The impact of sodium-glucose co-transporter-2 inhibitors on dementia and cardiovascular events in diabetic patients with atrial fibrillation.

AIMS: The effectiveness of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on incident dementia in patients with diabetes and atrial fibrillation (AF) remains unknown. This study aimed to investigate the association between SGLT2i and the risk of incident dementia in diabetic patients with AF, and to explore the interactions with oral anticoagulants or dipeptidyl peptidase-4 inhibitors (DPP4i). MATERIALS AND METHODS: We conducted a cohort study using Taiwan's National Health Insurance Research Database. Patients with diabetes and AFwithout a prior history of established cardiovascular diseases, were identified. Using propensity score matching, 810 patients receiving SGLT2i were matched with 1620 patients not receiving SGLT2i. The primary outcome was incident dementia, and secondary outcomes included composite cardiovascular events and mortality. RESULTS: After up to 5 years of follow-up, SGLT2i use was associated with a significantly lower risk of incident dementia (hazard: 0.71, 95% confidence interval: 0.51-0.98), particularly vascular dementia (HR: 0.44, 95% CI: 0.24-0.82). SGLT2i was related to reduced risks of AF-related hospitalisation (HR: 0.72, 95% CI: 0.56-0.93), stroke (HR: 0.75, 95% CI: 0.60-0.94), and all-cause death (HR: 0.33, 95% CI: 0.24-0.44). The protective effects were consistent irrespective of the concurrent use of non-vitamin K antagonist oral anticoagulants (NOACs) or DPP4i. CONCLUSIONS: In diabetic patients with AF, SGLT2i was associated with reduced risks of incident dementia, AF-related hospitalisation, stroke, and all-cause death. The protective effects were independent of either concurrent use of NOACs or DPP4i.

Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population.

BACKGROUND AND AIM: A large genetic effect of a novel gallstone-associated genetic variant, the hepatocyte nuclear factor 4α (HNF4A) rs1800961 polymorphism, has been identified through recent genome-wide association studies. However, this effect has not been validated in Asian populations. We investigated the association between the rs1800961 variant and gallstones among a Taiwanese population. METHODS: A total of 20 405 participants aged between 30 and 70 years voluntarily enrolled in the Taiwan Biobank. Self-report questionnaires, physical examinations, biochemical tests, and genotyping were used for analysis. The association of the HNF4A rs1800961 variant and other metabolic risks with gallstone disease was analyzed using multiple logistic regression models. RESULTS: The minor T allele of HNF4A rs1800961 was associated with an increased risk of gallstone, and the association remained significant even after adjustment for other risk factors including age, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and cigarette smoking (adjusted odds ratio [OR] = 1.90, 95% confidence interval [CI] = 1.31 to 2.75) in male participants. When further stratified by BMI and age, the lithogenic effect was the most significant in male participants with obesity (adjusted OR = 3.55, 95% CI = 1.92 to 6.56) and who were younger (adjusted OR = 2.45, 95% CI = 1.49 to 4.04). CONCLUSION: The novel gallstone-associated HNF4A rs1800961 variant was associated with the risk of gallstone in the Taiwanese men. Screening for the rs1800961 polymorphism may be particularly useful in assessing the risk of gallstone formation in younger or obese men.

The use of individual-based FDG-PET volume of interest in predicting conversion from mild cognitive impairment to dementia.

BACKGROUND: Based on a longitudinal cohort design, the aim of this study was to investigate whether individual-based 18F fluorodeoxyglucose positron emission tomography (18F-FDG-PET) regional signals can predict dementia conversion in patients with mild cognitive impairment (MCI). METHODS: We included 44 MCI converters (MCI-C), 38 non-converters (MCI-NC), 42 patients with Alzheimer's disease with dementia, and 40 cognitively normal controls. Data from annual cognitive measurements, 3D T1 magnetic resonance imaging (MRI) scans, and 18F-FDG-PET scans were used for outcome analysis. An individual-based FDG-PET approach was applied using seven volumes of interest (VOIs), Z transformed using a normal FDG-PET template. Hypometabolism was defined as a Z score < -2 of regional standard uptake value ratio. For the longitudinal cognitive test scores, generalized estimating equations were used. A linear mixed-effects model was used to compare the temporal impact of cortical hypometabolism and cortical thickness degeneration. RESULTS: The clinical follow-up period was 6.6 ± 3.8 years (range 3.1 to 16.0 years). The trend of cognitive decline could differentiate MCI-C from MCI-NC after 3 years of follow-up. In the baseline 18F-FDG-PET scan of the patients with MCI, medial temporal lobe (MTL; 94.7% sensitivity, 80.5% specificity) and posterior cingulate cortex (PCC; 89.5% sensitivity, 73.1% specificity) hypometabolism predicted conversion with high accuracy. 18F-FDG-PET hypometabolism preceded dementia conversion at an interval of 3.70 ± 1.68 years and was earlier than volumetric changes, with the exception of the MTL. CONCLUSIONS: Our finding supports the use of individual-based 18F-FDG-PET analysis to predict MCI conversion to dementia. Reduced FDG-PET metabolism in the MTL and PCC were strongly associated with future cognitive decline in the MCI-C group. Changes in 18F-FDG-PET occurred 1 to 8 years prior to conversion to dementia. Progressive hypometabolism in the PCC, precuneus and lateral temporal lobe, but not MTL, preceded MRI findings at the MCI stage.

Antenatal Corticosteroid Exposure is Associated with Childhood Mental Disorders in Late Preterm and Term Infants.

OBJECTIVES: To study the association between antenatal corticosteroids treatment and childhood mental disorders in infants born at different gestational ages, and to investigate the effect of different administration timing. STUDY DESIGN: This population-based cohort study used data from the Taiwan National Health Insurance Research Database. All singleton live births born between 2004 and 2010 were enrolled and followed up for at least 6 years. The primary outcome was any childhood mental disorder. Secondary outcomes included 7 specific subgroups of mental disorders. RESULTS: A total of 1 163 443 singleton infants were included in the analysis, and 16 847 (1.45%) infants were exposed to antenatal corticosteroid treatment. Children exposed to antenatal corticosteroids were found to have a higher risk of developing childhood mental disorders in the entire cohort (hazard ratio [HR], 1.13; 95% CI, 1.08-1.18), the term group (HR, 1.11; 95% CI, 1.05-1.16), and the late-preterm group (HR, 1.15; 95% CI, 1.06-1.25). The administration of corticosteroids in the early stage of pregnancy (<28 weeks of gestation) significantly increased the risk of childhood mental disorders (HR, 1.22; 95% CI, 1.14-1.31). CONCLUSIONS: Exposure to antenatal corticosteroid treatment increases the cumulative risk of childhood mental disorders and attention deficit hyperactivity disorders, both in term and late preterm infants. The administration of corticosteroids in the early stage of pregnancy tends to increase the risk of mental disorders.

Multi-ethnic Imputation System (MI-System): A genotype imputation server for high-dimensional data.

OBJECTIVE: Genotype imputation is a commonly used technique that infers un-typed variants into a study's genotype data, allowing better identification of causal variants in disease studies. However, due to overrepresentation of Caucasian studies, there's a lack of understanding of genetic basis of health-outcomes in other ethnic populations. Therefore, facilitating imputation of missing key-predictor-variants that can potentially improve a risk health-outcome prediction model, specifically for Asian ancestry, is of utmost relevance. METHODS: We aimed to construct an imputation and analysis web-platform, that primarily facilitates, but is not limited to genotype imputation on East-Asians. The goal is to provide a collaborative imputation platform for researchers in the public domain towards rapidly and efficiently conducting accurate genotype imputation. RESULTS: We present an online genotype imputation platform, Multi-ethnic Imputation System (MI-System) (https://misystem.cgm.ntu.edu.tw/), that offers users 3 established pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1 for conducting imputation analyses. In addition to 1000 Genomes and Hapmap3, a new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. MI-System further offers functions to create customized reference panels to be used for imputation, conduct quality control, split whole genome data into chromosomes, and convert genome builds. CONCLUSION: Users can upload their genotype data and perform imputation with minimum effort and resources. The utility functions further can be utilized to preprocess user uploaded data with easy clicks. MI-System potentially contributes to Asian-population genetics research, while eliminating the requirement for high performing computational resources and bioinformatics expertise. It will enable an increased pace of research and provide a knowledge-base for genetic carriers of complex diseases, therefore greatly enhancing patient-driven research. STATEMENT OF SIGNIFICANCE: Multi-ethnic Imputation System (MI-System), primarily facilitates, but is not limited to, imputation on East-Asians, through 3 established prephasing-imputation pipelines, SHAPEIT2-IMPUTE2, SHAPEIT4-IMPUTE5, and Beagle5.1, where users can upload their genotype data and perform imputation and other utility functions with minimum effort and resources. A new customized Taiwan Biobank (TWB) reference panel, specifically created for Taiwanese-Chinese ancestry is provided. Utility functions include (a) create customized reference panels, (b) conduct quality control, (c) split whole genome data into chromosomes, and (d) convert genome builds. Users can also combine 2 reference panels using the system and use combined panels as reference to conduct imputation using MI-System.

Handgrip strength is associated with mortality in community-dwelling older adults: the Yilan cohort study, Taiwan.

INTRODUCTION: Hand grip strength (HGS) is one of the methods to help early identification of physical frailty and sarcopenia, the major concerns in the aging societies. It is also crucial to evaluate its impact on mortality. However, the available evidence regarding such impact among specific age cohorts (65 to 74 years and above) is limited. This study tried to investigate the relationship between HGS and mortality among specific cohorts of the community-dwelling older individuals in Yilan, Taiwan. METHODS: A seven-year longitudinal follow-up study was conducted involving 2,468 community-dwelling older individuals in Yilan. The participants were divided into two groups based on their quartiles of hand grip strength: with poor HGS and with good HGS. The association between HGS and mortality was examined using Cox proportional hazards models. RESULTS: The analysis revealed that age, HGS, gender, medical history of cardiovascular diseases, body mass index, and wrist-hip ratio had significant impacts on seven-year survival. Specifically, individuals with poor HGS exhibited increased mortality, with an adjusted hazard ratio (HR) of 1.87 (95% CI: 1.52-2.30). Furthermore, the adverse effect of poor HGS on mortality was more pronounced in males aged 65-74 years (adjusted HR 4.12, 95% CI: 2.16-7.84), females aged 75 years or older (2.09, 1.43-3.04) and males aged 75 years or older (1.49, 1.07-2.07). CONCLUSION: Poor hand grip strength is an independent risk factor for mid-term mortality among community-dwelling older individuals in Yilan. The assessment of HGS can serve as a valuable tool in identifying older individuals at higher risk of death.

Association between periodontitis treatment and dementia in Taiwanese adults.

BACKGROUND: The chronic systemic inflammatory response in periodontitis may be a potential risk factor for dementia, especially in adults. This study determined the association between periodontal treatment and dementia in adults and evaluated the effect of regular scaling treatment on the risk of dementia in this population. METHODS: This case-control study identified 18,930 patients with a dementia-related diagnosis from the Taiwan National Health Insurance Research Database. Scaling and periodontal emergency treatments were evaluated after 1 year and 3 years. Using multivariable logistic regression analysis to evaluate the association between periodontal emergency treatment and dementia risk. RESULTS: The results showed that scaling treatment rates were lower in the dementia cohort than the non-dementia cohort after 1 and 3 years. Patients who received periodontal emergency treatment within 3 years had a significantly increased risk of dementia. Furthermore, patients with periodontitis who did not receive scaling treatment within 3 years had a higher risk of dementia than patients without periodontitis (OR, 1.22; 95% CI, 1.10-1.35). CONCLUSION: This study demonstrated that periodontitis and dementia are associated, and that periodontitis is a risk factor for dementia in adults. The risk of dementia was dependent on the periodontal health status of adults, and our findings suggest that regular scaling can reduce the incidence of dementia in adults. Therefore, regular and routine scaling treatment is suggested for adults.

Trends, correlates, and disease patterns of sedative-hypnotic use among elderly persons in Taiwan.

OBJECTIVE: The population-based National Health Insurance database was adopted to investigate the prevalence, correlates, and disease patterns of sedative-hypnotic use in elderly persons in Taiwan. METHODS: The National Health Research Institutes provided a database of 1,000,000 random subjects in the National Health Insurance program. We adopted this sample of subjects who were older than 65 years from 1997 to 2005 and examined the proportions of psychiatric and nonpsychiatric disorders with regard to sedative-hypnotic use. RESULTS: The 1-year prevalence of sedative-hypnotic use in elderly individuals increased from 1.7% in 1997 to 5.5% in 2005. The 1-year prevalence rates of benzodiazepine (BZD) and non-BZD hypnotics were 3.2 and 3.1%, respectively, in 2005. The overall hypnotic use was highest in ≥85-year-olds, males, those with lower amounts of insurance or higher Charlson Comorbidity Index scores and those living in eastern Taiwan. Both BZD and non-BZD hypnotic use were most commonly used in nonpsychiatric disorders instead of psychiatric disorders. Among the psychiatric disorders, the disorders that accounted for higher BZD and non-BZD hypnotic use were senile and presenile organic psychotic conditions (3.4 and 3.4%, respectively). Higher BZD and non-BZD use was for diseases of the respiratory system (30.4 and 17.8%, respectively), the circulatory system (20.4 and 22.4%, respectively), and neoplasms (12.6 and 13.8%, respectively). CONCLUSION: The prevalence rates of both BZD and non-BZD sedative-hypnotic use increased from 1997 to 2005 in the elderly. The risk factors for sedative-hypnotic use were aging, male sex, lower insurance amount, and higher Charlson Comorbidity Index scores. Most BZD and non-BZD sedative-hypnotic users were persons with nonpsychiatric disorders.

Impact of Amyloid Pathology in Mild Cognitive Impairment Subjects: The Longitudinal Cognition and Surface Morphometry Data.

The amyloid framework forms the central medical theory related to Alzheimer disease (AD), and the in vivo demonstration of amyloid positivity is essential for diagnosing AD. On the basis of a longitudinal cohort design, the study investigated clinical progressive patterns by obtaining cognitive and structural measurements from a group of patients with amnestic mild cognitive impairment (MCI); the measurements were classified by the positivity (Aß+) or absence (Aß-) of the amyloid biomarker. We enrolled 185 patients (64 controls, 121 patients with MCI). The patients with MCI were classified into two groups on the basis of their [18F]flubetaben or [18F]florbetapir amyloid positron-emission tomography scan (Aß+ vs. Aß-, 67 vs. 54 patients) results. Data from annual cognitive measurements and three-dimensional T1 magnetic resonance imaging scans were used for between-group comparisons. To obtain longitudinal cognitive test scores, generalized estimating equations were applied. A linear mixed effects model was used to compare the time effect of cortical thickness degeneration. The cognitive decline trajectory of the Aß+ group was obvious, whereas the Aß- and control groups did not exhibit a noticeable decline over time. The group effects of cortical thickness indicated decreased entorhinal cortex in the Aß+ group and supramarginal gyrus in the Aß- group. The topology of neurodegeneration in the Aß- group was emphasized in posterior cortical regions. A comparison of the changes in the Aß+ and Aß- groups over time revealed a higher rate of cortical thickness decline in the Aß+ group than in the Aß- group in the default mode network. The Aß+ and Aß- groups experienced different APOE ε4 effects. For cortical-cognitive correlations, the regions associated with cognitive decline in the Aß+ group were mainly localized in the perisylvian and anterior cingulate regions. By contrast, the degenerative topography of Aß- MCI was scattered. The memory learning curves, cognitive decline patterns, and cortical degeneration topographies of the two MCI groups were revealed to be different, suggesting a difference in pathophysiology. Longitudinal analysis may help to differentiate between these two MCI groups if biomarker access is unavailable in clinical settings.

Comparison of Renal Responses Between Continuous Mycophenolate Mofetil and Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Lupus Nephritis.

BACKGROUND: Mycophenolate mofetil (MMF) is extensively used for induction and maintenance therapy in patients with lupus nephritis (LN). Enteric-coated mycophenolate sodium (EC-MPS) was developed to reduce the adverse gastrointestinal effects of MMF. However, the therapeutic efficacy of MMF and EC-MPS in LN remains unclear. This study aimed to examine the treatment effects of EC-MPS in LN patients with prior MMF exposure. METHODS: In this medical records review study, we included 54 LN patients, of whom 34 converted from MMF to EC-MPS at equimolar doses in 2016-2018 (nonmedical switching group) and 20 received continuous MMF treatment. Patients achieving complete remission or partial remission before the conversion were categorized as responders, whereas those who had never achieved complete remission or partial remission were categorized as nonresponders. RESULTS: Baseline proteinuria was higher in the nonmedical switching group. Although elevation in proteinuria was observed after nonmedical switching, the serum creatinine concentration and estimated glomerular filtration rate both improved. Responders in the nonmedical switching group had lower proteinuria and higher complement 3 levels. In the subgroup analysis, albeit the modest increase in daily urine protein, anti-double-stranded DNA antibody levels, estimated glomerular filtration rate, and complements 3 and 4 seemed comparable after conversion. CONCLUSION: Switching to EC-MPS demonstrated a similar short-term renal response to continuous MMF treatment in LN patients. Prospective randomized trials are required to verify our findings.

Factors associated with incident severe pulmonary arterial hypertension in systemic autoimmune rheumatic diseases: a nationwide study.

OBJECTIVE: To assess the association of severe pulmonary arterial hypertension (PAH) with particulate matter <2.5 µm (p.m.2.5) and clinical data in patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: We used the 2003-2017 nationwide data in Taiwan to identify patients with SARDs, including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis/polymyositis and primary Sjögren's syndrome. We identified 479 cases with severe PAH and selected controls matched (1:4) for age, sex, and index year. We used conditional logistic regression analysis to determine factors associated with risks for severe PAH shown as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: We found that severe PAH was highly associated with interstitial lung disease (OR, 8.57; 95% CI: 5.52, 13.32), congestive heart failure (OR, 7.62; 95% CI: 5.02, 11.55), valvular heart disease (OR, 3.34; 95% CI: 2.03, 5.50) and slightly associated with thyroid diseases (OR, 1.88; 95% CI: 1.18, 3.00), but not the level of exposure to p.m.2.5. Increased risk for PAH was found in patients receiving corticosteroid (prednisolone equivalent dosage, mg/day, OR, 1.03; 95% CI: 1.01, 1.05), biologics (OR, 2.18; 95% CI: 1.15, 4.12) as well as immunosuppressants, including ciclosporin (OR, 2.17; 95% CI: 1.31, 3.59), azathioprine (OR, 1.96; 95% CI: 1.48, 2.61), cyclophosphamide (OR, 2.01; 95% CI: 1.30, 3.11) and mycophenolate mofetil/mycophenolic acid (OR, 2.42; 95% CI: 1.37, 4.27), and those with the highest level of insured amount (reference, lowest level; OR, 0.53; 95% CI: 0.34, 0.83). CONCLUSION: The population-based study identified risks for severe PAH in patients with SARDs, and these findings provide evidence for PAH risk stratification in patients with SARDs.

Association test using Copy Number Profile Curves (CONCUR) enhances power in rare copy number variant analysis.

Copy number variants (CNVs) are the gain or loss of DNA segments in the genome that can vary in dosage and length. CNVs comprise a large proportion of variation in human genomes and impact health conditions. To detect rare CNV associations, kernel-based methods have been shown to be a powerful tool due to their flexibility in modeling the aggregate CNV effects, their ability to capture effects from different CNV features, and their accommodation of effect heterogeneity. To perform a kernel association test, a CNV locus needs to be defined so that locus-specific effects can be retained during aggregation. However, CNV loci are arbitrarily defined and different locus definitions can lead to different performance depending on the underlying effect patterns. In this work, we develop a new kernel-based test called CONCUR (i.e., copy number profile curve-based association test) that is free from a definition of locus and evaluates CNV-phenotype associations by comparing individuals' copy number profiles across the genomic regions. CONCUR is built on the proposed concepts of "copy number profile curves" to describe the CNV profile of an individual, and the "common area under the curve (cAUC) kernel" to model the multi-feature CNV effects. The proposed method captures the effects of CNV dosage and length, accounts for the numerical nature of copy numbers, and accommodates between- and within-locus etiological heterogeneity without the need to define artificial CNV loci as required in current kernel methods. In a variety of simulation settings, CONCUR shows comparable or improved power over existing approaches. Real data analyses suggest that CONCUR is well powered to detect CNV effects in the Swedish Schizophrenia Study and the Taiwan Biobank.

Association between α-glucosidase inhibitor use and psoriatic disease risk in patients with type 2 diabetes mellitus: A population-based cohort study.

AIMS: To investigate the association between the use of alpha-glucosidase inhibitors (AGIs) and the risk of psoriatic disease (ie, psoriasis and psoriatic arthritis) in patients with type 2 diabetes mellitus (T2DM) treated with metformin. METHODS: Using the 1999-2013 Taiwanese Longitudinal Cohort of Diabetes Patients Database, we identified patients with T2DM who initiated hypoglycaemic treatment between 2003 and 2012. After excluding patients with a history of psoriatic disease (International Classification of Disease, Ninth Revision, Clinical Modification codes 696.0-1) before T2DM diagnosis, patients who received antidiabetic treatment for <90 days, and patients aged <20 or >100 years, we identified 1390 patients who received metformin+AGIs (AGI exposure group) and 47 514 patients who received metformin only (comparison group). We matched the two groups at a 1:10 ratio by age, sex, and index date of T2DM drug use. The association between AGI use and psoriatic disease risk was analysed using a Cox proportional hazard mode; time-dependent covariates for factors were reported in terms of hazard ratios (HRs) with 95% confidence intervals (CIs) after age, sex, T2DM duration, and comorbidities were controlled for. RESULTS: After adjusting the AGI exposure and comparison groups for potential confounders, we found that psoriatic disease risk was associated with metformin+AGI use when AGI was discontinued for 30 days (HR, 8.77; 95% CI, 1.58-48.5) and when a high AGI dose was administered; furthermore, the risk declined during AGI discontinuation. CONCLUSIONS: This population-based study reports that AGI use and interruption of AGI use may be associated with increased psoriatic disease risk in treated patients with T2DM.

Social Isolation, Loneliness, and All-Cause Mortality in Patients With Cardiovascular Disease: A 10-Year Follow-up Study.

OBJECTIVE: Social isolation and loneliness have been associated with increased incidence of cardiovascular disease (CVD), but few studies have evaluated the impact of social isolation and loneliness on mortality in people with existing CVD, and these are limited to Western populations. We examined whether social isolation and loneliness are associated with increased risk of mortality in individuals with established CVD in Taiwan. METHODS: The cohort was composed of 1267 patients with confirmed CVD 65 years or older followed up for up to 10 years. Cox proportional hazard regression models were used to examine the association between social isolation and loneliness at baseline and mortality at follow-up by adjusting for demographic variables, health-related behaviors, and health status. RESULTS: There were 593 deaths during the follow-up period. Social isolation was associated with increased risk of mortality after accounting for established risk factors (hazard ratio [HR] = 1.16; 95% confidence interval [CI] = 1.06-1.26), whereas loneliness was not associated with increased risk of mortality (HR = 0.95; 95% CI = 0.82-1.09). When both social isolation and loneliness were included in the model, social isolation maintained an association with mortality (HR = 1.16; 95% CI =1.07-1.27). CONCLUSIONS: Social isolation is associated with an increased risk of mortality in patients with CVD, and the effects are independent of loneliness. These findings expand our knowledge about the impact of social isolation on the outcomes of CVD in non-Western countries. Efforts to reduce isolation may have substantial benefits in terms of mortality in patients with CVD.

Hypoglycaemic episodes increase the risk of ventricular arrhythmia and sudden cardiac arrest in patients with type 2 diabetes-A nationwide cohort study.

BACKGROUND: The impact of hypoglycaemic episode (HE) on the risk of ventricular arrhythmia (VA) and sudden cardiac arrest (SCA) remains unclear. We hypothesized that HE increases the risk of both VA and SCA and that glucose-lowering agents causing HE also increase the risk of VA/SCA in patients with type 2 diabetes (T2D). METHODS: Patients aged 20 years or older with newly diagnosed T2D were identified using the Taiwan National Health Insurance Database. HE was defined as the presentation of hypoglycaemic coma or specified/unspecified hypoglycaemia. The control group consisted of T2D patients without HE. The primary outcome was the occurrence of VA (including ventricular tachycardia and fibrillation) and SCA during the defined follow-up periods. A multivariate Cox hazards regression model was used to evaluate the hazard ratio (HR) for VA or SCA. RESULTS: A total of 54 303 patients were screened, with 1037 patients with HE assigned to the HE group and 4148 frequency-matched patients without HE constituting the control group. During a mean follow-up period of 3.3 ± 2.5 years, 29 VA/SCA events occurred. Compared with the control group, HE group had a higher incidence of VA/SCA (adjusted HR: 2.42, P = .04). Patients who had used insulin for glycaemic control showed an increased risk of VA/SCA compared with patients who did not receive insulin (adjusted HR: 3.05, P = .01). CONCLUSIONS: The HEs in patients with T2D increased the risk of VA/SCA, compared with those who did not experience HEs. Use of insulin also independently increased the risk of VA/SCA.

Hydroxychloroquine may reduce risk of Pneumocystis pneumonia in lupus patients: a Nationwide, population-based case-control study.

BACKGROUND: Pneumocystis pneumonia (PCP) is increasingly being diagnosed in patients with systemic lupus erythematosus (SLE), and hydroxychloroquine (HCQ) has been found to possess antifungal activities. We hence aimed to investigate the association between HCQ and PCP risk among patients with SLE. METHODS: Using the 1997-2013 nationwide claim data, we identified 24,343 newly-diagnosed SLE patients. We then identified 58 PCP cases and selected 348 non-PCP controls matching (1:6) by age, sex, disease duration and the year of PCP diagnosis date. The risk of PCP was assessed by determing odds ratios (ORs) with 95% confidence intervals (CIs) by using multivariable conditional logistic regression. RESULTS: The risk of PCP was associated with moderate to severe renal disease (OR 6.73, 95% CI 1.98-22.92), higher doses of glucocorticoids (≤5 mg/day, reference; 5-10 mg/day, OR 25.88, 95% CI 2.97-225.33; > 10 mg/day, OR 286.58, 95% CI 28.58-> 999), higher 3-month cumulative dose of cyclophosphamide (not use, reference; ≤1.4 g, OR 0.64, 95% CI 0.14-3.01; > 1.4 g, OR 11.52, 95% CI 1.97-67.39) and use of mycophenolate mofetil/mycophenolic acid (OR 50.79, 95% CI 5.32-484.77), whereas 3-month cumulative dose of HCQ was associated with a reduced risk of PCP among patients with SLE (not use, reference; ≤14 g, OR 0.69, 95% CI 0.21-2.24; > 14 g, OR 0.20, 95% CI 0.05-0.71). CONCLUSIONS: This study demonstrated incident PCP was associated with mycophenolate mofetil/mycophenolic acid use and higher doses of cyclophosphamide or glucocorticoid, whereas the use of a higher dose of HCQ was associated with a reduced risk of PCP in lupus patients.

IMPLEMENTATION OF AN ELECTRONIC DASHBOARD WITH A REMOTE MANAGEMENT SYSTEM TO IMPROVE GLYCEMIC MANAGEMENT AMONG HOSPITALIZED ADULTS.

Objective: Better glycemic control for hospitalized diabetic patients significantly reduces health expenditures and improves disease outcomes. We developed a dynamic dashboard with a remote management system and evaluated its impact on inpatient glycemic control. Methods: This was an observational institution-wide study; study participants were enrolled from a 1,500-bed public medical center from 2016 to 2018. We evaluated the impact of a dynamic dashboard system, which analyzed and monitored all glucose data with virtual glycemic management recommendation by a team of endocrinologists, over 3 × 1-year periods: 2016 (pre-implementation), 2017 (development), and 2018 (implementation). Results: A total of 51,641 discharges with 878,159 blood glucose measurements were obtained during the 3-year period. After implementation of the dashboard system, the proportion of patients with poor glycemic control (hyperglycemia or hypoglycemia) was reduced by 31% (from 10.2 to 7.0 per day per 100 patients with glucose monitoring; P<.001); hyperglycemia decreased by 25% (from 6.1 to 4.6 per day per 100 patients with glucose monitoring; P<.001), and hypoglycemia decreased by 45% (from 4.2 to 2.3 per day per 100 patients with glucose monitoring; P<.001). Furthermore, the trend in the proportion of patients within the treat-to-target range showed significant improvement (P<.001) during the development period, with effectiveness maintained throughout the implementation period. Conclusion: We successfully installed a dynamic, electronic medical records-based dashboard monitoring system to improve inpatient glycemic control. The system, supported by a team of endocrinologists via remote recommendations, could efficiently fill an important need for improved glycemic management among hospitalized adults. Abbreviations: CDE = certified diabetes educator; DM = diabetes mellitus; EMR = electronic medical record; POC = point-of-care; TCVGH = Taichung Veterans General Hospital; UCSF = University of California, San Francisco; U.S. = United States; vGMS = virtual glucose management service.

Nephrotic Syndrome is Associated with Increased Risk of Ischemic Stroke.

BACKGROUND: To determine if the nephrotic syndrome (NS) is an independent risk factor of ischemic stroke. METHODS: This is a retrospective nationwide cohort study through an analysis of the National Health Insurance Research Database in Taiwan. To evaluate the risk of stroke, the corresponding controls were selected at a 4:1 ratio in the number of subjects, and they were matched with the study group in age, gender, Charlson comorbidity index (CCI), and index date. RESULTS: From a total of 16,245 surveyed subjects, ischemic stroke occurred in 1235 (7.6%) and hemorrhagic stroke in 129 (.74%) of them. The incidence of ischemic stroke was significantly higher in patients with NS (n = 3496) compared to control patients without NS (n = 13,984) (9.92 versus 7.10, per 1000 person-year, P < .001). In the multivariate analysis, the overall adjusted hazard ratio (aHR) of stroke in NS patients was 1.37 (95% CI, 1.21-1.54, P < .001). The risk factors of ischemic stroke were NS (aHR, 1.38 [95% confidence interval {CI}, 1.21-1.57]; P < .001), age greater than 45 years (aHR, 7.98 [95% CI, 6.47-9.48]; P < .001), male gender (aHR, 1.23 [95% CI, 1.10-1.38]; P < .001), CCI greater than or equal to 1 (aHR ≥ 1.25 in different CCI score groups, all at P ≤ .003), ischemic heart disease (aHR, 1.95 [95% CI, 1.67-2.29]; P < .001), heart failure (HR, 1.77 [95% CI, 1.30-2.42]; P < .001). Risk factors of hemorrhagic stroke were those aged greater than 45 years, or with systemic lupus erythematosus, but not NS. CONCLUSIONS: We provided the first evidence that patients with NS had an increased risk of ischemic stroke.

Antithrombotic Treatment May Reduce Mortality Among New-Onset Atrial Fibrillation Patients with Gray-Zone Risk of Stroke.

In clinical practice, some atrial fibrillation (AF) patients were classified as having low and moderate stroke risk by the CHADS2 score (≤ 1) in 2001 but in 2012 they were not truly classified as low risk of stroke according to the CHA2DS2-VASc score (≥ 2) (defined gray zone). Therefore, a treatment gap exists in gray zone AF patients. This study aimed to evaluate whether gray zone AF patients could benefit from reduced all-cause mortality under antithrombotic treatment. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance from January 2000 to December 2011. The new-onset AF patients consisted of a gray zone cohort with a total of 1237 patients being enrolled. The primary outcome was all-cause mortality between 2001 and 2011. Patients in the gray zone receiving antithrombotic treatment had a significant reduction in all-cause mortality [hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.16-0.28] compared with the no treatment group [warfarin only: HR, 0.28 (95% CI, 0.15-0.52); warfarin + Aspirin: HR, 0.21 (95% CI, 0.15-0.30); and Aspirin only: HR, 0.22 (95% CI, 0.16-0.29) ]. All-cause mortality was notably increased when any of the following risk factors were present: age 65-74 years, age ≥ 75 years, chronic kidney disease, and vascular disease. We concluded that AF patients in the gray zone must receive either anticoagulant and/or antiplatelet treatment and there is a lower mortality in these groups during long-term follow-up. Further investigation is needed to observe whether the antithrombotic drugs have benefits for patients with AF with a CHA2DS2-VASc score < 2.

Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study.

OBJECTIVE: Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. METHODS: T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE. RESULTS: A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE. CONCLUSION: Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.