Dose-Responsive Impacts of Social Frailty on Intrinsic Capacity and Healthy Aging among Community-Dwelling Middle-aged and Older Adults: Stronger Roles of Social Determinants over Biomarkers.

OBJECTIVE: The intricate relationship between social determinants, e.g., social frailty, biomarkers and healthy aging remains largely unexplored, despite the potential for social frailty to impact both intrinsic capacity (IC) and functional ability in the aging process. DESIGN: Retrospective longitudinal cohort study. SETTING AND PARTICIPANTS: Participants aged 50+ years from the Social Environment and Biomarkers of Aging Study (SEBAS) in Taiwan, stratified into three age groups: 50-64, 65-74 and 75+. MEASUREMENTS: Social frailty was defined based on a score derived from four domains: exclusion from general resources, social resources, social activity, and fulfillment of basic social needs. The scores were categorized as score=0 (no social frailty), 1 (social pre-frailty), and 2+ (social frailty). Multivariable logistic regression and Cox proportional hazard models were employed to examine the dose-responsive relationship between social frailty, low IC, functional and psychological health, and mortality. RESULTS: Of 1015 study participants, 24.9% and 7.9% were classified as social pre-frailty and social frailty, respectively. No significant differences were observed in most biomarkers between those with social frailty and those without. A dose-responsive relationship was found between social frailty and increased risk of low IC (social pre-frailty: aOR 2.20 [95% CI 1.59-3.04]; social frailty: 5.73 [3.39-9.69]). Similar results were found for functional and psychological health. However, no significant association between social frailty and all-cause mortality was found at the 4-year follow-up (social pre-frailty: aHR 1.52 [95% CI 0.94-2.43]; social frailty: 1.59 [0.81-3.09]). CONCLUSIONS: The significant association between social frailty and low IC, functional limitations, cognitive declines, and depressive symptoms underscores the pressing need for research on intervention strategies to enhance healthy aging in the lifespan course.

Roles of Baseline Intrinsic Capacity and its Subdomains on the Overall Efficacy of Multidomain Intervention in Promoting Healthy Aging among Community-Dwelling Older Adults: Analysis from a Nationwide Cluster-Randomized Controlled Trial.

BACKGROUND: Impaired intrinsic capacity (IC), which affects approximately 90% of older adults, is associated with a significantly heightened risk of frailty and cognitive decline. Existing evidence suggests that multidomain interventions have the potential to enhance cognitive performance and yield positive effects on physical frailty. OBJECTIVE: To examine roles of baseline IC and its subdomains on the efficacy of multidomain interventions in promoting healthy aging in older adults. DESIGN: a cluster-randomized controlled trial. SETTING AND PARTICIPANTS: 1,054 community-dwelling older adults from 40 community-based clusters across Taiwan. INTERVENTION: A 12-month pragmatic multidomain intervention of exercise, cognitive training, nutritional counseling and chronic condition management. MEASUREMENTS: Baseline IC was measured by 5 subdomains, including cognition (Montreal Cognitive Assessment, MoCA), sensory (visual and hearing impairment), vitality (handgrip strength or Mini-Nutritional Assessment-short form), psychological well-being (Geriatric Depression Scale-5), and locomotion (6m gait speed). Outcomes of interest were cognitive performance (MoCA scores) and physical frailty (CHS frailty score) over a follow-up period of 6 and 12 months. RESULTS: Of all participants (mean age:75.1±6.4 years, 68.6% female), about 90% participants had IC impairment at baseline (2.0±1.2 subdomains). After covariate adjustment using a generalized linear mixed model (GLMM), the multidomain intervention significantly prevented cognitive declines and physical frailty, particularly in those with IC impairment ≥ 3 subdomains (MoCA: coefficient: 1.909, 95% CI: 0.736 ~ 3.083; CHS frailty scores: coefficient = -0.405, 95% CI: -0.715 ~ -0.095). To assess the associations between baseline poor capacity in each IC subdomain and MoCA/CHS frailty scores over follow-up, a 3-way interaction terms (time*intervention*each poorer IC subdomains) were added to GLMM models. Significant improvements in MoCA scores were shown for participants with poorer baseline cognition (coefficient= 1.138, 95% CI: 0.080 ~ 2.195) and vitality domains (coefficient= 1.651, 95% CI: 0.541 ~ 2.760). The poor vitality domain also had a significant modulating effect on the reduction of CHS frailty score after the 6- and 12-month intervention period (6 months: coefficient= -0.311, 95% CI: -0.554 ~ -0.068; 12 months: coefficient= -0.257, 95% CI: -0.513 ~ -0.001). CONCLUSION AND IMPLICATIONS: A multidomain intervention in community-dwelling older adults improves cognitive decline and physical frailty, with its effectiveness influenced by baseline IC, highlighting the importance of personalized strategies for healthy aging.

Screening of Fracture Risk and Osteoporosis Among Older Long-term Care Residents: A Prospective Study.

This prospective study assessed the effectiveness of screening older long-term care residents (LTCRs) for fracture risk and osteoporosis in Taiwan. Fracture risk screening was done using the Fracture Risk Assessment Tool (FRAX), and those with high or moderate risk were offered osteoporosis workup and treatment at the hospital. Among 785 LTCRs screened, 338 men (mean age 75.6) and 447 women (mean age 81.2) were included. Only 5.2% of women and no men were using anti-osteoporosis medication. Based on the Bone Health and Osteoporosis Foundation (BHOF) recommendations, 69.2% of men and 92.6% of women were classified as high fracture risk. In 110 participants willing to receive bone mineral density examination, osteoporosis was diagnosed in 86.2% of women and half of men. FRAX could effectively differentiate fracture risk in 648 LTCRs who completed 2-year follow-ups; no fracture occurred in the low-risk group. The study emphasizes the importance of fracture risk screening to enhance osteoporosis diagnosis and treatment among LTCRs.

Untangling the Complex Interplay between Social Isolation, Anorexia, Sarcopenia, and Mortality: Insights from a Longitudinal Study.

BACKGROUND: Social isolation is a pervasive and debilitating condition that has adverse prognostic impacts. This condition often co-occurs with other geriatric syndromes, further exacerbating negative health outcomes. Given these considerations, the present study aims to elucidate the roles of social isolation in older adults with anorexia of aging and/or sarcopenia with respect to long-term mortality using a nationally representative cohort study. METHODS: Data were obtained from the Taiwan Longitudinal Study on Aging (TLSA), with a sample size of 3,762 study participants aged 50 years and older. Data from 1999 (wave 4) to 2015 (wave 9) were analyzed. The TLSA questionnaire was used to define social isolation, anorexia, and sarcopenia. Logistic regressions were employed to explore the associations between social isolation, anorexia, and sarcopenia. The Cox proportional hazard model was utilized to examine the synergistic effects of social isolation and anorexia or sarcopenia on 16-year all-cause mortality. RESULTS: After controlling for demographic information and comorbidities, older adults with social isolation were significantly associated with anorexia (adjusted odds ratio [aOR] 1.46 [95% confidence interval: 1.00-2.12, p=0.0475]) and sarcopenia (aOR 1.35 [95% CI: 1.12-1.64, p=0.0021]). Furthermore, the synergistic effects of social isolation with anorexia (aOR 1.65 [95% CI: 1.25-2.18, p=0.0004]) or sarcopenia (aOR 1.65 [95% CI: 1.42-1.92, p<0.0001]) were both significantly associated with higher risks of all-cause mortality, while social isolation alone revealed borderline statistical significance. CONCLUSIONS: Our findings indicate that social isolation is closely linked to anorexia and sarcopenia among middle-aged and older adults. Additionally, social isolation significantly exacerbates the long-term mortality risk associated with anorexia of aging and sarcopenia. However, social isolation alone appears to have borderline long-term mortality risk in this cohort. These findings underscore the importance of addressing social isolation in older adults with anorexia and/or sarcopenia to optimize their health outcomes and mitigate long-term mortality risk.

Cardiovascular Disease Risk Burden, Cognitive Impairments and Incident Dementia among Community-Dwelling Middle-Aged and Older Adults: An 8-Year Longitudinal Follow-up Study.

OBJECTIVES: To evaluate the associations between cardiovascular disease (CVD) risk burden (estimated by the World Health Organization (WHO) algorithm) and cognitive impairments (e.g., incident dementia, global and domain-specific impairments) among CVD-, dementia- and disability-free, community-dwelling middle-aged and older adults during an 8-year follow-up. DESIGN: A community-based longitudinal cohort study. SETTING: Yuanshan township in Yi-Lan County, Taiwan. PARTICIPANTS: A total of 889 community-dwelling residents aged 50 years or older. MEASUREMENTS: Age, sex, educational level, employment status, alcohol status, body mass index, physical activity, gait speed, depressive symptoms, WHO region-specific CVD risk scores (10-year CV risk, low: <10% vs. moderate-to-high: ≥ 10%), Chinese version of the Mini-Mental State Examination (MMSE), verbal memory by the delay-free recall in the Chinese Version Verbal Learning Test (CVVLT), language function by the Boston Naming Test and the category (animal) Verbal Fluency Test, visuospatial function by the Taylor Complex Figure Test, executive function by the digit backward and the Clock Drawing Test. RESULTS: Compared to those with low CVD risk, middle-aged and older adults with moderate-to-high CVD risk were at greater risk for cognitive impairments with respect to the MMSE (adjusted odds ratio (aOR) 1.60 [95% confidence interval (CI) 1.19-2.15], P=0.002), verbal memory (aOR 1.97 [1.43-2.70], P< 0.001) and language (aOR 1.99 [1.46-2.70], P< 0.001), as well as incident dementia (aOR 2.40 [1.33-4.33], P=0.004). After adjusting for all covariates, CVD risk was not associated with other domains of cognitive impairment. CONCLUSIONS: Among healthy, community-dwelling, middle-aged and older adults, those with moderate-to-high cardiovascular risk burden were significantly associated with incident dementia and global and domain-specific cognitive impairments (verbal memory and language), which suggests the existence of a relationship between early cognitive deficits and CVD risk burden. Further studies are needed to elucidate the pathophysiological mechanism of the link between CVD risk burden and cognitive impairment.

Long-Term Mortality Risk in Older Adults with Sarcopenia: An 11-Year Prospective Cohort Study Comparing AWGS 2014 and AWGS 2019 Guidelines for Enhanced Clinical Utility and Accurate Risk Prediction.

OBJECTIVES: To discern the diagnostic accuracy between the updated diagnostic consensus of the Asian Working Group for Sarcopenia (AWGS) in 2019 (AWGS 2019) and the previous AWGS 2014 guidelines. DESIGN: A prospective population-based cohort study. SETTING AND PARTICIPANTS: The study included 731 older community-dwelling adults aged ≥ 65 years who participated in face-to-face interviews and were followed up for 11-year mortality until 31 Mar 2022. MEASUREMENTS: We utilized a handgrip strength dynamometer to measure participants' muscle strength, while their walking speed was determined by a timed 6-meter walk test at their usual pace. Additionally, muscle mass was measured using dual-energy X-ray absorptiometry scanning. Sarcopenia was defined as the presence of low muscle mass in combination with weakness and/or slowness both by AWGS 2014 and 2019 criteria. RESULTS: The present study followed 731 participants (mean age 73.4 ± 5.4 years, men predominant 52.8%) over a period of 11 years, yielding 5927 person-years and 159 deaths. Prevalence of sarcopenia defined by AWGS 2019 and 2014 criteria were 8.5% and 6.8%, respectively. Sarcopenia defined by AWGS 2019 (HR 1.62, 95% CI 1.04-2.54, p=0.034) but not AWGS 2014 was significantly associated with mortality in community-living older adults after adjusting for potential confounders such as age, sex, education, drinking, disease burden and serum level of testosterone. The study also found that the AWGS 2019 criteria had a better model fitness than AWGS 2014 criteria in predicting mortality. CONCLUSION: AWGS 2019 criteria outperformed AWGS 2014 in identifying sarcopenia risk and predicting mortality. Screening for sarcopenia in older adults may improve health outcomes by identifying those at increased mortality risk.

Intrinsic Capacity Impairment Patterns and their Associations with Unfavorable Medication Utilization: A Nationwide Population-Based Study of 37,993 Community-Dwelling Older Adults.

OBJECTIVES: Our aim was to explore the patterns of intrinsic capacity (IC) impairments among community-dwelling older adults and the associations of these different patterns with excessive polypharmacy, potentially inappropriate medications, and adverse drug reactions in a nationwide population-based study. DESIGN: A cross-sectional study included older adults from the Taiwan Integrated Care for Older People (ICOPE) program in 2020. SETTING AND PARTICIPANTS: The study subjects comprised 38,308 adults aged 65 years and older who participated in the ICOPE Step 1 screening and assessed six domains of IC following the World Health Organization (WHO) ICOPE approach. METHODS: Latent class analysis was adopted to identify distinct subgroups with different IC impairments patterns. The associations between different IC impairments patterns and unfavorable medication utilization, including excess polypharmacy (EPP), potentially inappropriate medications (PIMs), and adverse drug reactions (ADRs), were assessed by multivariate logistic regression models. RESULTS: Latent class analysis identified five distinct subgroups with different IC impairment patterns: robust (latent class prevalence: 59.4%), visual impairment (17.7%), physio-cognitive decline (PCD) with sensory impairment (12.3%), depression with cognitive impairment (7.7%), and impairments in all domains (2.9%). Compared to the robust group, all other groups were at higher odds for unfavorable medication utilization. The "depression with cognitive impairment" group (EPP: aOR=4.35, 95% CI 3.52-5.39, p<0.01; PIMs: aOR=2.73, 95% CI 2.46-3.02, p<0.01) and the "impairment in all domains" group (EPP: aOR=9.02, 95% CI 7.16-11.37, p<0.01; PIMs: aOR=3.75, 95% CI 3.24-4.34, p<0.01) remained at higher odds for EPP and PIMs after adjustment. CONCLUSIONS: We identified five distinct impairment patterns of IC, and each impairment pattern, particularly the "depression with cognitive impairment" and "impairment in all domains", was associated with higher odds of EPP and PIMs. Further longitudinal and intervention studies are needed to explore long-term outcomes of different impairment pattern and their reversibility.

Prognostic Impact of Delirium in Older People With/Without Dementia: A Retrospective Cohort Study in Taiwan.

OBJECTIVES: To elucidate the hypothetically different interactions between delirium and post-discharge prognostic indicators in elderly hospital inpatients with versus without dementia. DESIGN: Retrospective cohort study of claims data by Taiwan National Health Insurance beneficiaries between 2002-2013. SETTING: Records of public hospital admissions in the Taiwan National Health Insurance Research database. PARTICIPANTS: Propensity-score matched subgroups of patients with delirium superimposed on dementia (n = 922) versus dementia alone (n = 922), delirium alone (n = 680) versus neither delirium nor dementia (n = 680). MEASUREMENTS: Mortality, emergency department visits, readmissions, and psychotropic drug use, within 30, 180, and 365 days of discharge, were analyzed using multivariate proportional hazards or logistic regression analyses. RESULTS: Delirium superimposed on dementia was not associated with increased post-discharge mortality, or emergency department visits, but significantly increased the risk of readmissions at 365-day follow-up (adjusted HR, 95% CI: 1.26, 1.01-1.56). However, delirium without dementia was significantly associated with increased post-discharge mortality, emergency department visits and readmissions at 180 days and 365 days (respective adjusted HRs: mortality, 1.63 and 1.79; adjusted ORs: emergency department visits, 1.89 and 1.81; readmissions, 1.47 and 1.53). Delirium in patients both with dementia and without, was associated with six-fold higher likelihood of in-hospital psychotropic drug use, and doubled post-discharge psychotropic drug usage. CONCLUSIONS: The obvious association between in-hospital delirium and worsened long-term prognosis, irrespective of dementia, raises awareness to warrants proactive and multimodal prevention and intervention strategies. Furthermore, the mechanisms about different influence of delirium for patients with/without dementia need to be further explored.

Association between teriparatide treatment persistence and adherence, and fracture incidence in Taiwan: analysis using the National Health Insurance Research Database.

UNLABELLED: Medication persistence and adherence are critical for osteoporosis outcomes. Using the Taiwan National Health Insurance Research Database, we found that persistence and adherence to teriparatide were low in Taiwanese patients with osteoporosis and that greater persistence and adherence were associated with a lower incidence of hip and other nonvertebral fractures. INTRODUCTION: The purpose of this study was to determine the persistence and adherence to teriparatide treatment in Taiwanese patients with osteoporosis, and to examine the association between persistence and adherence to teriparatide with fracture risks. METHODS: Medical and pharmacy claims for 4,692 patients with vertebral or hip fractures and teriparatide prescriptions between 2005 and 2008 were identified (Taiwan National Health Insurance Research Database). Persistence was the time from the start of treatment to the first 90-day gap between two teriparatide prescriptions. Adherence was the number of teriparatide pens (each pen is used over 1 month) prescribed over 24 months. Association of persistence and adherence to teriparatide with fracture incidence was assessed using adjusted Cox proportional hazards models. RESULTS: The proportion of patients persisting with teriparatide for >6 months and >12 months was 44.6 and 24.9 %, respectively. Over 24 months, 53.6 % of patients were adherent for >6 months and 33.9 % were adherent for >12 months. Patients persisting for >12 months had a significantly lower incidence of hip (adjusted hazard ratio [HR], 0.61 [95 % confidence interval (CI), 0.40-0.93], P = 0.0229) and nonvertebral fracture (HR, 0.79 [95 % CI, 0.63-0.99], P = 0.0462) compared with those who persisted for ≤12 months. Patients adherent for >12 months had a lower incidence of hip (HR, 0.66 [95 % CI, 0.46-0.96], P = 0.0286) and nonvertebral fracture (HR, 0.81 [95 % CI, 0.66-0.99], P = 0.0377) compared with those adherent for ≤12 months. CONCLUSIONS: Persistence and adherence to teriparatide over 24 months were low in Taiwanese patients with osteoporosis; greater adherence and persistence were associated with a lower incidence of nonvertebral fractures.

Serotonergic antidepressant use and the risk of fracture: a population-based nested case-control study.

UNLABELLED: This is the first study to investigate the association between the use of selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) and the risk of fractures using a nationwide representative cohort of ethnic Chinese. Current use of SSRI/SNRI and the co-morbidity, especially osteoporosis and history of falling, play an important role in the increased risk of fractures. INTRODUCTION: This nested case-control study examines the association between the timing, intensity, and individual components of serotonergic antidepressant (including SSRIs and SNRIs) use and the risk of all-cause fracture. METHODS: Using the 2002-2011 Taiwan National Health Insurance Research Database, we identified patients who received at least three prescriptions of antidepressants between January 1st 2002 and December 31st 2010 as our study cohort. In the study cohort, we identify 8250 patients who had first admission for fracture and 33,000 matched controls (1:4, matched by age, sex, and cohort entry date). Multivariate conditional logistic regression was used to estimate the association between the use of serotonergic antidepressants and the risk of fracture. RESULTS: Current users of serotonergic antidepressants were associated with an increased risk of fracture (adjusted odds ratio (aOR) 1.16 [95 % confidence interval 1.07-1.25]). Furthermore, a higher risk of fractures was found in patients with osteoporosis (aOR 3.05 [2.73-3.42]) or a history of falling (aOR 6.13 [3.41-11.0]). The risks of fracture between SSRI and SNRI users were comparable. CONCLUSION: Current use of SSRI/SNRI is associated with an increased risk of all caused fractures. Additionally, the co-morbidity, especially osteoporosis and a history of falling, plays an important role in the risk of fractures.

Adherence and medication utilisation patterns of fixed-dose and free combination of angiotensin receptor blocker/thiazide diuretics among newly diagnosed hypertensive patients: a population-based cohort study.

OBJECTIVE: The study aimed to compare the adherence and persistence among newly diagnosed hypertensive patients using fixed-dose (FDC) and free combinations (FC) of angiotensin receptor blocker (ARB)/thiazide diuretic using Taiwan's National Health Insurance Research Database. METHODS: General linear regression and Kaplan-Meier analyses were used to estimate the impact of FDC on adherence [measured by medication possession ratio (MPR)] and persistence (time from day of initiation to treatment discontinuation) of ARB/thiazide diuretic. RESULTS: The adjusted MPRs were all significantly higher among FDC group compared with FC group (6 months: 66.55% vs. 63.86%; 1 year: 52.58% vs. 46.73%, 1.5 year: 46.30% vs. 38.07%; 2 year: 42.06% vs. 32.45%, all p < 0.001). Patients received FDC therapy were less likely to discontinue their therapy [adjusted hazard ratio (HR) 0.79, 95% CI = 0.74-0.85]. CONCLUSIONS: Our findings suggest that use of FDC is associated with higher adherence and persistence rates than use of FC in newly diagnosed hypertensive patients.

Monitoring liver function among patients who initiated anti-tuberculosis drugs in Taiwan, 2000-2011.

OBJECTIVE: To investigate adherence to liver function monitoring as recommended in Taiwan's tuberculosis (TB) diagnosis and treatment guidelines for newly diagnosed TB patients. DESIGN: Retrospective cohort study of the National Health Insurance Research Database (NHIRD), Taiwan, 2000-2011. METHODS: From the NHIRD, we identified 11 397 newly diagnosed TB patients who initiated anti-tuberculosis treatment between 2000 and 2011 and categorised these into three groups: completely, partially and non-adherent. Logistic regression was used to explore potential factors associated with the adherence rate. RESULTS: The completely adherent rate increased from 0.5% in 2000 to 9.2% in 2011, while the non-adherent rate decreased from 17.5% to 1.2%. Compared to the non-adherent group, patients with a history of liver disease (OR 4.36, 95%CI 1.92-9.87) and viral hepatitis (OR 9.39, 95%CI 1.47-60.19), as well as patients whose prescribing physicians were specialists in chest (OR 4.59, 95%CI 1.91-11.05), TB (OR 2.55, 95%CI 1.01-6.40) and infectious diseases (OR 3.93, 95%CI 1.08-14.31), had higher odds of being completely adherent to the guidelines. CONCLUSION: Our findings could serve as an important reference for developing effective strategies to improve adherence to guidelines and prevent patients from developing anti-tuberculosis drug-associated hepatotoxicity.

Epidemiology of post-transplant malignancy in Asian renal transplant recipients: a population-based study.

OBJECTIVE: Using Taiwan's National Health Insurance Research Database, this large population-based study was conducted to explore the incidences and risk factors of post-transplant malignancy in Asian renal transplant recipients. PATIENTS AND METHODS: A total of 642 patients who firstly underwent renal transplant between January 1, 2000 and December 31, 2008 were identified from a 2 million cohort. The primary endpoint was a subsequent hospitalization with a primary diagnosis of malignancy (ICD-9-CM code: 140.xx-239.xx) after renal transplantation. All patients were followed until the occurrence of endpoints or the end of the study (December 31, 2010), whichever came first. Adjusted risks of post-transplant cancer were analyzed using Cox proportional hazards regression model. All models were adjusted for baseline characteristics, comorbid diseases, transplant year, and exposure to immunosuppressive agents. RESULTS: Among 642 renal transplant patients, 54 cancers (8.4 %) were identified. The median time between transplant and cancer diagnosis was 46.2 (range 8.5-107.4) months. Cancers of kidney and other unspecified urinary organs was the most common cancer sites, accounted for 18.5 % of the malignancies diagnosed. The next most common cancer sites were trachea, bronchus, and lung (14.8 %), bladder (13.0 %), liver and intrahepatic bile ducts (11.1 %), colon (5.6 %), and prostate (5.6 %). Age at transplantation was a statistically significant risk factor of post-transplant cancer in our study. Increased risks of post-transplant cancer were observed in patients who received immunosuppression agents (cyclosporine (HR 1.26, 95 % CI 0.58-2.77, p = 0.5603), tacrolimus (HR 1.99, 95 % CI 0.66-6.00, p = 0.2197), and mycophenolate (HR 1.00, 95 % CI 0.40-2.45, p = 0.9874)) although the estimates were not statistically significant. CONCLUSIONS: Our population-based cohort study offers additional insight into post-transplant cancers in Asian population. Further studies are warranted to assess the association between specific immunosuppression agents and post-transplant cancers.

Risk of heart failure associated with dopamine agonists: a nested case-control study.

BACKGROUND: Recent evidence has emerged that a dopamine agonist, pramipexole, may increase the risk of heart failure among Caucasian patients, but the association has not been examined among Asian patients. The aim of this study was to explore the relationship between use of dopamine agonists and the risk of heart failure. METHODS: Using data from Taiwan's National Health Insurance research database (NHIRD), we identified a population-based cohort comprising 27,135 patients who were prescribed anti-parkinsonian drugs between 2001 and 2010. We conducted a nested case-control study in which 1,707 cases of newly diagnosed heart failure were matched to 3,414 controls (1:2 matched according to age, gender and cohort entry year) within this cohort. Multivariable conditional logistic regressions were used to estimate the association between use of dopamine agonists and heart failure. RESULTS: An increased risk of heart failure was observed with current use of ergot-derived dopamine agonists (adjusted odds ratio [OR] 1.46, 95 % confidence interval [CI] 1.00-2.12) but not with current use of non-ergot-derived dopamine agonists (adjusted OR 1.24, 95 % CI 0.84-1.82). Among non-ergot-derived dopamine agonists, both pramipexole (adjusted OR 1.40, 95 % CI 0.75-2.61) and ropinirole (adjusted OR 1.22, 95 % CI 0.76-1.95) showed a non-significantly increased heart failure risk. Although the findings of our study were limited by lack of statistical power, a clear pattern of an increased duration of pramipexole use and an increased risk of heart failure were observed. CONCLUSION: Use of dopamine agonists, including pramipexole, was associated with non-significantly increased risks of heart failure in this population-based study in Taiwan. Further investigation is needed to clarify this potential association.

The association between thiazolidinediones and hospitalisation for fracture in type 2 diabetic patients: a Taiwanese population-based nested case-control study.

AIMS/HYPOTHESIS: Evidence from the USA has emerged that thiazolidinediones may have a negative effect on the skeleton and increase the risk of fracture, but the association between thiazolidinediones use and fractures has not been evaluated in an Asian population. Using the 2000-2005 Taiwan National Health Insurance claims database, this Taiwanese population-based nested case-control study explored the association between thiazolidinediones use and hospitalisation for bone fracture in type 2 diabetic patients. METHODS: In the study cohort of type 2 diabetic patients, we identified 18,003 patients with fracture and 90,015 matched controls. Multivariable conditional logistic regressions were used to estimate the association between exposure to thiazolidinediones and fractures. Duration of thiazolidinediones use was defined on the basis of cumulative days of exposure to thiazolidinediones during the year prior to the index date, i.e. <30 days, 30 to 180 days and >180 days. RESULTS: More type 2 diabetic patients with fractures than controls used thiazolidinediones (fractures 5.99% vs control 4.06%). Thiazolidinediones use was associated with hospitalisation for fracture and the association was stronger with longer term exposure to thiazolidinediones (<30 days OR 1.32 [95% CI 1.09-1.54], p = 0.005; 30-180 days 1.42 [1.24-1.62], p < 0.0001; and >180 days 1.54 [1.37-1.74], p < 0.0001). This dose-response relationship was significantly evident in women (<30 days, 1.20 [0.93-1.55], p = 0.17; 30-180 days, 1.57 [1.32-1.86], p < 0.0001; and >180 days, 1.76 [1.52-2.04], p < 0.0001), but not in men. CONCLUSIONS/INTERPRETATION: Long-term exposure of type 2 diabetic patients to thiazolidinediones was associated with higher odds of fractures among women without a significant increase in odds of fractures among men.