FNIH-defined Sarcopenia Predicts Adverse Outcomes Among Community-Dwelling Older People in Taiwan: Results From I-Lan Longitudinal Aging Study.

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.

Impact of living arrangements on clinical outcomes among older patients with dementia or cognitive impairment admitted to the geriatric evaluation and management unit in Taiwan.

AIM: To evaluate the impact of living arrangements on mortality and functional decline among older patients with dementia or cognitive impairment after discharge from a geriatric evaluation and management unit (GEMU) in Taiwan. METHODS: The present retrospective cohort study used data from the Veteran Affairs Comprehensive Geriatric Assessment from January 2015 to May 2016 for analysis. Data of patients aged 65 years and older with dementia or cognitive impairment at admission to the GEMU of Taipei Veterans General Hospital during the study period were retried for study. The Veteran Affairs Comprehensive Geriatric Assessment included demographic characteristics, Clinical Frailty Scale, Braden Scale, St. Thomas's Risk Assessment Tool in Falling Elderly Inpatients Scale, Cumulative Illness Rating Scale for Geriatrics, Barthel Index, Instrumental Activities of Daily Living, Mini-Mental State Examination, Geriatric Depression Scale-5 and Mini-Nutritional Assessment - Short Form, as well as common geriatric syndromes. All patients were categorized into the home care group and institutional care group based on their living arrangement before GEMU admissions. Six-month mortality and decline in Barthel Index were defined as adverse clinical outcomes. RESULTS: Overall, data of 395 patients were used for analysis. The baseline comparisons showed that the institutional care group was more likely to be unmarried, have lower education, lower risk of falls and less polypharmacy, but more likely to experience functional decline at follow up than the home care group. Multivariate logistic regression showed that male (OR 3.59, 95% CI 1.04-12.38, P = 0.043) and higher Cumulative Illness Rating Scale for Geriatrics score (OR 4.08, 95% CI 1.49-11.19, P = 0.006) were associated with mortality, whereas the institutional care group (OR 0.30, 95% 0.09-0.99, P = 0.048) and lower Braden Scale (OR 0.80, 95% CI 0.67-0.94, P = 0.008) were protective against mortality. However, the institutional care group was independently associated with functional decline during the follow-up period (OR 2.19, 95% CI 1.12-4.29, P = 0.022). CONCLUSIONS: Institutional care was associated with lower 6-month mortality risk for patients with dementia or cognitive impairment after discharge from the GEMU, but this group was more likely to experience functional decline. Further prospective study is required to clarify the clinical impact of living arrangements on long-term outcomes when people with dementia or cognitive impairment are admitted to acute hospitals. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 44-49.

Recurrent falls and its risk factors among older men living in the veterans retirement communities: A cross-sectional study.

AIM: To evaluate the prevalence of recurrent falls and their risk factors among older men living in the Veterans Homes in Taiwan. METHODS: This cross-sectional study enrolled 871 residents and all participants received the comprehensive geriatric assessment, including Barthel Index, Mini-Mental Status Examination (MMSE), Geriatric Depression Scale-5 questions (GDS-5), Mini-Nutrition Assessment Short Form (MNA-SF), the status of urinary incontinence, stool incontinence, polypharmacy, past history of falls, multimorbidity, and medication history. RESULTS: Overall, 871 subjects (mean age: 85.5±5.2years, all males) participated in this study, whereas 222(25.5%) of them had experienced falls in the past year, and 91 were recurrent fallers. Comparisons between non-fallers, single fallers and recurrent fallers disclosed that they were significantly different in the following characteristics: diabetes mellitus, chronic kidney disease, coronary artery disease, Charlson Comorbidity Index (CCI), Barthel Index, GDS-5, MNA-SF, polypharmacy, use of hypnotics, urinary incontinence, and stool incontinence (P for trend all <0.05). Multiple regression analysis identified that GDS-5 was significantly associated with single falls and recurrent falls (OR 1.256, 95% CI 1.094-1.441, P=0.001 for single fallers; OR 1.480, 95% CI 1.269-1.727, P<0.001 for recurrent fallers). Besides, urinary incontinence was the independently associated with recurrent fallers only (OR 2.369, 95% CI 1.449-3.817, P<0.001), but not single fallers. CONCLUSION: Urinary incontinence and depressive symptoms were independent associated factors for falls among older men living in the retirement communities. However, urinary incontinence was associated with recurrent falls, but not single falls. Intervention study is needed to reduce recurrent falls through management of urinary incontinence.

Association between using medications with anticholinergic properties and short-term cognitive decline among older men: A retrospective cohort study in Taiwan.

AIM: The use of anticholinergic drugs had been strongly linked to adverse health outcomes among older adults, especially in cognitive impairment or dementia. The present study aimed to evaluate the cognitive decline related to the use of anticholinergic drugs among older men living in the veterans' homes in Taiwan. METHODS: This retrospective cohort study was a substudy of The Longitudinal Older Veterans study. A total of 274 residents living in four Taiwan veterans' homes and receiving two consecutive Mini-Mental State Examinations within the interval of 6 months from January 2012 to December 2014 were enrolled in the present study. The medication lists for all participants were reviewed by the same physician, and the anticholinergic properties of the individual medications were evaluated by using the Anticholinergic Cognitive Burden scale. Cognitive decline was defined as the decrease of Mini-Mental State Examinations scores during the study period. RESULTS: Overall, 139 persons (50.7%) had exposure to anticholinergic drugs at baseline (designated as AC[+]), and the most frequently used anticholinergic drugs were cardiovascular drugs (48.2%), antipsychotics (21.6%), theophylline (20.1%), antidepressants (12.2%), gastrointestinal drugs (11.5%) and antihistamines (8.6%). After adjusting for covariates, AC(+) participants had a significantly higher risk for short-term cognitive decline (OR 2.69, 95% CI 1.36-5.31). After excluding 30 participants using antipsychotics, non-antipsychotics AC(+)participants still had a significantly higher risk for short-term cognitive decline (OR 2.24, 95% CI 1.26-3.99). CONCLUSIONS: Exposure to anticholinergic drugs significantly increased the risk for short-term cognitive decline among older men, and the adverse effects remained similar when antipsychotics were excluded for analysis. A further intervention study is required to evaluate whether reducing anticholinergic burden might improve cognitive function among older adults. Geriatr Gerontol Int 2017: 17 (Suppl. 1): 57-64.

Urinary Incontinence and Its Association with Frailty Among Men Aged 80 Years or Older in Taiwan: A Cross-Sectional Study.

AIMS: To evaluate the prevalence of urinary incontinence (UI) and its association with frailty among men aged 80 years and older in Taiwan. METHODS: Residents living in four veterans retirement communities were invited for study and 440 men aged 80 years and older were enrolled. Comprehensive geriatric assessment was performed for them, which composed of Clinical Frailty Scale, Northern Health and Social Care Trust (HSC)-Continence Assessment Form, Charlson's Comorbidity Index (CCI), Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Mini-Mental State Examination (MMSE), Geriatric Depression Scale-5 (GDS-5), and Mini-Nutritional Assessment-Short Form (MNA-SF). RESULTS: In this study, the overall prevalence of UI was 19.1% (mostly urgency incontinence and functional incontinence). Univariate analyses were performed to evaluate the associations between UI and other variables. Frailty was more common among subjects with UI than those without (60.7% vs 32.3%, p < 0.001). Besides, subjects with UI had more comorbidity (CCI: 1.40 ± 1.15 vs 0.89 ± 0.89, p < 0.001), poorer physical function (BI: 65.77 ± 33.39 vs 84.12 ± 24.08, p < 0.001; IADL: 3.46 ± 2.64 vs 4.41 ± 2.25, p = 0.003), more depressive symptoms (GDS-5: 1.83 ± 1.78 vs 1.18 ± 1.36, p = 0.02), poorer cognitive function (MMSE: 16.57 ± 7.65 vs 19.37 ± 6.82, p = 0.001), poorer nutritional status (MNA-SF: 10.0 ± 03.03 vs 11.23 ± 2.24, p = 0.001), more polypharmacy (66.7% vs 45.2%, p < 0.001) and higher chance of stool incontinence (22.6% vs 1.7%, p < 0.001). Multivariate logistic regression showed that UI was independently associated with frailty, (odds ratio [OR] = 2.1; 95% confidence interval [CI]: 1.2-3.6; p = 0.012), stool incontinence (OR = 14.4; 95% CI 5.2-39.7; p < 0.001) and depressive symptoms (OR = 1.30; 95% CI 1.10-1.54; p = 0.002). CONCLUSIONS: About one fifth of study subjects had UI (mostly urgency and functional incontinence type), which was significantly associated with frailty, stool incontinence and depressive symptoms. Further study is needed to evaluate the possibilities of reversing these geriatric syndromes by an integrated intervention program.

Characteristics of ambulatory care visits to family medicine specialists in Taiwan: a nationwide analysis.

Although family medicine (FM) is the most commonly practiced specialty among all the medical specialties, its practice patterns have seldom been analyzed. Looking at data from Taiwan's National Health Insurance Research Database, the current study analyzed ambulatory visits to FM specialists nationwide. From a sample dataset that randomly sampled one out of every 500 cases among a total of 309,880,000 visits in 2012, it was found that 18.8% (n = 116, 551) of the 619,760 visits in the dataset were made to FM specialists. Most of the FM services were performed by male FM physicians. Elderly patients above 80 years of age accounted for only 7.1% of FM visits. The most frequent diagnoses (22.8%) were associated acute upper respiratory infections (including ICD 460, 465 and 466). Anti-histamine agents were prescribed in 25.6% of FM visits. Hypertension, diabetes and dyslipidemia were the causes of 20.7% of the ambulatory visits made to FM specialists of all types, while those conditions accounted for only 10.6% of visits to FM clinics. The study demonstrated the relatively low proportion of chronic diseases that was managed in FM clinics in Taiwan, and our detailed results could contribute to evidence-based discussions on healthcare policymaking and residency training.

Small molecule amiloride modulates oncogenic RNA alternative splicing to devitalize human cancer cells.

Alternative splicing involves differential exon selection of a gene transcript to generate mRNA and protein isoforms with structural and functional diversity. Abnormal alternative splicing has been shown to be associated with malignant phenotypes of cancer cells, such as chemo-resistance and invasive activity. Screening small molecules and drugs for modulating RNA splicing in human hepatocellular carcinoma cell line Huh-7, we discovered that amiloride, distinct from four pH-affecting amiloride analogues, could "normalize" the splicing of BCL-X, HIPK3 and RON/MISTR1 transcripts. Our proteomic analyses of amiloride-treated cells detected hypo-phosphorylation of splicing factor SF2/ASF, and decreased levels of SRp20 and two un-identified SR proteins. We further observed decreased phosphorylation of AKT, ERK1/2 and PP1, and increased phosphorylation of p38 and JNK, suggesting that amiloride treatment down-regulates kinases and up-regulates phosphatases in the signal pathways known to affect splicing factor protein phosphorylation. These amiloride effects of "normalized" oncogenic RNA splicing and splicing factor hypo-phosphorylation were both abrogated by pre-treatment with a PP1 inhibitor. Global exon array of amiloride-treated Huh-7 cells detected splicing pattern changes involving 584 exons in 551 gene transcripts, many of which encode proteins playing key roles in ion transport, cellular matrix formation, cytoskeleton remodeling, and genome maintenance. Cellular functional analyses revealed subsequent invasion and migration defects, cell cycle disruption, cytokinesis impairment, and lethal DNA degradation in amiloride-treated Huh-7 cells. Other human solid tumor and leukemic cells, but not a few normal cells, showed similar amiloride-altered RNA splicing with devitalized consequence. This study thus provides mechanistic underpinnings for exploiting small molecule modulation of RNA splicing for cancer therapeutics.