Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease.

BACKGROUND: No studies have reported the long-term outcomes of initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis. OBJECTIVE: To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD). DESIGN: Target trial emulation study. SETTING: Taiwan's National Health Insurance Research Database (NHIRD). PARTICIPANTS: By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021. MEASUREMENTS: Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers. RESULTS: In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan-Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use. LIMITATION: This result may not apply to patients without T2D. CONCLUSION: This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD. PRIMARY FUNDING SOURCE: National Health Research Institutes, Taiwan.

Glucagon-like peptide-1 receptor agonists may benefit cardiopulmonary outcomes in patients with COPD.

BACKGROUND: Clinical studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RA) can have beneficial effects on cardiopulmonary function. We conducted this longitudinal cohort study to compare the risk of cardiopulmonary outcomes and mortality between GLP-1 RA use and no use in patients with type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD). METHODS: The study identified 8060 matched GLP-1 RA users and non-users from Taiwan's National Health Insurance Research Database from 1 January 2008 to 31 December 2019. Cox proportional hazards models were used to determine the risk of cardiopulmonary outcomes between GLP-1 RA users and non-users. RESULTS: The mean follow-up time was 2.51 and 2.46 years for GLP-1 RA users and non-users, respectively. In the matched cohorts, GLP-1 RA users had a significantly lower risk of mortality (adjusted HR (aHR) 0.46, 95% CI 0.38 to 0.56), cardiovascular events (aHR 0.73, 95% CI 0.65 to 0.82), non-invasive positive pressure ventilation (aHR 0.66, 95% CI 0.47 to 0.93), invasive mechanical ventilation (aHR 0.64, 95% CI 0.51 to 0.8) and bacterial pneumonia (aHR 0.76, 95% CI 0.65 to 0.88) than GLP-1 RA non-users. The subsequent analyses for various subgroup and medication duration also showed that GLP-1 RA was associated with a significantly lower risk of mortality, cardiovascular events, ventilation support and bacterial pneumonia than non-GLP-1 RA. CONCLUSION: This nationwide cohort study showed that GLP-1 RA had a lower risk of cardiopulmonary outcomes and all-cause mortality than non-GLP-1 RA in patients with T2D and COPD. GLP-1 RA may help manage diabetes in people with COPD.

Effects of glucagon-like peptide-1 receptor agonists on liver-related and cardiovascular mortality in patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis. METHODS: From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan's National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups. RESULTS: The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43-0.53), cardiovascular events (aHR 0.92, 95%CI 0.86-0.99), cardiovascular death (aHR 0.57, 95%CI 0.45-0.72), and liver-related death (aHR 0.32, 95%CI 0.13-0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use. CONCLUSIONS: This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.

Microvascular disease and its association with dementia in patients with type 2 diabetes: A nationwide cohort study in Taiwan.

AIM: To assess the likelihood of dementia in individuals with type 2 diabetes (T2D), distinguishing between those with and without microvascular diseases. METHODS: Leveraging the National Health Insurance Research Database in Taiwan, we identified individuals newly diagnosed with T2D from 1 January 2009 through 31 December 2014. Multivariable Cox proportional hazard models were used to compare the risk of outcomes. RESULTS: Individuals with microvascular disease had a significantly higher risk of all-cause dementia (adjusted hazard ratio [95% confidence interval] 1.13 [1.09, 1.17]) compared with matched individuals without microvascular disease. In addition, individuals with diabetic kidney disease and diabetic neuropathy were associated with a significantly increased risk of Alzheimer's disease (1.16 [1.02, 1.32] and 1.14 [1.03, 1.27]), vascular dementia (1.21 [1.06, 1.38] and 1.14 [1.02, 1.28]) and other dementia (1.11 [1.04, 1.19] and 1.10 [1.04, 1.16]), respectively, compared with those without microvascular disease. CONCLUSIONS: This nationwide cohort study showed that patients with T2D and microvascular disease, particularly diabetic kidney disease and diabetic neuropathy, were associated with a significantly higher risk of Alzheimer's disease, vascular dementia, other dementia and all-cause dementia than those without microvascular disease.

Cross-sectional and longitudinal associations of magnesium intake and cognition in the Healthy Aging Longitudinal Study in Taiwan.

PURPOSE: Previous cross-sectional studies have shown that higher magnesium intake is associated with better cognitive function, particularly in individuals with sufficient vitamin D status. The aim of this study was to evaluate the longitudinal associations between magnesium intake and cognitive impairment in a community-based cohort study in Taiwan. METHODS: The study population included 5663 community-dwelling adults aged ≥ 55 years old recruited from 2009 to 2013 and followed up from 2013 to 2020. Magnesium intake was evaluated from a validated food frequency questionnaire at baseline. Cognitive performance was measured at baseline and follow-up for participants' Mini-Mental Status Examination (MMSE), Digit Symbol Substitution Test (DSST), and Clock-Drawing Test (CDT), and impairment was defined as MMSE < 24, DSST < 21, and CDT < 3, respectively. Multivariate logistic regression models were used to examine the associations and were stratified by sex and plasma vitamin D levels (≥ 50 or < 50 nmol/L). RESULTS: Higher baseline magnesium intake was associated with lower odds of a poor performance on the MMSE in both men and women (4th vs. 1st. quartile: OR = 0.43, 95% CI = 0.23-0.82, ptrend < 0.01 in men and OR = 0.53, 95% CI = 0.29-0.97, ptrend = 0.12 in women) and on the DSST in men (OR = 0.23, 95% CI = 0.09-0.61, ptrend < 0.01) at follow-up. Inverse associations between baseline magnesium intake and a poor performance on the MMSE or DSST were observed in men regardless of vitamin D status. CONCLUSION: Our study suggested that higher magnesium intake was associated with the development of cognitive impairment in men in a median follow-up period of 6 years.

Examining the role of living alone and loneliness in predicting health-related quality of life: results from the Healthy Aging Longitudinal Study in Taiwan (HALST).

PURPOSE: This study aimed to investigate the distinct yet interconnected aspects of social isolation, namely living alone and loneliness, and their individual and combined effects on predicting health-related quality of life (HRQoL). METHODS: A comprehensive analysis, encompassing both cross-sectional and longitudinal approaches, was conducted using a nationally representative sample of 5644 community-dwelling adults aged 55 and older from the Healthy Aging Longitudinal Study in Taiwan (HALST). RESULTS: Baseline data revealed that 9% of the sample reported living alone, while 10.3% reported experiencing loneliness, with 2.5% reporting both living alone and feeling lonely. Regression analyses consistently demonstrated that loneliness was significantly associated with concurrent and subsequent lower physical (PCS) and mental (MCS) component of HRQoL. Conversely, additional analyses indicated that living alone could indirectly exacerbate the adverse effects of loneliness or contribute to prolonged feelings of loneliness, subsequently predicting lower HRQoL after 3.2 year. CONCLUSION: In terms of practical implications, interventions and policies aiming to enhance HRQoL in older adults should give particular attention to those who report feelings of loneliness, especially individuals living alone.

Residual risk of cardiovascular complications in statin-using patients with type 2 diabetes: the Taiwan Diabetes Registry Study.

BACKGROUND: The residual risks of atherosclerotic cardiovascular disease in statin-treated patients with diabetes remain unclear. This study was conducted to identify factors associated with these residual risks in patients with no prior vascular event. METHODS: Data on 683 statin-using patients with type 2 diabetes mellitus (T2DM) from the Taiwan Diabetes Registry were used in this study. Patients aged < 25 or > 65 years at the time of diabetes diagnosis and those with diabetes durations ≥ 20 years were excluded. The United Kingdom Prospective Diabetes Study risk engine (version 2.01; https://www.dtu.ox.ac.uk/riskengine/ ) was used to calculate 10-year residual nonfatal and fatal coronary heart disease (CHD) and stroke risks. Associations of these risks with physical and biochemical variables, including medication use and comorbidity, were examined. RESULTS: The 10-year risks of nonfatal CHD in oral anti-diabetic drug (OAD), insulin and OAD plus insulin groups were 11.8%, 16.0%, and 16.8%, respectively. The 10-year risks of nonfatal stroke in OAD, insulin and OAD plus insulin groups were 3.0%, 3.4%, and 4.3%, respectively. In the multivariate model, chronic kidney disease (CKD), neuropathy, insulin use, calcium-channel blocker (CCB) use, higher body mass indices (BMI), low-density lipoprotein (LDL), fasting glucose, log-triglyceride (TG), and log-alanine transaminase (ALT) levels were associated with an increased CHD risk. The residual risk of stroke was associated with CKD, neuropathy, CCB use, and lower LDL cholesterol levels, higher BMI and diastolic blood pressure. CONCLUSION: This study indicated that insulin was probably a residual risk factor of CHD but not stroke, and that there was a possible presence of obesity paradox in patients with T2DM on statin therapy. In addition to lowering TG and normalizing fasting glucose levels, lower LDL cholesterol level is better for reduction of risk of CHD on statin therapy. On the other hand, lower LDL cholesterol level could potentially be related to higher risk of stroke among populations receiving statin therapy. These findings suggest potential therapeutic targets for residual cardiovascular risk reduction in patients with T2DM on statin therapy.

Understanding and alleviating informal caregiver burden through the development and validation of a caregiver strain index-based model in Taiwan.

BACKGROUND: Quantifying the informal caregiver burden is important for understanding the risk factors associated with caregiver overload and for evaluating the effectiveness of services provided in Long-term Care (LTC). OBJECTIVE: This study aimed to develop and validate a Caregiver Strain Index (CSI)-based score for quantifying the informal caregiver burden, while the original dataset did not fully cover evaluation items commonly included in international assessments. Subsequently, we utilized the CSI-based score to pinpoint key caregiver burden risk factors, examine the initial timing of LTC services adoption, and assess the impact of LTC services on reducing caregiver burden. METHODS: The study analyzed over 28,000 LTC cases in Southern Taiwan from August 2019 to December 2022. Through multiple regression analysis, we identified significant risk factors associated with caregiver burden and examined changes in this burden after utilizing various services. Survival analysis was employed to explore the relationship between adopting the first LTC services and varying levels of caregiver burden. RESULTS: We identified 126 significant risk factors for caregiver burden. The most critical factors included caregiving for other disabled family members or children under the age of three (ß = 0.74, p < 0.001), the employment status of the caregiver (ß = 0.30-0.53, p < 0.001), the frailty of the care recipient (ß = 0.28-0.31, p < 0.001), and the behavioral symptoms of dementia in care recipients (ß = 0.28-2.60, p < 0.05). Generally, caregivers facing higher burdens sought LTC services earlier, and providing home care services alleviated the caregiver's burden. CONCLUSION: This comprehensive study suggests policy refinements to recognize high-risk caregivers better early and provide timely support to improve the overall well-being of both informal caregivers and care recipients.

Long-term exposure to NO2 and PM2.5 and the occurrence of chronic kidney disease among patients with type 2 diabetes in Taiwan.

BACKGROUND: Individuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan METHODS: Between 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 µm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. RESULTS: Of 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 µg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. CONCLUSIONS: This longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Statin therapy and upper tract urothelial carcinoma risk in hyperlipidemic patients with chronic kidney disease and end-stage kidney disease, a population-based 17-year follow-up study.

BACKGROUND: The upper tract urothelial carcinoma (UTUC) risk associated with statin therapy in hyperlipidemic patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) remains obscure. AIM: This retrospective cohort study investigated the UTUC risk for hyperlipidemic patients with CKD or ESKD associated with statin therapy. METHODS: From the national insurance claims data of Taiwan, we identified hyperlipidemic patients and established three pairs of statin users and non-users sub-cohorts matched by propensity scores: 401,490 pairs with normal kidney function, 37,734 pairs with CKD, and 6271 pairs with ESKD. Incidence rates and hazard ratio (HR) of UTUC were estimated, by the end of 2016, between statin and non-statin cohorts, and between hydrophilic statins users and lipophilic statins users. Time-dependent model estimated adjusted HR, and sub-distribution HR (sHR) accounting for the competing risk of deaths. RESULTS: The statin-users with ESKD were at increased UTUC risk (sHR 1.98; 95% confidence interval (CI), 1.28-3.06), significant for younger patients (40-64 years). The incidence was twofold greater in women than in men (31.8 versus 15.9 per 10,000 person-years). Receiving lipophilic statins was associated with increased UTUC risk in CKD and ESKD patients, while receiving hydrophilic statins was associated with increased UTUC risk in ESKD patients. CONCLUSIONS: Patients with ESKD receiving statin were at an increased UTUC risk, significant for younger group (<65 y/o). The positive associations between UTUC and statin persisted in both genders with ESKD, and in therapy with either lipophilic statins or hydrophilic statins. Statin users with ESKD deserve attention for UTUC prevention.

Development of a tool measuring various aspects of social detachment: The social detachment questionnaire for older population.

BACKGROUND: Social detachment includes the subjective aspect "loneliness" and the objective aspect "social isolation," but tools to assess both dimensions are limited. This study aims to develop a questionnaire, the Social Detachment Questionnaire for Older Population (SDQO), that considers multiple dimensions of social detachment simultaneously. METHODS: The study collected 600 valid samples from individuals aged 55 and above to examine the psychometric properties of the developed SDQO. Item analysis was conducted to assess the performance of each item, and exploratory factor analysis (EFA) was employed to analyze its initial structure and eliminate less ideal items. Subsequently, confirmatory factor analysis (CFA) was used to examine the model fit of the suggested structure by EFA, using different subsamples. Internal consistency, concurrent validity, and other analyses were also performed. RESULTS: The original 27-item SDQO was reduced to 17 items after removing 4 questions in item analysis and 6 questions in EFA. The Cronbach's alpha for the 17-item version of SDQO was 0.80. Both EFA and CFA supported its 6-factor structure, with factors identified as community activities, loneliness, personal resources, leisure activities, friendship, and family resources. SDQO also demonstrated expected performance in concurrent validity. CONCLUSION: The 17-item version of SDQO exhibited good reliability and validity, measuring various aspects of social detachment behavior, feelings, and resources. It holds value for future research applications.

Effectiveness of the lay health advisor program on oral function and quality of life in aboriginal older adults: A randomized controlled trial.

BACKGROUND: Aboriginal older adults residing in remote areas have poor oral function due to inadequate access to healthcare services. Lay health advisor (LHA) strategies can fill capacity shortages of healthcare professionals in rural communities and increase population acceptance of health care or healthy behaviours. OBJECTIVE(S): To evaluate the effectiveness the LHA program on oral function and oral health-related quality of life (OHRQoL) among older adults in aboriginal community. METHODS: Participants were randomly assigned to an experimental group (EG; n = 122) and a control group (CG; n = 118). All participants performed oral exercises, and the EG received additional one-on-one 30-min lessons by an LHA over 4 weeks. Data were collected through face-to-face interview and oral examination. The generalized estimating equation model was used to analyse changes in outcomes over time. RESULTS: The EG exhibited significantly greater improvement in swallowing (ß = .63) at the 6-month follow-up and in masticatory performance (ß = .52) and pronunciation of the syllable/pa/ (ß = 2.65) at the 2-week follow-up than the CG did. The EG had a significantly lower plaque control record (ß = -.14) and plaque index (ß = -.30) at the 3-month follow-up than the CG did. Moreover, the OHRQoL was significantly increased at 6-months follow-up in the EG (p = .010). CONCLUSION: The LHA program had positive effects on chewing, swallowing and plaque control in aboriginal older adults. LHA group also experienced positive long-term effect on OHRQoL after intervention.

Salivary Antimicrobial Peptide in Patients With Dementia Before and After Clinical Oral Rehabilitation Programme: A Randomised Controlled Trial.

BACKGROUND: Emerging evidence suggests a link between salivary metabolite changes and neurodegenerative dementia, with antimicrobial peptides (AMPs) implicated in its pathogenesis. OBJECTIVE: We investigated the effects of a clinical oral rehabilitation programme tailored for dementia patients on salivary flow rate, AMP levels and oral health-related quality of life (OHRQoL). METHODS: Eligible patients were randomly assigned to either the experimental group (EG; n = 28) or the control group (CG; n = 27). Both groups received a leaflet on oral health. In addition, the EG received an oral care intervention that included individual lessons on oral muscle exercises and oral self-care practices. Saliva samples and OHRQoL data were collected at baseline and follow-up visits. Generalised estimating equation models were used to analyse the changes over time. RESULTS: At the 3-month follow-up, EG showed significantly lower histatin 5 (HTN-5) levels (ß = -0.08; effect size [ES] = 0.72) than CG. At 6 months, EG exhibited improved salivary flow rate (ß = 0.89; ES = 0.89) and OHRQoL (ß = 6.99; ES = 1.31) compared to CG. Changes in salivary flow rate (ß = 4.03), HTN-5 level (ß = -0.78) and beta-defensin 2 level (BD-2) (ß = -0.91) at 3 months predicted improved OHRQoL at 6 months (all p < 0.05). CONCLUSIONS: Our clinical oral rehabilitation programme reduced the level of salivary HTN-5, increased salivary flow rate and enhanced OHRQoL in dementia patients. Furthermore, changes in salivary flow rate, HTN-5 level and BD-2 level were associated with improvements in patients' OHRQoL.

Prospective Impacts of Social Participation Activities on Cognitive and Psychopathological Statuses in Community-Dwelling Older Adults.

OBJECTIVES: This study investigated the impact of social activities on cognitive functioning and psychopathological symptoms. METHODS: Participants aged 55 or older were enrolled through communities. Initial measures assessed demographic data, neuropsychological functioning, psychopathological state, and happiness. Social activities were evaluated using a modified 12-item tool, with 3-4 activities as the cutoff. Follow-up after 6-9 months included Mini-Mental State Examination (MMSE), Beck Depression Inventory - II (BDI-II), Beck Anxiety Inventory (BAI), Health Assessment Questionnaire (HAQ), and Patient Health Questionnaire-15 (PHQ-15) measurements. Predictive models for psychiatric and cognitive statuses were built using multiple linear regression, adjusting for baseline conditions. RESULTS: Initially, 516 older individuals enrolled, with 403 undergoing follow-up. During follow-up, the low participation group reported lower MMSE scores, higher BAI scores, and increased PHQ-15 risk. Negative correlations between social activity numbers and PHQ-15 results were found. Engagement in social clubs correlated positively with higher MMSE scores, while regular interactions with one's adult child(ren) were linked to decreased BAI scores. CONCLUSIONS: The quantity of social activities was associated with lower somatic distress. Social club engagement positively influenced cognition, and regular interactions with one's adult child(ren) mitigated anxiety among older individuals. CLINICAL IMPLICATIONS: Enough types of social activities, participating in social clubs, and adequate interactions with children protected against psychopathologies.

Early Antiplatelet Resumption and the Risks of Major Bleeding After Intracerebral Hemorrhage.

BACKGROUND: The appropriate timing of resuming antithrombotic therapy after intracerebral hemorrhage (ICH) remains unclear. The aim of this study was to compare the risks of major bleeding between early and late antiplatelet resumption in ICH survivors. METHODS: Between 2008 and 2017, ICH patients were available in the National Health Insurance Research Database. Patients with a medication possession ratio of antiplatelet treatment ≥50% before ICH and after antiplatelet resumption were screened. We excluded patients with atrial fibrillation, heart failure, under anticoagulant or hemodialysis treatment, and developed cerebrovascular events or died before antiplatelet resumption. Finally, 1584 eligible patients were divided into EARLY (≤30 days) and LATE groups (31-365 days after the index ICH) based on the timing of antiplatelet resumption. Patients were followed until the occurrence of a clinical outcome, end of 1-year follow-up, death, or until December 31, 2018. The primary outcome was recurrent ICH. The secondary outcomes included all-cause mortality, major hemorrhagic events, major occlusive vascular events, and ischemic stroke. Cox proportional hazard model after matching was used for comparison between the 2 groups. RESULTS: Both the EARLY and LATE groups had a similar risk of 1-year recurrent ICH (EARLY versus LATE: 3.12% versus 3.27%; adjusted hazard ratio [AHR], 0.967 [95% CI, 0.522-1.791]) after matching. Both groups also had a similar risk of each secondary outcome at 1-year follow-up. Subgroup analyses disclosed early antiplatelet resumption in the patients without prior cerebrovascular disease were associated with lower risks of all-cause mortality (AHR, 0.199 [95% CI, 0.054-0.739]) and major hemorrhagic events (AHR, 0.090 [95% CI, 0.010-0.797]), while early antiplatelet resumption in the patients with chronic kidney disease were associated with a lower risk of ischemic stroke (AHR, 0.065 [95% CI, 0.012-0.364]). CONCLUSIONS: Early resumption of antiplatelet was as safe as delayed antiplatelet resumption in ICH patients. Besides, those without prior cerebrovascular disease or with chronic kidney disease may benefit more from early antiplatelet resumption.

Glucagon-like Peptide-1 Receptor Agonist Use in Patients With Liver Cirrhosis and Type 2 Diabetes.

BACKGROUND AND AIMS: Liver cirrhosis is often associated with type 2 diabetes (T2D), but research on treatment of T2D in cirrhotic patients is scarce. We investigated the long-term outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D and cirrhosis. METHODS: Using propensity score matching, we selected 467 matched pairs of GLP-1 RA users and nonusers from the National Health Insurance Research Database of Taiwan from January 1, 2008, to December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to compare the outcomes between GLP-1 RA users and nonusers. RESULTS: The mean follow-up time was 3.28 and 3.06 years for GLP-1 RA users and nonusers, respectively. The rates of death were 27.46 and 55.90 per 1000 person-years for GLP-1 RA users and nonusers, respectively. The multivariable-adjusted models showed that GLP-1 RA users had lower risks of mortality (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [CI], 0.32-0.69), cardiovascular events (aHR, 0.6; 95% CI, 0.41-0.87), decompensated cirrhosis (aHR, 0.7; 95% CI, 0.49-0.99), hepatic encephalopathy (aHR, 0.59; 95% CI, 0.36-0.97), and liver failure (aHR, 0.54; 95% CI, 0.34-0.85) than nonusers. A longer cumulative duration of GLP-1 RA use had a lower risk of these outcomes than GLP-1 RA nonuse. CONCLUSIONS: This population-based cohort study showed that GLP-1 RA users exhibited a significantly lower risk of death, cardiovascular events, decompensated cirrhosis, hepatic encephalopathy, and liver failure in patients with T2D and compensated liver cirrhosis. Additional studies are needed to confirm our results.

Metformin use and the risks of herpes zoster and postherpetic neuralgia in patients with type 2 diabetes.

Herpes zoster and postherpetic neuralgia cause substantial pain in patients. Persons with type 2 diabetes (T2D) are prone to zoster infection and postherpetic neuralgia due to compromised immunity. We conducted this study to evaluate the risks of herpes zoster and postherpetic neuralgia between metformin users and nonusers. Propensity score matching was utilized to select 47 472 pairs of metformin users and nonusers from Taiwan's National Health Insurance Research Database between January 1, 2000, and December 31, 2017. The Cox proportional hazards models were used for comparing the risks of herpes zoster and postherpetic neuralgia between metformin users and nonusers in patients with T2D. Compared with no-use of metformin, the adjusted hazard ratios (95% confidence interval) for metformin use in herpes zoster and postherpetic neuralgia were 0.70 (0.66, 0.75) and 0.510 (0.39, 0.68), respectively. A higher cumulative dose of metformin had further lower risks of herpes zoster and postherpetic neuralgia than metformin no-use. This nationwide cohort study demonstrated that metformin use was associated with a significantly lower risk of herpes zoster and postherpetic neuralgia than metformin no-use. Moreover, a higher cumulative dose of metformin was associated with further lower risks of these outcomes.

Impact of individual microvascular disease on the risks of macrovascular complications in type 2 diabetes: a nationwide population-based cohort study.

BACKGROUND: This study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases. METHODS: We identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality. RESULTS: Patients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03-1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1-1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03-1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3-1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71-0.87). CONCLUSIONS: T2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.

Dietary Inflammatory Patterns Are Associated With Serum TGs and Insulin in Adults: A Community-Based Study in Taiwan.

BACKGROUND: Dietary patterns related to inflammation have become a focus of disease prevention but the patterns may vary among populations. OBJECTIVES: The study was conducted to determine Taiwanese dietary inflammatory patterns and evaluate their associations with biomarkers of lipid and glucose. METHODS: Data were taken from 5664 community-dwelling individuals aged ≥55 y recruited in 2009-2013 in the Healthy Aging Longitudinal Study in Taiwan (HALST). Dietary data were obtained from an FFQ. An empirical dietary inflammatory pattern (EDIP) was derived from reduced rank regression models that explained the serum high-sensitivity CRP, plasma IL-6, and TNF receptor 1. Cross-sectional associations between dietary scores and biomarkers of total cholesterol (TC); HDL cholesterol; LDL cholesterol; TG; and ratios of TG/HDL cholesterol, TG/TC, fasting glucose, insulin, and HbA1c were analyzed via multiple linear regression and adjusted for major confounders. The false-discovery rate (FDR)-adjusted P < 0.05 was considered statistically significant. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥80 cm for women. RESULTS: Higher EDIP-HALST scores were associated with higher TG (per score increment: 1.62%, 95% CI: 0.58%, 2.76%; PFDR = 0.01), TG/HDL cholesterol (2.01%, 95% CI: 0.67%, 3.37%; PFDR = 0.01), and TG/TC (1.42%, 95% CI: 0.41%, 2.43%; PFDR = 0.01) and nonlinearly associated with insulin, with those in the middle tertile had the highest serum insulin concentrations (means: 5.12 µIU/mL, 95% CI: 4.78, 5.78; PFDR = 0.04) in men, but not in women. No heterogeneity was detected between sexes. The associations with TG (1.23%, 95% CI: 0.19, 2.23%; Ptrend = 0.02), TG/HDL cholesterol (1.62%, 95% CI: 0.30%, 2.96%; Ptrend = 0.02), and TG/TC (1.11%, 95% CI: 0.11%, 2.13%; Ptrend = 0.03) were stronger in participants with abdominal obesity, but were borderline associated in participants with normal abdominal circumferences (all Ptrend = 0.05). CONCLUSIONS: Inflammatory diets, as measured via EDIP-HALST, are associated with serum TG concentration, particularly in participants with abdominal obesity. These findings may suggest that developing disease prevention strategies using dietary inflammatory patterns may be different by populations. J Nutr 20xx;x:xx.

Interactions of Insomnia and Sedative-Hypnotic Drug Use Associated with Frailty Over Time Among Older Adults.

BACKGROUND: Insomnia and frailty are prevalent in older adults. This study aimed to elucidate the impact of insomnia and sedative-hypnotic use on the frailty rate over time. METHODS: We used data from community-dwelling older adults (mean ± SD age = 69.4 ± 8.2 years) from the Healthy Aging Longitudinal Study in Taiwan (HALST). A total of 4,744 participants were included in the study and were followed up for an average of 3.2 years. Frailty was assessed using the Fried criteria. Self-reported sleep problems, sedative-hypnotic use, and claims records from the National Health Insurance database were used. The generalized equation estimation (GEE) approach was applied to account for correlations between repeated measures. The average impact of insomnia and drug use on frailty over time was estimated by adjusting for potential confounding factors using the logic link in the GEE approach. RESULTS: The adjusted odds ratio (OR) of frailty was 1.41 (95% CI: [1.16, 1.72], Z-test statistics Z = 3.39, p <0.001) for insomnia and 1.52 ([1.16, 2.00], Z = 3.00, p = 0.0027) for sedative-hypnotic use. Interactions between insomnia and sedative-hypnotic use with frailty were not statistically significant. Long sleep duration > 8 hours, daytime sleepiness, and sleep apnea was also associated with an increased likelihood of developing frailty. Notably, a dose-response relationship between sedative-hypnotic drug use and frailty was observed. CONCLUSIONS: Insomnia and sedative-hypnotic use were independently associated with increased frailty. The implementation of nonpharmacological treatments to attenuate insomnia may reduce frailty rates.