analyses, the likelihood of high PM 2.5 exposure was higher in prefrail (OR 1.4, 95% CI 1.3-1.5) and frail adults (OR 1.5, 95% CI 1.2-1.9) than in robust individuals, with stronger associations in those who were male (frail: OR 2.1, 95% CI 1.5-3.1; prefrail: OR 2.2, 95% CI 1.9-2.6), ≥ 75 years old (frail: OR 1.8, 95% CI 1.3-2.4; prefrail: OR 1.5, 95% CI 1.3-1.8), non-smokers (frail: OR 1.6, 95% CI 1.3-2.0; prefrail: OR 1.4, 95% CI 1.2-1.5), had CCI ≥ 2 (frail: OR 5.1, 95% CI 2.1-12.6; prefrail: OR 2.1, 95% CI 1.2-3.8), and with low household income (frail: OR 4.0, 95% CI 2.8-5.8; prefrail: OR 2.7, 95% CI 2.2-3.3). This study revealed a significant association between PM 2.5 exposure and frailty, with a stronger effect in vulnerable groups.

Background: Residency training includes positive and negative aspects. Well-trained doctors must be educated, but the process may bring additional risks to patients. Anesthesiologists' performance when conducting neuraxial anesthesia is related to their experience. We hypothesized that a modified neuraxial anesthesia method would improve both residency training and patient safety., Methods: We recruited 518 patients who were scheduled for a cesarean section and used spinal anesthesia (n = 256), epidural anesthesia (n = 154), and combined spinal-epidural anesthesia (SEA; n = 108). We observed and evaluated the anesthesia performance of five second-year resident anesthesiologists in elective cesarean sections using the conventional and modified methods. The number of attempts, implant error rate, and the incidence of complications were recorded and analyzed., Results: Better success puncture attempts occurred in all three groups when the modified method was applied. For the groups with an implant assessment, the complication rate and implant error rate were lower when using the modified method. We employed generalized estimating equation (GEE) analysis to correct for possible confounding factors. When using the conventional method, the resident anesthesiologists required more attempts, made more implant errors, and caused more complications in patients., Conclusions: We found that a modified method for neuraxial anesthesia could improve residency performance and patient safety. The modified method may be a suitable training process for resident anesthesiologists when practicing neuraxial anesthesia., Trial Registration: The study was approved by the Research Ethics Committee of National Taiwan University (IRB:200812040R) Clinicaltrials register: NCT03389672 .

Purpose: The risk of diabetes mellitus increases with age but its characteristics, treatment patterns, and outcomes in people with onset at different ages are little studied. The aim of this study is Investigate longitudinal clinical characteristics, complications, anti-diabetes medication usage, and diabetes-related outcomes among people diagnosed at different ages., Methods: This retrospective cohort study using Taiwan National Health Insurance Research Database claims data from 2000 to 2013, recruited 123,172 ≥ 40-year-olds with newly diagnosed diabetes, stratified by age at diagnosis: 40-64 years (62.2 %), 65-74 (21.9 %), 75-84 (12.9 %), and ≥ 85 (3.0 %). Baseline characteristics, 10-year follow-up of anti-diabetes drug usage, and cumulative incidence of diabetes-related complications and outcomes, stratified by age., Results: Compared to people with younger-onset, those diagnosed when older had more multimorbidity, higher prevalence of diabetes-related complications, and proportionally lower anti-diabetes drug usage (all p < 0.01). During 10-year follow-up, people diagnosed when older had higher risks for cardiovascular and cerebrovascular disease, nephropathy, and peripheral artery disease, but lower cumulative incidence of retinopathy and peripheral neuropathy (all p < 0.001). People with later versus earlier onset had higher rates of all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, and diabetes-related hospitalization (all p < 0.001)., Conclusion: Over 10-year follow-up, people who are older versus younger at diabetes diagnosis have higher cumulative incidence of macrovascular complications but lower rates of microvascular complications (except nephropathy); they also have higher cumulative incidence of diabetes-related hospitalization, all-cause mortality, and cardiovascular morbidity and mortality., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: To elucidate the hypothetically different interactions between delirium and post-discharge prognostic indicators in elderly hospital inpatients with versus without dementia., Design: Retrospective cohort study of claims data by Taiwan National Health Insurance beneficiaries between 2002-2013., Setting: Records of public hospital admissions in the Taiwan National Health Insurance Research database., Participants: Propensity-score matched subgroups of patients with delirium superimposed on dementia (n = 922) versus dementia alone (n = 922), delirium alone (n = 680) versus neither delirium nor dementia (n = 680)., Measurements: Mortality, emergency department visits, readmissions, and psychotropic drug use, within 30, 180, and 365 days of discharge, were analyzed using multivariate proportional hazards or logistic regression analyses., Results: Delirium superimposed on dementia was not associated with increased post-discharge mortality, or emergency department visits, but significantly increased the risk of readmissions at 365-day follow-up (adjusted HR, 95% CI: 1.26, 1.01-1.56). However, delirium without dementia was significantly associated with increased post-discharge mortality, emergency department visits and readmissions at 180 days and 365 days (respective adjusted HRs: mortality, 1.63 and 1.79; adjusted ORs: emergency department visits, 1.89 and 1.81; readmissions, 1.47 and 1.53). Delirium in patients both with dementia and without, was associated with six-fold higher likelihood of in-hospital psychotropic drug use, and doubled post-discharge psychotropic drug usage., Conclusions: The obvious association between in-hospital delirium and worsened long-term prognosis, irrespective of dementia, raises awareness to warrants proactive and multimodal prevention and intervention strategies. Furthermore, the mechanisms about different influence of delirium for patients with/without dementia need to be further explored., Competing Interests: All authors, Chih-Kuang Liang, Hsien-Yeh Chuang, Fei-Yuan Hsiao, Ming-Yueh Chou, Tsung-Yun Liu, Chen-Chang Yang, and Liang-Kung Chen had no conflict of interest including financial and personal conflicts in this article.

Metabolic syndrome (MS) was conceptualized to identify people at risk for cardiovascular disease and type 2 diabetes; however, the epidemiology of MS and its combinations of components in older adults remains unclear. Data from the Senior Health Examination Program of the New Taipei City Government in Taiwan in 2014 were obtained for this study. All participants aged 65 years or older and those with a prior history of cardiovascular disease, cerebrovascular disease, or diabetes mellitus were excluded. 29,164 senior citizens were retrieved for this study, and 12,331 (41.28%) of the participants were male. Female participants were more likely to have MS (42.7% vs.31.3%, p <0.001). Female participants with MS were older than those without MS (73.15±6.5 vs. 72.10±6.14 years, p <0.001). Conversely, male participants with MS were younger than those without MS (72.93±6.70 vs. 73.52±6.98 years, p <0.001). The most common combination of MS components was the triad of high blood glucose, high blood pressure and central obesity (25.2% of all participants with MS). Age-related changes in MS component combinations were noted only when central obesity was present. The strongest MS component combination for new-onset diabetes mellitus was high blood glucose, hypertriglyceridemia, reduced HDL-C and central obesity (HR: 5.42, P<0.001). In conclusion, not all component combinations of MS were of the same prognostic impact or the risk for new-onset diabetes mellitus. Further study is needed to develop individualized intervention programs for MS based on risk profiles of older adults is needed., Competing Interests: The authors declare that they have no competing interests.

Objective: Existing evidence on long-term psychotropic polypharmacy in older people is scarce despite serious safety concerns regarding this issue. This study aims to identify distinct trajectories of longitudinal psychotropic agent use and to examine the association with the risk of mortality and unplanned hospitalization according to distinct trajectories., Design: A retrospective longitudinal cohort study based on data from Taiwan's National Health Insurance Research Database (NHIRD)., Setting and Participants: A population-based study including 39,803 eligible participants aged 65 years or older who were newly prescribed oral psychotropic agents in 2004., Measures: We assessed 5 years of monthly consumption of psychotropic agents among eligible participants and used group-based trajectory modeling to identify distinct groups of longitudinal psychotropic use. Cox proportional hazards models were used to examine the association between distinct trajectories of longitudinal psychotropic agent use and subsequent 1- and 3-year unplanned hospitalization and all-cause mortality., Results: Among 39,803 eligible participants, we identified 5 trajectories of longitudinal psychotropic agent use over a 5-year follow-up period: sustained intense (7.1%), moderate increasing (12.1%), decreasing (13.4%), slowly increasing (15.7%), and infrequent users (51.6%). Moderate increasing and sustained intense use were associated with significantly higher risks of unplanned hospitalization [moderate increasing use: hazard ratio [HR] 1.30, 95% confidence interval (CI) 1.18-1.44; sustained intense use: HR 1.40, 95% CI 1.24-1.58] and all-cause mortality (moderate increasing use: HR 1.25, 95% CI 1.09-1.44; sustained intense use: HR 1.32, 95% CI 1.12-1.56) than infrequent use. Similar results were observed at 3 years of follow-up., Conclusions/implications: Older people with moderately increasing and sustained intense use of psychotropic agents over time had higher risks of unplanned hospitalization and mortality. Tracking older people's use of psychotropic agents over time may help to identify individuals at greatest risk of unplanned hospitalization and mortality., (Copyright © 2019 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

In most western countries, postoperative nausea and vomiting (PONV) is an important issue and prophylaxis guideline for PONV will be followed in clinical practice. We tried to conduct a review study and a local study to elucidate the incidence and severity of PONV to see if considering ethnicity factor, should we still need to follow those prophylaxis guidelines from western countries. The PubMed, and MEDLINE were consulted from January 2000 to 2018 and also Cochrane Central Register of Controlled Trials (CENTRAL 2010). The key word for searching is PONV (incidence, severity and prevention strategy), without language limitation and focus on Asian countries. The results showed that the overall incidence and severity of PONV in Asian countries was less significant than in western countries. PONV in western countries could be a serious issue and prophylaxis strategy adjusted by Apfel score could be adopted in routine practice. After this review consultation, the issue of PONV in different ethnic countries (including Taiwan) might be over emphasized and we may suggest not to follow west countries PONV prophylaxis guideline as our routine practice., (Copyright © 2019. Published by Elsevier B.V.)

The emergence of biobanks has expanded the scope of biomedical research, ushering in an era of "precision medicine" to improve the treatment of disease. However, biobanks also face sustainability challenges comprising three dimensions-"financial," "operational," and "social." The Taiwan Biobank (TWB), as a large-scale national biobank that supplies valuable phenotypic and genetic information to biomedical researchers on an application basis to investigate the relationship among personal health, genes, lifestyle, environment and diseases of the Taiwanese population, has not been sufficiently explored by researchers. Although the TWB has successfully reached a few milestones since its inception, it faces many sustainability challenges. For the next chapter of the TWB, we propose three strategies to improve sustainability. First, the Ministry of Health and Welfare launched the TWB as an infrastructure project under the leadership of Academia Sinica in 2012. We now believe that it is time that the TWB is transformed into a legal entity as a nondepartmental public body. This would not only ensure efficient, effective, and flexible operation, but would also facilitate cooperation with commercial entities. Second, we suggest that the TWB integrates with other Taiwanese biobanks to reduce cost, improve low utilization, and expand specimen collection. Third, self-financing is important if funding is ceased. Besides implementing a cost-recovery model, the commodities developed by the TWB (e.g., TWB 2.0 microarray) will help increase income. After each of these strategies has been discussed in detail, this article will conclude by highlighting how these practices can help improve biobank sustainability.

Background: Sarcopenia is a well-recognized geriatric syndrome. We sought to determine the prevalence of sarcopenia and factors associated with it among community-dwelling older adults in Taiwan., Methods: A cross-sectional study was conducted in Yuanshan Township, Yilan County, Taiwan. Data of 731 community-dwelling adults aged 65 and older were evaluated. Demographic characteristics, anthropometry, medical history, biochemistry results, and dual-energy X-ray absorptiometry results were collected for analysis., Results: Males had a higher rate of sarcopenia than did females and had lower values for body weight, body mass index, waist circumference, percentage of body fat, and lean body mass. Poor nutritional status as determined by the Mini Nutritional Assessment correlated positively with markers for sarcopenia. Levels of vitamin D and folic acid correlated positively with some sarcopenia markers., Conclusions: Gender differences and nutritional factors may influence the development of sarcopenia. Vitamin D is positively correlated with relative appendicular skeletal muscle mass in males with sarcopenia, and folic acid was positively correlated with gait speed in females with sarcopenia., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Reciprocal age-related impairments in physical and cognitive functioning have been termed 'cognitive frailty', which is associated with adverse health outcomes and is a potential target for preventing or delaying the onset of disability in older people. However, cognitive frailty as currently defined is challenging to diagnose. To facilitate earlier diagnosis and intervention, we conducted this study to develop and validate a simple evidence-based instrument to identify community-dwelling elders at risk of cognitive frailty., Design: Retrospective analyses of data from the I-Lan Longitudinal Aging Study (ILAS) to develop a prediction model, and from the Longitudinal Aging Study of Taipei (LAST) for external validation., Setting: Community-dwelling adults from Taipei City, New Taipei City and Yilan (I-Lan) County, Taiwan., Participants: 1271 community residents ≥65 years old, without impaired global cognition or dependency for activities of daily living/instrumental activities of daily living., Measurements: Demographic characteristics, anthropometric measurements, medical history, Mini-Mental State Examination, Montreal Cognitive Assessment, Functional Autonomy Measuring System, Functional Assessment Staging Test, Center for Epidemiologic Studies Depression Scale, handgrip strength, 6-metre walk speed., Methods: Baseline characteristics of groups with/without cognitive frailty were analyzed and factors differing significantly in univariate analysis input to binary logistic regression to develop a cognitive frailty risk (CFR) score., Results: The prevalence of cognitive frailty was 15.8% overall; ILAS 21.4%, LAST 8.4%. Predictors of CFR comprised: age ≥75 years; female sex; waist circumference ≥90 cm (male), ≥80 cm (female); calf circumference <33 cm (male), <32 cm (female); memory deficits; and diabetes mellitus. CFR ≥5/14 had sensitivity of 70%, specificity of 60%, and predictive accuracy of 72%., Conclusions: A CFR score based on simple history-taking and anthropometric measurements integrates age, sex, cardiometabolic risk, memory deficits, sarcopenia, and nutrition, with validated predictive accuracy, and could be performed easily in community settings to identify seniors with cognitive frailty for appropriate interventions., Competing Interests: All authors declare no conflict of interest

The role of serum vitamin D (Vit D) in cardiometabolic and muscle health remains unclear. The study aimed to evaluate associations of Vit D and factors of healthy aging among community-living middle-aged and older people in Taiwan. Analytic data on 1839 community-living older adults were excerpted from I-Lan Longitudinal Aging Study. All participants were collected demographic characteristics, serum Vit D, functional assessment, and cardiometabolic risk factors. The prevalence of Vit D insufficiency and deficiency in this study was 50.5% and 33.6%, respectively. Among 617 participants with Vit D deficiency, 72.3% of them were women. In multivariate logistic regression, the independent risk factors of Vit D deficiency were male gender (odds ratio [OR]: 0.266; 95% confidence interval [CI]: 0.213-0.333; P < 0.001), higher BMI (OR: 1.036; 95% CI: 1.005-1.067; P = 0.022), high total cholesterol (OR: 1.437; 95% CI: 1.160-1.779; P = 0.001), and high triglyceride (OR: 1.865; 95% CI: 1.446-2.404; p < 0.001). In multinomial logistic regression for 3-level Vit D status analysis, similar trend was found among participants with Vit D insufficiency. Insulin resistance increased in 2.31 and 1.71-folds in Vit D deficiency and insufficiency groups. Besides, association between Vit D deficiency and osteopenia was found only in women. In conclusion, Vit D deficiency was more common in women, and associated with poorer musculoskeletal health and higher cardiovascular and metabolic risk, including higher BMI, DBP, insulin resistance, total cholesterol, and triglyceride.

The definition of cognitive frailty and its prediction for adverse outcome of community-living older adults remains controversial. This study aims to evaluate the association between cognitive frailty and all-cause mortality among community-living older adults. Data of the I-Lan Longitudinal Aging Study (ILAS) were retrieved for study. Frailty was defined by Fried's criteria, and a series of neuropsychological assessments, including the Mini-Mental State Examination, Center for Epidemiology Studies-Depression, the delayed free recall in the Chinese Version Verbal Learning Test, the Boston Naming Test, the category (animal) Verbal Fluency Test, the Taylor Complex Figure Test, the digital backward, and the Clock Drawing Test were performed. All participants received blood sampling after 10-hour overnight fast for various biochemical markers. Cognitive frailty was defined as the concomitant presence of dynapenia and cognitive declines in any domains. Overall, data of 678 participants aged 65 years and older (mean age: 73.3 ± 5.3 years) were obtained for the study. The prevalence of cognitive frailty in this study was 13.3%. People with cognitive frailty were significantly older, having higher multimorbidity burden, more likely to be women, and had less skeletal muscle mass. Adjusted for age and gender, both dynapenia without cognitive impairment (hazard ratio [HR]: 5.402; 95% confidence interval [CI]: 1.463-19.954; p = 0.011) and cognitive frailty (HR: 6.682; 95% CI: 1.803-26.116; p = 0.005) were significantly associated with all-cause mortality. The prevalence of cognitive frailty was 13.3% in Taiwan and was predictive for all-cause mortality. Further study is needed to explore the pathophysiology and reversibility of cognitive frailty.

Cardiovascular disease imposes substantial burdens of morbidity and mortality that increase with population aging. Estimating cardiometabolic risk accurately and expediently is challenging, and no single biomarker is satisfactory; hence, we investigated the potential of serum activin A for this purpose. Study data were collected from 433 community-dwelling adults age ≥53 years from Yilan County, Taiwan. Data included: demographics and medical history; physical measurements (blood pressure, body mass index, waist circumference); comprehensive functional assessments (frailty, cognitive function, depressive symptoms, nutritional status); fasting blood biochemistry (glucose, high-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, insulin-like growth factor-1, activin A, stratified into high, medium and low tertiles, and others); and dual-energy X-ray absorptiometry. Metabolic syndrome was considered a proxy for overall cardiometabolic risk. Subjects mean age was 69.3 ± 9.2 years, 48.3% were males. Compared to women, men had higher systolic blood pressure, education levels, relative appendicular skeletal muscle mass, waist circumference, physical activity, walking speed, free androgen index, and levels of serum uric acid, alanine aminotransferase, and dehydroepiandrosterone sulfate. High activin A was significantly associated with age, relative appendicular skeletal muscle mass in both gender, waist circumference in women, current alcohol drinking, hypertension, and Charlson Comorbidity Index. There were dose-dependent relationships (low to high) between serum activin A and frailty, cognitive impairment, malnutrition, metabolic syndrome, uric acid, and high-sensitivity C-reactive protein. Logistic regression analyses showed older age, serum uric acid, and metabolic syndrome were significantly associated with medium and high activin-A status, whereas, skeletal muscle mass, insulin-like growth factor-1 and dehydroepiandrosterone sulphate were associated with high, but not medium, serum activin A. This discovery of a dose-dependent association between serum activin A levels, age, and metabolic syndrome, suggests activin A may be a biomarker of overall cardiometabolic risk; however, further studies are needed to evaluate its potential applications in assessing and managing cardiometabolic risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Cognitive frailty (CF) featured as frailty plus cognitive impairment was deemed to be a novel target for dementia and disable prevention. The study was intended to investigate the epidemiology of CF and the association between CF and all-cause mortality., Methods: The national representative cohort study was comprised of 1,103 community-living middle-aged and older adults. CF was defined as the co-existence of dynapenia (weakness and/or slowness) and cognitive impairment (1.5 standard deviations below the age-, sex- and education-matched norms in cognitive tests) without known neurodegenerative diseases. Dynapenia was defined by the Asian Working Group for Sarcopenia and cognitive function was assessed by the Short Portable Mental Status Questionnaire., Results: The prevalence of CF was 8.6% in this study. Subjects with CF were older, more likely to be women, having less regular exercise, fewer educational years, more depressive symptoms and greater multimorbidity. Compared to robust individuals, CF was significantly associated with all-cause mortality (HR: 3.1, 95% CI:1.3-7.7, p = 0.012)., Conclusion: Dynapenia and cognitive impairment synergistically contribute to the mortality risk for the participants in this study. Further study is needed to explore the underlying pathophysiology and the reversibility of CF., Competing Interests: The authors have declared that no competing interests exist.

Activin A and its binding protein follistatin may be crucial in glucose homeostasis, as multifunctional proteins mediating inflammatory and anti-inflammatory effects. However, clinical data on the activin A level in prediabetes, and the association between the circulating activin A level and carotid intima-media thickness (cIMT), are lacking. We aimed to investigate activin A and follistatin levels and their associations with cIMT. In total, 470 inhabitants of I-Lan county (235 men; mean age 69 ± 9 years) with measurements of serum activin A and follistatin levels were included. Patients with prediabetes and diabetes had significantly increased activin A concentrations compared with those in the normal glycemic group (both p < 0.001). A multivariable logistic regression model demonstrated that the circulating activin A level was associated with prediabetes and diabetes independently of other risk factors. Moreover, the circulating activin A levels were associated positively with cIMT in prediabetes (r s  = 0.264, p = 0.001). In conclusion, activin A level, but not follistatin, was elevated independent of demographic variables with borderline significance and was correlated positively with cIMT in prediabetes. Activin A and follistatin levels were elevated in diabetes. In addition, elevated activin A was an independent risk factor for prediabetes and diabetes.

Background: To evaluate the predictive validity of sarcopenia defined by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project among Asian older adults., Methods: Data of the I-Lan Longitudinal Aging Study were obtained for analysis. Overall, 1,839 community-dwelling people aged 50 years and older, capable of completing a 6-m walk, with life expectancy of more than 6 months, and not institutionalized at time of data collection were enrolled for study. Data for subjects aged 65 years and older were obtained for study. The outcome measures were all-cause mortality and a composite adverse outcome which includes hospitalizations, emergency department visits, institutionalization, and falls., Results: Data of 728 eligible elderly participants (73.4 ± 5.4 years; 52.9% males) were analyzed. The prevalence of FNIH-diagnosed sarcopenia was 9.5%: 11.9% males; 6.7% females. Participants having FNIH-defined sarcopenia were considerably older, frailer, more obese, with poorer physical performance than nonsarcopenic subjects (All p < .001); during mean follow-up of 32.9 ± 8.8 months, they also had 3.8 times higher risk of dying, independent of age, sex, multimorbidity, cognitive function, and nutritional status (hazard ratio = 3.8; 95% confidence interval = 1.26-11.45; p = .018). Moreover, sarcopenia defined by grip strength-BMI ratio (WeakBMI) showed stronger association with composite adverse outcomes than traditional handgrip strength (hazard ratio = 1.99; 95% confidence interval = 1.01-3.93; p = .047 vs hazard ratio = 1.80; 95% confidence interval = 0.89-3.62; p = .102 in fully-adjusted model)., Conclusion: Among community-dwelling older people in Taiwan, participants with FNIH-defined sarcopenia had a significantly greater risk of all-cause mortality and composite falls, emergency department visits, institutionalization, and hospitalization.

Serum uric acid level is a risk factor for cardiovascular disease (CVD). However, whether it is an independent risk factor or not remains controversial. We analyzed the association between serum uric acid level and cardiovascular risk. In total, 973 nonhypertensive and nondiabetic participants in the I-Lan Longitudinal Aging Study were eligible for this study. Subjects were divided into tertiles according to uric acid levels. The 10-year cardiovascular risk was calculated using Framingham risk score (FRS). Study subjects in the highest tertile of serum uric acid level were older, more likely to be male, and had higher systolic blood pressure, body mass index, carotid artery intima-media thickness and serum triglyceride, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol levels and lower serum high-density lipoprotein cholesterol levels (all p < 0.05). Subjects in the highest tertile had significantly higher FRS (p < 0.001). After adjusting for other risk factors, serum uric acid level remained associated significantly with the FRS (p < 0.05). In binary logistic regression analysis, the serum uric acid level was an independent predictive factor for high (≥20%) FRS (odds ratio 1.33, 95% confidence interval 1.10-1.68). These findings warrant attention to this cardiovascular risk factor in apparently healthy adults.

Background: Hypertension is an important risk factor for cardiovascular disease. Activin A, a member of the transforming growth factor-β cytokine family, has been shown to regulate blood pressure through the renin-angiotensin system. However, the relationship between activin A and blood pressure remains uncertain. The objective of this study was to determine whether serum activin A levels are associated with blood pressure., Method: A total of 470 participants of I-Lan longitudinal Aging Study (ILAS) were eligible for this study. Serum levels of activin A were assessed by enzyme-linked immunosorbent assay. Cross-sectional analyses were performed, including comparisons of demographic characteristics, hypertensive status, and activin A levels., Results: Among the study participants (50% men, mean age, 69 years), 236 (50.2%) were hypertensive and 234 (49.8%) were normotensive. Hypertensive patients had significantly higher serum activin A levels than normotensives (normotensive vs. hypertensive: 507 ± 169 vs. 554 ± 176 pg/ml, mean ± SD, P < 0.001). All subjects were divided into 3 tertiles on the basis of serum activin A levels. Increasing tertiles of activin A were associated with higher systolic blood pressure (SBP), diastolic blood pressure and pulse pressure (PP) (all P < 0.001). After adjusting for all the potential confounding factors, serum activin A concentration was still significantly associated with SBP (P = 0.02) and PP (P = 0.03)., Conclusions: Serum activin A level was associated with SBP and PP. Further studies are required to assess their causal relationship and the clinical relevance., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Muscle mass and strength ineluctably decline with advancing age. Yet, the impact of ethnicity on the pattern of changes and their magnitude is unclear. The aims of the present study were to analyze age- and gender-specific changes in measures of muscle mass and strength among community-living persons and to identify differences between Caucasian and Asian participants., Methods: The Italian survey ("Longevity Check-up"), conducted during Milan EXPO 2015, consisted of a population assessment aimed at evaluating the prevalence of specific health metrics in persons outside of a conventional research setting (n=1924), with a special focus on muscle mass and strength. The Taiwanese survey used the first-wave sampling from the I-Lan Longitudinal Aging Study (ILAS) collected from August 2011 to August 2013 (n=1839). ILAS was designed to explore the interrelationship between sarcopenia and frailty in community-dwelling older people in Taiwan. In both studies, muscle mass was estimated by measuring the calf circumference (CC), whereas muscle strength was assessed by handgrip strength testing., Results: The mean age of the 1924 Italian participants was 62.5years (standard deviation 8.3, range from 50 to 98years), of whom 1031 (53.6%) were women. Similarly, the mean age of the Taiwanese sample was 63.9years (standard deviation 9.3, range from 50 to 92years), with 966 (52.5%) women. CC declined with age in both genders and was significantly greater among Italian participants compared with Taiwanese people in all age groups. A similar effect of age was observed for muscle strength. As for CC, muscle strength was significantly greater among Italian persons relative to Taiwanese participants., Conclusion: Muscle mass and strength declined with age in both ethnic groups. Caucasians showed greater muscle mass and performed better than their Asian counterparts. However, the age at which declines began to appear and the rate of decline during aging were comparable between the two populations., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The impact of dynapenia on the complexity of care for residents of long-term care facilities (LTCF) remains unclear. The present study evaluated associations between dynapenia, care problems and care complexity in 504 residents of Veterans Care Homes (VCHs) in Taiwan. Subjects with dynapenia, defined as low muscle strength (handgrip strength <26 kg), were older adults with lower body mass index (BMI), slow gait speed, and higher numbers of Resident Assessment Protocol (RAP) triggers. After adjusting for age, education, BMI, and Charlson's comorbidity index (CCI), only age, education, BMI and gait speed were independently associated with higher numbers of RAP triggers, but not dynapenia or handgrip strength (kg). Dividing subjects into groups based on quartiles of gait speed, those with gait speed ≤0.803 m/s were significantly associated with higher complexity of care needs (defined as ≥4 RAP triggers) compared to the reference group (gait speed >1 m/s). Significantly slow gait speed was associated with RAP triggers, including cognitive loss, poor communication ability, rehabilitation needs, urinary incontinence, depressed mood, falls, pressure ulcers, and use of psychotropic drugs. In conclusion, slow gait speed rather than dynapenia is a simple indicator for higher complexity of care needs of older male LTCF residents.