Associations of early retirement and mortality risk: a population-based study in Taiwan.

BACKGROUND: Early retirement is highly prevalent in Taiwan. This study assesses the association between early retirement and all-cause and cause-specific mortality risks while exploring the modifying effect of sociodemographic factors. METHODS: Using Taiwan's National Health Insurance Research Database between 2009 and 2019, 1 762 621 early retirees aged 45-64 and an equal number of employed comparators were included. The date and cause of death were identified using the National Death Registry. Cox regression models were used to estimate HRs of early retirement for all-cause mortality and cause-specific mortality. To explore modifying effects, we conducted subgroup analyses based on age groups, sexes, occupation types and general health status (Charlson Comorbid Index score). RESULTS: The analysis revealed that early retirees, compared with their concurrently employed counterparts, had a higher mortality risk (adjusted HR (aHR) 1.69, 95% CI (1.67 to 1.71)). Specifically, younger individuals (aged 45-54) (aHR 2.74 (95% CI 2.68 to 2.80)), males (aHR 1.78 (95% CI 1.76 to 1.81)), those in farming or fishing occupations (aHR 2.13 (95% CI 2.06 to 2.21)) or the private sector (aHR 1.92 (95% CI 1.89 to 1.96)), and those with the poorest health conditions (aHR 1.79 (95% CI 1.76 to 1.83)) had higher mortality risks of early retirement. Regarding specific causes of death, the top three highest risks were associated with gastrointestinal disorders, followed by suicide and neurological disorders. CONCLUSIONS: This study underscores the substantial mortality risk increase linked to early retirement, emphasising the importance of policy considerations, particularly regarding vulnerable populations and specific causes of death potentially linked to unhealthy lifestyles.

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.

Pulse pressure is associated with decline in physical function in older adults.

OBJECTIVES: This study examined the associations between pulse pressure, hypertension, and the decline in physical function in a prospective framework. STUDY DESIGN: The Healthy Aging Longitudinal Study tracked a group of Taiwanese adults aged 55 or more over an average of 6.19 years to assess pulse pressure and decline in physical function, including in handgrip strength, gait speed, and 6-min walking distance, at baseline (2009-2013) and in the second phase of assessments (2013-2020). MAIN OUTCOME MEASURES: Pulse pressure was calculated as the difference between systolic and diastolic blood pressure values. Weakness, slowness, and low endurance were defined as decreases of ≥0.23 m/s (one standard deviation) in gait speed, ≥5.08 kg in handgrip strength, and ≥ 57.73 m in a 6-min walk, as determined from baseline to the second phase of assessment. Linear and logistic regressions were employed to evaluate the associations between pulse pressure, hypertension, and decline in physical function. RESULTS: Baseline pulse pressure was associated with future handgrip strength (beta = -0.017, p = 0.0362), gait speed (beta = -0.001, p < 0.0001), and 6-min walking distance (beta = -0.470, p < 0001). In multivariable models, only handgrip strength (beta = -0.016, p = 0.0135) and walking speed (beta = -0.001, p = 0.0042) remained significantly associated with future pulse pressure. Older adults with high systolic blood pressure (≥140 mmHg) and elevated pulse pressure (≥60 mmHg) exhibited a significantly increased risk of weakness (odds ratio: 1.30, 95 % confidence interval: 1.08-1.58), slowness (1.29, 1.04-1.59), and diminished endurance (1.25, 1.04-1.50) compared with the reference group, who exhibited systolic blood pressure of <140 mmHg and pulse pressure of <60 mmHg. CONCLUSIONS: Among older adults, pulse pressure is associated with a decline in physical function, especially in terms of strength and locomotion.

Widowhood and mortality risk in Taiwan: a population-based matched cohort study.

BACKGROUND: Studying the causes of death among deceased spouses and surviving partners may provide insights into the underlying mechanisms of the association between widowhood and mortality. This study investigated the mortality risk of widowhood in Taiwan, examined the association of the cause of death between widowed individuals and their deceased spouses and explored potential modifying effects by age, gender and duration after widowhood. METHODS: This matched cohort study utilized Taiwan's National Health Insurance claims database and National Death Registry. In total, 204 010 widowed men and 596 136 widowed women were identified with a mean follow-up period of 6.9 and 7.9 years, respectively, and 816 040 comparison men and 2 384 544 comparison women were selected. RESULTS: Widowhood was associated with an increased mortality risk, with widowed men having a 1.32 increased risk and widowed women having a 1.27 increased risk. Age at spousal death and duration modified the associations after widowhood. The widowed individuals are more likely to die by the same cause as the deceased spouse if they died by suicide, accident, endocrine, gastrointestinal disorders or infection. CONCLUSIONS: The study suggests that healthcare policies and interventions should be developed to improve widowed individuals' health and overall welfare.

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes.

BACKGROUND: Patients with diabetes tend to have cellulitis, foot infections, and amputation. We conducted this research to compare the risks of cellulitis, foot infections, and amputation between metformin no-use and use in persons with type 2 diabetes. METHODS: Using propensity score matching, we identified 23 234 pairs of metformin nonusers and users from the National Health Insurance Research Database of Taiwan, since January 1, 2000, to December 31, 2017. Cox proportional hazards models were adopted to examine the risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation between metformin use and no-use. RESULTS: The mean follow-up period of metformin use and no-use was 6.31 (3.93) and 5.54 (3.97) years, respectively. Compared with metformin no-use, the adjusted hazard ratio and 95% confidence interval for metformin use in cellulitis development, recurrent cellulitis, foot infections, and amputation were 1.08 (1.04-1.12), 1.33 (1.14-1.55), 1.91 (1.75-2.09), and 1.88 (1.35-2.62), respectively. The longer cumulative duration of metformin usage had association with higher risks of these outcomes than metformin no-use. CONCLUSION: This population-based cohort study revealed that metformin use had association with significantly higher risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation than metformin no-use in patients with type 2 diabetes.

Develop and Validate a Prognostic Index With Laboratory Tests to Predict Mortality in Middle-Aged and Older Adults Using Machine Learning Models: A Prospective Cohort Study.

BACKGROUND: Prognostic indices can enhance personalized predictions of health burdens. However, a simple, practical, and reproducible tool is lacking for clinical use. This study aimed to develop a machine learning-based prognostic index for predicting all-cause mortality in community-dwelling older individuals. METHODS: We utilized the Healthy Aging Longitudinal Study in Taiwan (HALST) cohort, encompassing data from 5 663 participants. Over the 5-year follow-up, 447 deaths were confirmed. A machine learning-based routine blood examination prognostic index (MARBE-PI) was developed using common laboratory tests based on machine learning techniques. Participants were grouped into multiple risk categories by stratum-specific likelihood ratio analysis based on their MARBE-PI scores. The MARBE-PI was subsequently externally validated with an independent population-based cohort from Japan. RESULTS: Beyond age, sex, education level, and BMI, 6 laboratory tests (low-density lipoprotein, albumin, aspartate aminotransferase, lymphocyte count, high-sensitivity C-reactive protein, and creatinine) emerged as pivotal predictors via stepwise logistic regression (LR) for 5-year mortality. The area under curves of MARBE-PI constructed by LR were 0.799 (95% confidence interval [95% CI]: 0.778-0.819) and 0.756 (95% CI: 0.694-0.814) for the internal and external validation data sets, and were 0.801 (95% CI: 0.790-0.811) and 0.809 (95% CI: 0.774-0.845) for the extended 10-year mortality in both data sets, respectively. Risk categories stratified by MARBE-PI showed a consistent dose-response association with mortality. The MARBE-PI also performed comparably with indices constructed with clinical health deficits and/or laboratory results. CONCLUSIONS: The MARBE-PI is considered the most applicable measure for risk stratification in busy clinical settings. It holds potential to pinpoint older individuals at elevated mortality risk, thereby aiding clinical decision-making.

Predictors of live-in migrant caregiver employment for people with dementia in Taiwan.

BACKGROUND: With the increasing number of individuals with dementia, families have hired an increasing number of live-in migrant caregivers (LIMCs). Currently, limited evidence is available regarding the influence of long-term care resource utilization on the hiring of LIMCs for caring for individuals with dementia in Taiwan. METHODS: We recruited individuals with dementia who did not hire LIMCs and their primary family caregivers from nine hospitals in Taiwan as baseline. Multivariable logistic regression was used to evaluate the utilization of long-term care resources for individuals with dementia and other factors that may affect the decision to hire LIMCs. RESULTS: The users of non-long-term care resources had the highest likelihood of hiring LIMCs (odds ratio [OR] = 4.24, 95% CI, 2.30-7.84). Compared with spouses, nonimmediate family caregivers (OR = 3.40, 95% CI, 1.16-9.90) were significantly more likely to hire LIMCs. A higher likelihood of hiring LIMCs was observed for those with Lewy body dementia compared with other individuals (OR = 2.31, 95% CI, 1.03-5.14). Compared with individuals who did not hire LIMCs, those who hired LIMCs exhibited higher scores on the Neuropsychiatric Inventory (NPI) and higher severity of individual NPI items. CONCLUSION: Hiring LIMCs is strongly correlated with the utilization of non-long-term care resources and is influenced by the dynamics between individuals with dementia and their primary family caregivers. A higher likelihood of hiring LIMCs was observed for individuals with Lewy body dementia and individuals with elevated NPI scores compared with their counterparts. Given these observations, various support strategies and interventions should be tailored to the specific requirements of individuals with dementia and their families.

Gender difference on the mediation effects of filial piety on the association between chronic obstructive pulmonary disease and depressive symptoms in older adults: A community-based study.

Filial piety is viewed as strong family support for older Chinese people, and strongly associated with depressive symptoms. It is unknown if there exists gender difference in the mediation effects of filial piety on the relationship between chronic obstructive pulmonary disease (manifested as lung function) and depression. We investigated whether filial piety mediates the association between lung function and depression in community-dwelling older men and women using the Healthy Aging Longitudinal Study in Taiwan (HALST). Community dwelling adults aged 65 and above were analyzed. Pulmonary function, depressive symptoms, and filial piety expectation (FPE) and receipt of filial piety (RFP) were collected. The interaction and mediation of filial piety between lung function and depression was analyzed. We found that in older men, forced expiratory volume in the first second (FEV1) was inversely correlated with depression (ß = -0.1281, p = 0.004) with no mediation effect of FPE. In older women, FEV1 was negatively associated with FPE, but FPE did not increase the risk of depression (ß = 0.0605, p = 0.12). In both older men and women, FEV1 was negatively associated with RFP, while RFP reduced the risk of depression (p< 0.001). In older women, the correlation between FEV1 was complete mediation of RFP. Results indicate that feelings of insufficient filial piety may increase the likelihood of depression, especially in elderly women with worse lung function. Although modest, the main mediation effect of filial piety was improvement of lung function in older subjects, which might decrease depression.

Impact of physical activity on disability-free and disabled life expectancies in middle-aged and older adults: Data from the healthy aging longitudinal study in Taiwan.

AIM: Leisure-time physical activity (LTPA) promotes healthy aging; however, data on work-related physical activity (WPA) are inconsistent. This study was conducted to examine the disability-free life expectancy (DFLE) and disabled life expectancy (DLE) across physical activity levels, with a focus on WPA, in middle-aged and older adults. METHODS: Data from 5663 community-dwelling participants aged ≥55 years and enrolled in the Healthy Aging Longitudinal Study in Taiwan were evaluated. Energy expenditures from LTPA and WPA were calculated from baseline questionnaires and categorized into sex-specific cutoffs. Disability was based on repeat measures of participants' activities of daily living and instrumental activities of daily living. Mortality was confirmed via data linkage with the Death Certificate database. DFLE and DLE were estimated from discrete-time multistate life-table models. RESULTS: At age 65, women with low WPA had a DLE of 2.88 years (95% confidence interval [CI], 1.67-4.08), which was shorter than that of women without WPA (DLE, 5.24 years; 95% CI, 4.65-5.83) and with high WPA (DLE, 4.01 years; 95% CI, 2.69-5.34). DFLE and DLE were similar across WPA levels in men. DFLE tended to increase as the LTPA increased in men and women. CONCLUSION: Women with low WPA had shorter DLE than did those with no or high WPA. To reduce the risks of disability associated with physical activity, public policy should advocate for older people to watch the type, amount, and intensity of their activities as these may go ignored during WPA. Geriatr Gerontol Int 2024; 24: 229-239.

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.

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.

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.

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.

Effectiveness of health checkup with depression screening on depression treatment and outcomes in middle-aged and older adults: a target trial emulation study.

Background: Adult preventive health checkups with depression screening were launched in August 2011 in Taiwan; however, its impact has not yet been evaluated. This study aimed to use real-world data to assess the effectiveness of depression screening among middle-aged and older adults. Methods: A total of 4,972,228 adults aged 40 years and above who participated in a health checkup with depression screening between 2013 and 2019 and the same number of unscreened counterparts were included. The target trial emulation study was conducted to estimate the hazard ratios (HRs) for newly treated depression, psychiatric hospitalisation, and suicide. The changes in HRs during the study period were assessed using interval Cox models. Findings: The screening group had a higher rate of newly treated depression (HR 1.63 [95% CI 1.62, 1.64]) and a lower risk of psychiatric hospitalisation (HR 0.93 [95% CI 0.91, 0.95]). There was a null association between depression screening and suicide; however, a higher suicide risk was found in screened older adults aged 65 years and above. Only 10.8% received depression treatment during the study period among the screen-positive individuals. Interpretation: Health checkups with depression screening could potentially promote depression treatment and reduce the risk of psychiatric hospitalisation; however, there was no effect on suicide. The treatment rate for depression remained low after screening for depression. Further attention to enhance referral and treatment is required. Funding: The study was funded by the National Health Research Institutes, Taiwan.

A national survey on health-related quality of life for people with dementia in residential long-term care institutions.

BACKGROUND: Health-related quality of life (HRQoL) is an essential outcome parameter in geriatric research; however, the available evidence is mixed regarding the factors associated with HRQoL among people with dementia. We aimed to identify factors that contribute to HRQoL among people with dementia in residential long-term care (LTC) institutions. METHODS: We randomly selected 299 of 1607 registered residential LTC institutions in Taiwan. A cross-sectional survey was conducted between 2019 and 2020, including items on demographic characteristics, comorbidities, the EuroQol-5 dimensions-5 levels (EQ-5D-5L; utility and visual analog scale [VAS] scores), the Mini-Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), behavioral and psychological symptoms of dementia, activities of daily living (ADL), and instrumental ADL (IADL). RESULTS: In total, 1313 people with dementia from 267 institutions were enrolled (mean age, 76.4 ± 12.7 years). The mean EQ-5D-5L utility and VAS scores were 0.10 (standard deviation [SD] = 0.48) and 66.57 (SD = 20.67), respectively. In multivariate linear regression analysis, higher scores for ADL, IADL, and CDR sum of boxes were associated with higher utility scores. Higher VAS scores were associated with higher ADL and MMSE scores. Lower utility scores and VAS scores were associated with more frequent depressive symptoms. CONCLUSION: ADL, dementia severity, cognitive function, and depressive symptoms influenced the HRQoL of people with dementia in residential LTC institutions. Longitudinal studies should be conducted to better understand how HRQoL changes over time among people with disabilities.

Resting Heart Rate Independent of Cardiovascular Disease Risk Factors Is Associated With End-Stage Renal Disease: A Cohort Study Based on 476 347 Adults.

BACKGROUND: The relationship between resting heart rate (RHR) and the risk of end-stage renal disease (ESRD) among those without cardiovascular disease remains unclear. We aim to establish temporal consistency and elucidate the independent relationship between RHR and the risk of ESRD. METHODS AND RESULTS: This cohort enrolled participants from 476 347 individuals who had taken part in a screening program from 1996 to 2017. We identified 2504 participants who had ESRD, and the median follow-up was 13 years. RHR was extracted from electrocardiography results, and the study assessed the relationship between RHR and the risk of ESRD using the Cox proportional hazards model. Of the participants, 32.6% had an RHR of 60 to 69 beats per minute (bpm), and 22.2% had an RHR of ≥80 bpm. Participants with an RHR of ≥80 bpm had a higher stage of chronic kidney disease, lower estimated glomerular filtration rate, and more proteinuria than those with an RHR of 60 to 69 bpm. Participants with an RHR of 80 to 89 and ≥90 bpm had a 24% (hazard ratio [HR], 1.24 [95% CI, 1.09-1.42]) and 64% (HR, 1.64 [95% CI, 1.42-1.90]) higher risk of ESRD, respectively. The risk of ESRD remained significantly elevated (HR, 1.32 [95% CI, 1.10-1.58] per 10-beat increase from 60 bpm) after excluding participants who smoked; had hypertension, diabetes, or hyperlipidemia; or were overweight. CONCLUSIONS: An RHR of ≥80 bpm is significantly associated with an increased risk of ESRD. These results suggest that RHR may serve as a risk factor for kidney disease in individuals without established cardiovascular disease risk factors.

Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Retinopathy in Patients With Type 2 Diabetes.

Importance: Diabetic nephropathy and diabetic retinopathy share many similarities in pathophysiological processes. Preclinical studies have shown that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have a protective role in the risk of diabetic retinopathy. Objective: To compare the risk of sight-threatening retinopathy associated with SGLT2is and other second-line glucose-lowering medications (including pioglitazone, sulfonylureas, and dipeptidyl peptidase-4 inhibitors [DPP-4is]) in patients with type 2 diabetes (T2D). Design, Setting, and Participants: This cohort study in Taiwan applied a new-user and active-comparator design. Patient demographic and clinical data were obtained from the National Health Insurance Research Database. Adult patients with newly diagnosed T2D from January 1, 2009, to December 31, 2019, were recruited and followed up until December 31, 2020. Propensity score matching was used to identify pairs of patients treated with SGLT2i vs DPP-4i, SGLT2i vs pioglitazone, and SGLT2i vs sulfonylurea from January 1, 2016, to December 31, 2019. Data were analyzed between August 18, 2022, and May 5, 2023. Exposures: Treatment with SGLT2i, DPP-4i, pioglitazone, and sulfonylureas starting on January 1, 2016. Main Outcomes and Measures: The main outcome was sight-threatening retinopathy in participants. Cox proportional hazards regression models were used to assess relative hazards of sight-threatening retinopathy between the matched case and control groups. Results: A total of 3 544 383 patients with newly diagnosed T2D were identified. After 1:1 propensity score matching, 65 930 pairs of patients treated with SGLT2i vs DPP-4i, 93 760 pairs treated with SGLT2i vs pioglitazone, and 42 121 pairs treated with SGLT2i vs sulfonylurea were identified. These matched patients included 236 574 males (58.6%), with a mean (SD) age of 56.9 (11.8) years. In the matched cohorts, SGLT2i had a significantly lower risk of sight-threatening retinopathy than DPP-4i (adjusted hazard ratio [AHR], 0.57; 95% CI, 0.51-0.63), pioglitazone (AHR, 0.75; 95% CI, 0.69-0.81), and sulfonylureas (AHR, 0.62; 95% CI, 0.53-0.71). The Kaplan-Meier curves showed that SGLT2i was associated with a significantly lower cumulative incidence of sight-threatening retinopathy than DPP-4i (3.52 vs 6.13; P < .001), pioglitazone (4.32 vs 5.76; P < .001), and sulfonylureas (2.94 vs 4.67; P < .001). Conclusions and Relevance: This cohort study found that SGLT2i was associated with a lower risk of sight-threatening retinopathy compared with DPP-4i, pioglitazone, and sulfonylureas. This finding suggests that SGLT2i may play a role not only in reduced risk of diabetic nephropathy but also in the slow progression of diabetic retinopathy in patients with T2D.

Use of dipeptidyl peptidase-4 inhibitors was associated with a lower risk of Parkinson's disease in diabetic patients.

Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39-0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.

Exploring concepts and trends in informal caregiver burden: systematic review using citation network and content analysis.

BACKGROUND: With the increase in the aging population, informal caregivers have become an essential pillar for the long-term care of older individuals. However, providing care can have a negative impact and increase the burden on caregivers, which is a cause for concern. OBJECTIVE: This study aimed to comprehensively depict the concept of "informal caregiver burden" through bibliometric and content analyses. METHODS: We searched the Web of Science (WoS) database to obtain bibliometric data and included only papers published between 2013 and 2022. We used content analysis to extract and identify the core concepts within the text systematically. RESULTS: Altogether, 934 papers were included in the bibliometric analysis, from which we selected 19 highly impactful papers for content analysis. The results indicate that researchers have focused on exploring the factors that impact informal caregiver burden. Meanwhile, there has been a widespread discussion regarding the caregiver burden among those caring for recipients with specific illnesses, such as dementia, Alzheimer's disease, and cancer, as these illnesses can contribute to varying levels of burden on informal caregivers. In addition, questionnaires and interviews emerged as the predominant methods for data collection in the realm of informal caregiver research. Furthermore, we identified 26 distinct assessment tools specifically tailored for evaluating burden, such as caregiver strain index (CSI). CONCLUSION: For future studies, we suggest considering the intersectionality of factors contributing to the burden on informal caregivers. This approach could enhance the well-being of both caregivers and older care recipients.