Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.

Importance: The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. Objective: To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. Design, Setting, and Participants: This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Interventions: Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. Main Outcomes and Measures: The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Results: Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. Conclusions and Relevance: In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. Trial Registration: ClinicalTrials.gov Identifier: NCT04660643.

Trends in energy and macronutrient intake among Taiwanese older adults in 1999-2000, 2005-2008 and 2013-2016 periods.

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

BcMYB111 Responds to BcCBF2 and Induces Flavonol Biosynthesis to Enhance Tolerance under Cold Stress in Non-Heading Chinese Cabbage.

Flavonols have been shown to respond to a variety of abiotic stresses in plants, including cold stress. Higher total flavonoid content was found in non-heading Chinese cabbage (NHCC, Brassica campestris (syn. Brassica rapa) ssp. chinensis) after cold stress. A non-targeted metabolome analysis showed a significant increase in flavonol content, including that of quercetin and kaempferol. Here, we found that an R2R3-MYB transcription factor, BcMYB111, may play a role in this process. BcMYB111 was up-regulated in response to cold treatment, with an accompanying accumulation of flavonols. Then, it was found that BcMYB111 could regulate the synthesis of flavonols by directly binding to the promoters of BcF3H and BcFLS1. In the transgenic hairy roots of NHCC or stable transgenic Arabidopsis, overexpression of BcMYB111 increased flavonol synthesis and accumulation, while these were reduced in virus-induced gene silencing lines in NHCC. After cold stress, the higher proline content and lower malondialdehyde (MDA) content showed that there was less damage in transgenic Arabidopsis than in the wild-type (WT). The BcMYB111 transgenic lines performed better in terms of antioxidant capacity because of their lower H2O2 content and higher superoxide dismutase (SOD) and peroxidase (POD) enzyme activities. In addition, a key cold signaling gene, BcCBF2, could specifically bind to the DRE element and activate the expression of BcMYB111 in vitro and in vivo. The results suggested that BcMYB111 played a positive role in enhancing the flavonol synthesis and cold tolerance of NHCC. Taken together, these findings reveal that cold stress induces the accumulation of flavonols to increase tolerance via the pathway of BcCBF2-BcMYB111-BcF3H/BcFLS1 in NHCC.

Association between the amount of artificial hydration and quality of dying among terminally ill patients with cancer: The East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process.

BACKGROUND: Artificial hydration (AH) is a challenging issue in terminally ill patients with cancer, because it influences patients' symptoms control, quality of life, and quality of dying (QOD). To date, it is not clear how much AH supply is proper for imminently dying patients. This study aimed to investigate the association between the amount of AH and QOD. METHODS: This study is part of the East Asian Collaborative Cross-Cultural Study to Elucidate the Dying Process (EASED) conducted in Japan, Korea, and Taiwan from January 2017 to September 2018. Patients' demographics, symptoms, and managements on admission to palliative care units (PCUs) and before death were recorded. The AH amount was classified into different groups by 250-mL intervals to compare their difference. The Good Death Scale (GDS) was used to measure QOD, with patients classified into higher or lower QOD groups using GDS = 12 as the cutoff point. We used logistic regression analysis to assess the association between AH amount and QOD. RESULTS: In total, 1530 patients were included in the analysis. Country, religion, spiritual well-being, fatigue, delirium, dyspnea, AH, and antibiotics use before death were significantly associated with QOD. After conducting regression analysis, patients administered with 250 to 499 mL AH had significantly better QOD (odds ratio, 2.251; 95% confidence interval, 1.072-4.730; P = .032) than those without AH. CONCLUSIONS: AH use impacts the QOD of terminally ill patients with cancer admitted to PCUs. Communication with patients and their families on appropriate AH use has a positive effect on QOD. LAY SUMMARY: Our prospective cross-cultural multicenter study aims to investigate the relationship between artificial hydration (AH) amount and quality of dying among terminally ill patients with cancer. The findings reveal that country, religion, spiritual well-being, fatigue, delirium, dyspnea, AH, and antibiotics use before death were significantly associated with quality of death (QOD). After multivariable logistic regression, patients administered with AH amount 250 to 499 mL had significantly better QOD (odds ratio, 2.251; 95% confidence interval, 1.072-4.730; P = .032) than those without AH. Communication with patients and their families regarding AH is recommended as it may help them be better prepared for the end-of-life stage and achieve a good death.

The QseEF Two-Component System-GlmY Small RNA Regulatory Pathway Controls Swarming in Uropathogenic Proteus mirabilis.

Bacterial sensing of environmental signals through the two-component system (TCS) plays a key role in modulating virulence. In the search for the host hormone-sensing TCS, we identified a conserved qseEGF locus following glmY, a small RNA (sRNA) gene in uropathogenic Proteus mirabilis. Genes of glmY-qseE-qseG-qseF constitute an operon, and QseF binding sites were found in the glmY promoter region. Deletion of glmY or qseF resulted in reduced swarming motility and swarming-related phenotypes relative to the wild-type and the respective complemented strains. The qseF mutant had decreased glmYqseEGF promoter activity. Both glmY and qseF mutants exhibited decreased flhDC promoter activity and mRNA level, while increased rcsB mRNA level was observed in both mutants. Prediction by TargetRNA2 revealed cheA as the target of GlmY. Then, construction of the translational fusions containing various lengths of cheA 5'UTR for reporter assay and site-directed mutagenesis were performed to investigate the cheA-GlmY interaction in cheA activation. Notably, loss of glmY reduced the cheA mRNA level, and urea could inhibit swarming in a QseF-dependent manner. Altogether, this is the first report elucidating the underlying mechanisms for modulation of swarming motility by a QseEF-regulated sRNA GlmY, involving expression of cheA, rcsB and flhDC in uropathogenic P. mirabilis.

Metabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat.

BACKGROUND AND AIM: Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population. METHODS: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. RESULTS: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79). CONCLUSION: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level.

Frailty status changes are associated with healthcare utilization and subsequent mortality in the elderly population.

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

To hydrate or not to hydrate? The effect of hydration on survival, symptoms and quality of dying among terminally ill cancer patients.

BACKGROUND: Artificial nutrition and hydration do not prolong survival or improve clinical symptoms of terminally ill cancer patients. Nonetheless, little is known about the effect of artificial hydration (AH) alone on patients' survival, symptoms or quality of dying. This study explored the relationship between AH and survival, symptoms and quality of dying among terminally ill cancer patients. METHODS: A pilot prospective, observational study was conducted in the palliative care units of three tertiary hospitals in Taiwan between October 2016 and December 2017. A total of 100 patients were included and classified into the hydration and non-hydration group using 400 mL of fluid per day as the cut-off point. The quality of dying was measured by the Good Death Scale (GDS). Multivariate analyses using Cox's proportional hazards model were used to assess the survival status of patients, the Wilcoxon rank-sum test for within-group analyses and the Mann-Whitney U test for between-groups analyses to evaluate changes in symptoms between day 0 and 7 in both groups. Logistic regression analysis was used to assess the predictors of a good death. RESULTS: There were no differences in survival (p = 0.337) or symptom improvement between the hydration and non-hydration group, however, patients with AH had higher GDS scores. CONCLUSIONS: AH did not prolong survival nor significantly improve dehydration symptoms of terminally ill cancer patients but it may influence the quality of dying. Communication with patients and their families on the effect of AH may help them better prepared for the end-of-life experience.

Enhanced home palliative care could reduce emergency department visits due to non-organic dyspnea among cancer patients: a retrospective cohort study.

BACKGROUND: Dyspnea is a common trigger of emergency department visits among terminally ill and cancer patients. Frequent emergency department (ED) visits at the end of life are an indicator of poor-quality care. We examined emergency department visit rates due to dyspnea symptoms among palliative patients under enhanced home palliative care. METHODS: Our home palliative care team is responsible for patient management by palliative care specialists, residents, home care nurses, social workers, and chaplains. We enhanced home palliative care visits from 5 days a week to 7 days a week, corresponding to one to two extra visits per week based on patient needs, to develop team-based medical services and formulate standard operating procedures for dyspnea care. RESULTS: Our team cared for a total of 762 patients who exhibited 512 ED visits, 178 of which were due to dyspnea (mean ± SD age, 70.4 ± 13.0 years; 49.4% male). Dyspnea (27.8%) was the most common reason recorded for ED visits, followed by pain (19.0%), GI symptoms (15.7%), and fever (15.3%). The analysis of Group A versus Group B revealed that the proportion of nonfamily workers (42.9% vs. 19.4%) and family members (57.1% vs. 80.6%) acting as caregivers differed significantly (P < 0.05). Compared to the ED visits of the Group A, the risk was decreased by 30.7% in the Group B (P < 0.05). CONCLUSIONS: This study proves that enhanced home palliative care with two additional days per week and formulated standard operating procedures for dyspnea could significantly reduce the rate of ED visits due to non-organic dyspnea during the last 6 months of life.

Arecoline induces heart injure via Fas/Fas ligand apoptotic pathway in heart of Sprague-Dawley rat.

Habitual chewing of areca nut increases the risk of cardiovascular disease mortality, but less report demonstrate the toxic mechanism of areca nut on heart. To investigate toxicity of areca nut on cardiomyocytes, we induced the heart injury with arecoline to evaluate the acute damage of areca nut on heart. Different concentrations of are coline (lowdosage: 5 mg/kg/day and high dosage 50 mg/kg/day) were injected into Sprague-Dawley rat via intra-peritoneal method for 21 days to create negative effects of arecoline on cardiomyocyte. Themyocardial architecture of the rat heart was observed. The arecoline-induced apoptotic proteins were analysed via western blotting. The myocardialarchitecture of heart was injured with arecoline and TUNEL stain was also shown are coline-induced cardiac apoptosis. Arecoline promoted the protein expression of both Fas dependent snd mitochondrial dependent apoptosis. In summary, arecoline induces cardiac toxicity and apoptosis by inducing both death receptor and mitochondria-dependent apoptotic pathways on heart.

Association between glucose variation and lower extremity amputation incidence in individuals with type 2 diabetes: a nationwide retrospective cohort study.

AIMS/HYPOTHESIS: Elevated glucose level is one of the risk factors for lower extremity amputation (LEA), but whether glycaemic variability confers independent risks of LEA remains to be elucidated. This study aimed to investigate the association between visit-to-visit glycaemic variability and minor and major LEA risks during 8 years of follow-up in type 2 diabetic individuals aged 50 years and older. METHODS: This retrospective cohort study included 27,574 ethnic Chinese type 2 diabetic individuals aged ≥50 years from the National Diabetes Care Management Program in Taiwan. Glycaemic variability measures were presented as the CVs of fasting plasma glucose (FPG-CV) and of HbA1c (A1c-CV). The effect of glycaemic variability on the incidence of LEA events was analysed using Cox proportional hazards models. RESULTS: After a median follow-up of 8.9 years, 541 incident cases of LEA with a crude incidence density rate of 2.4 per 1000 person-years were observed. After multivariate adjustment, FPG-CV and A1c-CV were found to be significantly associated with minor LEA, with corresponding HRs of 1.53 (95% CI 1.15, 2.04) and 1.34 (95% CI 1.02, 1.77) for the third tertiles of FPG-CV and A1c-CV, respectively. In addition, these associations were stronger amongst older adults with longer diabetes duration (≥3 years) than amongst those with shorter duration (<3 years) (pinteraction < 0.01). CONCLUSIONS/INTERPRETATION: Our study suggests that visit-to-visit variations in HbA1c and FPG are important predictors of minor LEA amongst older adults with type 2 diabetes, particularly for those with more than 3 years of diabetes duration.

Metabolic profiles and fibrosis of nonalcoholic fatty liver disease in the elderly: A community-based study.

BACKGROUND AND AIMS: There are sparse data on the epidemiology of fatty liver in the elderly Asian population. We evaluated for predictors of fatty liver and high risk of advanced fibrosis in a community-based elderly population. METHODS: A total of 1091 participants (mean age was 74.6 ± 6.3 years) were enrolled from 2017 to 2018. Subjects with age younger than 65 years, alcoholism, and history of hepatitis B and hepatitis C were excluded. Fatty liver was diagnosed with abdominal ultrasound by using ultrasonographic fatty liver indicator, a semi-quantitative measurement grading the severity (normal, mild, and moderate-to-severe). Fibrosis-4 score was used for the prediction of the high risk of advanced fibrosis. Using a multivariable logistic regression model, we identified predictors of fatty liver and high risk of advanced fibrosis. RESULTS: In this ambulatory elderly Asian population, the prevalence of fatty liver is 41.9% and of high risk of advanced fibrosis is 12.3%. The prevalence of fatty liver decreases (44.5% to 31.8%), and the high risk of advanced fibrosis increases (3.9% to 27.0%) with aging significantly (both P < 0.05). Metabolic syndrome is a risk factor for fatty liver (odds ratio [OR], 3.19; 95% CI, 2.41-4.22) but not for high risk of advanced fibrosis (OR, 0.67; 95% CI, 0.41-1.08). Hypertriglyceridemia decreases the risk for high risk of advanced fibrosis (OR, 0.53; 95% CI, 0.33-0.87). CONCLUSION: Fatty liver is prevalent in the ambulatory elderly Asian population, affecting over 40% of this population. Age is a risk factor for high risk of advanced fibrosis, with the disease likely progressing from a steatotic to a fibrotic picture with age.

Cognitive function and its transitions in predicting all-cause mortality among urban community-dwelling older adults.

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

Independent associations of urinary albumin-to-creatinine ratio and serum cystatin C with carotid intima-media thickness in community-living Taiwanese adults.

BACKGROUND: Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults. METHODS: A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used. RESULTS: A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 µm for every one unit of increase in cystatin C level and by 0.07 and 0.14 µm for every one unit of increase in ACR, respectively (all p < 0.001 except ACR on IMT-maximum with p < 0.01). Lack of physical activity, low HDL, abdominal obesity, high hs-CRP, and high ACR were the determinants of cystatin C. CONCLUSION: Cystatin C and ACR were strongly and linearly associated with carotid thickening, a marker of subclinical atherosclerosis.

Frailty, transition in frailty status and all-cause mortality in older adults of a Taichung community-based population.

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

Gender Difference in the Relationship of Albuminuria and Arterial Stiffness in Chinese Adults - a 6.6-Year Follow-Up Longitudinal Study.

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

Cancer patient autonomy and quality of dying-a prospective nationwide survey in Taiwan.

BACKGROUND: Patient autonomy is an essential factor in the measurement of quality of dying. We aimed to conduct a study to investigate the factors affecting the autonomy of advanced cancer patients in Taiwan. METHODS: We conducted a prospective, multicenter study and recruited 574 advanced cancer patients from four inpatient hospice wards in Taiwan; their quality of dying was measured using the validated good death scale and the audit scale. Physician-assessed autonomy and the other scales were measured in a team conference by the primary care physician and the team 1 week after the patient had passed away. The good death scale was measured twice, once at admission and then after the patient had passed away for comparison. We measured factors affecting the improvement in quality of dying of these patients initially by applying multiple linear regression analysis. Then, taking physician-assessed autonomy as a dependent variable, we identified the factors that affected this variable. RESULTS: The good death score at admission, clear consciousness, number of admission days beyond 7, better physical care, higher physician-assessed autonomy, better emotional support, better communication, better continuity of life, and physician-reported rate of closure were factors affecting the quality of dying. Further analysis identified age (p = 0.031), consciousness (p = 0.01), and total good death scale score at death (p < 0.001) as determinants of physician-assessed autonomy. CONCLUSIONS: We concluded that physician-assessed autonomy would affect a good death and was highly correlated with age, consciousness level, and quality of dying at the end for advanced cancer patients in Taiwan.

Associations of TNF-α and IL-6 polymorphisms with osteoporosis through joint effects and interactions with LEPR gene in Taiwan: Taichung Community Health Study for Elders (TCHS-E).

Osteoporosis (OST) is a complex multifactorial disease considered to result from interactions of multiple gene and environmental factors. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 are pleiotropic cytokines essential for bone remodeling; and hormone leptin has immunomodulatory effects that stimulate the synthesis of IL-6 and TNF-α. Leptin is involved in the modulation of bone growth and turnover; and its actions are bound by leptin receptor (LEPR). Prior studies evaluated the effects of TNF-α, IL-6, and LEPR gene polymorphisms separately on bone mineral densities (BMD) or OST. In this study, we assessed the roles of TNF-α and IL-6 gene polymorphisms in OST through joint effects and interactions with LEPR gene. We also evaluated possible joint effects and interactions between these polymorphisms and physical activity. Ten tag-SNPs (rs1799964, rs1800629, rs3093662 in TNF-α; rs1880243, rs1800796, rs1554606 in IL-6; and rs1751492, rs8179183, rs1805096, rs1892534 in LEPR) were used to genotype 103 OST cases and 369 controls. BMD of lumbar spine (LS), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry. Our data showed that TNF-α and IL-6 polymorphisms were associated with overall and site-specific OST in both sexes, and that these associations were dependent on rs1805096 and rs1892534 genotypes of LEPR. In men, LEPR A-G-G-G haplotype was associated with FN OST (OR 4.65, 95 % CI 1.61-13.40, p = 0.004). Genotype AA/AG of LEPR rs1751492 was associated with overall and FN OST in women without physical activity, but not in women with physical activity (p < 0.05 for interaction between physical activity and LEPR rs1751492). In men, we detected significant interactions of IL-6 rs1800796 with LEPR rs1805096 and rs1892534 for FN and TH OST (all p < 0.05). Our data indicate that LEPR gene may play joint and interactive roles with TNF-α and IL-6 genes and physical inactivity in development of OST. Haplotype analyses revealed that the correlations tended to be prominent in men with FN OST.

Hyperglycemia and chronic liver diseases on risk of hepatocellular carcinoma in Chinese patients with type 2 diabetes--National cohort of Taiwan Diabetes Study.

This study examined whether glycated hemoglobin A1C (HbA1C) and chronic liver diseases are associated with hepatocellular carcinoma (HCC) risk in Type 2 diabetic patients. A retrospective cohort study consisting of 51,705 patients with Type 2 diabetes aged 30 and over enrolled in the National Diabetes Care Management Program before 2004 was used in Cox proportional hazards models. HbA1C was independently associated with HCC incidence, and multivariate-adjusted hazard ratio (HR) of HCC was 1.20 (95% confidence interval, CI: 1.02-1.41) for patients with a level of HbA1c ≥ 9% compared with patients with a level of HbA1c <7% after multivariate adjustment. We observed a significant linear trend in HCC incidence with increasing HbA1c (p for trend = 0.02, HR = 1.07, 95% CI = 1.01-1.12 for every 1% increment in HbA1c). We observed significant HRs of HCC for patients with a level of HbA1c ≥ 9% with alcoholic liver damage, liver cirrhosis, HBV, HCV and any one of chronic liver diseases compared with patients with a level of HbA1c <9% and no counterpart comorbidity in the entire sample (HR = 8.63, 95% CI = 1.41-52.68; HR = 5.02, 95% CI = 3.10-8.12; HR = 2.53, 95% CI = 1.10-5.85; HR = 1.79, 95% CI = 1.01-3.17; and HR = 3.59, 95% CI = 2.56-5.02, respectively). Our results suggest significant joint associations of HbA1c ≥ 9% and chronic liver diseases. Lifestyle or treatment interventions such as maintaining a satisfactory glycemic control and chronic liver diseases may reduce the burden of HCC.

Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly.

UNLABELLED: Limited data exist regarding metabolic risk factors for deaths from hepatocellular carcinoma (HCC) in aging individuals. We investigated the association between diabetes, dyslipidemia, and HCC mortality in those aged 40 years or more (middle-aged and elderly). In this prospective cohort study based on nationwide health screening units, we consecutively followed middle-aged and elderly participants who had no chronic hepatitis B or C virus infection and received health screening from January 1 1998 to December 31 2008. There were 235 deaths from HCC among 50,080 individuals, ascertained by validated death certificates and the national death registry. Diabetes (adjusted hazard ratio [HR], 3.38; 95% confidence interval [CI], 2.35 to 4.86) was positively associated with deaths from HCC. However, hypertriglyceridemia (HR, 0.38; 95% CI, 0.26 to 0.55) and hypercholesterolemia (HR, 0.50; 95% CI, 0.37 to 0.67) were inversely associated with HCC mortality. The above significant associations remained in the lag time analyses, applied to check for reverse causation. Metabolic syndrome, as defined by the American Heart Association / National Heart Lung Blood Institute criteria (HR, 0.63; 95% CI, 0.46 to 0.86) or by the International Diabetes Federation criteria (HR, 0.62; 95% CI, 0.43 to 0.89), was inversely associated with deaths from HCC, especially in men. CONCLUSION: Middle-aged and elderly individuals, once having diabetes, deserve HCC surveillance to reduce HCC mortality. More research is needed to elucidate why having baseline dyslipidemia relates to lower future HCC mortality.